MMP14

Summary

MMP14 (matrix metallopeptidase 14, HGNC:7160) is a protein-coding gene on chromosome 14q11.2, encoding Matrix metalloproteinase-14 (P50281). Endopeptidase that degrades various components of the extracellular matrix such as collagen.

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP’s are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion.

Source: NCBI Gene 4323 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Winchester syndrome (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 382 total — 2 pathogenic (top 9% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 8 tissues, sQTL in 26 (q < 0.05)
• Phenotypes (HPO): 47
• Drug target: yes — 2 curated mechanism-of-action drugs; 13 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.31 (highly constrained)
• MANE Select transcript: NM_004995
• Interaction hub: 2,434 STRING partners (top 4% of genes corpus-wide)
• Notable: 382 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7160
Approved symbol	MMP14
Name	matrix metallopeptidase 14
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MT1-MMP
Ensembl gene	ENSG00000157227
Ensembl biotype	protein_coding
OMIM	600754
Entrez	4323

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 non_stop_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000311852

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 1, TSL 5: 1

ENST00000311852, ENST00000547074, ENST00000547279, ENST00000547596, ENST00000548162, ENST00000548761, ENST00000680097, ENST00000680941, ENST00000928197, ENST00000928199, ENST00000984063, ENST00001137697

RefSeq mRNA: 1 — MANE Select: NM_004995 NM_004995

CCDS: CCDS9577

Canonical transcript exons

ENST00000311852 — 10 exons

Exon	Start	End
ENSE00001431522	22845708	22847758
ENSE00002374150	22836585	22836925
ENSE00003493963	22841491	22841639
ENSE00003495503	22843710	22843870
ENSE00003499980	22844371	22844509
ENSE00003503061	22844630	22844780
ENSE00003548702	22845251	22845366
ENSE00003555079	22842410	22842717
ENSE00003635990	22841913	22842035
ENSE00003660436	22843257	22843418

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 195.0155 / max 7643.4905, expressed in 1488 samples.

Highest expression (Bgee): stromal cell of endometrium, mucosa of stomach, gall bladder, endocervix, body of uterus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MMP14 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 26 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	2.0e-23	-0.61	14:22842999:A:G
Esophagus Mucosa	sqtl	2.0e-21	+0.60	14:22842999:A:G
Skin Sun Exposed Lower leg	sqtl	2.6e-16	+0.52	14:22842999:A:G
Skin Not Sun Exposed Suprapubic	sqtl	1.3e-15	+0.53	14:22842999:A:G
Nerve Tibial	sqtl	4.6e-14	+0.53	14:22842999:A:G
Thyroid	sqtl	2.1e-12	+0.52	14:22842999:A:G
Colon Transverse	sqtl	4.4e-11	+0.61	14:22842999:A:G
Lung	sqtl	2.9e-08	+0.42	14:22842999:A:G
Artery Tibial	sqtl	4.8e-08	-0.41	14:22842999:A:G
Adipose Visceral Omentum	sqtl	1.4e-07	-0.45	14:22842999:A:G
Breast Mammary Tissue	sqtl	2.0e-07	-0.51	14:22842999:A:G
Small Intestine Terminal Ileum	sqtl	2.4e-07	+0.69	14:22842999:A:G
Esophagus Muscularis	sqtl	5.8e-07	+0.49	14:22842999:A:G
Esophagus Gastroesophageal Junction	sqtl	1.7e-06	+0.47	14:22842999:A:G
Adrenal Gland	eqtl	3.4e-06	-0.34	14:22839777:A:G
Artery Aorta	sqtl	7.8e-06	+0.47	14:22842999:A:G
Colon Sigmoid	sqtl	2.2e-04	-0.48	14:22842999:A:G
Cells Cultured fibroblasts	eqtl	4.8e-04	+0.11	14:22828035:A:C
Esophagus Mucosa	eqtl	2.3e-03	-0.14	14:22557312:TC:T
Vagina	sqtl	2.4e-03	+0.58	14:22842999:A:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
138824	158.6884	1478
138823	19.8304	1397
138825	7.5058	1136
138826	6.9820	1208
138827	1.8970	662
138829	0.1120	39

Top tissues by expression

showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.72	gold quality
mucosa of stomach	UBERON:0001199	99.16	gold quality
gall bladder	UBERON:0002110	98.68	gold quality
endocervix	UBERON:0000458	98.62	gold quality
body of uterus	UBERON:0009853	98.30	gold quality
ectocervix	UBERON:0012249	98.22	gold quality
smooth muscle tissue	UBERON:0001135	97.70	gold quality
right coronary artery	UBERON:0001625	97.67	gold quality
popliteal artery	UBERON:0002250	97.62	gold quality
tibial artery	UBERON:0007610	97.62	gold quality
skin of leg	UBERON:0001511	97.59	gold quality
thoracic aorta	UBERON:0001515	97.48	gold quality
aorta	UBERON:0000947	97.46	gold quality
ascending aorta	UBERON:0001496	97.46	gold quality
descending thoracic aorta	UBERON:0002345	97.42	gold quality
right ovary	UBERON:0002118	97.34	gold quality
left coronary artery	UBERON:0001626	97.20	gold quality
skin of abdomen	UBERON:0001416	97.16	gold quality
left uterine tube	UBERON:0001303	97.15	gold quality
left ovary	UBERON:0002119	97.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.94	gold quality
minor salivary gland	UBERON:0001830	96.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.57	gold quality
lower esophagus	UBERON:0013473	96.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.54	gold quality
islet of Langerhans	UBERON:0000006	96.44	gold quality
omental fat pad	UBERON:0010414	96.39	gold quality
coronary artery	UBERON:0001621	96.35	gold quality
peritoneum	UBERON:0002358	96.35	gold quality
right lung	UBERON:0002167	96.34	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.13	gold quality
esophagus	UBERON:0001043	96.05	gold quality
upper lobe of left lung	UBERON:0008952	96.02	gold quality
esophagus mucosa	UBERON:0002469	95.81	gold quality
nerve	UBERON:0001021	95.53	gold quality
tibial nerve	UBERON:0001323	95.53	gold quality
transverse colon	UBERON:0001157	95.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.34	gold quality
lower esophagus mucosa	UBERON:0035834	95.16	gold quality
right lobe of thyroid gland	UBERON:0001119	94.92	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.81	gold quality
body of stomach	UBERON:0001161	94.71	gold quality
upper lobe of lung	UBERON:0008948	94.34	gold quality
vagina	UBERON:0000996	94.25	gold quality
saliva-secreting gland	UBERON:0001044	94.25	gold quality
zone of skin	UBERON:0000014	94.18	gold quality
sural nerve	UBERON:0015488	94.11	gold quality
left lobe of thyroid gland	UBERON:0001120	94.06	gold quality
uterine cervix	UBERON:0000002	93.96	gold quality
stomach	UBERON:0000945	93.93	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.88	gold quality
mouth mucosa	UBERON:0003729	93.75	gold quality
small intestine	UBERON:0002108	93.73	gold quality
colonic epithelium	UBERON:0000397	93.63	gold quality
right uterine tube	UBERON:0001302	93.40	gold quality
rectum	UBERON:0001052	93.07	gold quality
right atrium auricular region	UBERON:0006631	92.90	gold quality
thyroid gland	UBERON:0002046	92.43	gold quality
ovary	UBERON:0000992	92.33	gold quality
metanephros cortex	UBERON:0010533	92.28	gold quality
myometrium	UBERON:0001296	92.00	gold quality
left adrenal gland	UBERON:0001234	91.95	gold quality
pancreas	UBERON:0001264	91.91	gold quality
left adrenal gland cortex	UBERON:0035825	91.82	gold quality
colon	UBERON:0001155	91.70	gold quality
fundus of stomach	UBERON:0001160	91.70	gold quality
intestine	UBERON:0000160	91.69	gold quality
cardiac atrium	UBERON:0002081	91.30	gold quality
body of pancreas	UBERON:0001150	91.29	gold quality
large intestine	UBERON:0000059	91.01	gold quality
sigmoid colon	UBERON:0001159	90.96	gold quality
right adrenal gland	UBERON:0001233	90.78	gold quality
adrenal cortex	UBERON:0001235	90.51	gold quality
female reproductive system	UBERON:0000474	90.35	gold quality
vermiform appendix	UBERON:0001154	90.31	gold quality
uterus	UBERON:0000995	90.11	gold quality
adrenal gland	UBERON:0002369	90.06	gold quality
adipose tissue	UBERON:0001013	90.00	gold quality
right adrenal gland cortex	UBERON:0035827	89.98	gold quality
urinary bladder	UBERON:0001255	89.94	gold quality
caecum	UBERON:0001153	89.84	gold quality
cartilage tissue	UBERON:0002418	89.69	gold quality
connective tissue	UBERON:0002384	89.50	gold quality
apex of heart	UBERON:0002098	89.36	gold quality
prostate gland	UBERON:0002367	89.20	gold quality
nasal cavity mucosa	UBERON:0001826	88.91	gold quality
ventricular zone	UBERON:0003053	88.80	gold quality
heart	UBERON:0000948	88.72	gold quality
pancreatic ductal cell	CL:0002079	88.69	gold quality
spleen	UBERON:0002106	88.55	gold quality
lymph node	UBERON:0000029	87.99	gold quality
mucosa of transverse colon	UBERON:0004991	87.88	gold quality
type B pancreatic cell	CL:0000169	87.85	gold quality
calcaneal tendon	UBERON:0003701	87.85	gold quality
cervix squamous epithelium	UBERON:0006922	87.85	gold quality
tendon of biceps brachii	UBERON:0008188	87.72	gold quality
heart left ventricle	UBERON:0002084	87.36	gold quality
cardiac ventricle	UBERON:0002082	87.07	gold quality
cervix epithelium	UBERON:0004801	86.62	gold quality
lung	UBERON:0002048	86.36	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	100.01
E-MTAB-8142	yes	100.01
E-MTAB-8410	yes	43.26
E-CURD-112	yes	14.95
E-ANND-3	yes	12.64
E-GEOD-83139	yes	7.70
E-ENAD-27	yes	7.28
E-MTAB-7249	yes	3.65

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Endometrium 1	tissue	149.2	medium
Gallbladder	tissue	138.8	low
Choroid plexus	tissue	126.1
Placenta	tissue	111.7	low
Ovary	tissue	106.5	low
Vagina	tissue	105.0	low
Smooth muscle	tissue	99.0	low
Urinary bladder	tissue	95.5	medium
Cervix	tissue	91.5	medium
Skin 1	tissue	62.9	low
Parathyroid gland	tissue	61.4	low
Spinal cord	tissue	60.7
Superior colliculi	tissue	58.6
Appendix	tissue	56.5	low
Adipose tissue	tissue	53.6	medium
Lung	tissue	44.8	medium
Seminal vesicle	tissue	42.9	medium
Esophagus	tissue	39.5	low
Substantia nigra	tissue	39.4
Fallopian tube	tissue	37.9	medium
Small intestine	tissue	37.8	medium
Duodenum	tissue	37.1	medium
Stomach 1	tissue	36.2	medium
Colon	tissue	34.6	low
Rectum	tissue	34.4	low
Medulla oblongata	tissue	32.3
Prostate	tissue	30.9	medium
Midbrain	tissue	29.4
Tonsil	tissue	28.9	low
Breast	tissue	28.8	medium
Salivary gland	tissue	26.3	not detected
Pancreas	tissue	26.2	low
Hypothalamus	tissue	24.1
Pons	tissue	23.8
Lymph node	tissue	23.2	not detected
Cerebellum	tissue	22.8	not detected
Thalamus	tissue	21.2
Periaqueductal gray	tissue	21.0
Hippocampal formation	tissue	20.9
Olfactory bulb	tissue	20.4
Spleen	tissue	19.9	not detected
Entorhinal cortex	tissue	18.1
Adrenal gland	tissue	18.0	low
Epididymis	tissue	17.9	low
Corpus callosum	tissue	17.9
Septum	tissue	17.5
Thyroid gland	tissue	17.0	not detected
Cerebral cortex	tissue	15.7	low
Motor cortex	tissue	15.7
Heart muscle	tissue	15.5	low
Temporal cortex	tissue	15.2
Tongue	tissue	15.1
Ventral forebrain	tissue	14.8
Kidney	tissue	14.7	medium
Amygdala	tissue	14.6
Prefrontal cortex	tissue	14.0
Basal ganglia	tissue	13.9	low
Pituitary gland	tissue	13.0
Insular cortex	tissue	12.9
Somatosensory cortex	tissue	12.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (124.8), Dorsal spinal cord (60.7), Ventral spinal cord (46.1), Anterior thalamic nucleus, ventral (26.1), Nucleus raphe pallidus (22.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, CTNNBIP1, E2F1, EGR1, EPAS1, ETV4, FHIT, GLI1, HIF1A, HNF4A, HOXA3, KAT5, KLF8, MAZ, NFATC1, NFKB1, NFKB, RELA, RUNX2, SP1, SP3, SRF, STAT3, ZBTB7A

miRNA regulators (miRDB)

Targeting MMP14 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 80 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.312, missense Z 2.72 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000311852 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:22,836,818–22,841,493	45 / 48.8	0.92	no
14:22,841,494–22,843,293	179 / 283.4	0.63	no
14:22,843,294–22,843,352	6 / 26.3	0.23	yes (p 7.4e-05)
14:22,843,353–22,846,036	364 / 425.2	0.86	no

Literature-anchored findings (GeneRIF, showing 40)

• MT1-MMP plays an important role during endothelial cell migration, and its activity can modulate endothelial migration, invasion, and formation of capillary tubes during the angiogenic response. (PMID:11448964)
• Thus, MT1-MMP oligomerization through the hemopexin, transmembrane, and cytoplasmic domains controls its catalytic activity. (PMID:11779859)
• Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis. (PMID:11809713)
• shed as membrane vesicle associated components by endothelial cells and this may be a mechanism for regulating focalized proteolytic activity vital to invasive and morphogenic events during angiogenesis (PMID:11839588)
• Expression of membrane-type-1-matrix metalloproteinase and metalloproteinase-2 in nonsmall cell lung carcinomas (PMID:11844598)
• Refolding of the catalytic and hinge domains of human MT1-mMP expressed in Escherichia coli and its characterization. (PMID:11911461)
• increasing expression and endometrial carcinoma appear closely related (PMID:11920503)
• Levels of MMP14 mRNA were reduced in two neuroblastoma clones treated with 300 nM PAF, which was accompanied by an inhibition of invasiveness through Matrigel and by a promotion of differentiation. (PMID:11928813)
• studies suggest that ectodomain shedding regulates the pericellular and extracellular activities of MT1-MMP through a delicate balance of active and inactive enzyme-soluble fragments (PMID:12004057)
• Plasmin activates pro-matrix metalloproteinase-2 with a membrane-type 1 matrix metalloproteinase-dependent mechanism. (PMID:12115722)
• CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain. (PMID:12145196)
• MT1-MMP is primarily secreted in the oral squamous cell carcinoma (OSCC) cells and is involved in the invasiveness of the OSCC and lymphatic metastasis. (PMID:12169394)
• Expression of MT1-MMP was elevated in 22 of 24 colon carcinomas we examined.DNA fragment between -1169 bp and -1163 bp in the 5’ flanking region of this gene to be a target of the beta-catenin/Tcf4 complex. (PMID:12185585)
• required for calcium regulation of matrix metalloproteinase-2 activation in oral squamous cell carcinoma cells (PMID:12194986)
• demonstrate that MT1-MMP via its cytoplasmic tail directly associates with a chaperone-like compartment-specific regulator gC1qR (PMID:12220632)
• endometrium from women with endometriosis expressed higher levels of MMP-2 and MT1-MMP and lower levels of TIMP-2 than did endometrium from normal women (PMID:12372458)
• MT1-MMP may play a pivotal role in the formation of capillarylike tubular structures in a collagen-containing fibrin matrix in vitro and may be involved in angiogenesis in a fibrinous exudate in vivo. (PMID:12393408)
• Data show a novel mechanism by which ECM regulates membrane-type 1 matrix metalloproteinase (MT1-MMP) association with beta1 or alphavbeta3 integrins, thus modulating its internalization, activity, and function on human endothelial cells. (PMID:12427871)
• laminin-5 as a substrate for mTLD, suggesting a role for laminin-5 processing by mTLD in the skin. (PMID:12473650)
• Results demonstrate the ability of hepatitis B virus X protein to promote tumor cell invasion by a mechanism involving the upregulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) and cyclooxygenase-2 (COX-2). (PMID:12488433)
• matrix metalloproteinase-2 and 9 and membrane-type 1 matrix metalloproteinase mRNA expression in endometriosis was higher than in normal endometrium whereas E-cadherin, alpha- and beta-catenin mRNA expression was not suppressed in endometriosis (PMID:12587534)
• down-regulation of most MT-MMPs is typical for prostate carcinoma; seems to occur mainly in epithelial cells (PMID:12661033)
• results implicate myofibroblasts as major producer of MT1-MMP in breast cancer and emphasize the importance of stromal-epithelial cell interactions in their progression (PMID:12672023)
• Data demonstrate that blockade of the ERK pathway suppressed the expression of matrix metalloproteinases 3, 9, and 14, and CD44, and markedly inhibited the invasiveness of tumor cells. (PMID:12727228)
• identify the surface epitopes that render TIMP-1 inactive against MT1-MMP (PMID:12869573)
• shedding of syndecan-1 promoted by MT1-MMP through the preferential cleavage of Gly245-Leu246 peptide bond stimulates cell migration (PMID:12904296)
• MT1-MMP-controlled cross-talk between alphavbeta3 and alpha2beta1 integrins supports binding of aggressive, MT1-MMP-, and alphavbeta3 integrin-expressing malignant cells on type I collagen, the most common substratum of the extracellular matrix (PMID:14597417)
• the presentation of LDL receptor-related protein LRP and the subsequent uptake of its ligands by malignant cells are both strongly regulated by MT1-MMP (PMID:14645246)
• data provide evidence for an additional mechanism for post-translational control of membrane type 1 matrix metalloproteinase (MT1-MMP) activity and suggest that glycosylation of MT1-MMP may regulate its substrate targeting (PMID:14670950)
• Expression of MT1-MMP is transcriptionally induced by FGF1 in a prostate carcinoma cell line/ (PMID:14673954)
• Low levels of MT1-MMP, MMP-1 and AI were found to be favourable markers significantly associated with longer survival in advanced colorectal carcinoma (PMID:14707454)
• during angiogenesis the full enzymatic activity of MT1-MMP is required for a specific up-regulation of VEGF-A through an activation of Src tyrosine kinase pathways. (PMID:14729679)
• MT1-MMP activity is regulated by ERK 1/2- and p38 MAPK-modulated TIMP-2 expression which controls TGF-beta1-induced pericellular collagenolysis (PMID:15247230)
• Data suggest that in furin-negative colon carcinoma cells membrane type-1 matrix metalloproteinase is autocatalytically processed and the active protease then operates as a prointegrin convertase. (PMID:15260832)
• The activity of membrane-type 1 matrix metalloproteinase (MT1-MMP) is a double-edged sword-it is crucial for both physiological processes and disease progression. (PMID:15276180)
• Collagenolytic MMP-14 is found to be more efficient at processing triple-helical peptidase substrates than is MMP-1. (PMID:15350133)
• MT1-MMP intracellular transport toward the plasma membrane is regulated by syntaxin 4 (PMID:15351710)
• MT1-MMP cleaves complement C3b (PMID:15381670)
• the hemopexin domain of MT1-MMP is not required for the activation of proMMP2 on cell surface but is essential for MT1-MMP-mediated invasion in three-dimensional type I collagen (PMID:15381707)
• identified substrates of MMP-14 in plasma (PMID:15450852)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp14a	ENSDARG00000002235
danio_rerio	mmp14b	ENSDARG00000008388
mus_musculus	Mmp14	ENSMUSG00000000957
rattus_norvegicus	Mmp14	ENSRNOG00000010947
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP11 (ENSG00000099953), MMP9 (ENSG00000100985), MMP15 (ENSG00000102996), HPX (ENSG00000110169), MMP8 (ENSG00000118113), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:101900) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 117 distinct phenotype terms.

Mouse phenotype (MP)	Records
premature death	5
domed cranium	4
short snout	4
decreased body weight	4
decreased body size	4
abnormal chondrocyte morphology	3
abnormal joint morphology	3
abnormal bone ossification	3
decreased bone mineral density	2
abnormal neurocranium morphology	2
short mandible	2
short maxilla	2
abnormal parietal bone morphology	2
abnormal cartilage morphology	2
abnormal cartilage development	2
abnormal cranium morphology	2
overexpanded pulmonary alveolus	2
decreased locomotor activity	2
abnormal skeleton physiology	2
abnormal osteoclast physiology	2
abnormal skeleton development	2
abnormal pulmonary alveolus morphology	2
abnormal cranial suture morphology	2
abnormal skeletal muscle fiber morphology	2
cachexia	2

+92 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RES1	98.8%	Diamond
Sus scrofa	Q9XT90	96.7%	Diamond
Bos taurus	Q9GLE4	95.2%	Diamond
Oryctolagus cuniculus	Q95220	91.1%	Diamond
Equus caballus	O18927	90.5%	Diamond
Tupaia belangeri	Q9GKE1	85.2%	Diamond
Canis lupus familiaris	Q6Y4Q5	78.9%	Diamond
Aquarana catesbeiana	Q11133	75.3%	Diamond
Felis catus	P55032	72.5%	Diamond
Arabidopsis thaliana	Q5XF51	71.1%	Diamond
Paracentrotus lividus	P22757	70.4%	Diamond
Hemicentrotus pulcherrimus	P91953	70.4%	Diamond
Xenopus laevis	Q10835	69.4%	Diamond
Glycine max	P29136	48.7%	Diamond
Tannerella forsythia 92A2	D0EM77	45.2%	Diamond
Heliothis virescens ascovirus 3e	A4KX75	59.2%	Diamond
Spodoptera frugiperda ascovirus 1a	Q0E587	59.2%	Diamond
Invertebrate iridescent virus 6	O55761	46.9%	Diamond
Invertebrate iridescent virus 3	Q196W5	43.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MRPL52	protein-coding	122704
REM2	protein-coding	161253
LRP10	protein-coding	26020
OXA1L	protein-coding	5018
SLC7A7	protein-coding	9056
OXA1L-DT	ncRNA	105370404
PRMT5-AS1	ncRNA	100505758
PRMT5	protein-coding	10419
RBM23	protein-coding	55147

Protein

Protein identifiers

Matrix metalloproteinase-14 — P50281 (reviewed: P50281)

Alternative names: MMP-X1, Membrane-type matrix metalloproteinase 1, Membrane-type-1 matrix metalloproteinase

All UniProt accessions (5): A0A7P0TAG0, A0A7P0TAV6, A0A7P0TBK8, P50281, F8VP90

UniProt curated annotations — full annotation on UniProt →

Function. Endopeptidase that degrades various components of the extracellular matrix such as collagen. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development. Activates progelatinase A/MMP2, thereby acting as a positive regulator of cell growth and migration. Involved in the formation of the fibrovascular tissues in association with pro-MMP2. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a regulator of Notch signaling by mediating cleavage and inhibition of DLL1. Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis. Acts as a negative regulator of the GDF15-GFRAL aversive response by mediating cleavage and inactivation of GFRAL.

Subunit / interactions. Interacts (via C-terminal cytoplasmic tail) with BST2.

Subcellular location. Cell membrane. Melanosome. Cytoplasm.

Tissue specificity. Expressed in stromal cells of colon, breast, and head and neck. Expressed in lung tumors.

Post-translational modifications. The precursor is cleaved by a furin endopeptidase. Tyrosine phosphorylated by PKDCC/VLK.

Disease relevance. Winchester syndrome (WNCHRS) [MIM:277950] A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Induction. Up-regulated by NANOS1.

Similarity. Belongs to the peptidase M10A family.

RefSeq proteins (1): NP_004986* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000585	Hemopexin-like_dom	Domain
IPR001818	Pept_M10_metallopeptidase	Domain
IPR002477	Peptidoglycan-bd-like	Domain
IPR006026	Peptidase_Metallo	Domain
IPR018486	Hemopexin_CS	Conserved_site
IPR018487	Hemopexin-like_repeat	Repeat
IPR021158	Pept_M10A_Zn_BS	Binding_site
IPR021190	Pept_M10A	Family
IPR021805	Pept_M10A_metallopeptidase_C	Domain
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain
IPR036365	PGBD-like_sf	Homologous_superfamily
IPR036366	PGBDSf	Homologous_superfamily
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily

Pfam: PF00045, PF00413, PF01471, PF11857

Enzyme classification (BRENDA)

• EC 3.4.24.80 — membrane-type matrix metalloproteinase-1 (BRENDA: 10 organisms, 200 substrates, 146 inhibitors, 32 Km, 29 kcat entries)
• EC 3.4.24.B5 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
(GLY-PRO-HYP)5-GLY-PRO-LYS(MCA)-GLY-PRO-GLN-GLY-	0.0151–0.0368	4
COLLAGEN I ALPHA-1 CHAIN	0.0003–0.32	4
COLLAGEN I ALPHA-2 CHAIN	0.0006–0.12	4
COLLAGEN TYPE I ALPHA-1 CHAIN	0.0009–0.17	4
COLLAGEN TYPE I ALPHA-2 CHAIN	0.0003–0.53	4
METHOXYCOUMARIN-4-ACETYL-LYS-PRO-LEU-GLY-LEU-LYS	0.0006–0.0028	4
MOCACPLGLA2PR-DINITROPHENOL-A-RNH2	0.009–0.01	2
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-LEU-GLY-LEU-N	0.0034	1
TYPE I COLLAGEN CHAIN ALPHA-1	—	1
TYPE I COLLAGEN CHAIN ALPHA-2	—	1

UniProt features (90 total): strand 30, binding site 17, helix 11, sequence variant 9, turn 5, repeat 4, topological domain 2, sequence conflict 2, signal peptide 1, propeptide 1, region of interest 1, short sequence motif 1, active site 1, chain 1, modified residue 1, disulfide bond 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

12 structures by resolution:

PDB	Title	Method	Resolution (Å)
3C7X	Hemopexin-like domain of matrix metalloproteinase 14	X-RAY DIFFRACTION	1.7
4P3C	MT1-MMP:Fab complex (Form I)	X-RAY DIFFRACTION	1.94
4P3D	MT1-MMP:Fab complex (Form II)	X-RAY DIFFRACTION	1.95
3MA2	Complex membrane type-1 matrix metalloproteinase (MT1-MMP) with tissue inhibitor of …	X-RAY DIFFRACTION	2.05
5H0U	Crystal structure of the catalytic domain of membrane type 1 matrix metalloproteinase	X-RAY DIFFRACTION	2.24
4QXU	Novel Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling …	X-RAY DIFFRACTION	2.3
3X23	Radixin complex	X-RAY DIFFRACTION	2.4
1BQQ	CRYSTAL STRUCTURE OF THE MT1-MMP–TIMP-2 COMPLEX	X-RAY DIFFRACTION	2.75
1BUV	CRYSTAL STRUCTURE OF THE MT1-MMP-TIMP-2 COMPLEX	X-RAY DIFFRACTION	2.75
2MQS	Transient Collagen Triple Helix Binding to a Key Metalloproteinase in Invasion and …	SOLUTION NMR
6CLZ	MT1-MMP HPX domain with Blade 4 Loop Bound to Nanodiscs	SOLUTION NMR
6CM1	MT1-MMP HPX Domain with Blade 2 Loop Bound to Nanodiscs	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50281-F1	81.66	0.58

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 4P3C, 4P3D, 4QXU

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Metallopeptidases, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; intermediate filaments

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
240

Ligand- & substrate-binding residues (17)

Position	Role
93	Zn(2+)
186	Zn(2+)
188	Zn(2+)
193	Ca(2+)
194	Ca(2+)
196	Ca(2+)
198	Ca(2+)
201	Zn(2+)
208	Ca(2+)
210	Ca(2+)
212	Ca(2+)
214	Zn(2+)
216	Ca(2+)
219	Ca(2+)
239	Zn(2+)
243	Zn(2+)
249	Zn(2+)

Post-translational modifications (1)

Type	Positions
Phosphotyrosine	399

Disulfide bonds (1)

Type	Positions
Disulfide bond	319–508

Mutagenesis-validated functional residues (1)

Position	Phenotype
240	in mt1 ea mutant; abolished endopeptidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

ID	Pathway	Evidence
R-HSA-1592389	Activation of Matrix Metalloproteinases	curated
R-HSA-9839383	TGFBR3 PTM regulation	curated
R-HSA-9855142	Cellular responses to mechanical stimuli	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-1442490	Collagen degradation	electronic
R-HSA-1474228	Degradation of the extracellular matrix	electronic
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	electronic
R-HSA-9860931	Response of endothelial cells to shear stress	—
R-HSA-162582	Signal Transduction	—
R-HSA-9006936	Signaling by TGFB family members	—
R-HSA-9839373	Signaling by TGFBR3	—

MSigDB gene sets: 565 (showing top): MODULE_172, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_POSITIVE_REGULATION_OF_MYOTUBE_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_255, GOBP_B_CELL_ACTIVATION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, TGCACTT_MIR519C_MIR519B_MIR519A

GO Biological Process (35): skeletal system development (GO:0001501), ossification (GO:0001503), angiogenesis (GO:0001525), ovarian follicle development (GO:0001541), response to hypoxia (GO:0001666), endothelial cell proliferation (GO:0001935), proteolysis (GO:0006508), response to oxidative stress (GO:0006979), male gonad development (GO:0008584), response to mechanical stimulus (GO:0009612), positive regulation of myotube differentiation (GO:0010831), positive regulation of protein processing (GO:0010954), protein processing (GO:0016485), extracellular matrix disassembly (GO:0022617), protein catabolic process (GO:0030163), extracellular matrix organization (GO:0030198), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), collagen catabolic process (GO:0030574), zymogen activation (GO:0031638), endodermal cell differentiation (GO:0035987), astrocyte cell migration (GO:0043615), response to estrogen (GO:0043627), positive regulation of B cell differentiation (GO:0045579), negative regulation of Notch signaling pathway (GO:0045746), tissue remodeling (GO:0048771), cell motility (GO:0048870), negative regulation of focal adhesion assembly (GO:0051895), cellular response to genistein (GO:0071412), negative regulation of GDF15-GFRAL signaling pathway (GO:0160145), regulation of protein localization to plasma membrane (GO:1903076), positive regulation of macrophage migration (GO:1905523), response to odorant (GO:1990834), anatomical structure morphogenesis (GO:0009653), response to hormone (GO:0009725)

GO Molecular Function (11): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), integrin binding (GO:0005178), zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (10): nucleus (GO:0005634), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), focal adhesion (GO:0005925), extracellular matrix (GO:0031012), cytoplasmic vesicle (GO:0031410), melanosome (GO:0042470), macropinosome (GO:0044354), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	1
Signaling by TGFBR3	1
Response of endothelial cells to shear stress	1
Signal Transduction	1
Signaling by TGFB family members	1
Cellular responses to stimuli	1
Cellular responses to mechanical stimuli	1

GO top-level categories

showing 60 of 65 GO namespaces:

Category	Terms
animal gross anatomical part developmental process	2
response to stress	2
protein metabolic process	2
protein processing	2
peptidase activity	2
endopeptidase activity	2
cellular anatomical structure	2
system development	1
multicellular organismal process	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
female gonad development	1
response to decreased oxygen levels	1
epithelial cell proliferation	1
gonad development	1
development of primary male sexual characteristics	1
response to external stimulus	1
response to abiotic stimulus	1
regulation of myotube differentiation	1
myotube differentiation	1
positive regulation of striated muscle cell differentiation	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
proteolysis	1
protein maturation	1
cellular component disassembly	1
extracellular matrix organization	1
macromolecule catabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
catabolic process	1
collagen metabolic process	1
metallopeptidase activity	1
serine-type peptidase activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
transition metal ion binding	1
aminopeptidase activity	1
metalloexopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
cell-substrate junction	1
external encapsulating structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 16 of 57 annotations. The rest are phylogenetic / computational / electronic (IEA).

16 experimentally-supported GO terms:

GO term	NS	Evidence
endodermal cell differentiation	BP	expression pattern
negative regulation of GDF15-GFRAL signaling pathway	BP	direct assay
positive regulation of cell growth	BP	direct assay
positive regulation of cell migration	BP	direct assay
protein catabolic process	BP	direct assay
proteolysis	BP	direct assay
regulation of protein localization to plasma membrane	BP	mutant phenotype
zymogen activation	BP	direct assay
cytoplasmic vesicle	CC	direct assay
focal adhesion	CC	high-throughput assay
macropinosome	CC	direct assay
nucleus	CC	mutant phenotype
plasma membrane	CC	direct assay
endopeptidase activity	MF	direct assay
metalloaminopeptidase activity	MF	direct assay
metalloendopeptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,434 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP14	TIMP2	P16035	930
MMP14	MMP2	P08253	827
MMP14	TIMP1	P01033	826
MMP14	SH3PXD2B	A1X283	815
MMP14	RECK	O95980	810
MMP14	TIMP4	Q99727	793
MMP14	TIMP3	P35625	766
MMP14	FN1	P02751	713
MMP14	CD44	P16070	686
MMP14	ADI1	Q9BV57	682
MMP14	MMP13	P45452	678
MMP14	FURIN	P09958	658
MMP14	TGFB1	P01137	654
MMP14	SPOCK3	Q9BQ16	649
MMP14	CTTN	Q14247	642

IntAct

Human interaction partners of MMP14 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

29 partners by confidence:

Partner	Interaction type	MIscore	Records
ADI1	physical association	0.600	4
TIMP2	association	0.560	4
AQP6	physical association	0.560	3
EBP	physical association	0.560	3
ELOVL4	physical association	0.560	3
F11R	physical association	0.560	3
FHL3	physical association	0.560	3
FURIN	physical association	0.560	3
HSD17B13	physical association	0.560	3
KASH5	physical association	0.560	3
MSMO1	physical association	0.560	3
STOM	physical association	0.560	3
ZUP1	physical association	0.560	3
LUM	cleavage reaction	0.560	2
C1QBP	direct interaction	0.540	2
LIMK1	colocalization	0.460	4
BCAR1	colocalization	0.460	3
GORASP2	physical association	0.460	2
FGFR4	physical association	0.400	6
FGFR2	physical association	0.400	1
TIMP1	physical association	0.400	1
PLLP	physical association	0.370	1
RRAD	physical association	0.370	1
BIN1	association	0.350	1
TMEM120B	association	0.350	1
ACTB	colocalization	0.270	1
ENG	proximity	0.270	1
GOLGB1	colocalization	0.270	1
TGOLN2	colocalization	0.270	1

BioGRID (98 interactions; top human partners by supporting records): TIMP2 (Reconstituted Complex; 6 records), ACE2 (Biochemical Activity; 4 records), CA9 (Proximity Label-MS; 3 records), FBXO6 (Affinity Capture-MS; 3 records), CAV1 (Affinity Capture-Western; 2 records), CORO1C (Affinity Capture-Luminescence; 2 records), FURIN (Biochemical Activity; 2 records), MMP3 (Reconstituted Complex; 2 records), SPOCK3 (Affinity Capture-Western; 2 records), TIMP1 (Reconstituted Complex; 2 records), USP12 (Affinity Capture-Western; 2 records), WISP2 (Two-hybrid; 2 records), AQP6 (Two-hybrid), B3GNT2 (Affinity Capture-MS), BCAR1 (Affinity Capture-Western)

SIGNOR signaling

showing 11 of 15 signaling interactions:

A	Effect	B	Mechanism
SRC	unknown	MMP14	phosphorylation
FHIT	“down-regulates quantity by repression”	MMP14	“transcriptional regulation”
MMP14	“down-regulates quantity by destabilization”	ADAM9	cleavage
MAP3K14	“up-regulates activity”	MMP14	phosphorylation
TIMP3	“down-regulates activity”	MMP14	binding
MMP14	up-regulates	Adipogenesis
MMP14	“down-regulates quantity by destabilization”	F12	cleavage
MMP14	“down-regulates quantity by destabilization”	FGG	cleavage
MMP14	“down-regulates quantity by destabilization”	FGA	cleavage
MMP14	up-regulates	ECM_disassembly
MMP14	down-regulates	ECM

Protein complexes (CORUM) (9)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

9 complexes by size:

Complex	Subunits	Members
ITGAV-ITGB8-MMP14-TGFB1 complex	4	ITGAV, ITGB8, MMP14, TGFB1
★ ADAM12-alphaVbeta3-integrin-MMP-14 complex	4	MMP14, ADAM12, ITGAV, ITGB3
★ KDR-MMP14-SRC complex	3	SRC, KDR, MMP14
★ BCAR1-MMP14-PTK2 complex	3	BCAR1, MMP14, PTK2
MMP2-MMP14-TIMP2 complex	3	TIMP2, MMP14, MMP2
★ FLT1-MMP14 complex	2	FLT1, MMP14
★ FGFR4-MMP14 complex	2	FGFR4, MMP14
CLDN1-MMP14 complex	2	CLDN1, MMP14
MMP14-TIMP2 complex	2	MMP14, TIMP2

Disease & clinical

Genetic variants

Variant evidence for MMP14: 382 ClinVar records (2 pathogenic / likely pathogenic); 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

382 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	210
Likely benign	117
Benign	39

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
65463	NM_004995.4(MMP14):c.50C>G (p.Thr17Arg)	Pathogenic	no assertion criteria provided	1
3064215	NM_004995.4(MMP14):c.332G>A (p.Arg111His)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore MMP14’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 903):

Position(s)	Effect	Δscore	Sites
14:22841490	acceptor_loss	1.0000	2
14:22841640–22841641	donor_loss	1.0000	4
14:22842397	acceptor_gain	1.0000
14:22842400	acceptor_gain	1.0000
14:22842718–22842719	donor_loss	1.0000	5
14:22843255–22843256	acceptor_loss	1.0000	3
14:22844356–22844357	acceptor_gain	1.0000	2
14:22844510	donor_loss	1.0000	2
14:22844629	acceptor_loss	1.0000
14:22844781–22844782	donor_loss	1.0000	4

AlphaMissense

1,797 missense substitutions predicted likely pathogenic (of 3,825 scored), across 389 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M257	9	0.997	1.000
M68	9	0.915	0.994
M88	9	0.870	0.993
H201	8	1.000	1.000
H239	8	1.000	1.000
H186	8	0.999	1.000
H214	8	0.999	1.000
H243	8	0.999	1.000
H249	8	0.999	1.000
D188	8	0.998	0.999
F192	8	0.998	1.000
D216	8	0.998	0.999
D275	8	0.998	1.000
D97	8	0.997	0.999
D274	8	0.994	0.998
D212	8	0.993	0.998
F215	8	0.993	1.000
F181	8	0.992	0.999
D193	8	0.991	0.998
F336	8	0.989	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (validation)	unfavorable	2.56e-05
Ovary Serous Cystadenocarcinoma (TCGA)	unfavorable	0.000712

Disease associations

OMIM: gene MIM:600754 | disease phenotypes: MIM:277950

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
Winchester syndrome	Moderate	Autosomal recessive	3
multicentric osteolysis-nodulosis-arthropathy spectrum	Supportive	Autosomal recessive

Mondo (2): Winchester syndrome (MONDO:0010201), multicentric osteolysis-nodulosis-arthropathy spectrum (MONDO:0018298)

Orphanet (2): Torg-Winchester syndrome (Orphanet:3460), Multicentric osteolysis-nodulosis-arthropathy spectrum (Orphanet:371428)

HPO phenotypes

47 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0000212	Gingival overgrowth
HP:0000248	Brachycephaly
HP:0000280	Coarse facial features
HP:0000315	Abnormality of the orbital region
HP:0000612	Iris coloboma
HP:0000822	Hypertension
HP:0000916	Broad clavicle
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001007	Hirsutism
HP:0001059	Pterygium
HP:0001085	Papilledema
HP:0001230	Broad metacarpals
HP:0001249	Intellectual disability
HP:0001369	Arthritis
HP:0001482	Subcutaneous nodule
HP:0001495	Carpal osteolysis
HP:0001539	Omphalocele
HP:0001626	Abnormality of the cardiovascular system
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001634	Mitral valve prolapse
HP:0001647	Bicuspid aortic valve
HP:0001678	Atrioventricular block
HP:0001680	Coarctation of aorta
HP:0001719	Double outlet right ventricle
HP:0001999	Abnormal facial shape
HP:0002659	Increased susceptibility to fractures
HP:0002797	Osteolysis
HP:0002808	Kyphosis
HP:0003040	Arthropathy
HP:0003312	Abnormal vertebral body morphology
HP:0003593	Infantile onset
HP:0005441	Sclerotic cranial sutures
HP:0005922	Abnormal hand morphology
HP:0005994	Nodular goiter
HP:0006234	Osteolysis involving tarsal bones
HP:0007957	Corneal opacity
HP:0009139	Osteolysis involving bones of the lower limbs
HP:0010314	Premature thelarche
HP:0011355	Localized skin lesion
HP:0011463	Childhood onset
HP:0040160	Generalized osteoporosis
HP:0045039	Osteolysis involving bones of the upper limbs
HP:0100651	Type I diabetes mellitus

GWAS associations

11 associations:

Study	Trait	p-value
GCST006979_1040	Heel bone mineral density	1e-34
GCST004858_17	Dupuytren’s disease	2e-19
GCST006288_622	Heel bone mineral density	9e-14
GCST006630_19	Diastolic blood pressure	6e-13
GCST90000025_127	Appendicular lean mass	2e-10
GCST006085_22	Prostate cancer	2e-8
GCST007492_1	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3e-8
GCST007494_1	Waist-to-hip ratio adjusted for BMI (additive genetic model)	1e-7
GCST006288_352	Heel bone mineral density	4e-7
GCST006288_292	Heel bone mineral density	6e-7
GCST010483_2	Cardiovascular death, myocardial infarction or stroke in response to clopidogrel treatment	5e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0009270	heel bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0006919	cardiovascular event measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C536709	Winchester syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3869 (SINGLE PROTEIN), CHEMBL4523971 (SELECTIVITY GROUP)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MMP14 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
CTS-1027	Small molecule	2
REBIMASTAT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 127,176 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

13 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1200596	CHLOROXINE	4	1,799
CHEMBL497	CLIOQUINOL	4	13,056
CHEMBL1350	TILUDRONIC ACID	4	14,868
CHEMBL4303669	ZOLEDRONIC ACID	4	528
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	23,201
CHEMBL279785	MARIMASTAT	3	29,705
CHEMBL75094	PRINOMASTAT	3	8,942
CHEMBL440498	CTS-1027	2	651
CHEMBL76222	REBIMASTAT	2	363
CHEMBL4650334	ALDUMASTAT	2	61
CHEMBL279786	BATIMASTAT	2	21,436
CHEMBL115653	CIPEMASTAT	2	380
CHEMBL19611	ILOMASTAT	2	12,186

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
ilomastat	Inhibition	8.96	pIC50
compound 29e [PMID: 23631440]	Inhibition	8.4	pKi
CGS-27023A	Inhibition	7.64	pIC50
(R)-ND-336	Inhibition	6.92	pKi
TP0556351	Inhibition	5.65	pIC50

Binding affinities (BindingDB)

999 measured of 1322 human assays (1324 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
alpha-tetrahydropyran beta-sulfone 1B	IC50	0.029 nM
CHEMBL5412341	IC50	0.034 nM
N-Hydroxy-2-(4-phenoxy-benzenesulfonylamino)-acetamide	IC50	0.04 nM
AG-3340	IC50	0.048 nM
CHEMBL473539	IC50	0.05 nM
CHEMBL5182207	IC50	0.055 nM
CHEMBL5185612	IC50	0.068 nM
6-Hydroxy-2-(4-nitro-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline-1-carboxylic acid hydroxyamide	IC50	0.076 nM
(R)-2-[(Biphenyl-4-sulfonyl)-isopropoxy-amino]-N-hydroxy-3-methyl-butyramide	IC50	0.09 nM
CHEMBL1801396	IC50	0.1 nM
CHEMBL1801424	IC50	0.1 nM
CHEMBL1801417	IC50	0.1 nM
CHEMBL1801413	IC50	0.1 nM
CHEMBL1229868	IC50	0.1 nM
CHEMBL1801050	IC50	0.1 nM
CHEMBL1801412	IC50	0.1 nM
(R)-N*4*-Hydroxy-N*1*-[2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide	IC50	0.104 nM
CHEMBL3617404	IC50	0.13 nM
CHEMBL3900422	IC50	0.16 nM
CHEMBL1801431	IC50	0.2 nM
CHEMBL1801428	IC50	0.2 nM
CHEMBL1801427	IC50	0.2 nM
CHEMBL1801423	IC50	0.2 nM
CHEMBL1801420	IC50	0.2 nM
CHEMBL1801057	IC50	0.2 nM
CHEMBL1801048	IC50	0.2 nM
CHEMBL5169565	IC50	0.2 nM
CHEMBL1801421	IC50	0.25 nM
(2R,3S)-N*4*-Hydroxy-2-isobutyl-3-methyl-N*1*-[(S)-1-methylcarbamoyl-2-(5,6,7,8-tetrahydro-naphthalen-1-yl)-ethyl]-succinamide	IC50	0.3 nM
CHEMBL1801426	IC50	0.3 nM
CHEMBL1800089	IC50	0.3 nM
CHEMBL1801045	IC50	0.3 nM
CHEMBL1801416	IC50	0.3 nM
CHEMBL5199189	IC50	0.3 nM
N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}-1-(prop-2-yn-1-yl)piperidine-4-carboxamide hydrochloride	IC50	0.33 nM
CHEMBL3617402	IC50	0.33 nM
(R)-N*1*-((S)-2,2-Dimethyl-1-methylcarbamoyl-propyl)-N*4*-hydroxy-2-(3-phenyl-propyl)-succinamide	IC50	0.339 nM
N-(4-Phenoxybenzenesulfonyl)-N-{[2-(4-sulfamoylphenyl)ethylcarbamoyl]methyl}-D-valinehydroxamic Acid	IC50	0.35 nM
CHEMBL1801047	IC50	0.35 nM
CHEMBL3617405	IC50	0.37 nM
[(R)-1-(4’-ethoxy-biphenyl-4-sulfonylamino)-2-methyl-propyl]-phosphonic acid	IC50	0.39 nM
CHEMBL1801419	IC50	0.4 nM
CHEMBL1801054	IC50	0.4 nM
marimastat	IC50	0.41 nM
{(S)-4-[(Biphenyl-4-sulfonyl)-isopropoxy-amino]-4-hydroxycarbamoyl-butyl}-carbamic acid benzyl ester	IC50	0.41 nM
CHEMBL5177819	IC50	0.41 nM
CHEMBL2337697	IC50	0.43 nM
(2R,3S)-N*4*-Hydroxy-2-isobutyl-N*1*-((S)-1-methylcarbamoyl-2-phenyl-ethyl)-3-(thiophen-2-ylsulfanylmethyl)-succinamide	IC50	0.5 nM
N-(4-Phenoxybenzenesulfonyl)-N-hydroxycarbonylmethyl-D-valinehydroxamicAcid	IC50	0.5 nM
CHEMBL1801422	IC50	0.5 nM

ChEMBL bioactivities

768 potent at pChembl≥5 of 966 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	PRINOMASTAT
9.49	IC50	0.32	nM	CHEMBL471537
9.48	IC50	0.33	nM	CHEMBL473539
9.39	IC50	0.41	nM	ILOMASTAT
9.14	IC50	0.73	nM	CHEMBL1801422
9.05	IC50	0.9	nM	CHEMBL1092104
8.96	IC50	1.1	nM	CTS-1027
8.96	IC50	1.1	nM	ILOMASTAT
8.92	IC50	1.2	nM	CHEMBL1766900
8.89	IC50	1.3	nM	CHEMBL1766899
8.88	IC50	1.33	nM	CHEMBL1801397
8.82	IC50	1.5	nM	CHEMBL263750
8.77	IC50	1.71	nM	CHEMBL1801048
8.74	IC50	1.8	nM	MARIMASTAT
8.74	IC50	1.82	nM	MARIMASTAT
8.72	IC50	1.9	nM	RO-319790
8.72	IC50	1.9	nM	CHEMBL20154
8.68	IC50	2.1	nM	CHEMBL234530
8.68	IC50	2.08	nM	CHEMBL279078
8.64	IC50	2.3	nM	CHEMBL281371
8.60	IC50	2.5	nM	CHEMBL20043
8.54	IC50	2.9	nM	BATIMASTAT
8.52	IC50	3	nM	CHEMBL367133
8.52	IC50	3	nM	CHEMBL5205063
8.52	IC50	3	nM	BATIMASTAT
8.51	IC50	3.1	nM	CHEMBL1801057
8.47	IC50	3.4	nM	CHEMBL1078281
8.44	IC50	3.63	nM	CHEMBL1801053
8.43	IC50	3.7	nM	CHEMBL1801393
8.42	IC50	3.8	nM	CHEMBL3932562
8.41	IC50	3.9	nM	CHEMBL3617407
8.41	IC50	3.9	nM	CHEMBL515980
8.40	IC50	4	nM	CHEMBL198778
8.40	Ki	4	nM	CHEMBL2380402
8.40	IC50	4	nM	CHEMBL1801421
8.39	IC50	4.1	nM	CHEMBL1801431
8.37	IC50	4.3	nM	CHEMBL1089843
8.35	IC50	4.5	nM	CHEMBL1801045
8.34	IC50	4.6	nM	BATIMASTAT
8.34	IC50	4.6	nM	CHEMBL1801430
8.33	IC50	4.7	nM	ILOMASTAT
8.30	Ki	5	nM	CHEMBL2380403
8.30	IC50	5	nM	CHEMBL1957606
8.28	IC50	5.2	nM	ILOMASTAT
8.27	IC50	5.4	nM	CHEMBL3889936
8.25	IC50	5.6	nM	CHEMBL1801046
8.22	Ki	6	nM	CHEMBL2380389
8.21	Ki	6.2	nM	CHEMBL2380387
8.18	Ki	6.6	nM	CHEMBL2380403
8.17	IC50	6.8	nM	CHEMBL1801412

PubChem BioAssay actives

695 with measured affinity, of 1443 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R)-N-hydroxy-3-methyl-2-[[2-oxo-2-[2-(4-sulfamoylphenyl)ethylamino]ethyl]-(4-phenoxyphenyl)sulfonylamino]butanamide	413961: Inhibition of MMP14	ic50	0.0003	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-phenoxyphenyl)sulfonylthiomorpholine-3-carboxamide	1863882: Inhibition of MMP-14 (unknown origin)	ic50	0.0003	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	241672: Inhibition of human matrix metalloprotease-14	ic50	0.0003	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	628296: Inhibition of MMP14	ic50	0.0004	uM
4-[4-(1,3-benzodioxol-5-yloxy)phenyl]sulfonyl-1-cyclopropyl-N-hydroxypiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0007	uM
(2R)-2-[(4-bromophenyl)sulfonylamino]-4-(1,3-dioxoisoindol-2-yl)-N-hydroxybutanamide	473232: Inhibition of human recombinant MMP14 by fluorometric assay	ic50	0.0009	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1162791: Inhibition of human recombinant MMP14 using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	0.0011	uM
(1S,2R,3R)-2-methyl-1-[[5-(4-methylpyrazol-1-yl)thiophen-2-yl]sulfonylamino]-3-phenylcyclopropane-1-carboxylic acid	593446: Inhibition of human recombinant MMP14 after 60 mins by fluorescence plate reader	ic50	0.0012	uM
N-hydroxy-1-prop-2-ynyl-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0013	uM
(1S,2R,3R)-1-[[5-(4-methoxypyrazol-1-yl)thiophen-2-yl]sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	593446: Inhibition of human recombinant MMP14 after 60 mins by fluorescence plate reader	ic50	0.0013	uM
(2S)-2-[[4-[4-[(5-methoxy-1-benzofuran-2-carbonyl)amino]phenyl]phenyl]sulfonylamino]-3-methylbutanoic acid	240552: Inhibitory concentration against MMP-14	ic50	0.0015	uM
N-hydroxy-4-[4-(4-hydroxyphenoxy)phenyl]sulfonyloxane-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0017	uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’,3-dihydroxy-2-(2-methylpropyl)butanediamide	1863882: Inhibition of MMP-14 (unknown origin)	ic50	0.0018	uM
(2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-2-(3-phenylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0019	uM
(2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0019	uM
(2S,3R)-N-hydroxy-2-methyl-N’-[(2S)-1-(methylamino)-1-oxo-3-(5,6,7,8-tetrahydronaphthalen-1-yl)propan-2-yl]-3-(2-methylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0021	uM
2-[[2-(hydroxyamino)-2-oxoethyl]-(4-phenoxyphenyl)sulfonylamino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide	413961: Inhibition of MMP14	ic50	0.0021	uM
(2R)-N-[(1S)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0023	uM
(2R)-N’-hydroxy-N-[(2S)-3-methyl-1-(methylamino)-1-oxobutan-2-yl]-2-(3-phenylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0025	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-3-(2-methylpropyl)-2-(thiophen-2-ylsulfanylmethyl)butanediamide	109549: Inhibition of Matrix metalloprotease-14	ic50	0.0029	uM
5-amino-3-(2-ethoxyethyl)-3-[4-[4-(1,3-oxazol-5-yl)phenoxy]phenoxy]piperidine-2,4,6-trione	241034: Inhibitory concentration against matrix metalloprotease 14	ic50	0.0030	uM
(2S,3R,6R)-6-benzyl-N-hydroxy-N’-methyl-3-(2-methylpropyl)-4-oxo-2-(thiophen-2-ylsulfanylmethyl)heptanediamide	1863882: Inhibition of MMP-14 (unknown origin)	ic50	0.0030	uM
N-hydroxy-4-[4-(4-methoxyphenoxy)phenyl]sulfonyl-1-(pyridin-2-ylmethyl)piperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0031	uM
(1S,2R,3R)-1-[[5-(4-chloropyrazol-1-yl)thiophen-2-yl]sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	593446: Inhibition of human recombinant MMP14 after 60 mins by fluorescence plate reader	ic50	0.0034	uM
N-hydroxy-4-[4-(4-methylsulfanylphenoxy)phenyl]sulfonyloxane-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0036	uM
N-hydroxy-1-(pyridin-3-ylmethyl)-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0037	uM
N-[[3-[4-[[(2S)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]sulfamoyl]phenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328783: Inhibition of recombinant human GST-tagged MMP14 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0038	uM
(2R)-4-(1,3-dioxoisoindol-2-yl)-N-hydroxy-2-[[4-(4-methoxyphenyl)phenyl]sulfonyl-propan-2-yloxyamino]butanamide	1246458: Inhibition of recombinant human catalytic domain MMP14 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as fluorogenic substrate incubated for 4 hrs followed by substrate addition measured every 10 secs for 20 mins by fluorometric assay	ic50	0.0039	uM
2-[[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-phenoxyphenyl)sulfonylamino]acetic acid	413961: Inhibition of MMP14	ic50	0.0039	uM
4-[4-(1,3-benzodioxol-5-yloxy)phenyl]sulfonyl-N-hydroxy-1-(2-methoxyethyl)piperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0040	uM
N-hydroxy-2-[(4-phenoxyphenyl)sulfonylamino]acetamide	736083: Inhibition of human recombinant MMP14 catalytic domain using Mca-Lys-Pro- Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate incubated for 2 hrs prior to substrate addition measured every 15 secs for 15 mins by fluorometric analysis	ic50	0.0040	uM
N-[6-oxo-6-[(3S,4S)-3-[(4-phenoxyphenyl)sulfonylamino]-4-sulfanylpyrrolidin-1-yl]hexyl]acetamide	747691: Inhibition of MMP-14 (unknown origin) using Mca-PLGLDpa-AR-NH2 as substrate preincubated for 30 mins by fluorescence assay	ki	0.0040	uM
N-hydroxy-1-(pyridin-2-ylmethyl)-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0041	uM
(2R)-2-[(4-but-2-ynoxyphenyl)sulfonylamino]-4-(1,3-dioxoisoindol-2-yl)-N-hydroxybutanamide	473232: Inhibition of human recombinant MMP14 by fluorometric assay	ic50	0.0043	uM
4-[4-(3-chlorophenoxy)phenyl]sulfonyl-N-hydroxyoxane-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0045	uM
1-cyclopropyl-N-hydroxy-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0046	uM
(4R)-3-[4-(4-chlorophenoxy)phenyl]sulfonyl-N-hydroxy-1,1-dioxo-1,3-thiazolidine-4-carboxamide	648199: Inhibition of MMP14 catalytic domain using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate preincubated for 1 hr prior substrate addition measured after 30 mins by spectrofluorimetry	ic50	0.0050	uM
N-[(3S,4S)-1-(6-aminohexanoyl)-4-sulfanylpyrrolidin-3-yl]-4-phenoxybenzenesulfonamide;hydrochloride	1937797: Inhibition of MMP14 (unknown origin) assessed as inhibition constant	ki	0.0050	uM
N-[[3-[4-[2-[formyl(hydroxy)amino]-3-methylbutyl]sulfonylphenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328783: Inhibition of recombinant human GST-tagged MMP14 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0054	uM
4-[4-(4-chlorophenoxy)phenyl]sulfonyl-N-hydroxyoxane-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0056	uM
(2R)-2-[(3S,4R)-1-[4-(1,3-dioxoisoindol-2-yl)butanoyl]-4-sulfanylpyrrolidin-3-yl]sulfanyl-4-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide	747691: Inhibition of MMP-14 (unknown origin) using Mca-PLGLDpa-AR-NH2 as substrate preincubated for 30 mins by fluorescence assay	ki	0.0060	uM
(2R)-2-[(3S,4R)-1-acetyl-4-sulfanylpyrrolidin-3-yl]sulfanyl-4-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide	747691: Inhibition of MMP-14 (unknown origin) using Mca-PLGLDpa-AR-NH2 as substrate preincubated for 30 mins by fluorescence assay	ki	0.0062	uM
1-cyclopropyl-4-[4-(4-ethoxyphenoxy)phenyl]sulfonyl-N-hydroxypiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0068	uM
1-N,3-N-bis[4-[2-[[(2R)-4-(1,3-dioxoisoindol-2-yl)-1-(hydroxyamino)-1-oxobutan-2-yl]-[4-(4-methoxyphenyl)phenyl]sulfonylamino]ethylamino]-4-oxobutyl]benzene-1,3-dicarboxamide	1574102: Inhibition of recombinant human MT1-MMP catalytic domain using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 3 hrs followed by substrate addition and measured every 10 secs for 15 min by fluorometric assay	ic50	0.0070	uM
(2R)-2-[(3S,4R)-1-[6-(1,3-dioxoisoindol-2-yl)hexanoyl]-4-sulfanylpyrrolidin-3-yl]sulfanyl-4-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide	747691: Inhibition of MMP-14 (unknown origin) using Mca-PLGLDpa-AR-NH2 as substrate preincubated for 30 mins by fluorescence assay	ki	0.0070	uM
1-benzyl-4-[4-(4-chlorophenoxy)phenyl]sulfonyl-N-hydroxypiperidine-4-carboxamide	109565: Inhibition of Matrix metalloprotease-14	ic50	0.0070	uM
N-hydroxy-1-propan-2-yl-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0071	uM
N-hydroxy-1-(2-morpholin-4-ylethyl)-4-[4-[4-(trifluoromethyl)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0074	uM
4-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-N-hydroxyoxane-4-carboxamide	109566: Inhibition of matrix metalloprotease-14	ic50	0.0074	uM
(2R)-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(pyridin-3-ylmethyl)amino]-3-methylbutanamide;hydrochloride	352557: Inhibition of MMP14	ic50	0.0075	uM

CTD chemical–gene interactions

101 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, decreases expression, affects expression, affects cotreatment, increases expression	5
Progesterone	affects cotreatment, increases expression, decreases reaction, decreases expression	5
sodium arsenite	decreases reaction, increases expression	4
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	4
Arsenic Trioxide	affects expression, affects cotreatment, decreases expression, decreases reaction, increases expression	3
Tetradecanoylphorbol Acetate	decreases reaction, increases expression	3
Genistein	decreases expression, increases expression	3
bisphenol A	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	increases expression, affects cotreatment	2
Manganese	increases abundance, increases expression, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Particulate Matter	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
biochanin A	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
carvone	decreases expression	1
glycidyl methacrylate	affects expression, increases expression	1
lead acetate	increases expression	1
piperine	decreases reaction, increases expression	1
salinomycin	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	affects expression	1

ChEMBL screening assays

274 unique, capped per target: 252 binding, 18 admet, 3 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001087	Binding	Ratio of kcat/km for human recombinant MMP14 assessed as drug cleavage	Development of an optimized activatable MMP-14 targeted SPECT imaging probe. — *Bioorg Med Chem*
CHEMBL2354273	Functional	PubChem BioAssay. SAR confirmation of uHTS hits for a small molecule inhibitors of MT1-MMP activation in a fluorescence assay. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL3868406	ADMET	Inhibition of recombinant human GST-tagged MMP14 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	Design, synthesis, and biological activity of novel, potent, and highly selective fused pyrimidine-2-carboxamide-4-one-based matrix metalloproteinase (MMP)-13 zinc-binding inhibitors. — *Bioorg Med Chem*

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4T29	GM02295	Finite cell line	Female
CVCL_B1CE	Abcam A-431 MMP14 KO	Cancer cell line	Female
CVCL_D8QQ	Ubigene HCT 116 MMP14 KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MMP14 across ~30M SureChEMBL compounds — explore on Sugi Predict.