MMP3

Summary

MMP3 (matrix metallopeptidase 3, HGNC:7173) is a protein-coding gene on chromosome 11q22.2, encoding Stromelysin-1 (P08254). Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans.

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. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.

Source: NCBI Gene 4314 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 109 total
• GTEx eGene: eQTL in 8 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs; 14 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.26 (unconstrained)
• MANE Select transcript: NM_002422
• Interaction hub: 2,794 STRING partners (top 3% of genes corpus-wide)
• Notable: 109 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7173
Approved symbol	MMP3
Name	matrix metallopeptidase 3
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000149968
Ensembl biotype	protein_coding
OMIM	185250
Entrez	4314

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000299855

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1, TSL 4: 1

ENST00000299855, ENST00000434103, ENST00000524478, ENST00001142606

RefSeq mRNA: 1 — MANE Select: NM_002422 NM_002422

CCDS: CCDS8323

Canonical transcript exons

ENST00000299855 — 10 exons

Exon	Start	End
ENSE00001105420	102842154	102842279
ENSE00001105427	102840108	102840252
ENSE00001105439	102839110	102839243
ENSE00001105448	102837298	102837401
ENSE00001292630	102835801	102836226
ENSE00002171374	102843442	102843609
ENSE00002448882	102838551	102838710
ENSE00002477135	102840429	102840593
ENSE00003601812	102842672	102842916
ENSE00003674848	102842431	102842579

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 99.16.

FANTOM5 (CAGE): breadth broad, TPM avg 29.9682 / max 6404.1810, expressed in 440 samples.

Highest expression (Bgee): calcaneal tendon, cartilage tissue, pericardium, tendon of biceps brachii, synovial joint.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MMP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.6e-08	+1.00	11:102849416:A:G
Adrenal Gland	eqtl	3.4e-06	+0.67	11:102938492:T:G
Cells Cultured fibroblasts	eqtl	6.7e-05	-0.20	11:102865116:G:GAT
Skin Not Sun Exposed Suprapubic	eqtl	8.6e-04	+0.96	11:102849416:A:G
Heart Atrial Appendage	eqtl	1.8e-02	+0.91	11:102999312:T:A
Minor Salivary Gland	eqtl	2.0e-02	-1.07	11:103447989:C:A
Artery Coronary	eqtl	4.4e-02	+0.37	11:102582531:G:C
Breast Mammary Tissue	eqtl	4.9e-02	+0.17	11:102914532:C:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
122025	29.9682	440

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.16	gold quality
cartilage tissue	UBERON:0002418	98.82	gold quality
pericardium	UBERON:0002407	98.42	gold quality
tendon of biceps brachii	UBERON:0008188	97.17	gold quality
synovial joint	UBERON:0002217	94.61	gold quality
synovial membrane of synovial joint	UBERON:0002018	94.12	gold quality
minor salivary gland	UBERON:0001830	94.08	gold quality
tendon	UBERON:0000043	93.66	gold quality
islet of Langerhans	UBERON:0000006	87.94	gold quality
mouth mucosa	UBERON:0003729	87.58	gold quality
stromal cell of endometrium	CL:0002255	86.97	gold quality
layer of synovial tissue	UBERON:0007616	85.43	gold quality
saliva-secreting gland	UBERON:0001044	83.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.04	gold quality
tibial nerve	UBERON:0001323	82.88	gold quality
vermiform appendix	UBERON:0001154	79.92	gold quality
skin of leg	UBERON:0001511	77.32	gold quality
gastrocnemius	UBERON:0001388	76.52	gold quality
periodontal ligament	UBERON:0008266	76.08	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.17	gold quality
caecum	UBERON:0001153	73.01	gold quality
muscle of leg	UBERON:0001383	71.92	gold quality
tongue squamous epithelium	UBERON:0006919	70.44	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.61	gold quality
body of stomach	UBERON:0001161	68.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	67.68	silver quality
rectum	UBERON:0001052	67.10	gold quality
epithelial cell of pancreas	CL:0000083	66.92	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	66.74	gold quality
zone of skin	UBERON:0000014	66.59	gold quality
tibialis anterior	UBERON:0001385	66.22	silver quality
skeletal muscle organ	UBERON:0014892	66.11	gold quality
muscle organ	UBERON:0001630	66.10	gold quality
gall bladder	UBERON:0002110	65.79	gold quality
stomach	UBERON:0000945	64.98	gold quality
urinary bladder	UBERON:0001255	64.98	gold quality
ileal mucosa	UBERON:0000331	64.57	silver quality
smooth muscle tissue	UBERON:0001135	64.25	gold quality
pancreatic ductal cell	CL:0002079	64.22	silver quality
descending thoracic aorta	UBERON:0002345	64.03	gold quality
sigmoid colon	UBERON:0001159	63.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	63.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	63.15	gold quality
popliteal artery	UBERON:0002250	62.80	gold quality
tibial artery	UBERON:0007610	62.67	gold quality
aorta	UBERON:0000947	62.52	gold quality
pancreas	UBERON:0001264	62.46	gold quality
thoracic aorta	UBERON:0001515	62.45	gold quality
ascending aorta	UBERON:0001496	61.98	gold quality
large intestine	UBERON:0000059	61.57	gold quality
colon	UBERON:0001155	61.50	gold quality
intestine	UBERON:0000160	61.43	gold quality
skin of abdomen	UBERON:0001416	61.40	gold quality
transverse colon	UBERON:0001157	61.35	gold quality
colonic mucosa	UBERON:0000317	61.13	silver quality
small intestine	UBERON:0002108	61.11	gold quality
colonic epithelium	UBERON:0000397	60.86	gold quality
tibia	UBERON:0000979	60.62	silver quality
mucosa of urinary bladder	UBERON:0001259	60.59	gold quality
fundus of stomach	UBERON:0001160	60.04	gold quality
penis	UBERON:0000989	58.94	gold quality
lower esophagus	UBERON:0013473	57.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	57.94	gold quality
pylorus	UBERON:0001166	57.26	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	57.11	gold quality
decidua	UBERON:0002450	57.04	gold quality
connective tissue	UBERON:0002384	56.96	gold quality
mucosa of transverse colon	UBERON:0004991	56.79	gold quality
skin of hip	UBERON:0001554	56.67	silver quality
duodenum	UBERON:0002114	56.58	gold quality
adipose tissue	UBERON:0001013	55.83	gold quality
right lobe of thyroid gland	UBERON:0001119	55.03	gold quality
urethra	UBERON:0000057	54.91	gold quality
nasal cavity mucosa	UBERON:0001826	54.54	gold quality
upper leg skin	UBERON:0004262	54.23	gold quality
thoracic mammary gland	UBERON:0005200	53.71	gold quality
mammary gland	UBERON:0001911	53.49	gold quality
prostate gland	UBERON:0002367	53.39	gold quality
quadriceps femoris	UBERON:0001377	52.61	gold quality
cauda epididymis	UBERON:0004360	52.56	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
cervix squamous epithelium	UBERON:0006922	52.32	silver quality
myometrium	UBERON:0001296	52.27	gold quality
muscle tissue	UBERON:0002385	51.76	gold quality
vastus lateralis	UBERON:0001379	51.58	gold quality
esophagus	UBERON:0001043	51.57	gold quality
anatomical system	UBERON:0000467	51.32	gold quality
multicellular organism	UBERON:0000468	51.19	gold quality
material anatomical entity	UBERON:0000465	51.18	gold quality
metanephros	UBERON:0000081	50.98	gold quality
trachea	UBERON:0003126	50.92	gold quality
body of pancreas	UBERON:0001150	50.69	gold quality
tonsil	UBERON:0002372	50.65	gold quality
skeletal muscle tissue	UBERON:0001134	50.60	gold quality
metanephros cortex	UBERON:0010533	50.58	gold quality
adult organism	UBERON:0007023	50.46	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	39992.32
E-MTAB-7052	yes	10105.19
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

55 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Endometrium 1	tissue	35.9
Appendix	tissue	18.9
Urinary bladder	tissue	13.0
Stomach 1	tissue	3.7
Duodenum	tissue	2.3
Rectum	tissue	2.1
Seminal vesicle	tissue	2.0
Colon	tissue	2.0
Gallbladder	tissue	1.8
Breast	tissue	1.5
Smooth muscle	tissue	1.5
Tonsil	tissue	1.2
Small intestine	tissue	1.0
Pituitary gland	tissue	0.9
Prostate	tissue	0.6
Vagina	tissue	0.5
Adipose tissue	tissue	0.5
Hypothalamus	tissue	0.4
Placenta	tissue	0.4
Substantia nigra	tissue	0.4
Tongue	tissue	0.3
Spinal cord	tissue	0.3
Hippocampus	tissue	0.3
Corpus callosum	tissue	0.3
Postcentral gyrus	tissue	0.3
Skin 1	tissue	0.2
Skeletal muscle	tissue	0.2
Epididymis	tissue	0.2
Basal ganglia	tissue	0.2
Amygdala	tissue	0.2
Medulla oblongata	tissue	0.2
Thalamus	tissue	0.2
Superior colliculi	tissue	0.2
Hippocampal formation	tissue	0.2
Ventral forebrain	tissue	0.2
Olfactory bulb	tissue	0.2
Septum	tissue	0.2
Prefrontal cortex	tissue	0.1
Testis	tissue	0.1
Cerebral cortex	tissue	0.1
Pons	tissue	0.1
Salivary gland	tissue	0.1
Parathyroid gland	tissue	0.1
Motor cortex	tissue	0.1
Putamen	tissue	0.1
Midbrain	tissue	0.1
Lung	tissue	0.1
Locus coeruleus	tissue	0.1
Adrenal gland	tissue	0.1
Thymus	tissue	0.1
Entorhinal cortex	tissue	0.1
Retrosplenial and cingulate cortex	tissue	0.1
Periaqueductal gray	tissue	0.1
Retrosplenial cortex	tissue	0.1
Insular cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 152; highest nTPM — Anterior thalamic nucleus, ventral (15.4), Blood vessel (4.9), Arcuate nucleus (3.1), Transversal temporal gyrus, posterior (2.8), Area striata (2.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, CTSH, ERG, ESR1, ETS1, ETS2, ETV1, ETV6, ETV7, FOS, FOXC1, FOXO3, HIF1A, IL1B, JUN, JUNB, MAFB, NFKB1, NFKB, NFKBIA, NR3C1, NR4A2, RELA, SOX2, STAT3, TBP, TCF20, TCF3, UBTF, ZMYND8, ZNF148

miRNA regulators (miRDB)

Targeting MMP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 37 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-5581-5P	97.91	66.50	965

Functional genomics

gnomAD constraint: pLI 5.35e-16, LOEUF 1.26, missense Z 0.486 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000299855 — one region, missense o/e 0.99.

Literature-anchored findings (GeneRIF, showing 40)

• induction in fibroblasts by basic calcium phosphate crystals (PMID:11836255)
• can cleave all subclasses of igG at a specific conserved site (PMID:11841844)
• The 6A6A MMP3 genotype is a genetic susceptibility factor for restenosis after angioplasty without stenting. (PMID:11977998)
• Stromelysin-1 activation correlates with invasiveness in squamous cell carcinoma (PMID:11982752)
• involvement of MAPKs, AP-1 and NF-kappa B transcription factors in the IL-1 induction of MMP-3 and MMP-13 in chondrocytes (PMID:12009331)
• destruction of the surrounding matrix by endometriosis might be caused by various MMPs, which are mainly produced in stromal cells. (PMID:12034345)
• cooperative binding of promoter with ETS-1 transcription factor (PMID:12034715)
• lack of expresion in Ewing sarcoma may be due to loss of accessibility of regulatory element to the specific fusion protein in vivo (PMID:12054564)
• Activation of protein kinase CK2 is an early step in the ultraviolet B-mediated increase in interstitial collagenase (matrix metalloproteinase-1; MMP-1) and stromelysin-1 (MMP-3) protein levels in human dermal fibroblasts. (PMID:12071839)
• The severe coronary atherosclerotic lesions were significantly associated with the MMP3 genotype as an independent factor of the coronary lesions. (PMID:12204805)
• data provide evidence that MMP-3 can inhibit breast tumour cell invasion in vitro by a mechanism involving plasminogen degradation to fragments that limit plasminogen activation and the degradation of laminin (PMID:12230559)
• With regard to the MMP-3 polymorphism, unexpectedly, the frequency of the 6A/6A genotype causing lower enzyme activity was significantly increased in patients (p = 0.0129; OR = 2.110; 95% CI = 1.165-3.822). (PMID:12432557)
• A single nucleotide polymorphism in MMP-3 promoter is associated with invasive behaviour in breast cancer (PMID:12473595)
• The presence of this protein has a higher risk for arteriosclerosis in men who are smokers. (PMID:12485468)
• N-TIMP-1 interaction with the catalytic domain of MMP-3 investigation by titration calorimetry and 15N NMR (PMID:12634064)
• expression and regulation by intestinal myofibroblasts in inflammatory bowel disease (PMID:12651627)
• 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)
• stromelysin-1, which has the ability to degrade the mucosal extra-cellular matrix, may be responsible for the extensive tissue injury in infants with necrotizing enterocolitis (PMID:12736398)
• Matrix metalloproteinase-3 polymorphism contributes to age-related aortic stiffening through modulation of gene and protein expression. (PMID:12750310)
• regulation of expression by ATP (PMID:12761889)
• The proliferative response to a MMP-3 epitope was similar in rheumatoid arthritis patients and controls; the MMP-3 epitope increased IL-4, and IL-1beta and tumor necrosis factor-a production of arthritis lymphocytes, but not cytokines in controls. (PMID:12784383)
• The increase in antigenic levels of uPA and MMP-3 in endometrium of women with endometriosis might contribute to the invasive potential of endometrial cells (PMID:12832381)
• MMP3 is a senescence-associated gene in normal human oral keratinocytes. (PMID:12837283)
• Increased matrix metalloproteinase-3 expression accounts for invasive properties of human astrocytoma cell lines (PMID:12866026)
• proteolysis of SPARC by MMP-3 produced peptides that regulate endothelial cell proliferation and influence angiogenesis (PMID:12867428)
• The present results indicate that MMP-2 can be helpful in diagnosing Takayasu arteritis [TA] and that MMP-3 and MMP-9 can be used as activity markers for TA (PMID:12952836)
• Cultured vascular smooth muscle cells infected with Chlamydia pneumoniae secreted increased quantities of MMP-3 protein (PMID:13129650)
• The observations are consistent with a downstream mediation role of MMP-3 in phosphoglucose isomerase/AMF-stimulated tumor cell metastasis. (PMID:14715248)
• The results suggest that the 5A/6A polymorphism of MMP-3 gene may not be linked with appearance and/or progression of ovarian cancer. (PMID:14998290)
• Polymorphism is not associated with myocardial infarct in Japan. (PMID:15009479)
• MMP3, MMP9, and TGFbeta1 are important for the modulation, composition, and maintenance of the ECM in oral squamous cell carcinoma (PMID:15033492)
• cleaves IGFBP-1 at (145)Lys/Lys(146), resulting in a small (9-kDa) C-terminal peptide of IGFBP-1 in first trimester decidua (PMID:15070833)
• MMP-3 is specifically expressed in squamous cell carcinomas of the head and neck and its expression correlates with their invasion capacity. (PMID:15094779)
• MMP3 may have a role in response to chemotherapy in head and neck squamous cell carcinoma, as demonstrated by an analysis of its polymorphism (PMID:15102660)
• MMP3 5A/6A promoter polymorphism does not appear to influence breast cancer susceptibility but may be linked to a higher risk for metastasizing among breast cancer patients (PMID:15161710)
• Data suggest that proMMP-3 (prostromelysin 1) may play an essential role in degrading and remodeling the extracellular matrix in workers with pneumoconiosis, and that proMMP-3 may also reflect the stage of pneumoconiosis disease. (PMID:15203551)
• Recent large Japanese case-control studies identified connexin-37 (GJA-4), plasminogen activator inhibitor-1 (PAI-1), and stromelysin-1 (MMP-3) polymorphisms as risk factors for myocardial infarction. (PMID:15234427)
• The presence of the MMP1-2G and MMP3-6A alleles seemed to be associated with decreased risk of head and neck squamous cell carcinoma but mainly when they were carried by the same haplotype. (PMID:15274394)
• No general associations of MMP-1 and MMP-3 genes to primary sclerosing cholangitis(PSC) or ulcerative colitis(UC) among Norwegians, but specific alleles were associated to subsets of PSC patients with UC and cholangiocarcinoma. (PMID:15288468)
• CD154 induced production of TNF-alpha, IL-6, and MMP-3 in rheumatoid arthritis chondrocytes. (PMID:15290728)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp23bb	ENSDARG00000009825
danio_rerio	mmp25b	ENSDARG00000010556
danio_rerio	hpxa	ENSDARG00000012609
danio_rerio	mmp30	ENSDARG00000045887
danio_rerio	mmp25a	ENSDARG00000077290
danio_rerio	mmp13b	ENSDARG00000100794
mus_musculus	Mmp3	ENSMUSG00000043613
rattus_norvegicus	Mmp3	ENSRNOG00000032626
drosophila_melanogaster	Mmp1	FBGN0035049
caenorhabditis_elegans		WBGENE00006987
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00020646
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), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97010) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal neuromuscular synapse morphology	1
increased susceptibility to bacterial infection	1
delayed wound healing	1
joint inflammation	1
autoimmune arthritis	1
osteoarthritis	1
abnormal lymphocyte physiology	1
abnormal miniature endplate potential	1
decreased susceptibility to injury	1
abnormal CD4-positive, alpha-beta T cell physiology	1
decreased susceptibility to type IV hypersensitivity reaction	1

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
Oryctolagus cuniculus	P50757	95.2%	Diamond
Bos taurus	Q9GLE4	95.2%	Diamond
Equus caballus	O18927	90.5%	Diamond
Tupaia belangeri	Q9GKE1	85.2%	Diamond
Gallus gallus	Q90611	85.0%	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
Trichoplusia ni ascovirus 2c	Q06VC5	41.0%	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
MMP1	protein-coding	4312
MMP10	protein-coding	4319
MMP12	protein-coding	4321
MMP13	protein-coding	4322

Protein

Protein identifiers

Stromelysin-1 — P08254 (reviewed: P08254)

Alternative names: Matrix metalloproteinase-3, Transin-1

All UniProt accessions (3): E9PKX2, P08254, H7C139

UniProt curated annotations — full annotation on UniProt →

Function. Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates different molecules including growth factors, plasminogen or other matrix metalloproteinases such as MMP9. Once released into the extracellular matrix (ECM), the inactive pro-enzyme is activated by the plasmin cascade signaling pathway. Also acts intracellularly. For example, in dopaminergic neurons, gets activated by the serine protease HTRA2 upon stress and plays a pivotal role in DA neuronal degeneration by mediating microglial activation and alpha-synuclein/SNCA cleavage. In addition, plays a role in immune response and possesses antiviral activity against various viruses such as vesicular stomatitis virus, influenza A virus (H1N1) and human herpes virus 1. Mechanistically, translocates from the cytoplasm into the cell nucleus upon virus infection to influence NF-kappa-B activities.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Nucleus. Cytoplasm.

Post-translational modifications. Directly cleaved by HTRA2 to produce active form.

Disease relevance. Coronary heart disease 6 (CHDS6) [MIM:614466] A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. Disease susceptibility is associated with variants affecting the gene represented in this entry. A polymorphism in the MMP3 promoter region is associated with the risk of coronary heart disease and myocardial infarction, due to lower MMP3 proteolytic activity and higher extracellular matrix deposition in atherosclerotic lesions.

Activity regulation. Enzymatic activity is activated by HTRA2 in dopaminergic cells upon mitochondrial stress.

Cofactor. Binds 4 Ca(2+) ions per subunit. Binds 2 Zn(2+) ions 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.

Similarity. Belongs to the peptidase M10A family.

RefSeq proteins (1): NP_002413* (*=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
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain
IPR036365	PGBD-like_sf	Homologous_superfamily
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily

Pfam: PF00045, PF00413, PF01471

Enzyme classification (BRENDA)

• EC 3.4.24.17 — stromelysin 1 (BRENDA: 6 organisms, 110 substrates, 260 inhibitors, 9 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ARG-PRO-LYS-PRO-GLN-GLN-PHE-PHE-GLY-LEU-NORLEUCI	0.9–1.4	2
(7-METHOXYCOUMARIN-4-YL)ACETYL-ARG-PRO-LYS-PRO-T	0.066	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-ARG-PRO-LYS-PRO-V	0.025	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-LYS-PRO-GLN-G	0.05	1
2,4-DINITROPHENYL-PRO-TYR-ALA-TYR-TRP-MET-ARG-NH	0.1	1
ACETYL-PRO-LEU-GLY-THIOESTER-LEU-LEU-GLY-ETHYLES	0.27	1
ACETYL-PRO-LEU-GLY-[2-MERCAPTO-4-METHYL-PENTANOY	0.395	1
ACETYL-PRO-LEU-GLY-THIOESTER-LEU-LEU-GLY ETHYL E	—	0
ARG-PRO-LYS-PRO-GLN-GLN-PHE-PHE-GLY-LEU-NLE-NH2	—	0
BETA-CASEIN	—	0

UniProt features (65 total): binding site 24, strand 17, helix 9, repeat 4, signal peptide 1, propeptide 1, active site 1, chain 1, disulfide bond 1, sequence variant 1, sequence conflict 1, turn 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

showing 30 of 44 structures by resolution:

PDB	Title	Method	Resolution (Å)
1HY7	A CARBOXYLIC ACID BASED INHIBITOR IN COMPLEX WITH MMP3	X-RAY DIFFRACTION	1.5
1CIZ	X-RAY STRUCTURE OF HUMAN STROMELYSIN CATALYTIC DOMAIN COMPLEXES WITH NON-PEPTIDE …	X-RAY DIFFRACTION	1.64
1HFS	CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN FIBROBLAST STROMELYSIN-1 INHIBITED …	X-RAY DIFFRACTION	1.7
1CAQ	X-RAY STRUCTURE OF HUMAN STROMELYSIN CATALYTIC DOMAIN COMPLEXES WITH NON-PEPTIDE …	X-RAY DIFFRACTION	1.8
1USN	CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN FIBROBLAST STROMELYSIN-1 INHIBITED …	X-RAY DIFFRACTION	1.8
1C3I	HUMAN STROMELYSIN-1 CATALYTIC DOMAIN COMPLEXED WITH RO-26-2812	X-RAY DIFFRACTION	1.83
4G9L	Structure of MMP3 complexed with NNGH inhibitor.	X-RAY DIFFRACTION	1.88
1G49	A CARBOXYLIC ACID BASED INHIBITOR IN COMPLEX WITH MMP3	X-RAY DIFFRACTION	1.9
1SLM	CRYSTAL STRUCTURE OF FIBROBLAST STROMELYSIN-1: THE C-TRUNCATED HUMAN PROENZYME	X-RAY DIFFRACTION	1.9
4DPE	Structure of MMP3 complexed with a platinum-based inhibitor.	X-RAY DIFFRACTION	1.96
4JA1	Structure of MMP3 complexed with a platinum-based inhibitor	X-RAY DIFFRACTION	1.96
1B8Y	X-RAY STRUCTURE OF HUMAN STROMELYSIN CATALYTIC DOMAIN COMPLEXED WITH NON-PEPTIDE …	X-RAY DIFFRACTION	2
1CQR	CRYSTAL STRUCTURE OF THE STROMELYSIN CATALYTIC DOMAIN AT 2.0 A RESOLUTION	X-RAY DIFFRACTION	2
1D7X	CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A MODIFIED PROLINE SCAFFOLD BASED INHIBITOR.	X-RAY DIFFRACTION	2
1G4K	X-ray Structure of a Novel Matrix Metalloproteinase Inhibitor Complexed to Stromelysin	X-RAY DIFFRACTION	2
1QIA	CRYSTAL STRUCTURE OF STROMELYSIN CATALYTIC DOMAIN	X-RAY DIFFRACTION	2
1QIC	CRYSTAL STRUCTURE OF STROMELYSIN CATALYTIC DOMAIN	X-RAY DIFFRACTION	2
2D1O	Stromelysin-1 (MMP-3) complexed to a hydroxamic acid inhibitor	X-RAY DIFFRACTION	2.02
2USN	CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN FIBROBLAST STROMELYSIN-1 INHIBITED …	X-RAY DIFFRACTION	2.2
1SLN	CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN FIBROBLAST STROMELYSIN-1 INHIBITED …	X-RAY DIFFRACTION	2.27
1B3D	STROMELYSIN-1	X-RAY DIFFRACTION	2.3
1BQO	DISCOVERY OF POTENT, ACHIRAL MATRIX METALLOPROTEINASE INHIBITORS	X-RAY DIFFRACTION	2.3
7S7L	Complex of tissue inhibitor of metalloproteinases-1 (TIMP-1) mutant …	X-RAY DIFFRACTION	2.34
3OHL	catalytic domain of stromelysin-1 in complex with …	X-RAY DIFFRACTION	2.36
6MAV	Complex of tissue inhibitor of metalloproteinase-1 (TIMP-1) mutant L34G with matrix …	X-RAY DIFFRACTION	2.37
1D8F	CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A PIPERAZINE BASED INHIBITOR.	X-RAY DIFFRACTION	2.4
1D8M	CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A HETEROCYCLE-BASED INHIBITOR	X-RAY DIFFRACTION	2.44
1G05	HETEROCYCLE-BASED MMP INHIBITOR WITH P2’SUBSTITUENTS	X-RAY DIFFRACTION	2.45
1BIW	DESIGN AND SYNTHESIS OF CONFORMATIONALLY-CONSTRAINED MMP INHIBITORS	X-RAY DIFFRACTION	2.5
3OHO	catalytic domain of stromelysin-1 in complex with …	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08254-F1	86.12	0.59

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Metallopeptidases, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH uncertain · IF supported

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
219

Ligand- & substrate-binding residues (24)

Position	Role
92	Zn(2+)
124	Ca(2+)
158	Ca(2+)
168	Zn(2+)
170	Zn(2+)
175	Ca(2+)
176	Ca(2+)
178	Ca(2+)
180	Ca(2+)
183	Zn(2+)
190	Ca(2+)
192	Ca(2+)
194	Ca(2+)
196	Zn(2+)
198	Ca(2+)
199	Ca(2+)
201	Ca(2+)
218	Zn(2+)
222	Zn(2+)
228	Zn(2+)
297	Ca(2+)
389	Ca(2+)
438	Ca(2+)

Disulfide bonds (1)

Type	Positions
Disulfide bond	290–477

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 19; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

19 pathways:

ID	Pathway	Evidence
R-HSA-1592389	Activation of Matrix Metalloproteinases	curated
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures	curated
R-HSA-9009391	Extra-nuclear estrogen signaling	curated
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	curated
R-HSA-1442490	Collagen degradation	electronic
R-HSA-1474290	Collagen formation	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-1474228	Degradation of the extracellular matrix	electronic
R-HSA-2179392	EGFR Transactivation by Gastrin	electronic
R-HSA-8939211	ESR-mediated signaling	—
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-416476	G alpha (q) signalling events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-881907	Gastrin-CREB signalling pathway via PKC and MAPK	—
R-HSA-168256	Immune System	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-9006931	Signaling by Nuclear Receptors	—

MSigDB gene sets: 238 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, MODULE_172, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, chr11q22, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (16): proteolysis (GO:0006508), extracellular matrix disassembly (GO:0022617), protein catabolic process (GO:0030163), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574), positive regulation of protein-containing complex assembly (GO:0031334), cellular response to reactive oxygen species (GO:0034614), innate immune response (GO:0045087), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), cellular response to lipopolysaccharide (GO:0071222), cellular response to UV-A (GO:0071492), cellular response to nitric oxide (GO:0071732), regulation of neuroinflammatory response (GO:0150077), response to amyloid-beta (GO:1904645), negative regulation of reactive oxygen species metabolic process (GO:2000378), immune system process (GO:0002376)

GO Molecular Function (9): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), nucleus (GO:0005634), mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular matrix (GO:0031012), cytoplasm (GO:0005737)

Reactome top-level categories

13 top-level categories:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	2
Signal Transduction	2
Collagen formation	1
Gastrin-CREB signalling pathway via PKC and MAPK	1
Signaling by Interleukins	1
ESR-mediated signaling	1
Immune System	1
Signaling by GPCR	1
GPCR downstream signalling	1
Cytokine Signaling in Immune system	1
G alpha (q) signalling events	1
Signaling by Nuclear Receptors	1

GO top-level categories

50 GO namespaces:

Category	Terms
cellular response to oxygen-containing compound	3
cellular anatomical structure	3
protein metabolic process	2
peptidase activity	2
endopeptidase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular component disassembly	1
extracellular matrix organization	1
macromolecule catabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
immune response	1
defense response to symbiont	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to UV	1
response to UV-A	1
response to nitric oxide	1
cellular response to reactive nitrogen species	1
regulation of inflammatory response	1
neuroinflammatory response	1
response to nitrogen compound	1
response to oxygen-containing compound	1
negative regulation of metabolic process	1
reactive oxygen species metabolic process	1
regulation of reactive oxygen species metabolic process	1
biological_process	1
metallopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
external encapsulating structure	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 32 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to UV-A	BP	direct assay
negative regulation of reactive oxygen species metabolic process	BP	direct assay
positive regulation of protein-containing complex assembly	BP	direct assay
proteolysis	BP	direct assay
endopeptidase activity	MF	direct assay
metallopeptidase activity	MF	direct assay
peptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,794 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP3	TIMP1	P01033	928
MMP3	ADAMTS5	Q9UNA0	872
MMP3	TIMP2	P16035	854
MMP3	IL1B	P01584	851
MMP3	ADAMTS3	O15072	848
MMP3	ADAMTS4	O75173	841
MMP3	FN1	P02751	835
MMP3	ACAN	P16112	810
MMP3	TNF	P01375	794
MMP3	TIMP4	Q99727	784
MMP3	ELN	P15502	784
MMP3	IL6	P05231	773
MMP3	TIMP3	P35625	765
MMP3	MMP9	P14780	748
MMP3	IL1A	P01583	738

IntAct

Human interaction partners of MMP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
MEOX2	physical association	0.560	3
APOE	association	0.530	2
MMP10	association	0.530	1
TIMP1	direct interaction	0.440	1
IFNG	association	0.350	1
TIGD7	association	0.350	1
VGF	association	0.350	1

BioGRID (39 interactions; top human partners by supporting records): APOE (Affinity Capture-MS; 3 records), KIAA0319L (Affinity Capture-MS; 3 records), MMP10 (Affinity Capture-MS; 3 records), NUCB1 (Affinity Capture-MS; 3 records), PTPRS (Affinity Capture-MS; 3 records), CLU (Affinity Capture-MS; 2 records), LTBP1 (Affinity Capture-MS; 2 records), MMP14 (Reconstituted Complex; 2 records), TIMP3 (Affinity Capture-MS; 2 records), BCAN (Biochemical Activity), BMP4 (Affinity Capture-MS), CLN5 (Affinity Capture-MS), HBD (Affinity Capture-MS), MEOX2 (Two-hybrid), MMP1 (Negative Genetic)

SIGNOR signaling

10 signaling interactions:

A	Effect	B	Mechanism
ZMYND8	“down-regulates quantity by repression”	MMP3	“transcriptional regulation”
MMP3	“down-regulates quantity by destabilization”	ACAN	cleavage
MMP3	up-regulates	HBEGF	cleavage
TCF20	“up-regulates quantity by expression”	MMP3	“transcriptional regulation”
SRC	“up-regulates activity”	MMP3
MMP3	“up-regulates activity”	SPP1	cleavage
MMP3	“down-regulates quantity by destabilization”	HAPLN1	cleavage
MMP3	“down-regulates quantity by destabilization”	DCN	cleavage
MMP3	up-regulates	ECM_disassembly
MMP3	down-regulates	ECM

Disease & clinical

Genetic variants

Variant evidence for MMP3: 109 ClinVar records (0 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 15 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	12
Benign	26

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 609):

Position(s)	Effect	Δscore	Sites
11:102837296–102837297	donor_loss	1.0000	5
11:102837404	acceptor_gain	1.0000
11:102837409	acceptor_gain	1.0000
11:102838593	donor_gain	1.0000
11:102838599	donor_gain	1.0000
11:102839108–102839109	donor_loss	1.0000	4
11:102840133	donor_gain	1.0000
11:102840427–102840428	donor_loss	1.0000	5
11:102842152–102842153	donor_loss	1.0000	4
11:102842281	acceptor_loss	1.0000

AlphaMissense

680 missense substitutions predicted likely pathogenic (of 3,149 scored), across 185 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
M236	9	0.853	0.970
D255	8	0.941	0.975
H222	8	0.937	0.974
H218	8	0.932	0.974
F174	8	0.925	0.982
F163	8	0.923	0.990
H183	8	0.915	0.961
H228	8	0.900	0.963
D198	8	0.864	0.943
H196	8	0.858	0.943
H168	8	0.856	0.936
D170	8	0.853	0.923
F197	8	0.818	0.970
F309	8	0.810	0.953
D96	8	0.683	0.833
W109	7	0.958	0.990
W141	7	0.954	0.989
W203	7	0.945	0.980
C92	7	0.941	0.967
E219	7	0.920	0.972

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Head and Neck Squamous Cell Carcinoma)

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000142
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000429
Lung Adenocarcinoma (TCGA)	unfavorable	0.000431

Disease associations

OMIM: gene MIM:185250 | disease phenotypes:

GWAS associations

15 associations:

Study	Trait	p-value
GCST009731_27	Blood protein levels in cardiovascular risk	5e-160
GCST002665_4	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2e-44
GCST006585_557	Blood protein levels	2e-33
GCST008474_13	Peripheral artery disease	4e-9
GCST003264_1073	Post bronchodilator FEV1/FVC ratio	2e-7
GCST003264_109	Post bronchodilator FEV1/FVC ratio	2e-7
GCST003264_116	Post bronchodilator FEV1/FVC ratio	2e-7
GCST003264_216	Post bronchodilator FEV1/FVC ratio	3e-7
GCST003264_217	Post bronchodilator FEV1/FVC ratio	3e-7
GCST003265_176	Post bronchodilator FEV1/FVC ratio in COPD	6e-7
GCST003265_291	Post bronchodilator FEV1/FVC ratio in COPD	6e-7
GCST003265_180	Post bronchodilator FEV1/FVC ratio in COPD	7e-7
GCST003265_467	Post bronchodilator FEV1/FVC ratio in COPD	7e-7
GCST001529_3	Alzheimer’s disease	1e-6
GCST003265_1	Post bronchodilator FEV1/FVC ratio in COPD	1e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004744	matrix metalloproteinase measurement
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0004713	FEV/FVC ratio
EFO:0010608	stromelysin‐1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111321 (SELECTIVITY GROUP), CHEMBL283 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MMP3 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
MARIMASTAT	Small molecule	3
CTS-1027	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: 286,171 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

14 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1200699	DOXYCYCLINE	4	94,976
CHEMBL1356238	PYRITHIONE	4	15,697
CHEMBL279785	MARIMASTAT	3	29,705
CHEMBL75094	PRINOMASTAT	3	8,942
CHEMBL50	QUERCETIN	3	75,572
CHEMBL440498	CTS-1027	2	651
CHEMBL206815	APRATASTAT	2	271
CHEMBL279786	BATIMASTAT	2	21,436
CHEMBL115653	CIPEMASTAT	2	380
CHEMBL19611	ILOMASTAT	2	12,186
CHEMBL151	LUTEOLIN	2	23,845
CHEMBL76222	REBIMASTAT	2	363
CHEMBL2107228	SOLIMASTAT	2	109
CHEMBL261932	TANOMASTAT	2	2,038

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs35068180	Efficacy	3	chlorthalidone;lisinopril	Hypertension
rs35068180	Efficacy	3	pravastatin	Coronary Artery Disease

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs35068180	MMP3	3	6.00	2	pravastatin;chlorthalidone;lisinopril

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

3 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs35068180	pravastatin	Efficacy	Genotypes A/del + AA are associated with increased response to pravastatin in men with Coronary Artery Disease.	PMID:10190398
rs35068180	lisinopril	Efficacy	Genotype AA is associated with increased risk of Stroke when treated with lisinopril in people with Hypertension.	PMID:21183746
rs35068180	lisinopril	Efficacy	Genotype del/del is associated with decreased risk of Stroke when treated with lisinopril in people with Hypertension.	PMID:21183746

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
batimastat	Inhibition	9.19	pIC50
UK-356618	Inhibition	8.2	pIC50
CM-352	Inhibition	7.92	pIC50
CGS-27023A	Inhibition	7.8	pIC50
ilomastat	Inhibition	7.49	pIC50
marimastat	Inhibition	6.64	pIC50

Binding affinities (BindingDB)

2070 measured of 2463 human assays (2484 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2R)-2-{[4-(4-bromophenyl)benzene]sulfonamido}-3-methylbutanoic acid	IC50	0.004 nM
N*1*-(2-Cyclohexyl-1-{2-[2-(4-sulfamoyl-phenyl)-ethylcarbamoyl]-ethylcarbamoyl}-ethyl)-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
3-(3-{2-[5-(4-Chloro-phenyl)-2-hydroxycarbamoylmethyl-pentanoylamino]-3-cyclohexyl-propionylamino}-propionylamino)-propionic acid methyl ester	KI	0.01 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-(2-cyclohexyl-1-{2-[2-(morpholine-4-sulfonylamino)-ethylcarbamoyl]-ethylcarbamoyl}-ethyl)-N*4*-hydroxy-succinamide	KI	0.01 nM
N*1*-(2-Cyclohexyl-1-{2-[2-(morpholine-4-sulfonylamino)-ethylcarbamoyl]-ethylcarbamoyl}-ethyl)-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
N*1*-{2-Cyclohexyl-1-[2-(2-morpholin-4-yl-ethylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
3-(3-{2-[5-(4-Chloro-phenyl)-2-hydroxycarbamoylmethyl-pentanoylamino]-3-cyclohexyl-propionylamino}-propionylamino)-propionic acid	KI	0.01 nM
3-{(S)-2-[(R)-5-(4-Chloro-phenyl)-2-hydroxycarbamoylmethyl-pentanoylamino]-3-cyclohexyl-propionylamino}-propionic acid	KI	0.01 nM
(R)-N*1*-{(S)-2-Cyclohexyl-1-[2-(4-sulfamoyl-phenyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
(R)-N*1*-[(S)-2-Cyclohexyl-1-(2-morpholin-4-yl-ethylcarbamoyl)-ethyl]-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{(S)-2-cyclohexyl-1-[2-(morpholine-4-sulfonylamino)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.01 nM
3-{(S)-2-[(R)-5-(4-Chloro-phenyl)-2-hydroxycarbamoylmethyl-pentanoylamino]-3-cyclohexyl-propionylamino}-propionic acid methyl ester	KI	0.01 nM
(R)-N*1*-{(S)-2-Cyclohexyl-1-[2-(morpholine-4-sulfonylamino)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
N*1*-{2-Cyclohexyl-1-[2-(4-dimethylamino-butylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.02 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{2-cyclohexyl-1-[2-(3-morpholin-4-yl-3-oxo-propylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.02 nM
N*1*-{2-Cyclohexyl-1-[2-(4-morpholin-4-yl-butylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.02 nM
(R)-N*1*-[(S)-2-Cyclohexyl-1-(4-morpholin-4-yl-butylcarbamoyl)-ethyl]-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.02 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-[(S)-2-cyclohexyl-1-(3-morpholin-4-yl-3-oxo-propylcarbamoyl)-ethyl]-N*4*-hydroxy-succinamide	KI	0.02 nM
(R)-N*1*-[(S)-2-Cyclohexyl-1-(4-dimethylamino-butylcarbamoyl)-ethyl]-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.02 nM
alpha-tetrahydropyran beta-sulfone 1B	IC50	0.029 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-((S)-2-cyclohexyl-1-phenethylcarbamoyl-ethyl)-N*4*-hydroxy-succinamide	KI	0.03 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{2-cyclohexyl-1-[2-(4-morpholin-4-yl-butylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.03 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-(2-cyclohexyl-1-{2-[2-(4-sulfamoyl-phenyl)-ethylcarbamoyl]-ethylcarbamoyl}-ethyl)-N*4*-hydroxy-succinamide	KI	0.03 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{(S)-2-cyclohexyl-1-[2-(4-sulfamoyl-phenyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.03 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-[(S)-2-cyclohexyl-1-(4-morpholin-4-yl-butylcarbamoyl)-ethyl]-N*4*-hydroxy-succinamide	KI	0.03 nM
CHEMBL5412341	IC50	0.034 nM
(2R)-3-methyl-2-[(4-phenylbenzene)sulfonamido]butanoic acid	IC50	0.04 nM
AG-3340	IC50	0.048 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{2-cyclohexyl-1-[2-(4-dimethylamino-butylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.05 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-[(S)-2-cyclohexyl-1-(4-dimethylamino-butylcarbamoyl)-ethyl]-N*4*-hydroxy-succinamide	KI	0.05 nM
CHEMBL473539	IC50	0.05 nM
CHEMBL5182207	IC50	0.055 nM
(R)-N*1*-((S)-2-Cyclohexyl-1-phenethylcarbamoyl-ethyl)-N*4*-hydroxy-2-(3-phenyl-propyl)-succinamide	KI	0.06 nM
(R)-N*1*-((S)-2-Cyclohexyl-1-phenethylcarbamoyl-ethyl)-2-[3-(4-fluoro-phenyl)-propyl]-N*4*-hydroxy-succinamide	KI	0.06 nM
N*1*-(2-Cyclohexyl-1-phenethylcarbamoyl-ethyl)-N*4*-hydroxy-2-[3-(4-methoxy-phenyl)-propyl]-succinamide	KI	0.06 nM
2-(4’-Chloro-biphenyl-4-ylsulfanylmethyl)-N-hydroxy-4-(4-oxo-4H-benzo[d][1,2,3]triazin-3-yl)-butyramide	IC50	0.06 nM
CHEMBL5185612	IC50	0.068 nM
(R)-N*1*-((S)-2-Cyclohexyl-1-phenethylcarbamoyl-ethyl)-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.08 nM
(R)-2-[(Biphenyl-4-sulfonyl)-isopropoxy-amino]-N-hydroxy-3-methyl-butyramide	IC50	0.09 nM
N-hydroxy-1-(2-methoxyethyl)-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide hydrochloride	KI	0.1 nM
1-Cyclopropyl-N-hydroxy-4-{[4-(phenylthio)phenyl]-sulfonyl}piperidine-4-carboxamide Hydrochloride	KI	0.1 nM
(7S,8R,11S)-9-Oxo-8-[2-(4-propyl-phenyl)-ethyl]-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide	IC50	0.1 nM
(R)-4-[(Z)-Benzyloxyimino]-1-(4-butoxy-benzenesulfonyl)-pyrrolidine-2-carboxylic acid hydroxyamide	IC50	0.1 nM
2-(4’-Chloro-biphenyl-4-yloxymethyl)-N-hydroxy-4-(4-oxo-4H-benzo[d][1,2,3]triazin-3-yl)-butyramide	IC50	0.1 nM
(R)-N*1*-((S)-2-Cyclohexyl-1-phenethylcarbamoyl-ethyl)-2-[3-(4-ethyl-phenyl)-propyl]-N*4*-hydroxy-succinamide	KI	0.1 nM
(R)-2-((R)-3-amino-3-(4-((2-methylquinolin-4-yl)methoxy)phenyl)-2-oxopyrrolidin-1-yl)-N-hydroxy-3-methylbutanamide	IC50	0.1 nM
CHEMBL1801396	IC50	0.1 nM
CHEMBL1801424	IC50	0.1 nM
CHEMBL1801413	IC50	0.1 nM
CHEMBL1229868	IC50	0.1 nM

ChEMBL bioactivities

2188 potent at pChembl≥5 of 2422 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	PRINOMASTAT
10.42	IC50	0.038	nM	CHEMBL330028
9.72	IC50	0.191	nM	ILOMASTAT
9.70	IC50	0.2	nM	CHEMBL1801056
9.64	IC50	0.23	nM	PRINOMASTAT
9.57	Ki	0.27	nM	PRINOMASTAT
9.52	IC50	0.3	nM	CTS-1027
9.52	IC50	0.3	nM	CHEMBL400083
9.52	IC50	0.3	nM	CHEMBL473539
9.46	Ki	0.35	nM	CHEMBL56837
9.44	Ki	0.36	nM	CHEMBL168150
9.40	IC50	0.4	nM	CHEMBL251918
9.37	Ki	0.43	nM	CHEMBL291264
9.30	Ki	0.5	nM	CHEMBL425316
9.30	IC50	0.5	nM	CHEMBL154044
9.30	IC50	0.5012	nM	CHEMBL154044
9.29	Ki	0.51	nM	CHEMBL61193
9.28	Ki	0.53	nM	CHEMBL355797
9.25	IC50	0.56	nM	BATIMASTAT
9.22	IC50	0.6	nM	CHEMBL279078
9.19	IC50	0.65	nM	BATIMASTAT
9.15	IC50	0.7	nM	CHEMBL104022
9.15	IC50	0.7	nM	CHEMBL140970
9.15	IC50	0.7	nM	CHEMBL4088630
9.15	IC50	0.7079	nM	CHEMBL140970
9.15	IC50	0.7	nM	CHEMBL320402
9.15	IC50	0.7	nM	CHEMBL296911
9.15	IC50	0.7	nM	CHEMBL342172
9.15	IC50	0.7	nM	CHEMBL141080
9.14	IC50	0.73	nM	BATIMASTAT
9.12	IC50	0.75	nM	BATIMASTAT
9.10	Ki	0.8	nM	CHEMBL76158
9.10	Ki	0.8	nM	CHEMBL93395
9.10	IC50	0.8	nM	CHEMBL288896
9.05	Ki	0.9	nM	CHEMBL72511
9.05	IC50	0.9	nM	CHEMBL102438
9.02	Ki	0.96	nM	CHEMBL308533
9.02	Ki	0.96	nM	CHEMBL92828
9.00	IC50	1	nM	CHEMBL252117
9.00	IC50	1	nM	CHEMBL251917
9.00	IC50	1	nM	CHEMBL398641
9.00	IC50	1	nM	CHEMBL149977
9.00	IC50	1	nM	CHEMBL337594
8.96	IC50	1.1	nM	CHEMBL317508
8.96	IC50	1.1	nM	PRINOMASTAT
8.96	IC50	1.1	nM	CHEMBL344633
8.96	IC50	1.1	nM	CHEMBL105311
8.92	IC50	1.2	nM	CHEMBL125901
8.92	IC50	1.2	nM	CHEMBL321180
8.92	IC50	1.2	nM	CHEMBL111798

PubChem BioAssay actives

1980 with measured affinity, of 3111 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
3-methyl-2-[(4-phenylphenyl)sulfonylamino]butanoic acid	732014: Inhibition of MMP3 (unknown origin)	ic50	<0.0001	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	1929084: Inhibition of MMP-3 (unknown origin)	ki	<0.0001	uM
2-[[4-(4-bromophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid	732014: Inhibition of MMP3 (unknown origin)	ic50	<0.0001	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	107503: Inhibition of human matrix metalloprotease-3	ic50	0.0002	uM
N-hydroxy-4-[4-(4-methoxyphenoxy)phenyl]sulfonyl-1-prop-2-ynylpiperidine-4-carboxamide	604450: Inhibition of human MMP3 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0002	uM
N-hydroxy-1-(2-methoxyethyl)-4-(4-phenoxyphenyl)sulfonylpiperidine-4-carboxamide	1796811: Enzyme Inhibition Assay from Article 10.1021/jm0500875: “Synthesis and structure-activity relationships of beta- and alpha-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy.”	ki	0.0003	uM
1-cyclopropyl-N-hydroxy-4-(4-phenoxyphenyl)sulfonylpiperidine-4-carboxamide	1796811: Enzyme Inhibition Assay from Article 10.1021/jm0500875: “Synthesis and structure-activity relationships of beta- and alpha-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy.”	ki	0.0003	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1162786: Inhibition of human recombinant MMP3 using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	0.0003	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-phenoxyphenyl)sulfonylthiomorpholine-3-carboxamide	1863876: Inhibition of MMP-3 (unknown origin)	ic50	0.0003	uM
(2R,3R,4R,5R)-N,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide	107528: Inhibition of human recombinant matrix metalloprotease 3	ki	0.0003	uM
N-hydroxy-2-methyl-2-[4-[3-methyl-4-[3-[2-(methylamino)ethoxy]phenyl]phenyl]piperidin-1-yl]sulfonylpropanamide	311965: Inhibition of MMP3	ic50	0.0003	uM
(2R,3R,4R,5R)-1-(4-but-2-ynoxyphenyl)sulfonyl-N,4,5-trihydroxy-3-methoxypiperidine-2-carboxamide	107660: Inhibition of recombinant human matrix metalloprotease-3	ki	0.0004	uM
2-[4-[4-[3-(2-aminoethoxy)phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-N-hydroxy-2-methylpropanamide	311965: Inhibition of MMP3	ic50	0.0004	uM
(2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-2-[3-(3-methyl-4-phenylphenyl)propyl]butanediamide	107362: Concentration required to inhibit the catalytic domain Matrix metalloprotease-3 using Nagase fluorogenic as a substrate.	ic50	0.0005	uM
2-[ethoxy-(4-phenoxyphenyl)phosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	107530: Inhibitory activity against matrix metalloprotease-3 (MMP-3)(stromelysin-1).	ki	0.0005	uM
2-[[4-(4-aminophenoxy)phenyl]-ethoxyphosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	107530: Inhibitory activity against matrix metalloprotease-3 (MMP-3)(stromelysin-1).	ki	0.0005	uM
(2R,3R,4R,5S)-N,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide	107528: Inhibition of human recombinant matrix metalloprotease 3	ki	0.0005	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	107358: Activity against Matrix metalloprotease-3 (MMP-3).	ic50	0.0006	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-3-(2-methylpropyl)-2-(thiophen-2-ylsulfanylmethyl)butanediamide	107358: Activity against Matrix metalloprotease-3 (MMP-3).	ic50	0.0006	uM
(3S)-N-hydroxy-4-(4-methoxyphenyl)sulfonyl-2,2-dimethylthiomorpholine-3-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0007	uM
(6S)-N-hydroxy-7-(4-methoxyphenyl)sulfonyl-5,5-dimethyl-1,4,7-oxathiazonane-6-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0007	uM
4-benzylsulfanyl-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]butanamide	107491: In vitro inhibitory activity against matrix metalloprotease-3	ic50	0.0007	uM
N-hydroxy-4-(4-methoxyphenyl)sulfonyl-2,2-dimethylthiomorpholine-3-carboxamide	1454755: Inhibition of truncated human recombinant MMP3 catalytic domain expressed in Escherichia coli BL21(DE3) after 3 hrs in presence of [H]-transferrin	ic50	0.0007	uM
(2S)-4-benzylsulfanyl-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]butanamide	104747: Inhibition of matrix metalloprotease-3	ic50	0.0007	uM
(2R)-4-benzylsulfanyl-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]butanamide	107512: Inhibition of matrix metalloprotease-3	ic50	0.0007	uM
(3S)-N-hydroxy-4-(4-methoxyphenyl)sulfonyl-2,2-dimethyl-1,4-thiazepane-3-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0007	uM
3-[3-[[(2S)-2-[[(2R)-5-(4-chlorophenyl)-2-[2-(hydroxyamino)-2-oxoethyl]pentanoyl]amino]-3-cyclohexylpropanoyl]amino]propanoylamino]propanoic acid	107656: Inhibitory constant against matrix metalloprotease-3	ki	0.0008	uM
4-benzylsulfanyl-N-hydroxy-2-[[2-[(4-methoxyphenyl)methylamino]-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]butanamide	107491: In vitro inhibitory activity against matrix metalloprotease-3	ic50	0.0009	uM
(2S,3R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-3-(hydroxymethyl)-2-(4-methoxyphenyl)butanediamide	107685: Inhibitory potency against Matrix metalloprotease-3 (MMP-3)	ki	0.0009	uM
(2R,4Z)-1-[4-(4-fluorophenoxy)phenyl]sulfonyl-N-hydroxy-4-methoxyiminopyrrolidine-2-carboxamide	107492: In vitro inhibition activity of human recombinant stromelysin (Matrix metalloprotease-3)	ic50	0.0010	uM
(2R,4Z)-1-(4-butoxyphenyl)sulfonyl-N-hydroxy-4-methoxyiminopyrrolidine-2-carboxamide	107492: In vitro inhibition activity of human recombinant stromelysin (Matrix metalloprotease-3)	ic50	0.0010	uM
tert-butyl (6S,9R,10S)-10-(hydroxycarbamoyl)-6-(methylcarbamoyl)-9-(2-methylpropyl)-8-oxo-1,7-diazacyclotridecane-1-carboxylate	107532: Inhibition of matrix metalloprotease-3 (MMP-3).	ki	0.0010	uM
(2R,4Z)-1-[4-(4-fluorophenoxy)phenyl]sulfonyl-N-hydroxy-4-[(2-methylpropan-2-yl)oxyimino]pyrrolidine-2-carboxamide	107492: In vitro inhibition activity of human recombinant stromelysin (Matrix metalloprotease-3)	ic50	0.0010	uM
methyl 3-[3-[[(2S)-2-[[(2R)-5-(4-chlorophenyl)-2-[2-(hydroxyamino)-2-oxoethyl]pentanoyl]amino]-3-cyclohexylpropanoyl]amino]propanoylamino]propanoate	107656: Inhibitory constant against matrix metalloprotease-3	ki	0.0010	uM
(3S)-N-hydroxy-6-(methoxymethoxy)-4-(4-methoxyphenyl)sulfonyl-2,2-dimethyl-1,4-thiazepane-3-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0010	uM
N-hydroxy-2-[4-[4-[3-(2-hydroxyethoxy)phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanamide	311965: Inhibition of MMP3	ic50	0.0010	uM
2-[4-[4-[3-[2-(dimethylamino)ethoxy]phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-N-hydroxy-2-methylpropanamide	311965: Inhibition of MMP3	ic50	0.0010	uM
N-hydroxy-2-[4-[4-[6-(2-hydroxyethoxy)-2-pyridinyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanamide	311965: Inhibition of MMP3	ic50	0.0010	uM
4-benzylsulfanyl-2-[[2-(dipyridin-2-ylmethylamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]-N-hydroxybutanamide	107491: In vitro inhibitory activity against matrix metalloprotease-3	ic50	0.0011	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(5-pyridin-2-ylthiophen-2-yl)sulfonyl-1,4-thiazepane-3-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0011	uM
2-[[4-(4-cyanophenyl)phenoxy]methyl]-N-hydroxy-4-(4-oxo-1,2,3-benzotriazin-3-yl)butanamide	107502: Inhibition of Matrix metalloprotease-3	ic50	0.0011	uM
(2S,3R)-N,2-dihydroxy-N’-[(2S)-1-(1H-indol-3-yl)-3,3-dimethyl-1-oxobutan-2-yl]-3-(2-methylpropyl)butanediamide	104927: In vitro inhibitory activity against human recombinant matrix metalloprotease 3	ic50	0.0012	uM
(1R,2R,5S)-2-[(4-oxo-1,2,3-benzotriazin-3-yl)methyl]-5-(4-pyridin-4-ylphenyl)sulfanylcyclopentane-1-carboxylic acid	107514: Inhibitory activity against matrix metalloprotease-3 (MMP3)	ic50	0.0012	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(1H-indol-3-yl)-3,3-dimethyl-1-oxobutan-2-yl]-3-(2-methylpropyl)-2-prop-2-enylbutanediamide	104927: In vitro inhibitory activity against human recombinant matrix metalloprotease 3	ic50	0.0012	uM
(4R)-1-tert-butyl-N-hydroxy-3-(4-methoxyphenyl)sulfonyl-6-oxo-1,3-diazinane-4-carboxamide	107360: Inhibition of Matrix metalloprotease-3	ic50	0.0013	uM
[(2S)-2-[[(2R)-1-anilino-4-methyl-1-oxopentan-2-yl]carbamoyl]-4-phenylbutyl]-[4-(1,3-dioxoisoindol-2-yl)butyl]phosphinic acid	104899: Inhibition of recombinant matrix metalloprotease-3 (MMP-3)	ki	0.0014	uM
(2R)-2-[3-(4-chlorophenyl)propyl]-N-[(2S)-3-cyclohexyl-1-[[3-[(3-morpholin-4-yl-3-oxopropyl)amino]-3-oxopropyl]amino]-1-oxopropan-2-yl]-N’-hydroxybutanediamide	107656: Inhibitory constant against matrix metalloprotease-3	ki	0.0014	uM
(7S,8R,11S)-7-N-hydroxy-11-N-methyl-9-oxo-8-[2-(4-propylphenyl)ethyl]-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,11-dicarboxamide	104742: Inhibition of fibroblast stromelysin (MMP-3)	ic50	0.0015	uM
N-hydroxy-4-[(4-phenoxyphenyl)sulfonylmethyl]-1-prop-2-ynylpiperidine-4-carboxamide	313839: Inhibition of MMP3	ic50	0.0015	uM
N-[[3-[4-[[(2S)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]sulfamoyl]phenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328777: Inhibition of recombinant human AMPA-activated MMP3 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases secretion, increases expression	9
Glucosamine	decreases activity, decreases reaction, increases expression, increases secretion, decreases expression (+2 more)	7
sodium arsenite	decreases reaction, increases expression, affects cotreatment, decreases expression	6
Particulate Matter	increases expression, decreases expression, decreases reaction	6
Estradiol	affects cotreatment, decreases secretion, decreases reaction, increases expression, decreases expression (+1 more)	5
Lipopolysaccharides	increases expression, increases reaction, affects response to substance, decreases reaction	5
Progesterone	increases expression, decreases expression, decreases reaction, affects cotreatment, decreases secretion	5
pyrazolanthrone	decreases reaction, increases expression	4
Resveratrol	decreases reaction, increases secretion, increases expression, increases activity	4
Benzo(a)pyrene	increases expression, increases methylation, affects methylation, affects cotreatment	4
Endosulfan	affects expression, increases expression	4
Tetrachlorodibenzodioxin	decreases reaction, increases expression, decreases secretion	4
Tetradecanoylphorbol Acetate	increases expression, increases reaction, decreases reaction	4
Bleomycin	decreases reaction, increases expression	3
Copper	affects binding, decreases expression, affects cotreatment, increases activity, increases expression	3
Dexamethasone	decreases expression, increases secretion, decreases reaction, increases expression	3
Hydrogen Peroxide	decreases expression, increases expression, decreases reaction, affects reaction	3
Nicotine	increases expression, increases reaction, affects reaction	3
Quercetin	decreases expression, decreases reaction, increases expression, increases reaction	3
Aflatoxin B1	affects expression, increases expression	3
cobaltiprotoporphyrin	decreases reaction, increases expression, increases reaction	2
2-methyl-4-isothiazolin-3-one	increases expression, increases secretion	2
hydroquinone	affects expression, increases expression	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases secretion	2
2,2’,4,6,6’-pentachlorobiphenyl	increases expression, decreases reaction	2
Acetylcysteine	decreases reaction, increases expression, increases secretion, increases reaction	2
Calcitriol	increases expression	2
Cisplatin	affects cotreatment, increases expression, affects response to substance	2
Curcumin	increases expression	2
Folic Acid	affects expression, increases secretion	2

ChEMBL screening assays

448 unique, capped per target: 439 binding, 7 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL709182	Binding	Selectivity ratio for Matrix metalloprotease-2 over Matrix metalloprotease-3 (IC50)	MMPs inhibitors: new succinylhydroxamates with selective inhibition of MMP-2 over MMP-3. — *Bioorg Med Chem Lett*
CHEMBL827459	Functional	Ratio of IC50 value for MMP2 and MMP-3	N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP. — *Bioorg Med Chem Lett*
CHEMBL4000931	ADMET	Inhibition of APMA-activated recombinant human MMP-3 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	Discovery of Novel, Highly Potent, and Selective Matrix Metalloproteinase (MMP)-13 Inhibitors with a 1,2,4-Triazol-3-yl Moiety as a Zinc Binding Group Using a Structure-Based Design Approach. — *J Med Chem*

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AB53	BHK-MMP3	Spontaneously immortalized cell line	Male
CVCL_C7D9	Abcam A-549 MMP3 KO	Cancer cell line	Male
CVCL_C7DZ	Abcam HCT 116 MMP3 KO	Cancer cell line	Male
CVCL_C7EL	Abcam THP-1 MMP3 KO	Cancer cell line	Male
CVCL_D1TK	Abcam U-87MG MMP3 KO	Cancer cell line	Male
CVCL_D9KI	Ubigene HEK293 MMP3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MMP3 across ~30M SureChEMBL compounds — explore on Sugi Predict.