MMP27

Summary

MMP27 (matrix metallopeptidase 27, HGNC:14250) is a protein-coding gene on chromosome 11q22.2, encoding Matrix metalloproteinase-27 (Q9H306). Matrix metalloproteinases degrade protein components of the extracellular matrix such as fibronectin, laminin, gelatins and/or collagens.

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.

Source: NCBI Gene 64066 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_022122

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14250
Approved symbol	MMP27
Name	matrix metallopeptidase 27
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137675
Ensembl biotype	protein_coding
OMIM	618101
Entrez	64066

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000260229

RefSeq mRNA: 1 — MANE Select: NM_022122 NM_022122

CCDS: CCDS8319

Canonical transcript exons

ENST00000260229 — 10 exons

Exon	Start	End
ENSE00000930311	102691487	102692010
ENSE00000930312	102692938	102693041
ENSE00000930313	102693906	102694065
ENSE00000930314	102694967	102695097
ENSE00000930315	102696371	102696491
ENSE00000930316	102696674	102696835
ENSE00001105515	102702970	102703118
ENSE00001105520	102704537	102704775
ENSE00001105525	102702753	102702881
ENSE00001293236	102705613	102705769

Expression profiles

Bgee: expression breadth broad, 77 present calls, max score 78.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0595 / max 23.3554, expressed in 23 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121982	0.0595	23

Top tissues by expression

269 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of hip	UBERON:0001554	78.08	gold quality
upper leg skin	UBERON:0004262	74.31	gold quality
minor salivary gland	UBERON:0001830	66.70	gold quality
skin of leg	UBERON:0001511	65.93	gold quality
calcaneal tendon	UBERON:0003701	65.90	gold quality
zone of skin	UBERON:0000014	64.93	gold quality
mouth mucosa	UBERON:0003729	63.35	gold quality
skin of abdomen	UBERON:0001416	63.15	gold quality
saliva-secreting gland	UBERON:0001044	61.59	gold quality
tibialis anterior	UBERON:0001385	61.45	silver quality
subcutaneous adipose tissue	UBERON:0002190	60.35	gold quality
pancreatic ductal cell	CL:0002079	58.43	silver quality
ileal mucosa	UBERON:0000331	56.30	silver quality
tendon	UBERON:0000043	56.18	gold quality
deltoid	UBERON:0001476	54.61	gold quality
epithelium of nasopharynx	UBERON:0001951	52.62	gold quality
epithelial cell of pancreas	CL:0000083	50.93	gold quality
adipose tissue	UBERON:0001013	50.21	gold quality
connective tissue	UBERON:0002384	50.07	gold quality
muscle tissue	UBERON:0002385	49.93	silver quality
quadriceps femoris	UBERON:0001377	49.53	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
skeletal muscle tissue	UBERON:0001134	49.12	silver quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.56

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• MMP-27 is efficiently retained within the ER due to its unique CTE, which does not lead to stable membrane insertion. This could represent a novel ER retention system (PMID:24548619)
• MMP-27 is expressed in a subset of endometrial macrophages related to menstruation and in ovarian and peritoneal endometriotic lesions. (PMID:24810263)
• Two polymorphisms of MMP-8 and MMP-27 were significantly associated with recurrent pregnancy loss (RPL) risk, both individually and in combination. Therefore, these two polymorphisms are potential biomarkers for RPL susceptibility. (PMID:31067818)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp25b	ENSDARG00000010556
danio_rerio	hpxa	ENSDARG00000012609
danio_rerio	mmp30	ENSDARG00000045887
danio_rerio	mmp25a	ENSDARG00000077290
danio_rerio	mmp13b	ENSDARG00000100794
mus_musculus	Mmp27	ENSMUSG00000070323
rattus_norvegicus	Mmp27	ENSRNOG00000040208
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), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-27 — Q9H306 (reviewed: Q9H306)

All UniProt accessions (1): Q9H306

UniProt curated annotations — full annotation on UniProt →

Function. Matrix metalloproteinases degrade protein components of the extracellular matrix such as fibronectin, laminin, gelatins and/or collagens.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Expressed in B-cells. Expressed in a subset of endometrial macrophages related to menstruation and in ovarian and peritoneal endometriotic lesions (at protein level).

Post-translational modifications. N-glycosylated.

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_071405* (*=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

UniProt features (44 total): binding site 20, sequence variant 7, repeat 4, glycosylation site 3, mutagenesis site 3, signal peptide 1, propeptide 1, chain 1, disulfide bond 1, region of interest 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H306-F1	80.64	0.45

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): 217

Ligand- & substrate-binding residues (20): 91 (in inhibited form); 121; 155; 165; 173; 174; 178; 181; 188; 192; 194; 196 …

Disulfide bonds (1): 279–465

Glycosylation sites (3): 55, 110, 452

Mutagenesis-validated functional residues (3):

Position	Phenotype
55	loss of n-glycosylation; when associated with q-110 and q-452.
110	loss of n-glycosylation; when associated with q-55 and q-452.
452	loss of n-glycosylation; when associated with q-55 and q-110.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOMF_METALLOPEPTIDASE_ACTIVITY, chr11q22, HNF1_Q6, LHX3_01, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, HP1SITEFACTOR_Q6, AFP1_Q6, MODULE_207, TAATTA_CHX10_01, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, CHEN_METABOLIC_SYNDROM_NETWORK, CEBPB_02, GOBP_COLLAGEN_CATABOLIC_PROCESS

GO Biological Process (3): proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), zinc ion binding (GO:0008270), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): endoplasmic reticulum (GO:0005783), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
external encapsulating structure	1

Protein interactions and networks

STRING

344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP27	OR7G2	Q8NG99	429
MMP27	TIMP2	P16035	426
MMP27	TIMP4	Q99727	374
MMP27	SLC35F1	Q5T1Q4	368
MMP27	MMP24OS	A0A0U1RRL7	366
MMP27	WFDC13	Q8IUB5	355
MMP27	TMEM123	Q8N131	334
MMP27	TIMP1	P01033	330
MMP27	ATP8B3	O60423	324
MMP27	ATP13A3	Q9H7F0	318
MMP27	MMP23B	O75900	299
MMP27	COL6A6	A6NMZ7	298
MMP27	SLC4A9	Q96Q91	298
MMP27	GDPD5	Q8WTR4	297
MMP27	TIMP3	P35625	290

IntAct

0 interactions, top by confidence:

BioGRID (10): MMP27 (Negative Genetic), MMP27 (Negative Genetic), MMP27 (Negative Genetic), MMP27 (Negative Genetic), MMP9 (Negative Genetic), MMP27 (Negative Genetic), MMP8 (Negative Genetic), MMP27 (Affinity Capture-MS), MMP27 (Cross-Linking-MS (XL-MS)), MMP27 (Affinity Capture-MS)

ESM2 similar proteins: A0A0C5PRQ1, A0FKN6, C9D7R2, C9D7R3, D5FM34, D5FM37, G5EGM1, K7Z9Q9, O17264, O35548, O57460, O60882, O62243, P0DJJ2, P0DM62, P42662, P50280, P50281, P51512, P57748, P79227, P79287, P91828, P98060, P98070, Q10738, Q10739, Q10835, Q11005, Q18206, Q21178, Q21181, Q21252, Q22396, Q22398, Q22710, Q5RES1, Q61EX6, Q7Z0M7, Q93542

Diamond homologs: D0EM77, G5EBU3, O04529, O13065, O18733, O18767, O18927, O23507, O35548, O44836, O54732, O55123, O55761, O60882, O62806, O70138, O75900, O77656, O88272, O88676, O88766, O93470, P03956, P03957, P07152, P08253, P08254, P09237, P09238, P13943, P14780, P21692, P22757, P22894, P23097, P24347, P28053, P28862, P28863, P29136

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MMP27	up-regulates	ECM_disassembly
MMP27	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1350 predictions. Top by Δscore:

Variant	Effect	Δscore
11:102692011:CT:C	acceptor_loss	1.0000
11:102692933:CTTA:C	donor_loss	1.0000
11:102692934:TTA:T	donor_loss	1.0000
11:102692935:TACCT:T	donor_loss	1.0000
11:102692936:A:AC	donor_gain	1.0000
11:102692936:A:AG	donor_loss	1.0000
11:102692937:C:CC	donor_gain	1.0000
11:102692937:C:CG	donor_loss	1.0000
11:102693037:CAAAC:C	acceptor_gain	1.0000
11:102693040:ACCTG:A	acceptor_loss	1.0000
11:102693042:C:CC	acceptor_gain	1.0000
11:102693042:CTGC:C	acceptor_loss	1.0000
11:102693043:T:A	acceptor_loss	1.0000
11:102693901:CTTA:C	donor_loss	1.0000
11:102693902:TTA:T	donor_loss	1.0000
11:102693903:TA:T	donor_loss	1.0000
11:102693904:A:AC	donor_gain	1.0000
11:102693904:AC:A	donor_gain	1.0000
11:102693904:ACCT:A	donor_gain	1.0000
11:102693904:ACCTC:A	donor_gain	1.0000
11:102693905:C:CA	donor_gain	1.0000
11:102693905:CC:C	donor_gain	1.0000
11:102693905:CCT:C	donor_gain	1.0000
11:102693905:CCTC:C	donor_gain	1.0000
11:102693905:CCTCC:C	donor_gain	1.0000
11:102694061:TTCAT:T	acceptor_gain	1.0000
11:102694062:TCAT:T	acceptor_gain	1.0000
11:102694063:CAT:C	acceptor_gain	1.0000
11:102694063:CATC:C	acceptor_gain	1.0000
11:102694064:AT:A	acceptor_gain	1.0000

AlphaMissense

3419 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102702980:A:C	F160L	0.995
11:102702980:A:T	F160L	0.995
11:102702982:A:G	F160L	0.995
11:102702823:A:C	F183L	0.992
11:102702823:A:T	F183L	0.992
11:102702825:A:G	F183L	0.992
11:102702769:C:A	W201C	0.991
11:102702769:C:G	W201C	0.991
11:102702856:A:C	F172L	0.990
11:102702856:A:T	F172L	0.990
11:102702858:A:G	F172L	0.990
11:102704606:C:G	C91S	0.990
11:102704607:A:T	C91S	0.990
11:102703048:A:G	W138R	0.989
11:102703048:A:T	W138R	0.989
11:102693967:C:G	A378P	0.988
11:102704607:A:G	C91R	0.988
11:102695009:C:G	A331P	0.987
11:102702771:A:G	W201R	0.987
11:102702771:A:T	W201R	0.987
11:102702788:A:G	F195S	0.987
11:102704560:C:A	W106C	0.985
11:102704560:C:G	W106C	0.985
11:102696701:C:G	D252H	0.984
11:102696784:A:G	L224P	0.984
11:102702857:A:C	F172C	0.984
11:102704605:A:C	C91W	0.984
11:102696777:G:C	H226Q	0.983
11:102696777:G:T	H226Q	0.983
11:102696809:G:C	H216D	0.983

dbSNP variants (sampled 300 via entrez): RS1000064298 (11:102707313 A>G), RS1000424342 (11:102697301 C>T), RS1000455273 (11:102697546 G>T), RS1000762695 (11:102698406 C>T), RS1001047367 (11:102697575 C>T), RS1001385538 (11:102698788 A>G), RS1001524188 (11:102698210 A>G,T), RS1002065079 (11:102703550 T>A), RS1002328686 (11:102704375 A>G), RS1002399845 (11:102694358 T>C), RS1002435120 (11:102699610 G>A,T), RS1002700576 (11:102695411 A>T), RS1002761080 (11:102700729 G>T), RS1002776700 (11:102694027 G>T), RS1003059217 (11:102700162 G>A)

Disease associations

OMIM: gene MIM:618101 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001942_2	Prostate cancer	2.000000e-11
GCST003542_184	Night sleep phenotypes	7.000000e-07
GCST006608_1	Response to TNF inhibitor in rheumatoid arthritis (change in patient global heath assessment score)	8.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004778	self rated health

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
Estradiol	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression	2
Arsenic	affects methylation	1
Nickel	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.