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Protein

Matrix metalloproteinase-21

Gene

MMP21

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Plays a specialized role in the generation of left-right asymmetry during embryogenesis. May act as a negative regulator of the NOTCH-signaling pathway (PubMed:26429889, PubMed:26437028). Cleaves alpha-1-antitrypsin (PubMed:12617721).3 Publications

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
  • Ca2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi117Zinc; in inhibited formBy similarity1
Metal bindingi283Zinc; catalyticPROSITE-ProRule annotation1
Active sitei284PROSITE-ProRule annotation1
Metal bindingi287Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi293Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Protein family/group databases

MEROPSiM10.026.

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix metalloproteinase-21 (EC:3.4.24.-)
Short name:
MMP-21
Gene namesi
Name:MMP21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:14357. MMP21.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Heterotaxy, visceral, 7, autosomal (HTX7)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can been associated with a variety of congenital defects including cardiac malformations. HTX7 inheritance is autosomal recessive.
See also OMIM:616749
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07631931R → W in HTX7; found associated with K-215. 1 PublicationCorresponds to variant rs746379956dbSNPEnsembl.1
Natural variantiVAR_076320215E → K in HTX7; found associated with W-31. 1 PublicationCorresponds to variant rs145789868dbSNPEnsembl.1
Natural variantiVAR_076321226I → T in HTX7. 1 PublicationCorresponds to variant rs781127723dbSNPEnsembl.1
Natural variantiVAR_076322283H → Y in HTX7. 1 Publication1
Natural variantiVAR_076323285I → T in HTX7. 1 PublicationCorresponds to variant rs747668147dbSNPEnsembl.1
Natural variantiVAR_076324321A → P in HTX7. 1 PublicationCorresponds to variant rs773125891dbSNPEnsembl.1
Natural variantiVAR_076325360R → C in HTX7. 1 Publication1
Natural variantiVAR_076326375R → H in HTX7. 1 Publication1
Natural variantiVAR_076327408R → G in HTX7; unknown pathological significance. 1 PublicationCorresponds to variant rs150320323dbSNPEnsembl.1

Keywords - Diseasei

Heterotaxy

Organism-specific databases

DisGeNETi118856.
MIMi616749. phenotype.
OpenTargetsiENSG00000154485.
PharmGKBiPA134885721.

Chemistry databases

DrugBankiDB00786. Marimastat.

Polymorphism and mutation databases

BioMutaiMMP21.
DMDMi317373390.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
PropeptideiPRO_000002883925 – 144By similarityAdd BLAST120
ChainiPRO_0000028840145 – 569Matrix metalloproteinase-21Add BLAST425

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi329 ↔ 560By similarity
Glycosylationi372N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ8N119.
PRIDEiQ8N119.

PTM databases

iPTMnetiQ8N119.
PhosphoSitePlusiQ8N119.

Expressioni

Tissue specificityi

Identified in fetal brain, kidney and liver. In adult tissues found primarily in ovary, kidney, liver, lung, placenta, brain and peripheral blood leukocytes. Expressed as well in various cancer cell lines.2 Publications

Gene expression databases

BgeeiENSG00000154485.
CleanExiHS_MMP21.
GenevisibleiQ8N119. HS.

Organism-specific databases

HPAiHPA024429.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000357798.

Structurei

3D structure databases

ProteinModelPortaliQ8N119.
SMRiQ8N119.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati330 – 389Hemopexin 1Add BLAST60
Repeati391 – 447Hemopexin 2Add BLAST57
Repeati448 – 496Hemopexin 3Add BLAST49
Repeati503 – 559Hemopexin 4Add BLAST57

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi115 – 122Cysteine switchBy similarity8

Domaini

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.

Sequence similaritiesi

Belongs to the peptidase M10A family.Curated
Contains 4 hemopexin repeats.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00860000133713.
HOGENOMiHOG000113608.
HOVERGENiHBG052483.
InParanoidiQ8N119.
KOiK08000.
OMAiEFAHAWR.
OrthoDBiEOG091G0C9G.
PhylomeDBiQ8N119.
TreeFamiTF315428.

Family and domain databases

CDDicd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
Gene3Di1.10.101.10. 1 hit.
2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR033739. M10A_MMP.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PfamiPF00045. Hemopexin. 3 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8N119-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLAASIFRPT LLLCWLAAPW PTQPESLFHS RDRSDLEPSP LRQAKPIADL
60 70 80 90 100
HAAQRFLSRY GWSGVWAAWG PSPEGPPETP KGAALAEAVR RFQRANALPA
110 120 130 140 150
SGELDAATLA AMNRPRCGVP DMRPPPPSAP PSPPGPPPRA RSRRSPRAPL
160 170 180 190 200
SLSRRGWQPR GYPDGGAAQA FSKRTLSWRL LGEALSSQLS VADQRRIVAL
210 220 230 240 250
AFRMWSEVTP LDFREDLAAP GAAVDIKLGF GRGRHLGCPR AFDGSGQEFA
260 270 280 290 300
HAWRLGDIHF DDDEHFTPPT SDTGISLLKV AVHEIGHVLG LPHTYRTGSI
310 320 330 340 350
MQPNYIPQEP AFELDWSDRK AIQKLYGSCE GSFDTAFDWI RKERNQYGEV
360 370 380 390 400
MVRFSTYFFR NSWYWLYENR NNRTRYGDPI QILTGWPGIP THNIDAFVHI
410 420 430 440 450
WTWKRDERYF FQGNQYWRYD SDKDQALTED EQGKSYPKLI SEGFPGIPSP
460 470 480 490 500
LDTAFYDRRQ KLIYFFKESL VFAFDVNRNR VLNSYPKRIT EVFPAVIPQN
510 520 530 540 550
HPFRNIDSAY YSYAYNSIFF FKGNAYWKVV NDKDKQQNSW LPANGLFPKK
560
FISEKWFDVC DVHISTLNM
Length:569
Mass (Da):65,043
Last modified:January 11, 2011 - v2
Checksum:i6785EF34F5B5105E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07631931R → W in HTX7; found associated with K-215. 1 PublicationCorresponds to variant rs746379956dbSNPEnsembl.1
Natural variantiVAR_02229195A → E.1 PublicationCorresponds to variant rs28381282dbSNPEnsembl.1
Natural variantiVAR_022292115P → Q.1 PublicationCorresponds to variant rs28381284dbSNPEnsembl.1
Natural variantiVAR_019393191V → A.2 PublicationsCorresponds to variant rs10901425dbSNPEnsembl.1
Natural variantiVAR_076320215E → K in HTX7; found associated with W-31. 1 PublicationCorresponds to variant rs145789868dbSNPEnsembl.1
Natural variantiVAR_076321226I → T in HTX7. 1 PublicationCorresponds to variant rs781127723dbSNPEnsembl.1
Natural variantiVAR_032824263D → E.Corresponds to variant rs34811493dbSNPEnsembl.1
Natural variantiVAR_076322283H → Y in HTX7. 1 Publication1
Natural variantiVAR_076323285I → T in HTX7. 1 PublicationCorresponds to variant rs747668147dbSNPEnsembl.1
Natural variantiVAR_057803311A → T.Corresponds to variant rs17173746dbSNPEnsembl.1
Natural variantiVAR_076324321A → P in HTX7. 1 PublicationCorresponds to variant rs773125891dbSNPEnsembl.1
Natural variantiVAR_022293349E → G.1 PublicationCorresponds to variant rs28381302dbSNPEnsembl.1
Natural variantiVAR_076325360R → C in HTX7. 1 Publication1
Natural variantiVAR_057804360R → H.Corresponds to variant rs17153524dbSNPEnsembl.1
Natural variantiVAR_076326375R → H in HTX7. 1 Publication1
Natural variantiVAR_076327408R → G in HTX7; unknown pathological significance. 1 PublicationCorresponds to variant rs150320323dbSNPEnsembl.1
Natural variantiVAR_022294454A → V.1 PublicationCorresponds to variant rs28381319dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF331526 mRNA. Translation: AAM92903.1.
AY121358 Genomic DNA. Translation: AAM78033.1.
AF520613 mRNA. Translation: AAM75352.1.
AY885252 Genomic DNA. Translation: AAW62254.1.
AL158835, AL360176 Genomic DNA. Translation: CAH73211.1.
AL360176, AL158835 Genomic DNA. Translation: CAI12086.1.
CCDSiCCDS7647.1.
RefSeqiNP_671724.1. NM_147191.1.
UniGeneiHs.314141.

Genome annotation databases

EnsembliENST00000368808; ENSP00000357798; ENSG00000154485.
GeneIDi118856.
KEGGihsa:118856.
UCSCiuc001liu.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF331526 mRNA. Translation: AAM92903.1.
AY121358 Genomic DNA. Translation: AAM78033.1.
AF520613 mRNA. Translation: AAM75352.1.
AY885252 Genomic DNA. Translation: AAW62254.1.
AL158835, AL360176 Genomic DNA. Translation: CAH73211.1.
AL360176, AL158835 Genomic DNA. Translation: CAI12086.1.
CCDSiCCDS7647.1.
RefSeqiNP_671724.1. NM_147191.1.
UniGeneiHs.314141.

3D structure databases

ProteinModelPortaliQ8N119.
SMRiQ8N119.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000357798.

Chemistry databases

DrugBankiDB00786. Marimastat.

Protein family/group databases

MEROPSiM10.026.

PTM databases

iPTMnetiQ8N119.
PhosphoSitePlusiQ8N119.

Polymorphism and mutation databases

BioMutaiMMP21.
DMDMi317373390.

Proteomic databases

PaxDbiQ8N119.
PRIDEiQ8N119.

Protocols and materials databases

DNASUi118856.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368808; ENSP00000357798; ENSG00000154485.
GeneIDi118856.
KEGGihsa:118856.
UCSCiuc001liu.5. human.

Organism-specific databases

CTDi118856.
DisGeNETi118856.
GeneCardsiMMP21.
HGNCiHGNC:14357. MMP21.
HPAiHPA024429.
MIMi608416. gene.
616749. phenotype.
neXtProtiNX_Q8N119.
OpenTargetsiENSG00000154485.
PharmGKBiPA134885721.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00860000133713.
HOGENOMiHOG000113608.
HOVERGENiHBG052483.
InParanoidiQ8N119.
KOiK08000.
OMAiEFAHAWR.
OrthoDBiEOG091G0C9G.
PhylomeDBiQ8N119.
TreeFamiTF315428.

Miscellaneous databases

GeneWikiiMMP21.
GenomeRNAii118856.
PROiQ8N119.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000154485.
CleanExiHS_MMP21.
GenevisibleiQ8N119. HS.

Family and domain databases

CDDicd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
Gene3Di1.10.101.10. 1 hit.
2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR033739. M10A_MMP.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PfamiPF00045. Hemopexin. 3 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMMP21_HUMAN
AccessioniPrimary (citable) accession number: Q8N119
Secondary accession number(s): Q5VZP9, Q8NG02
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.