Reviewed, UniProtKB/Swiss-Prot Q8N119 (MMP21_HUMAN)

Names and origin

Protein names

Recommended name:
Matrix metalloproteinase-21
Short name=MMP-21
EC=3.4.24.-

Gene names

Name:

MMP21

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	569 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	May have an important and specific function in tumor progression and embryogenesis. Cleaves alpha-1-antitrypsin.
Cofactor	Binds 1 zinc ion per subunit By similarity. Calcium By similarity.
Subcellular location	Secreted Potential.
Tissue specificity	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. Ref.1 Ref.2
Domain	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.
Post-translational modification	The precursor is cleaved by a furin endopeptidase By similarity.
Sequence similarities	Belongs to the peptidase M10A family. Contains 4 hemopexin-like domains.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: InterPro
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Propeptide	25 – 144	120	By similarity		PRO_0000028839
	Chain	145 – 569	425	Matrix metalloproteinase-21		PRO_0000028840
Regions
	Domain	333 – 391	59	Hemopexin-like 1
	Domain	394 – 449	56	Hemopexin-like 2
	Domain	451 – 499	49	Hemopexin-like 3
	Domain	506 – 549	44	Hemopexin-like 4
	Motif	115 – 122	8	Cysteine switch By similarity
Sites
	Active site	284	1	By similarity
	Metal binding	117	1	Zinc; in inhibited form By similarity
	Metal binding	283	1	Zinc; catalytic By similarity
	Metal binding	287	1	Zinc; catalytic By similarity
	Metal binding	293	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	372	1	N-linked (GlcNAc...) Potential
	Disulfide bond	329 ↔ 560		By similarity
Natural variations
	Natural variant	95	1	A → E: dbSNP rs28381282. Ref.3		VAR_022291
	Natural variant	115	1	P → Q: dbSNP rs28381284. Ref.3		VAR_022292
	Natural variant	191	1	A → V: dbSNP rs10901425. Ref.1 Ref.3 Ref.4		VAR_019393
	Natural variant	263	1	D → E: dbSNP rs34811493.		VAR_032824
	Natural variant	311	1	A → T: dbSNP rs17173746.		VAR_057803
	Natural variant	349	1	E → G: dbSNP rs28381302. Ref.3		VAR_022293
	Natural variant	360	1	R → H: dbSNP rs17153524.		VAR_057804
	Natural variant	454	1	A → V: dbSNP rs28381319. Ref.3		VAR_022294

Sequences

	Sequence		Length	Mass (Da)
	Q8N119-1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 6DB9BD18ADA515D5	FASTA	569	65,015
	10 20 30 40 50 60 MLAASIFRPT LLLCWLAAPW PTQPESLFHS RDRSDLEPSP LRQAKPIADL HAAQRFLSRY 70 80 90 100 110 120 GWSGVWAAWG PSPEGPPETP KGAALAEAVR RFQRANALPA SGELDAATLA AMNRPRCGVP 130 140 150 160 170 180 DMRPPPPSAP PSPPGPPPRA RSRRSPRAPL SLSRRGWQPR GYPDGGAAQA FSKRTLSWRL 190 200 210 220 230 240 LGEALSSQLS AADQRRIVAL AFRMWSEVTP LDFREDLAAP GAAVDIKLGF GRGRHLGCPR 250 260 270 280 290 300 AFDGSGQEFA HAWRLGDIHF DDDEHFTPPT SDTGISLLKV AVHEIGHVLG LPHTYRTGSI 310 320 330 340 350 360 MQPNYIPQEP AFELDWSDRK AIQKLYGSCE GSFDTAFDWI RKERNQYGEV MVRFSTYFFR 370 380 390 400 410 420 NSWYWLYENR NNRTRYGDPI QILTGWPGIP THNIDAFVHI WTWKRDERYF FQGNQYWRYD 430 440 450 460 470 480 SDKDQALTED EQGKSYPKLI SEGFPGIPSP LDTAFYDRRQ KLIYFFKESL VFAFDVNRNR 490 500 510 520 530 540 VLNSYPKRIT EVFPAVIPQN HPFRNIDSAY YSYAYNSIFF FKGNAYWKVV NDKDKQQNSW 550 560 LPANGLFPKK FISEKWFDVC DVHISTLNM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Matrix metalloproteinase-21, the human orthologue for XMMP, is expressed during fetal development and in cancer." Ahokas K., Lohi J., Lohi H., Elomaa O., Karjalainen-Lindsberg M.-L., Kere J., Saarialho-Kere U. Gene 301:31-41(2002) [PubMed: 12490321] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT VAL-191.
[2]	"The structure and regulation of the human and mouse matrix metalloproteinase-21 gene and protein." Marchenko G.N., Marchenko N.D., Strongin A.Y. Biochem. J. 372:503-515(2003) [PubMed: 12617721] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY. Tissue: Kidney.
[3]	NIEHS SNPs program Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLU-95; GLN-115; VAL-191; GLY-349 AND VAL-454.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-191.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00295606.
RefSeq	NP_671724.1.
UniGene	Hs.314141
3D structure databases
SMR	Q8N119. Positions 38-533.
ModBase	Search...
Protein family/group databases
MEROPS	M10.026.
Proteomic databases
PRIDE	Q8N119.
Genome annotation databases
Ensembl	ENST00000368808; ENSP00000357798; ENSG00000154485; Homo sapiens. [Genome view]
GeneID	118856.
KEGG	hsa:118856.
UCSC	uc001liu.1. human.
Organism-specific databases
CTD	118856.
GeneCards	GC10M127445.
HGNC	HGNC:14357. MMP21.
HPA	HPA024429.
MIM	608416. gene.
PharmGKB	PA134885721.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14948.
HOGENOM	HBG443919.
HOVERGEN	HBG052483.
InParanoid	Q8N119.
Gene expression databases
ArrayExpress	Q8N119.
Bgee	Q8N119.
CleanEx	HS_MMP21.
Genevestigator	Q8N119.
GermOnline	ENSG00000154485. Homo sapiens.
Family and domain databases
InterPro	IPR000585. Hemopexin/matrixin. IPR018487. Hemopexin/matrixin_repeat. IPR001818. Pept_M10_metallopeptidase. IPR016293. Pept_M10A_matrix. IPR006026. Peptidase_Metallo. IPR002477. Peptidoglycan-bd-like. [Graphical view]
Gene3D	G3DSA:2.110.10.10. Hemopexin. 1 hit.
Pfam	PF00045. Hemopexin. 3 hits. PF00413. Peptidase_M10. 1 hit. PF01471. PG_binding_1. 1 hit. [Graphical view]
PIRSF	PIRSF001191. Peptidase_M10A_matrix. 1 hit.
SMART	SM00120. HX. 4 hits. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF50923. Hemopexin. 1 hit. SSF47090. PGBD_like. 1 hit.
PROSITE	PS00546. CYSTEINE_SWITCH. False negative. PS00024. HEMOPEXIN. False negative. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	80358.
SOURCE	Search...

Entry information

Entry name

MMP21_HUMAN

Accession

Primary (citable) accession number: Q8N119
Secondary accession number(s): Q5VZP9, Q8NG02

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	October 1, 2002
Last modified:	March 2, 2010
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.