O60882 (MMP20_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Matrix metalloproteinase-20
Short name=MMP-20
EC=3.4.24.-

Alternative name(s):
Enamel metalloproteinase
Enamelysin

Gene names

Name:

MMP20

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	483 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Degrades amelogenin, the major protein component of the enamel matrix and two of the macromolecules characterizing the cartilage extracellular matrix: aggrecan and the cartilage oligomeric matrix protein (COMP). May play a central role in tooth enamel formation. Ref.1 Ref.4
Catalytic activity	Cleaves aggrecan at the 360-Asn-|-Phe-361 site.
Cofactor	Binds 2 zinc ions per subunit. Ref.6 Binds 2 calcium ions per subunit. Ref.6
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Expressed specifically in the enamel organ.
Developmental stage	Expression initiates prior to the onset of dentin mineralization and continues throughout the secretory stage of amelogenesis.
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	Autoactivates at least at the 107-Asn-|-Tyr-108 site By similarity.
Involvement in disease	Amelogenesis imperfecta, hypomaturation type, 2A2 (AI2A2) [MIM:612529]: A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	Belongs to the peptidase M10A family. Contains 4 hemopexin-like domains.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Disease	Amelogenesis imperfecta
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Autocatalytic cleavage Disulfide bond Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amelogenesis Inferred from electronic annotation. Source: Compara proteolysis Traceable author statement Ref.1. Source: ProtInc regulation of enamel mineralization Traceable author statement PubMed 18434575. Source: BHF-UCL
Cellular_component	extracellular space Traceable author statement Ref.1. Source: ProtInc proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro metalloendopeptidase activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Propeptide

23 – 107

85

By similarity

PRO_0000028833

Chain

108 – 483

376

Matrix metalloproteinase-20

PRO_0000028834

Regions

Domain

302 – 345

44

Hemopexin-like 1

Domain

347 – 389

43

Hemopexin-like 2

Domain

394 – 441

48

Hemopexin-like 3

Domain

443 – 483

41

Hemopexin-like 4

Motif

98 – 105

8

Cysteine switch By similarity

Sites

Active site

227

1

By similarity

Metal binding

100

1

Zinc 1; in inhibited form By similarity

Metal binding

164

1

Calcium 1

Metal binding

165

1

Calcium 1; via carbonyl oxygen

Metal binding

166

1

Calcium 1; via carbonyl oxygen

Metal binding

176

1

Zinc 2

Metal binding

178

1

Zinc 2

Metal binding

183

1

Calcium 2

Metal binding

184

1

Calcium 2; via carbonyl oxygen

Metal binding

186

1

Calcium 2; via carbonyl oxygen

Metal binding

188

1

Calcium 2; via carbonyl oxygen

Metal binding

191

1

Zinc 2

Metal binding

197

1

Calcium 1; via carbonyl oxygen

Metal binding

198

1

Calcium 1; via carbonyl oxygen

Metal binding

200

1

Calcium 1; via carbonyl oxygen

Metal binding

202

1

Calcium 1

Metal binding

204

1

Zinc 2

Metal binding

206

1

Calcium 2

Metal binding

209

1

Calcium 2

Metal binding

226

1

Zinc 1; catalytic

Metal binding

230

1

Zinc 1; catalytic

Metal binding

236

1

Zinc 1; catalytic

Amino acid modifications

Disulfide bond

296 ↔ 483

Potential

Natural variations

Natural variant

18

1

K → T. Ref.2
Corresponds to variant rs2245803 [ dbSNP | Ensembl ].

VAR_020511

Natural variant

139

1

D → N. Ref.2
Corresponds to variant rs17099014 [ dbSNP | Ensembl ].

VAR_020512

Natural variant

169

1

I → L. Ref.2
Corresponds to variant rs17099008 [ dbSNP | Ensembl ].

VAR_020513

Natural variant

275

1

V → A. Ref.2
Corresponds to variant rs1784423 [ dbSNP | Ensembl ].

VAR_020514

Natural variant

281

1

T → N. Ref.2
Corresponds to variant rs1784424 [ dbSNP | Ensembl ].

VAR_057802

Experimental info

Sequence conflict

208

1

A → P in CAA73317. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

483

Helix Strand Turn

Details...

Beta strand

120 – 126

7

Beta strand

131 – 133

3

Helix

135 – 152

18

Beta strand

156 – 159

4

Beta strand

161 – 163

3

Beta strand

166 – 172

7

Beta strand

176 – 180

5

Beta strand

184 – 187

4

Beta strand

189 – 192

4

Beta strand

195 – 199

5

Beta strand

203 – 206

4

Beta strand

211 – 219

9

Helix

220 – 232

13

Turn

253 – 255

3

Helix

261 – 270

10

Sequences

	Sequence		Length	Mass (Da)
	O60882 [UniParc]. Last modified February 8, 2011. Version 3. Checksum: 561B0A03E0BB0399	FASTA	483	54,387
	10 20 30 40 50 60 MKVLPASGLA VFLIMALKFS TAAPSLVAAS PRTWRNNYRL AQAYLDKYYT NKEGHQIGEM 70 80 90 100 110 120 VARGSNSMIR KIKELQAFFG LQVTGKLDQT TMNVIKKPRC GVPDVANYRL FPGEPKWKKN 130 140 150 160 170 180 TLTYRISKYT PSMSSVEVDK AVEMALQAWS SAVPLSFVRI NSGEADIMIS FENGDHGDSY 190 200 210 220 230 240 PFDGPRGTLA HAFAPGEGLG GDTHFDNAEK WTMGTNGFNL FTVAAHEFGH ALGLAHSTDP 250 260 270 280 290 300 SALMYPTYKY KNPYGFHLPK DDVKGIQALY GPRKVFLGKP TLPHAPHHKP SIPDLCDSSS 310 320 330 340 350 360 SFDAVTMLGK ELLLFKDRIF WRRQVHLRTG IRPSTITSSF PQLMSNVDAA YEVAERGTAY 370 380 390 400 410 420 FFKGPHYWIT RGFQMQGPPR TIYDFGFPRH VQQIDAAVYL REPQKTLFFV GDEYYSYDER 430 440 450 460 470 480 KRKMEKDYPK NTEEEFSGVN GQIDAAVELN GYIYFFSGPK TYKYDTEKED VVSVVKSSSW IGC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and structural and functional characterization of human enamelysin (MMP-20)." Llano E., Pendas A.M., Knaeuper V., Sorsa T., Salo T., Salido E., Murphy G., Simmer J.P., Bartlett J.D., Lopez-Otin C. Biochemistry 36:15101-15108(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Odontoblast.
[2]	NIEHS SNPs program Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-18; ASN-139; LEU-169; ALA-275 AND ASN-281.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)." Stracke J.O., Fosang A.J., Last K., Mercuri F.A., Pendas A.M., Llano E., Perris R., Di Cesare P.E., Murphy G., Knaeuper V. FEBS Lett. 478:52-56(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta." Kim J.-W., Simmer J.P., Hart T.C., Hart P.S., Ramaswami M.D., Bartlett J.D., Hu J.C.-C. J. Med. Genet. 42:271-275(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN AI2A2.
[6]	"Catalytic domain of MMP20 (Enamelysin) - the NMR structure of a new matrix metalloproteinase." Arendt Y., Banci L., Bertini I., Cantini F., Cozzi R., Del Conte R., Gonnelli L. FEBS Lett. 581:4723-4726(2007) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 113-272 IN COMPLEX WITH INHIBITOR, COFACTOR, ZINC-BINDING SITES, CALCIUM-BINDING SITES.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y12779 mRNA. Translation: CAA73317.1.
AY673603 Genomic DNA. Translation: AAT70722.1.
AP000851 Genomic DNA. No translation available.

IPI

IPI00032404.

RefSeq

NP_004762.2. NM_004771.3.

UniGene

Hs.591946.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JSD	NMR	-	A	113-272	[»]

ProteinModelPortal

O60882.

SMR

O60882. Positions 40-483.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000260228.

Protein family/group databases

MEROPS

M10.019.

PTM databases

PhosphoSite

O60882.

Proteomic databases

PaxDb

O60882.

PRIDE

O60882.

Protocols and materials databases

DNASU

9313.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000260228; ENSP00000260228; ENSG00000137674.

GeneID

9313.

KEGG

hsa:9313.

UCSC

uc001phc.3. human.

Organism-specific databases

CTD

9313.

GeneCards

GC11M102481.

H-InvDB

HIX0036038.

HGNC

HGNC:7167. MMP20.

MIM

604629. gene.
612529. phenotype.

neXtProt

NX_O60882.

Orphanet

100033. Hypomaturation amelogenesis imperfecta.

PharmGKB

PA30878.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG328389.

HOGENOM

HOG000217927.

HOVERGEN

HBG052484.

InParanoid

O60882.

KO

K07999.

OMA

PDVANYR.

OrthoDB

EOG447FT2.

PhylomeDB

O60882.

Enzyme and pathway databases

Reactome

REACT_118779. Extracellular matrix organization.

Gene expression databases

Bgee

O60882.

CleanEx

HS_MMP20.

Genevestigator

O60882.

GermOnline

ENSG00000137674. Homo sapiens.

Family and domain databases

Gene3D

2.110.10.10. 1 hit.
3.40.390.10. 1 hit.

InterPro

IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_Metazoans.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]

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.

PRINTS

PR00138. MATRIXIN.

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. 1 hit.
PS00024. HEMOPEXIN. False negative.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O60882.

ChEMBL

CHEMBL1938226.

EvolutionaryTrace

O60882.

GenomeRNAi

9313.

NextBio

34887.

SOURCE

Search...

Entry information

Entry name

MMP20_HUMAN

Accession

Primary (citable) accession number: O60882
Secondary accession number(s): Q6DKT9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	February 8, 2011
Last modified:	May 1, 2013
This is version 126 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.