P45452 (MMP13_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Collagenase 3
EC=3.4.24.-

Alternative name(s):
Matrix metalloproteinase-13
Short name=MMP-13

Gene names

Name:

MMP13

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	471 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 collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.
Cofactor	Binds 4 calcium ions per subunit. Binds 2 zinc ions per subunit.
Subcellular location	Secreted › extracellular space › extracellular matrix Probable.
Tissue specificity	Seems to be specific to breast carcinomas.
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.
Involvement in disease	Spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:602111]: A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Metaphyseal anadysplasia 1 (MANDP1) [MIM:602111]: A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the peptidase M10A family. Contains 4 hemopexin-like domains.

Ontologies

Keywords
Biological process	Collagen degradation
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone mineralization Inferred from electronic annotation. Source: Compara cartilage development Inferred from electronic annotation. Source: Compara cellular protein metabolic process Inferred from electronic annotation. Source: Compara collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW extracellular matrix disassembly Traceable author statement. Source: Reactome proteolysis Traceable author statement Ref.1. Source: ProtInc
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 PubMed 8609233. 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 – 19

19

Potential

Propeptide

20 – 103

84

Activation peptide Potential

PRO_0000028788

Chain

104 – 471

368

Collagenase 3

PRO_0000028789

Regions

Domain

290 – 332

43

Hemopexin-like 1

Domain

334 – 377

44

Hemopexin-like 2

Domain

382 – 429

48

Hemopexin-like 3

Domain

431 – 471

41

Hemopexin-like 4

Motif

94 – 101

8

Cysteine switch By similarity

Sites

Active site

223

1

By similarity

Metal binding

96

1

Zinc 2; in inhibited form By similarity

Metal binding

162

1

Calcium 1 By similarity

Metal binding

172

1

Zinc 1 By similarity

Metal binding

174

1

Zinc 1 By similarity

Metal binding

179

1

Calcium 2 By similarity

Metal binding

180

1

Calcium 2; via carbonyl oxygen By similarity

Metal binding

187

1

Zinc 1 By similarity

Metal binding

194

1

Calcium 1; via carbonyl oxygen By similarity

Metal binding

196

1

Calcium 1; via carbonyl oxygen By similarity

Metal binding

198

1

Calcium 1 By similarity

Metal binding

200

1

Zinc 1 By similarity

Metal binding

205

1

Calcium 2 By similarity

Metal binding

222

1

Zinc 2; catalytic By similarity

Metal binding

226

1

Zinc 2; catalytic By similarity

Metal binding

232

1

Zinc 2; catalytic By similarity

Metal binding

291

1

Calcium 3; via carbonyl oxygen By similarity

Metal binding

293

1

Calcium 4; via carbonyl oxygen By similarity

Metal binding

335

1

Calcium 3; via carbonyl oxygen By similarity

Metal binding

337

1

Calcium 4; via carbonyl oxygen By similarity

Metal binding

383

1

Calcium 3; via carbonyl oxygen By similarity

Metal binding

385

1

Calcium 4; via carbonyl oxygen By similarity

Metal binding

432

1

Calcium 3; via carbonyl oxygen By similarity

Metal binding

434

1

Calcium 4; via carbonyl oxygen By similarity

Amino acid modifications

Glycosylation

117

1

N-linked (GlcNAc...) Potential

Glycosylation

152

1

N-linked (GlcNAc...) Potential

Disulfide bond

284 ↔ 471

Natural variations

Natural variant

2

1

H → L.
Corresponds to variant rs554797 [ dbSNP | Ensembl ].

VAR_011971

Natural variant

74

1

F → S in MANDP1. Ref.7

VAR_063432

Natural variant

75

1

F → S in SEMD-MO; abnormal intracellular autoactivation and autodegradation within the ER/Golgi resulting in the secretion of small and inactive fragments. Ref.6

VAR_032753

Natural variant

91

1

M → T in MANDP1. Ref.7

VAR_063433

Natural variant

232

1

H → N in MANDP1. Ref.7

VAR_063434

Natural variant

390

1

D → G. Ref.3
Corresponds to variant rs17860568 [ dbSNP | Ensembl ].

VAR_020534

Secondary structure

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471

Helix Strand Turn

Details...

Beta strand

109 – 111

3

Beta strand

116 – 122

7

Beta strand

127 – 129

3

Helix

131 – 146

16

Beta strand

148 – 150

3

Beta strand

152 – 155

4

Beta strand

157 – 159

3

Beta strand

162 – 168

7

Beta strand

173 – 175

3

Beta strand

180 – 183

4

Beta strand

186 – 188

3

Beta strand

191 – 193

3

Turn

194 – 197

4

Beta strand

199 – 202

4

Beta strand

207 – 215

9

Helix

216 – 228

13

Beta strand

235 – 237

3

Beta strand

241 – 243

3

Beta strand

249 – 251

3

Helix

256 – 266

11

Beta strand

291 – 296

6

Beta strand

299 – 304

6

Beta strand

307 – 311

5

Beta strand

313 – 316

4

Beta strand

319 – 322

4

Helix

323 – 326

4

Beta strand

336 – 340

5

Turn

341 – 344

4

Beta strand

345 – 350

6

Beta strand

353 – 358

6

Beta strand

367 – 370

4

Turn

371 – 374

4

Beta strand

384 – 387

4

Turn

389 – 391

3

Beta strand

392 – 398

7

Beta strand

401 – 406

6

Turn

407 – 409

3

Helix

420 – 423

4

Beta strand

432 – 437

6

Beta strand

440 – 445

6

Beta strand

448 – 453

6

Turn

454 – 457

4

Beta strand

458 – 464

7

Helix

465 – 469

5

Sequences

	Sequence		Length	Mass (Da)
	P45452 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: E110F50628B57B60	FASTA	471	53,820
	10 20 30 40 50 60 MHPGVLAAFL FLSWTHCRAL PLPSGGDEDD LSEEDLQFAE RYLRSYYHPT NLAGILKENA 70 80 90 100 110 120 ASSMTERLRE MQSFFGLEVT GKLDDNTLDV MKKPRCGVPD VGEYNVFPRT LKWSKMNLTY 130 140 150 160 170 180 RIVNYTPDMT HSEVEKAFKK AFKVWSDVTP LNFTRLHDGI ADIMISFGIK EHGDFYPFDG 190 200 210 220 230 240 PSGLLAHAFP PGPNYGGDAH FDDDETWTSS SKGYNLFLVA AHEFGHSLGL DHSKDPGALM 250 260 270 280 290 300 FPIYTYTGKS HFMLPDDDVQ GIQSLYGPGD EDPNPKHPKT PDKCDPSLSL DAITSLRGET 310 320 330 340 350 360 MIFKDRFFWR LHPQQVDAEL FLTKSFWPEL PNRIDAAYEH PSHDLIFIFR GRKFWALNGY 370 380 390 400 410 420 DILEGYPKKI SELGLPKEVK KISAAVHFED TGKTLLFSGN QVWRYDDTNH IMDKDYPRLI 430 440 450 460 470 EEDFPGIGDK VDAVYEKNGY IYFFNGPIQF EYSIWSNRIV RVMPANSILW C

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas." Freije J.M.P., Diez-Itza I., Balbin M., Sanchez L.M., Blasco R., Tolivia J., Lopez-Otin C. J. Biol. Chem. 269:16766-16773(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary carcinoma.
[2]	"A matrix metalloproteinase gene expressed in human T lymphocytes is identical with collagenase 3 from breast carcinomas." Willmroth F., Peter H.H., Conca W. Immunobiology 198:375-384(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	NIEHS SNPs program Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-390.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"The helping hand of collagenase-3 (MMP-13): 2.7 A crystal structure of its C-terminal haemopexin-like domain." Gomis-Rueth F.-X., Gohlke U., Betz M., Knaeuper V., Murphy G., Lopez-Otin C., Bode W. J. Mol. Biol. 264:556-566(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 265-471.
[6]	"MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO)." Kennedy A.M., Inada M., Krane S.M., Christie P.T., Harding B., Lopez-Otin C., Sanchez L.M., Pannett A.A.J., Dearlove A., Hartley C., Byrne M.H., Reed A.A.C., Nesbit M.A., Whyte M.P., Thakker R.V. J. Clin. Invest. 115:2832-2842(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SEMD-MO SER-75, CHARACTERIZATION OF VARIANT SEMD-MO SER-75.
[7]	"Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia." Lausch E., Keppler R., Hilbert K., Cormier-Daire V., Nikkel S., Nishimura G., Unger S., Spranger J., Superti-Furga A., Zabel B. Am. J. Hum. Genet. 85:168-178(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MANDP1 SER-74; THR-91 AND ASN-232.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X75308 mRNA. Translation: CAA53056.1.
X81334 mRNA. Translation: CAA57108.1.
AY741163 Genomic DNA. Translation: AAU13907.1.
BC067522 mRNA. Translation: AAH67522.1.
BC074807 mRNA. Translation: AAH74807.1.
BC074808 mRNA. Translation: AAH74808.1.

IPI

IPI00021738.

PIR

A53711.

RefSeq

NP_002418.1. NM_002427.3.

UniGene

Hs.2936.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EUB	NMR	-	A	104-274	[»]
1FLS	NMR	-	A	104-268	[»]
1FM1	NMR	-	A	104-268	[»]
1PEX	X-ray	2.70	A	265-471	[»]
1UC1	model	-	A	1-471	[»]
1XUC	X-ray	1.70	A/B	104-274	[»]
1XUD	X-ray	1.80	A/B	104-274	[»]
1XUR	X-ray	1.85	A/B	104-274	[»]
1YOU	X-ray	2.30	A/B	104-271	[»]
1ZTQ	X-ray	2.00	A/B/C/D	104-268	[»]
2D1N	X-ray	2.37	A/B	104-269	[»]
2E2D	X-ray	2.00	A	104-268	[»]
2OW9	X-ray	1.74	A/B	104-270	[»]
2OZR	X-ray	2.30	A/B/C/D/E/F/G/H	104-270	[»]
2PJT	X-ray	2.80	A/B/C/D	104-268	[»]
2YIG	X-ray	1.70	A/B	104-274	[»]
3ELM	X-ray	1.90	A/B	104-274	[»]
3I7G	X-ray	1.95	A/B	104-274	[»]
3I7I	X-ray	2.21	A/B	104-274	[»]
3KEC	X-ray	2.05	A/B	105-267	[»]
3KEJ	X-ray	2.30	A/B	104-270	[»]
3KEK	X-ray	1.97	A/B	105-270	[»]
3KRY	X-ray	1.90	A/B/C/D	104-267	[»]
3LJZ	X-ray	2.00	A/B/C/D	105-267	[»]
3O2X	X-ray	1.90	A/B/C/D	105-267	[»]
3TVC	X-ray	2.43	A	104-272	[»]
3ZXH	X-ray	1.30	A/B	104-274	[»]
456C	X-ray	2.40	A/B	104-271	[»]
4A7B	X-ray	2.20	A/B	104-272	[»]
830C	X-ray	1.60	A/B	104-271	[»]

ProteinModelPortal

P45452.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000260302.

Protein family/group databases

MEROPS

M10.013.

PTM databases

PhosphoSite

P45452.

Polymorphism databases

DMDM

1168998.

Proteomic databases

PaxDb

P45452.

PRIDE

P45452.

Protocols and materials databases

DNASU

4322.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000260302; ENSP00000260302; ENSG00000137745.
ENST00000571284; ENSP00000461440; ENSG00000262325.

GeneID

4322.

KEGG

hsa:4322.

UCSC

uc001phl.3. human.

Organism-specific databases

CTD

4322.

GeneCards

GC11M102847.

HGNC

HGNC:7159. MMP13.

MIM

600108. gene.
602111. phenotype.

neXtProt

NX_P45452.

Orphanet

1040. Metaphyseal anadysplasia.
93356. Spondyloepimetaphyseal dysplasia, Missouri type.

PharmGKB

PA30871.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG299356.

HOGENOM

HOG000217927.

HOVERGEN

HBG052484.

KO

K07994.

OrthoDB

EOG41ZF9Q.

Enzyme and pathway databases

Reactome

REACT_118779. Extracellular matrix organization.
REACT_133391. Extracellular matrix organization.

Gene expression databases

ArrayExpress

P45452.

Bgee

P45452.

CleanEx

HS_MMP13.

Genevestigator

P45452.

GermOnline

ENSG00000137745. 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.
IPR018486. Hemopexin_CS.
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. 4 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. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P45452.

ChEMBL

CHEMBL280.

EvolutionaryTrace

P45452.

GenomeRNAi

4322.

NextBio

17005.

PMAP-CutDB

P45452.

SOURCE

Search...

Entry information

Entry name

MMP13_HUMAN

Accession

Primary (citable) accession number: P45452

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 139 of the entry and version 1 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.