P03956 (MMP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interstitial collagenase
EC=3.4.24.7

Alternative name(s):
Fibroblast collagenase
Matrix metalloproteinase-1
Short name=MMP-1

Cleaved into the following 2 chains:

1. 22 kDa interstitial collagenase
2. 27 kDa interstitial collagenase

Gene names

Name:	MMP1
Synonyms:	CLG

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	469 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	Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity. Ref.12
Catalytic activity	Cleavage of the triple helix of collagen at about three-quarters of the length of the molecule from the N-terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1' is a hydrophobic residue.
Cofactor	Binds 4 calcium ions per subunit. Binds 2 zinc ions per subunit.
Enzyme regulation	Can be activated without removal of the activation peptide.
Subunit structure	Interacts with HIV-1 Tat. Ref.13
Subcellular location	Secreted › extracellular space › extracellular matrix Probable Ref.1.
Domain	There are two distinct domains in this protein; the catalytic N-terminal, and the C-terminal which is involved in substrate specificity and in binding TIMP (tissue inhibitor of metalloproteinases). 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	Undergoes autolytic cleavage to two major forms (22 kDa and 27 kDa). A minor form (25 kDa) is the glycosylated form of the 22 kDa form. The 27 kDa form has no activity while the 22/25 kDa form can act as activator for collagenase.
Sequence similarities	Belongs to the peptidase M10A family. Contains 4 hemopexin-like domains.

Ontologies

Keywords
Biological process	Collagen degradation Host-virus interaction
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Autocatalytic cleavage Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW extracellular matrix disassembly Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome proteolysis Traceable author statement Ref.1. Source: ProtInc virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Traceable author statement. Source: Reactome proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro metalloendopeptidase activity Inferred from direct assay PubMed 9920899. Source: BHF-UCL 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

Propeptide

20 – 99

80

Activation peptide

PRO_0000028703

Chain

100 – 469

370

Interstitial collagenase

PRO_0000028704

Chain

100 – 269

170

22 kDa interstitial collagenase

PRO_0000028705

Chain

270 – 469

200

27 kDa interstitial collagenase

PRO_0000028706

Regions

Domain

284 – 326

43

Hemopexin-like 1

Domain

328 – 372

45

Hemopexin-like 2

Domain

377 – 424

48

Hemopexin-like 3

Domain

426 – 466

41

Hemopexin-like 4

Region

98 – 276

179

Metalloprotease

Motif

90 – 97

8

Cysteine switch By similarity

Sites

Active site

219

1

Metal binding

92

1

Zinc 2; in inhibited form

Metal binding

124

1

Calcium 1

Metal binding

158

1

Calcium 2

Metal binding

168

1

Zinc 1

Metal binding

170

1

Zinc 1

Metal binding

175

1

Calcium 3

Metal binding

176

1

Calcium 3; via carbonyl oxygen

Metal binding

178

1

Calcium 3; via carbonyl oxygen

Metal binding

180

1

Calcium 3; via carbonyl oxygen

Metal binding

183

1

Zinc 1

Metal binding

190

1

Calcium 2; via carbonyl oxygen

Metal binding

192

1

Calcium 2; via carbonyl oxygen

Metal binding

194

1

Calcium 2

Metal binding

196

1

Zinc 1

Metal binding

198

1

Calcium 3

Metal binding

199

1

Calcium 1

Metal binding

201

1

Calcium 3

Metal binding

218

1

Zinc 2; catalytic

Metal binding

222

1

Zinc 2; catalytic

Metal binding

228

1

Zinc 2; catalytic

Metal binding

285

1

Calcium 4; via carbonyl oxygen By similarity

Metal binding

329

1

Calcium 4; via carbonyl oxygen By similarity

Metal binding

378

1

Calcium 4; via carbonyl oxygen By similarity

Metal binding

427

1

Calcium 4; via carbonyl oxygen By similarity

Site

269 – 270

2

Cleavage; by autolysis

Amino acid modifications

Glycosylation

120

1

N-linked (GlcNAc...)

CAR_000105

Disulfide bond

278 ↔ 466

By similarity

Natural variations

Natural variant

29

1

Q → P.
Corresponds to variant rs554499 [ dbSNP | Ensembl ].

VAR_011969

Natural variant

191

1

I → V. Ref.6
Corresponds to variant rs17879973 [ dbSNP | Ensembl ].

VAR_021024

Natural variant

252

1

D → G.
Corresponds to variant rs513964 [ dbSNP | Ensembl ].

VAR_011970

Natural variant

262

1

R → S.
Corresponds to variant rs12282811 [ dbSNP | Ensembl ].

VAR_054005

Natural variant

405

1

R → Q. Ref.6
Corresponds to variant rs17879165 [ dbSNP | Ensembl ].

VAR_021025

Natural variant

406

1

S → T. Ref.6
Corresponds to variant rs17884120 [ dbSNP | Ensembl ].

VAR_021026

Experimental info

Sequence conflict

43

1

N → K in AAA35700. Ref.9

Sequence conflict

64

1

Missing in AAA35700. Ref.9

Sequence conflict

115

1

T → R in AAA35699. Ref.3

Sequence conflict

200

1

D → H in CAA28858. Ref.2

Sequence conflict

208

1

R → T in CAA28858. Ref.2

Sequence conflict

317

1

I → T in CAA28858. Ref.2

Sequence conflict

410

1

G → S in AAA35699. Ref.3

Secondary structure

1

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469

Helix Strand Turn

Details...

Helix

33 – 41

9

Helix

59 – 70

12

Helix

81 – 87

7

Beta strand

103 – 106

4

Beta strand

112 – 118

7

Beta strand

123 – 125

3

Helix

127 – 142

16

Beta strand

144 – 146

3

Beta strand

148 – 151

4

Beta strand

153 – 155

3

Beta strand

158 – 164

7

Beta strand

169 – 171

3

Beta strand

176 – 179

4

Beta strand

182 – 184

3

Beta strand

187 – 189

3

Turn

190 – 193

4

Beta strand

195 – 198

4

Beta strand

204 – 209

6

Helix

212 – 223

12

Beta strand

237 – 239

3

Helix

250 – 260

11

Beta strand

285 – 290

6

Beta strand

293 – 298

6

Beta strand

301 – 304

4

Beta strand

309 – 311

3

Beta strand

313 – 316

4

Helix

317 – 319

3

Beta strand

330 – 334

5

Helix

335 – 337

3

Beta strand

339 – 344

6

Beta strand

347 – 352

6

Beta strand

361 – 363

3

Helix

364 – 368

5

Beta strand

379 – 382

4

Turn

384 – 386

3

Beta strand

388 – 393

6

Beta strand

396 – 401

6

Turn

402 – 405

4

Beta strand

412 – 414

3

Helix

415 – 418

4

Beta strand

427 – 432

6

Beta strand

435 – 440

6

Beta strand

443 – 448

6

Turn

449 – 452

4

Beta strand

453 – 459

7

Turn

460 – 463

4

Sequences

	Sequence		Length	Mass (Da)
	P03956 [UniParc]. Last modified December 1, 1992. Version 3. Checksum: 4B1361DCF4C54B20	FASTA	469	54,007
	10 20 30 40 50 60 MHSFPPLLLL LFWGVVSHSF PATLETQEQD VDLVQKYLEK YYNLKNDGRQ VEKRRNSGPV 70 80 90 100 110 120 VEKLKQMQEF FGLKVTGKPD AETLKVMKQP RCGVPDVAQF VLTEGNPRWE QTHLTYRIEN 130 140 150 160 170 180 YTPDLPRADV DHAIEKAFQL WSNVTPLTFT KVSEGQADIM ISFVRGDHRD NSPFDGPGGN 190 200 210 220 230 240 LAHAFQPGPG IGGDAHFDED ERWTNNFREY NLHRVAAHEL GHSLGLSHST DIGALMYPSY 250 260 270 280 290 300 TFSGDVQLAQ DDIDGIQAIY GRSQNPVQPI GPQTPKACDS KLTFDAITTI RGEVMFFKDR 310 320 330 340 350 360 FYMRTNPFYP EVELNFISVF WPQLPNGLEA AYEFADRDEV RFFKGNKYWA VQGQNVLHGY 370 380 390 400 410 420 PKDIYSSFGF PRTVKHIDAA LSEENTGKTY FFVANKYWRY DEYKRSMDPG YPKMIAHDFP 430 440 450 460 GIGHKVDAVF MKDGFFYFFH GTRQYKFDPK TKRILTLQKA NSWFNCRKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of human tumor cell interstitial collagenase." Templeton N.S., Brown P.D., Levy A.T., Margulies I.M.K., Liotta L.A., Stetler-Stevenson W.G. Cancer Res. 50:5431-5437(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
[2]	"Comparison of human stromelysin and collagenase by cloning and sequence analysis." Whitham S.E., Murphy G., Angel P., Rahmsdorf H.J., Smith B., Lyons A., Harris T.J.R., Reynolds J.J., Herrlich P., Docherty A.J.P. Biochem. J. 240:913-916(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein." Goldberg G.I., Wilhelm S.M., Kronberger A., Bauer E.A., Grant G.A., Eisen A.Z. J. Biol. Chem. 261:6600-6605(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Three matrix metalloproteinases on 81kb of P1 insert." Lin D., Duncan M., Allen E., Araujo R., Aparicio A., Chai A., Chung E., Davis K., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lashkari D., Lew H., Namath A., Oefner P., Roberts D., Heller R., Davis R.W. Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	NIEHS SNPs program Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-191; GLN-405 AND THR-406.
[7]	"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: Ovary.
[8]	"12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region." Angel P., Baumann I., Stein B., Delius H., Rahmsdorf H.J., Herrlich P. Mol. Cell. Biol. 7:2256-2266(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
[9]	"Molecular cloning of human synovial cell collagenase and selection of a single gene from genomic DNA." Brinckerhoff C.E., Ruby P.L., Austin S.D., Fini M.E., White H.D. J. Clin. Invest. 79:542-546(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-70. Tissue: Synovial cell.
[10]	"Fragments of human fibroblast collagenase. Purification and characterization." Clark I.M., Cawston T.E. Biochem. J. 263:201-206(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 100-112 AND 270-287. Tissue: Fibroblast.
[11]	"Human fibroblast collagenase contains an amino acid sequence homologous to the zinc-binding site of Serratia protease." McKerrow J.H. J. Biol. Chem. 262:5943-5943(1987) [PubMed] [Europe PMC] [Abstract] Cited for: SIMILARITY TO THERMOLYSIN TYPE PROTEASES.
[12]	"Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity." Desrochers P.E., Jeffrey J.J., Weiss S.J. J. Clin. Invest. 87:2258-2265(1991) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Interaction of HIV Tat and matrix metalloproteinase in HIV neuropathogenesis: a new host defense mechanism." Rumbaugh J., Turchan-Cholewo J., Galey D., St Hillaire C., Anderson C., Conant K., Nath A. FASEB J. 20:1736-1738(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 TAT.
[14]	"Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor." Borkakoti N., Winkler F.K., Williams D.H., D'Arcy A., Broadhurst M.J., Brown P.A., Johnson W.H., Murray E.J. Nat. Struct. Biol. 1:106-110(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 100-269.
[15]	"Crystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself." Lovejoy B., Hassell A.M., Luther M.A., Weigl D., Jordan S.R. Biochemistry 33:8207-8217(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 102-269.
[16]	"Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor." Lovejoy B., Cleasby A., Hassell A.M., Longley K., Luther M.A., Weigl D., McGeehan G., McElroy A.B., Drewry D., Lambert M.H., Jordan S.R. Science 263:375-377(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 102-269.
[17]	"1.56-A structure of mature truncated human fibroblast collagenase." Spurlino J.C., Smallwood A.M., Carlton D.D., Banks T.M., Vavra K.J., Johnson J.S., Cook E.R., Falvo J., Wahl R.C., Pulvino T.A., Et A.L. Proteins 19:98-109(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 101-269.
[18]	"High-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase determined by multidimensional NMR." Moy F.J., Chanda P.K., Cosmi S., Pisano M.R., Urbano C., Wilhelm J., Powers R. Biochemistry 37:1495-1504(1998) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 101-269.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Collagenase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X54925 mRNA. Translation: CAA38691.1.
X05231 mRNA. Translation: CAA28858.1.
M13509 mRNA. Translation: AAA35699.1.
U78045 Genomic DNA. Translation: AAB36941.1.
BT006874 mRNA. Translation: AAP35520.1.
AY769434 Genomic DNA. Translation: AAV28732.1.
BC013875 mRNA. Translation: AAH13875.1.
M16567 Genomic DNA. Translation: AAA52033.1.
M15996 mRNA. Translation: AAA35700.1.

IPI

IPI00008561.

PIR

KCHUI. A37308.

RefSeq

NP_002412.1. NM_002421.3.

UniGene

Hs.83169.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AYK	NMR	-	A	101-269	[»]
1CGE	X-ray	1.90	A	102-269	[»]
1CGF	X-ray	2.10	A/B	102-263	[»]
1CGL	X-ray	2.40	A/B	101-269	[»]
1HFC	X-ray	1.50	A	101-269	[»]
1SU3	X-ray	2.20	A/B	20-469	[»]
2AYK	NMR	-	A	101-269	[»]
2CLT	X-ray	2.67	A/B	100-466	[»]
2J0T	X-ray	2.54	A/B/C	101-269	[»]
2TCL	X-ray	2.20	A	101-269	[»]
3AYK	NMR	-	A	101-269	[»]
3SHI	X-ray	2.20	A/G/M	106-261	[»]
4AUO	X-ray	3.00	A/B	100-466	[»]
4AYK	NMR	-	A	101-269	[»]
966C	X-ray	1.90	A	108-264	[»]

ProteinModelPortal

P03956.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-529N.

IntAct

P03956. 1 interaction.

STRING

9606.ENSP00000322788.

Protein family/group databases

MEROPS

M10.001.

PTM databases

GlycoSuiteDB

P03956.

PhosphoSite

P03956.

Polymorphism databases

DMDM

116852.

Proteomic databases

PaxDb

P03956.

PeptideAtlas

P03956.

PRIDE

P03956.

Protocols and materials databases

DNASU

4312.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000315274; ENSP00000322788; ENSG00000196611.

GeneID

4312.

KEGG

hsa:4312.

UCSC

uc001phi.2. human.

Organism-specific databases

CTD

4312.

GeneCards

GC11M102660.

H-InvDB

HIX0201751.

HGNC

HGNC:7155. MMP1.

MIM

120353. gene.

neXtProt

NX_P03956.

PharmGKB

PA30867.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG258253.

HOGENOM

HOG000217927.

HOVERGEN

HBG052484.

InParanoid

P03956.

KO

K01388.

OMA

ETQEQDV.

OrthoDB

EOG4X97GX.

PhylomeDB

P03956.

Enzyme and pathway databases

Pathway_Interaction_DB

endothelinpathway. Endothelins.

Reactome

REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_132934. Extracellular matrix organization.
REACT_133391. Extracellular matrix organization.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P03956.

Bgee

P03956.

CleanEx

HS_MMP1.

Genevestigator

P03956.

GermOnline

ENSG00000196611. 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

P03956.

ChEMBL

CHEMBL332.

EvolutionaryTrace

P03956.

GenomeRNAi

4312.

NextBio

16969.

PMAP-CutDB

P03956.

SOURCE

Search...

Entry information

Entry name

MMP1_HUMAN

Accession

Primary (citable) accession number: P03956
Secondary accession number(s): P08156

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 23, 1986
Last sequence update:	December 1, 1992
Last modified:	May 1, 2013
This is version 160 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.