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P03956 (MMP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 171. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interstitial collagenase

EC=3.4.24.7
Alternative name(s):
Fibroblast collagenase
Matrix metalloproteinase-1
Short name=MMP-1
Gene names
Name:MMP1
Synonyms:CLG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length469 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.14

Subcellular location

Secretedextracellular spaceextracellular 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. Ref.13

Sequence similarities

Belongs to the peptidase M10A family.

Contains 4 hemopexin repeats.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919
Propeptide20 – 9980Activation peptide
PRO_0000028703
Chain100 – 469370Interstitial collagenase
PRO_0000028704
Chain100 – 26917022 kDa interstitial collagenase
PRO_0000028705
Chain270 – 46920027 kDa interstitial collagenase
PRO_0000028706

Regions

Repeat275 – 32450Hemopexin 1
Repeat325 – 37147Hemopexin 2
Repeat374 – 42249Hemopexin 3
Repeat423 – 46644Hemopexin 4
Region98 – 276179Metalloprotease
Motif90 – 978Cysteine switch By similarity

Sites

Active site2191
Metal binding921Zinc 2; in inhibited form
Metal binding1241Calcium 1
Metal binding1581Calcium 2
Metal binding1681Zinc 1
Metal binding1701Zinc 1
Metal binding1751Calcium 3
Metal binding1761Calcium 3; via carbonyl oxygen
Metal binding1781Calcium 3; via carbonyl oxygen
Metal binding1801Calcium 3; via carbonyl oxygen
Metal binding1831Zinc 1
Metal binding1901Calcium 2; via carbonyl oxygen
Metal binding1921Calcium 2; via carbonyl oxygen
Metal binding1941Calcium 2
Metal binding1961Zinc 1
Metal binding1981Calcium 3
Metal binding1991Calcium 1
Metal binding2011Calcium 3
Metal binding2181Zinc 2; catalytic
Metal binding2221Zinc 2; catalytic
Metal binding2281Zinc 2; catalytic
Metal binding2851Calcium 4; via carbonyl oxygen By similarity
Metal binding3291Calcium 4; via carbonyl oxygen By similarity
Metal binding3781Calcium 4; via carbonyl oxygen By similarity
Metal binding4271Calcium 4; via carbonyl oxygen By similarity
Site1431Not glycosylated (PubMed:10092871)
Site269 – 2702Cleavage; by autolysis

Amino acid modifications

Glycosylation1201N-linked (GlcNAc...) Ref.13
CAR_000105
Disulfide bond278 ↔ 466 By similarity

Natural variations

Natural variant291Q → P.
Corresponds to variant rs554499 [ dbSNP | Ensembl ].
VAR_011969
Natural variant1911I → V. Ref.6
Corresponds to variant rs17879973 [ dbSNP | Ensembl ].
VAR_021024
Natural variant2521D → G.
Corresponds to variant rs513964 [ dbSNP | Ensembl ].
VAR_011970
Natural variant2621R → S.
Corresponds to variant rs12282811 [ dbSNP | Ensembl ].
VAR_054005
Natural variant4051R → Q. Ref.6
Corresponds to variant rs17879165 [ dbSNP | Ensembl ].
VAR_021025
Natural variant4061S → T. Ref.6
Corresponds to variant rs17884120 [ dbSNP | Ensembl ].
VAR_021026

Experimental info

Sequence conflict431N → K in AAA35700. Ref.9
Sequence conflict641Missing in AAA35700. Ref.9
Sequence conflict1151T → R in AAA35699. Ref.3
Sequence conflict2001D → H in CAA28858. Ref.2
Sequence conflict2081R → T in CAA28858. Ref.2
Sequence conflict3171I → T in CAA28858. Ref.2
Sequence conflict4101G → S in AAA35699. Ref.3

Secondary structure

.................................................................................... 469
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P03956 [UniParc].

Last modified December 1, 1992. Version 3.
Checksum: 4B1361DCF4C54B20

FASTA46954,007
        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 

« Hide

References

« Hide '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]"N-glycan structures of matrix metalloproteinase-1 derived from human fibroblasts and from HT-1080 fibrosarcoma cells."
Saarinen J., Welgus H.G., Flizar C.A., Kalkkinen N., Helin J.
Eur. J. Biochem. 259:829-840(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-120.
[14]"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.
[15]"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.
[16]"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.
[17]"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.
[18]"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.
[19]"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.
PIRKCHUI. A37308.
RefSeqNP_002412.1. NM_002421.3.
UniGeneHs.83169.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AYKNMR-A101-269[»]
1CGEX-ray1.90A102-269[»]
1CGFX-ray2.10A/B102-263[»]
1CGLX-ray2.40A/B101-269[»]
1HFCX-ray1.50A101-269[»]
1SU3X-ray2.20A/B20-469[»]
2AYKNMR-A101-269[»]
2CLTX-ray2.67A/B100-466[»]
2J0TX-ray2.54A/B/C101-269[»]
2TCLX-ray2.20A101-269[»]
3AYKNMR-A101-269[»]
3SHIX-ray2.20A/G/M106-261[»]
4AUOX-ray3.00A/B100-466[»]
4AYKNMR-A101-269[»]
966CX-ray1.90A108-264[»]
ProteinModelPortalP03956.
SMRP03956. Positions 32-466.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110456. 6 interactions.
DIPDIP-529N.
IntActP03956. 1 interaction.
MINTMINT-198818.
STRING9606.ENSP00000322788.

Chemistry

BindingDBP03956.
ChEMBLCHEMBL2095216.
GuidetoPHARMACOLOGY1628.

Protein family/group databases

MEROPSM10.001.

PTM databases

PhosphoSiteP03956.
UniCarbKBP03956.

Polymorphism databases

DMDM116852.

Proteomic databases

PaxDbP03956.
PeptideAtlasP03956.
PRIDEP03956.

Protocols and materials databases

DNASU4312.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315274; ENSP00000322788; ENSG00000196611.
GeneID4312.
KEGGhsa:4312.
UCSCuc001phi.2. human.

Organism-specific databases

CTD4312.
GeneCardsGC11M102660.
H-InvDBHIX0201751.
HGNCHGNC:7155. MMP1.
MIM120353. gene.
neXtProtNX_P03956.
Orphanet79408. Severe generalized recessive dystrophic epidermolysis bullosa.
PharmGKBPA30867.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG258253.
HOGENOMHOG000217927.
HOVERGENHBG052484.
InParanoidP03956.
KOK01388.
OMAMRTNPFY.
OrthoDBEOG7XPZ57.
PhylomeDBP03956.
TreeFamTF315428.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.
REACT_17015. Metabolism of proteins.
REACT_196873. Extracellular matrix organization.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP03956.
BgeeP03956.
CleanExHS_MMP1.
GenevestigatorP03956.

Family and domain databases

Gene3D2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR028709. MMP1/MMP8.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERPTHR10201. PTHR10201. 1 hit.
PTHR10201:SF37. PTHR10201:SF37. 1 hit.
PfamPF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSPR00138. MATRIXIN.
SMARTSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP03956.
GeneWikiMMP1.
GenomeRNAi4312.
NextBio16969.
PMAP-CutDBP03956.
PROP03956.
SOURCESearch...

Entry information

Entry nameMMP1_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 171 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM