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UniProtKB/Swiss-Prot entry P03956


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name MMP1_HUMAN
Primary accession number P03956
Secondary accession number P08156
Integrated into Swiss-Prot on October 23, 1986
Sequence was last modified on December 1, 1992 (Sequence version 3)
Annotations were last modified on    June 16, 2009 (Entry version 122)
Name and origin of the protein
Protein name Interstitial collagenase [Precursor]
Synonyms EC 3.4.24.7
Matrix metalloproteinase-1
MMP-1
Fibroblast collagenase
Contains 22 kDa interstitial collagenase
27 kDa interstitial collagenase
Gene name
Name: MMP1
Synonyms: CLG
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
PubMed=2167156 [NCBI, ExPASy, EBI, Israel, Japan]
Templeton N.S., Brown P.D., Levy A.T., Margulies I.M.K., Liotta L.A., Stetler-Stevenson W.G.;
"Cloning and characterization of human tumor cell interstitial collagenase.";
Cancer Res. 50:5431-5437(1990).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3030290 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Comparison of human stromelysin and collagenase by cloning and sequence analysis.";
Biochem. J. 240:913-916(1986).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3009463 [NCBI, ExPASy, EBI, Israel, Japan]
Goldberg G.I., Wilhelm S.M., Kronberger A., Bauer E.A., Grant G.A., Eisen A.Z.;
"Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein.";
J. Biol. Chem. 261:6600-6605(1986).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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.;
"Three matrix metalloproteinases on 81kb of P1 insert.";
Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-191; GLN-405 AND THR-406.
NIEHS SNPs program;
Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Ovary;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
PubMed=3037355 [NCBI, ExPASy, EBI, Israel, Japan]
Angel P., Baumann I., Stein B., Delius H., Rahmsdorf H.J., Herrlich P.;
"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.";
Mol. Cell. Biol. 7:2256-2266(1987).
[9]
NUCLEOTIDE SEQUENCE [MRNA] OF 1-70.
TISSUE=Synovial cell;
PubMed=3027129 [NCBI, ExPASy, EBI, Israel, Japan]
Brinckerhoff C.E., Ruby P.L., Austin S.D., Fini M.E., White H.D.;
"Molecular cloning of human synovial cell collagenase and selection of a single gene from genomic DNA.";
J. Clin. Invest. 79:542-546(1987).
[10]
PROTEIN SEQUENCE OF 100-112 AND 270-287.
TISSUE=Fibroblast;
PubMed=2557822 [NCBI, ExPASy, EBI, Israel, Japan]
Clark I.M., Cawston T.E.;
"Fragments of human fibroblast collagenase. Purification and characterization.";
Biochem. J. 263:201-206(1989).
[11]
SIMILARITY TO THERMOLYSIN TYPE PROTEASES.
PubMed=3032950 [NCBI, ExPASy, EBI, Israel, Japan]
McKerrow J.H.;
"Human fibroblast collagenase contains an amino acid sequence homologous to the zinc-binding site of Serratia protease.";
J. Biol. Chem. 262:5943-5943(1987).
[12]
FUNCTION.
PubMed=1645757 [NCBI, ExPASy, EBI, Israel, Japan]
Desrochers P.E., Jeffrey J.J., Weiss S.J.;
"Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity.";
J. Clin. Invest. 87:2258-2265(1991).
[13]
INTERACTION WITH HIV-1 TAT.
DOI=10.1096/fj.05-5619fje; PubMed=16807369 [NCBI, ExPASy, EBI, Israel, Japan]
Rumbaugh J., Turchan-Cholewo J., Galey D., St Hillaire C., Anderson C., Conant K., Nath A.;
"Interaction of HIV Tat and matrix metalloproteinase in HIV neuropathogenesis: a new host defense mechanism.";
FASEB J. 20:1736-1738(2006).
[14]
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 100-269.
DOI=10.1038/nsb0294-106; PubMed=7656013 [NCBI, ExPASy, EBI, Israel, Japan]
Borkakoti N., Winkler F.K., Williams D.H., D'Arcy A., Broadhurst M.J., Brown P.A., Johnson W.H., Murray E.J.;
"Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor.";
Nat. Struct. Biol. 1:106-110(1994).
[15]
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 102-269.
DOI=10.1021/bi00193a006; PubMed=8031754 [NCBI, ExPASy, EBI, Israel, Japan]
Lovejoy B., Hassell A.M., Luther M.A., Weigl D., Jordan S.R.;
"Crystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself.";
Biochemistry 33:8207-8217(1994).
[16]
X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 102-269.
DOI=10.1126/science.8278810; PubMed=8278810 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor.";
Science 263:375-377(1994).
[17]
X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 101-269.
DOI=10.1002/prot.340190203; PubMed=8090713 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"1.56-A structure of mature truncated human fibroblast collagenase.";
Proteins 19:98-109(1994).
[18]
STRUCTURE BY NMR OF 101-269.
DOI=10.1021/bi972181w; PubMed=9484219 [NCBI, ExPASy, EBI, Israel, Japan]
Moy F.J., Chanda P.K., Cosmi S., Pisano M.R., Urbano C., Wilhelm J., Powers R.;
"High-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase determined by multidimensional NMR.";
Biochemistry 37:1495-1504(1998).
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.
  • 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.
  • COFACTOR: Binds 2 zinc ions per subunit.
  • ENZYME REGULATION: Can be activated without removal of the activation peptide.
  • SUBUNIT: Interacts with HIV-1 Tat.
  • SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix (Probable).
  • 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).
  • 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.
  • PTM: 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.
  • SIMILARITY: Belongs to the peptidase M10A family [view classification].
  • SIMILARITY: Contains 4 hemopexin-like domains.
  • WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mmp1/";.
  • WEB RESOURCE: Name=Wikipedia; Note=Collagenase entry; URL="http://en.wikipedia.org/wiki/Collagenase";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X54925; CAA38691.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X05231; CAA28858.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M13509; AAA35699.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U78045; AAB36941.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT006874; AAP35520.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY769434; AAV28732.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC013875; AAH13875.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M16567; AAA52033.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M15996; AAA35700.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00008561; -.
PIR A37308; KCHUI.
RefSeq NP_002412.1; -.
UniGene Hs.83169
3D structure databases
PDB
1AYK; NMR; -; A=101-269.[ExPASy / RCSB / EBI]
1CGE; X-ray; 1.90 A; A=102-269.[ExPASy / RCSB / EBI]
1CGF; X-ray; 2.10 A; A/B=102-263.[ExPASy / RCSB / EBI]
1CGL; X-ray; 2.40 A; A/B=101-269.[ExPASy / RCSB / EBI]
1HFC; X-ray; 1.50 A; A=101-269.[ExPASy / RCSB / EBI]
1SU3; X-ray; 2.20 A; A/B=20-469.[ExPASy / RCSB / EBI]
2AYK; NMR; -; A=101-269.[ExPASy / RCSB / EBI]
2CLT; X-ray; 2.67 A; A/B=100-466.[ExPASy / RCSB / EBI]
2J0T; X-ray; 2.54 A; A/B/C=101-269.[ExPASy / RCSB / EBI]
2TCL; X-ray; 2.20 A; A=101-269.[ExPASy / RCSB / EBI]
3AYK; NMR; -; A=101-269.[ExPASy / RCSB / EBI]
4AYK; NMR; -; A=101-269.[ExPASy / RCSB / EBI]
966C; X-ray; 1.90 A; A=108-264.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1AYK; -.
1CGE; -.
1CGF; -.
1CGL; -.
1HFC; -.
1SU3; -.
2AYK; -.
2CLT; -.
2J0T; -.
2TCL; -.
3AYK; -.
4AYK; -.
966C; -.
ModBase P03956.
Protein-protein interaction databases
DIP DIP:529N; -.
Protein family/group databases
MEROPS M10.001; -.
PTM databases
GlycoSuiteDB P03956; -.
Enzyme and pathway databases
BRENDA 3.4.24.7; 247.
Pathway_Interaction_DB endothelinpathway; Endothelins.
Organism-specific databases
GeneCards GC11M102165; -.
H-InvDB HIX0010067; -.
HGNC HGNC:7155; MMP1.
GenAtlas MMP1.
MIM 120353; gene. [NCBI / EBI]
PharmGKB PA30867; -.
Gene expression databases
ArrayExpress P03956; -.
Bgee P03956; -.
CleanEx HS_MMP1; -.
GermOnline ENSG00000196611; Homo sapiens.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005578; Cellular component: proteinaceous extracellular matrix (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005509; Molecular function: calcium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004222; Molecular function: metalloendopeptidase activity (inferred from direct assay from UniProtKB).
GO:0008270; Molecular function: zinc ion binding (traceable author statement from ProtInc).
GO:0030574; Biological process: collagen catabolic process (inferred from electronic annotation from UniProtKB-KW).
GO:0044419; Biological process: interspecies interaction between organisms (inferred from electronic annotation from UniProtKB-KW).
GO:0006508; Biological process: proteolysis (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR000585; Hemopexin/matrixin.
IPR018486; Hemopexin/matrixin_CS.
IPR018487; Hemopexin/matrixin_repeat.
IPR001818; Pept_M10A_M12B.
IPR016293; Pept_M10A_matrix.
IPR006025; Pept_M_Zn_BS.
IPR006026; Peptidase_M.
IPR002477; Peptidoglycan-bd-like.
Graphical view of domain structure.
Gene3D G3DSA:2.110.10.10; Hemopexin; 1.
Pfam PF00045; Hemopexin; 4.
PF00413; Peptidase_M10; 1.
PF01471; PG_binding_1; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF001191; Peptidase_M10A_matrix; 1.
PRINTS PR00138; MATRIXIN.
SMART SM00120; HX; 4.
SM00235; ZnMc; 1.
SMART graphical view of domain structure.
PROSITE PS00546; CYSTEINE_SWITCH; 1.
PS00024; HEMOPEXIN; 1.
PS00142; ZINC_PROTEASE; 1.
Proteomic databases
PeptideAtlas P03956; -.
PRIDE P03956; -.
Genome annotation databases
Ensembl ENSG00000196611; Homo sapiens. [Contig view]
GeneID 4312; -.
KEGG hsa:4312; -.
Phylogenomic databases
HOGENOM P03956; -.
HOVERGEN P03956; -.
OMA P03956; MRTNPFY.
Other
BindingDB P03956; -.
NextBio 16969; -.
PMAP-CutDB P03956; -.
SOURCE MMP1; Homo sapiens.
ProtoNet P03956.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Autocatalytic cleavage; Calcium; Collagen degradation; Direct protein sequencing; Disulfide bond; Extracellular matrix; Glycoprotein; Host-virus interaction; Hydrolase; Metal-binding; Metalloprotease; Polymorphism; Protease; Repeat; Secreted; Signal; Zinc; Zymogen.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    19  19      
PROPEP   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
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). 
ACT_SITE   219   219         
METAL   92    92        Zinc 2; in inhibited form. 
METAL   124   124        Calcium 1. 
METAL   158   158        Calcium 2. 
METAL   168   168        Zinc 1. 
METAL   170   170        Zinc 1. 
METAL   175   175        Calcium 3. 
METAL   176   176        Calcium 3; via carbonyl oxygen. 
METAL   178   178        Calcium 3; via carbonyl oxygen. 
METAL   180   180        Calcium 3; via carbonyl oxygen. 
METAL   183   183        Zinc 1. 
METAL   190   190        Calcium 2; via carbonyl oxygen. 
METAL   192   192        Calcium 2; via carbonyl oxygen. 
METAL   194   194        Calcium 2. 
METAL   196   196        Zinc 1. 
METAL   198   198        Calcium 3. 
METAL   199   199        Calcium 1. 
METAL   201   201        Calcium 3. 
METAL   218   218        Zinc 2; catalytic. 
METAL   222   222        Zinc 2; catalytic. 
METAL   228   228        Zinc 2; catalytic. 
METAL   285   285        Calcium 4; via carbonyl oxygen (By similarity). 
METAL   329   329        Calcium 4; via carbonyl oxygen (By similarity). 
METAL   378   378        Calcium 4; via carbonyl oxygen (By similarity). 
METAL   427   427        Calcium 4; via carbonyl oxygen (By similarity). 
SITE   269   270  2     Cleavage; by autolysis. 
CARBOHYD   120   120        N-linked (GlcNAc...) [GlycoSuiteDB]. CAR_000105
DISULFID   278   466        By similarity. 
VARIANT   29    29  1     Q -> P (in dbSNP:rs554499 [NCBI]). VAR_011969 
VARIANT   191   191  1     I -> V (in dbSNP:rs17879973 [NCBI]). VAR_021024 [3D]
VARIANT   252   252  1     D -> G (in dbSNP:rs513964 [NCBI]). VAR_011970 [3D]
VARIANT   262   262  1     R -> S (in dbSNP:rs12282811 [NCBI]). VAR_054005 [3D]
VARIANT   405   405  1     R -> Q (in dbSNP:rs17879165 [NCBI]). VAR_021025 
VARIANT   406   406  1     S -> T (in dbSNP:rs17884120 [NCBI]). VAR_021026 
CONFLICT   43    43        N -> K (in Ref. 9; AAA35700). 
CONFLICT   64    64        Missing (in Ref. 9; AAA35700). 
CONFLICT   115   115        T -> R (in Ref. 3; AAA35699). 
CONFLICT   200   200        D -> H (in Ref. 2; CAA28858). 
CONFLICT   208   208        R -> T (in Ref. 2; CAA28858). 
CONFLICT   317   317        I -> T (in Ref. 2; CAA28858). 
CONFLICT   410   410        G -> S (in Ref. 3; AAA35699). 
HELIX   33    41  9      
HELIX   59    70  12      
HELIX   81    87  7      
STRAND   110   118  9      
HELIX   127   142  16      
STRAND   148   151  4      
STRAND   153   155  3      
STRAND   158   164  7      
STRAND   169   172  4      
STRAND   176   179  4      
STRAND   182   184  3      
STRAND   187   189  3      
TURN   190   193  4      
STRAND   195   198  4      
STRAND   204   209  6      
HELIX   212   223  12      
HELIX   250   260  11      
STRAND   285   290  6      
STRAND   293   298  6      
STRAND   301   304  4      
STRAND   309   311  3      
STRAND   313   316  4      
HELIX   317   319  3      
STRAND   330   334  5      
HELIX   335   337  3      
STRAND   339   344  6      
STRAND   347   352  6      
STRAND   361   363  3      
HELIX   364   368  5      
STRAND   379   382  4      
TURN   384   386  3      
STRAND   388   393  6      
STRAND   396   401  6      
TURN   402   405  4      
STRAND   412   414  3      
HELIX   415   418  4      
STRAND   427   432  6      
STRAND   435   440  6      
STRAND   443   448  6      
TURN   449   452  4      
STRAND   453   459  7      
TURN   460   463  4      
Sequence information
Length: 469 AA [This is the length of the unprocessed precursor] Molecular weight: 54007 Da [This is the MW of the unprocessed precursor] CRC64: 4B1361DCF4C54B20 [This is a checksum on the sequence]
        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 

P03956 in FASTA format

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