MMP13_RAT
ID MMP13_RAT Reviewed; 466 AA.
AC P23097;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Collagenase 3;
DE EC=3.4.24.-;
DE AltName: Full=Matrix metalloproteinase-13;
DE Short=MMP-13;
DE AltName: Full=UMRCASE;
DE Flags: Precursor; Fragment;
GN Name=Mmp13;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2176215; DOI=10.1016/s0021-9258(18)45711-0;
RA Quinn C.O., Scott D.K., Brinckerhoff C.E., Matrisian L.M., Jeffrey J.J.,
RA Partridge N.C.;
RT "Rat collagenase. Cloning, amino acid sequence comparison, and parathyroid
RT hormone regulation in osteoblastic cells.";
RL J. Biol. Chem. 265:22342-22347(1990).
CC -!- FUNCTION: Plays a role in the degradation of extracellular matrix
CC proteins including fibrillar collagen, fibronectin, TNC and ACAN.
CC Cleaves triple helical collagens, including type I, type II and type
CC III collagen, but has the highest activity with soluble type II
CC collagen. Can also degrade collagen type IV, type XIV and type X. May
CC also function by activating or degrading key regulatory proteins, such
CC as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling,
CC cartilage degradation, bone development, bone mineralization and
CC ossification. Required for normal embryonic bone development and
CC ossification. Plays a role in the healing of bone fractures via
CC endochondral ossification. Plays a role in wound healing, probably by a
CC mechanism that involves proteolytic activation of TGFB1 and degradation
CC of CCN2. Plays a role in keratinocyte migration during wound healing.
CC May play a role in cell migration and in tumor cell invasion (By
CC similarity). {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Can bind about 5 Ca(2+) ions per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000305}. Secreted {ECO:0000250}.
CC -!- DOMAIN: The C-terminal region binds to collagen. {ECO:0000250}.
CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC dissociation of the cysteine from the zinc ion upon the activation-
CC peptide release activates the enzyme (By similarity). {ECO:0000250}.
CC -!- PTM: The proenzyme is activated by removal of the propeptide; this
CC cleavage can be effected by other matrix metalloproteinases, such as
CC MMP2, MMP3 and MMP14 and may involve several cleavage steps. Cleavage
CC can also be autocatalytic, after partial maturation by another protease
CC or after treatment with 4-aminophenylmercuric acetate (APMA) (in vitro)
CC (By similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- PTM: Tyrosine phosphorylated by PKDCC/VLK.
CC {ECO:0000250|UniProtKB:P45452}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; M60616; AAA72124.1; -; mRNA.
DR PIR; A23685; A23685.
DR AlphaFoldDB; P23097; -.
DR SMR; P23097; -.
DR STRING; 10116.ENSRNOP00000011507; -.
DR BindingDB; P23097; -.
DR ChEMBL; CHEMBL4944; -.
DR MEROPS; M10.013; -.
DR GlyGen; P23097; 3 sites.
DR PhosphoSitePlus; P23097; -.
DR PaxDb; P23097; -.
DR UCSC; RGD:620196; rat.
DR RGD; 620196; Mmp13.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; P23097; -.
DR PhylomeDB; P23097; -.
DR BRENDA; 3.4.24.B4; 5301.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-RNO-2022090; Assembly of collagen fibrils and other multimeric structures.
DR PRO; PR:P23097; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0046581; C:intercellular canaliculus; IDA:RGD.
DR GO; GO:0005764; C:lysosome; IDA:RGD.
DR GO; GO:0005509; F:calcium ion binding; IDA:RGD.
DR GO; GO:0048306; F:calcium-dependent protein binding; IDA:RGD.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0001968; F:fibronectin binding; IPI:RGD.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IPI:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:RGD.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0051216; P:cartilage development; ISO:RGD.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IEP:RGD.
DR GO; GO:0030574; P:collagen catabolic process; ISS:UniProtKB.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEP:RGD.
DR GO; GO:0001958; P:endochondral ossification; IEP:RGD.
DR GO; GO:0044849; P:estrous cycle; IEP:RGD.
DR GO; GO:0022617; P:extracellular matrix disassembly; ISS:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0003417; P:growth plate cartilage development; ISO:RGD.
DR GO; GO:0007507; P:heart development; IDA:RGD.
DR GO; GO:0001554; P:luteolysis; IEP:RGD.
DR GO; GO:0001503; P:ossification; IEP:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:RGD.
DR GO; GO:0007567; P:parturition; IEP:RGD.
DR GO; GO:1904244; P:positive regulation of pancreatic trypsinogen secretion; IDA:RGD.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.110.10.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR028711; Collagenase_3.
DR InterPro; IPR000585; Hemopexin-like_dom.
DR InterPro; IPR036375; Hemopexin-like_dom_sf.
DR InterPro; IPR018487; Hemopexin-like_repeat.
DR InterPro; IPR018486; Hemopexin_CS.
DR InterPro; IPR033739; M10A_MMP.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR021158; Pept_M10A_Zn_BS.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR PANTHER; PTHR10201:SF165; PTHR10201:SF165; 1.
DR Pfam; PF00045; Hemopexin; 4.
DR Pfam; PF00413; Peptidase_M10; 1.
DR Pfam; PF01471; PG_binding_1; 1.
DR PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1.
DR PRINTS; PR00138; MATRIXIN.
DR SMART; SM00120; HX; 4.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50923; SSF50923; 1.
DR PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR PROSITE; PS00024; HEMOPEXIN; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Collagen degradation; Direct protein sequencing; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Phosphoprotein; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Zinc; Zymogen.
FT SIGNAL <1..13
FT /evidence="ECO:0000255"
FT PROPEP 14..98
FT /note="Activation peptide"
FT /id="PRO_0000028794"
FT CHAIN 99..466
FT /note="Collagenase 3"
FT /id="PRO_0000028795"
FT REPEAT 276..325
FT /note="Hemopexin 1"
FT REPEAT 326..372
FT /note="Hemopexin 2"
FT REPEAT 374..422
FT /note="Hemopexin 3"
FT REPEAT 423..466
FT /note="Hemopexin 4"
FT REGION 171..241
FT /note="Interaction with TIMP2"
FT /evidence="ECO:0000250"
FT REGION 258..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..466
FT /note="Interaction with collagen"
FT /evidence="ECO:0000250"
FT MOTIF 89..96
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 123
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 174
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 177
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 191
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 198
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 221
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 286
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 332
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 378
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 380
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 427
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 429
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT MOD_RES 361
FT /note="Phosphotyrosine; by PKDCC"
FT /evidence="ECO:0000250|UniProtKB:P45452"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 279..466
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 466 AA; 53375 MW; BF66021BD734813D CRC64;
ATFFLLSWTH CWSLPLPYGD DDDDDLSEED LEFAEHYLKS YYHPVTLAGI LKKSTVTSTV
DRLREMQSFF GLDVTGKLDD PTLDIMRKPR CGVPDVGVYN VFPRTLKWSQ TNLTYRIVNY
TPDISHSEVE KAFRKAFKVW SDVTPLNFTR IHDGTADIMI SFGTKEHGDF YPFDGPSGLL
AHAFPPGPNL GGDAHFDDDE TWTSSSKGYN LFIVAAHELG HSLGLDHSKD PGALMFPIYT
YTGKSHFMLP DDDVQGIQSL YGPGDEDPNP KHPKTPEKCD PALSLDAITS LRGETMIFKD
RFFWRLHPQQ VEPELFLTKS FWPELPNHVD AAYEHPSRDL MFIFRGRKFW ALNGYDIMEG
YPRKISDLGF PKEVKRLSAA VHFEDTGKTL FFSGNHVWSY DDANQTMDKD YPRLIEEEFP
GIGDKVDAVY EKNGYIYFFN GPIQFEYSIW SNRIVRVMPT NSLLWC
