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 08-NOV-2023, entry version 169. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P23097; 3 sites, No reported glycans. DR GlyGen; P23097; 3 sites. DR PhosphoSitePlus; P23097; -. DR PaxDb; 10116-ENSRNOP00000011507; -. DR UCSC; RGD:620196; rat. DR AGR; RGD:620196; -. 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:0046581; C:intercellular canaliculus; 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: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:0019538; P:protein metabolic process; ISO: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; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 2.110.10.10; Hemopexin-like domain; 1. 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; COLLAGENASE 3; 1. DR PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 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; SSF50923; Hemopexin-like domain; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR SUPFAM; SSF47090; PGBD-like; 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 //