MMP13_HORSE
ID MMP13_HORSE Reviewed; 472 AA.
AC O18927;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Collagenase 3;
DE EC=3.4.24.-;
DE AltName: Full=Matrix metalloproteinase-13;
DE Short=MMP-13;
DE Flags: Precursor;
GN Name=MMP13;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Richardson D.W.;
RT "Dose dependent effects of corticosteroids on the expression of matrix
RT related genes in equine articular chondrocytes.";
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
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 -!- TISSUE SPECIFICITY: Seems to be specific to breast carcinomas.
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; AF034087; AAB86893.1; -; mRNA.
DR RefSeq; NP_001075273.1; NM_001081804.1.
DR AlphaFoldDB; O18927; -.
DR SMR; O18927; -.
DR STRING; 9796.ENSECAP00000005084; -.
DR MEROPS; M10.013; -.
DR PaxDb; O18927; -.
DR GeneID; 100009711; -.
DR KEGG; ecb:100009711; -.
DR CTD; 4322; -.
DR InParanoid; O18927; -.
DR OrthoDB; 1075463at2759; -.
DR BRENDA; 3.4.24.B4; 2120.
DR Proteomes; UP000002281; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; ISS:UniProtKB.
DR GO; GO:0022617; P:extracellular matrix disassembly; ISS:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Calcium; Collagen degradation; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Phosphoprotein;
KW Protease; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..104
FT /note="Activation peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000028786"
FT CHAIN 105..472
FT /note="Collagenase 3"
FT /id="PRO_0000028787"
FT REPEAT 282..331
FT /note="Hemopexin 1"
FT REPEAT 332..378
FT /note="Hemopexin 2"
FT REPEAT 380..428
FT /note="Hemopexin 3"
FT REPEAT 429..472
FT /note="Hemopexin 4"
FT REGION 177..247
FT /note="Interaction with TIMP2"
FT /evidence="ECO:0000250"
FT REGION 269..472
FT /note="Interaction with collagen"
FT /evidence="ECO:0000250"
FT MOTIF 95..102
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 97
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 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 163
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 188
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 195
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 203
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 204
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 223
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 233
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 294
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 336
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 338
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 384
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 386
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT MOD_RES 367
FT /note="Phosphotyrosine; by PKDCC"
FT /evidence="ECO:0000250|UniProtKB:P45452"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 285..472
FT /evidence="ECO:0000250"
SQ SEQUENCE 472 AA; 54226 MW; 92B2697583F016D1 CRC64;
MHPGVLAAFL FLSWTRCWSL PVPNDDDDDD DMSEEDFQLA ERYLKSYYYP LNPAGILKKT
AANSVVDRLR EMQSFFGLEV TGKLDDNTLD IMKKPRCGVP DVGEYNVFPR TLKWPKMNLT
YRIVNYTPDL THSEVEKAFK KAFKVWSDVT PLNFTRLYNG TADIMISFGT KEHGDFYPFD
GPSGLLAHAF PPGPNYGGDA HFDDDETWTS SSKGYNLFLV AAHEFGHSLG LDHSKDPGAL
MFPIYTYTGK SHFVLPDDDV QGIQYLYGPG DEDPNPKHPK TPDKCDPSLS LDAITSLRGE
TMVFKDRFFW RLHPQLVDAE LFLTKSFWPE LPNRIDAAYE HPSKDLIFIF RGRKFWALNG
YDILEGYPQK ISELGFPKDV KKISAAVHFE DTGKTLFFSG NQVWRYDDTN RMMDKDYPRL
IEEDFPGIGD KVDAVYEKNG YIYFFNGPIQ FEYSIWSNRI VRVMPTNSLL WC
