ID COMP_RAT Reviewed; 755 AA. AC P35444; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 02-SEP-2026, entry version 169. DE RecName: Full=Cartilage oligomeric matrix protein {ECO:0000305}; DE Short=COMP; DE Flags: Precursor; GN Name=Comp {ECO:0000312|RGD:2378}; 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]. RC TISSUE=Cartilage; RX PubMed=1429587; DOI=10.1016/s0021-9258(18)41677-8; RA Oldberg A., Antonsson P., Lindblom K., Heinegaard D.; RT "COMP (cartilage oligomeric matrix protein) is structurally related to the RT thrombospondins."; RL J. Biol. Chem. 267:22346-22350(1992). RN [2] RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH ITGA7. RX PubMed=20019333; DOI=10.1161/circresaha.109.202762; RA Wang L., Zheng J., Du Y., Huang Y., Li J., Liu B., Liu C.J., Zhu Y., RA Gao Y., Xu Q., Kong W., Wang X.; RT "Cartilage oligomeric matrix protein maintains the contractile phenotype of RT vascular smooth muscle cells by interacting with alpha(7)beta(1) RT integrin."; RL Circ. Res. 106:514-525(2010). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 27-72, AND DISULFIDE BONDS. RX PubMed=8864111; DOI=10.1126/science.274.5288.761; RA Malashkevich V.N., Kammerer R.A., Efimov V.P., Schulthess T., Engel J.; RT "The crystal structure of a five-stranded coiled coil in COMP: a prototype RT ion channel?"; RL Science 274:761-765(1996). CC -!- FUNCTION: Plays a role in the structural integrity of cartilage via its CC interaction with other extracellular matrix proteins such as the CC collagens and fibronectin. Can mediate the interaction of chondrocytes CC with the cartilage extracellular matrix through interaction with cell CC surface integrin receptors. Could play a role in the pathogenesis of CC osteoarthritis. Potent suppressor of apoptosis in both primary CC chondrocytes and transformed cells. Suppresses apoptosis by blocking CC the activation of caspase-3 and by inducing the IAP family of survival CC proteins (BIRC3, BIRC2, BIRC5 and XIAP) (By similarity). Essential for CC maintaining a vascular smooth muscle cells (VSMCs) CC contractile/differentiated phenotype under physiological and CC pathological stimuli. Maintains this phenotype of VSMCs by interacting CC with ITGA7 (PubMed:20019333). {ECO:0000250|UniProtKB:P49747, CC ECO:0000269|PubMed:20019333}. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000250|UniProtKB:P49747}; CC Note=Binds 11-14 calcium ions per subunit. CC {ECO:0000250|UniProtKB:P49747}; CC -!- SUBUNIT: Pentamer; disulfide-linked. Exists in a more compact CC conformation in the presence of calcium and shows a more extended CC conformation in the absence of calcium. Interacts with ITGB3, ITGA5 and CC FN1. Binding to FN1 requires the presence of divalent cations (Ca(2+), CC Mg(2+) or Mn(2+)). The greatest amount of binding is seen in the CC presence of Mn(2+). Interacts with MATN1, MATN3, MATN4 and ACAN. Binds CC heparin, heparan sulfate and chondroitin sulfate. EDTA dimishes CC significantly its binding to ACAN and abolishes its binding to MATN3, CC MATN4 and chondroitin sulfate. Interacts with collagen I, II and IX, CC and interaction with these collagens is dependent on the presence of CC zinc ions. Interacts with ADAMTS12 (By similarity). Interacts with CC ITGA7 (PubMed:20019333). {ECO:0000250|UniProtKB:P49747, CC ECO:0000269|PubMed:20019333}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000250|UniProtKB:P49747}. CC -!- DOMAIN: The cell attachment motif mediates the attachment to CC chondrocytes. It mediates the induction of both the IAP family of CC survival proteins and the antiapoptotic response. CC {ECO:0000250|UniProtKB:P49747}. CC -!- DOMAIN: The TSP C-terminal domain mediates interaction with FN1 and CC ACAN. {ECO:0000250|UniProtKB:P49747}. CC -!- DOMAIN: Each of the eight TSP type-3 repeats binds two calcium ions. CC The TSP C-terminal domain binds three calcium ions. CC {ECO:0000250|UniProtKB:P49747}. CC -!- PTM: Proteolytically cleaved by metalloproteases ADAMTS4 and ADAMTS1 CC with ADAMTS4 showing more potent activity. CC {ECO:0000250|UniProtKB:P49747}. CC -!- SIMILARITY: Belongs to the thrombospondin 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; X72914; CAA51419.1; -; mRNA. DR PIR; A44315; A44315. DR RefSeq; NP_036966.2; NM_012834.2. DR PDB; 1FBM; X-ray; 2.70 A; A/B/C/D/E=27-72. DR PDB; 1VDF; X-ray; 2.05 A; A/B/C/D/E=28-72. DR PDB; 6SF6; X-ray; 1.90 A; C/D=232-250. DR AlphaFoldDB; P35444; -. DR MDRepo; P35444; -. DR SMR; P35444; -. DR BioGRID; 247343; 2. DR FunCoup; P35444; 333. DR STRING; 10116.ENSRNOP00000067037; -. DR GlyCosmos; P35444; 2 sites, No reported glycans. DR GlyGen; P35444; 2 sites. DR PhosphoSitePlus; P35444; -. DR PaxDb; 10116-ENSRNOP00000067037; -. DR ABCD; P35444; 1 sequenced antibody. DR GeneID; 25304; -. DR KEGG; rno:25304; -. DR AGR; RGD:2378; -. DR CTD; 1311; -. DR RGD; 2378; Comp. DR eggNOG; ENOG502QRK8; Eukaryota. DR InParanoid; P35444; -. DR PhylomeDB; P35444; -. DR Reactome; R-RNO-216083; Integrin cell surface interactions. DR EvolutionaryTrace; P35444; -. DR PRO; PR:P35444; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0031012; C:extracellular matrix; IDA:RGD. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISO:RGD. DR GO; GO:0036122; F:BMP binding; ISO:RGD. DR GO; GO:0005509; F:calcium ion binding; ISO:RGD. DR GO; GO:0005518; F:collagen binding; ISO:RGD. DR GO; GO:0005201; F:extracellular matrix structural constituent; IDA:RGD. DR GO; GO:0001968; F:fibronectin binding; IDA:RGD. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISO:RGD. DR GO; GO:0008201; F:heparin binding; ISO:RGD. DR GO; GO:0005178; F:integrin binding; ISO:RGD. DR GO; GO:0002020; F:protease binding; ISO:RGD. DR GO; GO:0043394; F:proteoglycan binding; ISO:RGD. DR GO; GO:0005499; F:vitamin D binding; IMP:RGD. DR GO; GO:0006915; P:apoptotic process; ISO:RGD. DR GO; GO:0048844; P:artery morphogenesis; ISO:RGD. DR GO; GO:0007596; P:blood coagulation; ISO:RGD. DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD. DR GO; GO:0098868; P:bone growth; ISO:RGD. DR GO; GO:0030282; P:bone mineralization; ISO:RGD. DR GO; GO:0060349; P:bone morphogenesis; ISO:RGD. DR GO; GO:0051216; P:cartilage development; ISO:RGD. DR GO; GO:1990079; P:cartilage homeostasis; ISS:UniProtKB. DR GO; GO:0090398; P:cellular senescence; ISO:RGD. DR GO; GO:0002063; P:chondrocyte development; ISO:RGD. DR GO; GO:0035988; P:chondrocyte proliferation; ISO:RGD. DR GO; GO:0030199; P:collagen fibril organization; ISO:RGD. DR GO; GO:0003416; P:endochondral bone growth; ISO:RGD. DR GO; GO:0003417; P:growth plate cartilage development; ISO:RGD. DR GO; GO:0060173; P:limb development; ISO:RGD. DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD. DR GO; GO:0055001; P:muscle cell development; ISO:RGD. DR GO; GO:0050881; P:musculoskeletal movement; ISO:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD. DR GO; GO:1900047; P:negative regulation of hemostasis; ISO:RGD. DR GO; GO:0050905; P:neuromuscular process; ISO:RGD. DR GO; GO:0001503; P:ossification; ISO:RGD. DR GO; GO:0070527; P:platelet aggregation; ISO:RGD. DR GO; GO:1902732; P:positive regulation of chondrocyte proliferation; ISO:RGD. DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB. DR GO; GO:0016485; P:protein processing; ISO:RGD. DR GO; GO:0009306; P:protein secretion; ISO:RGD. DR GO; GO:0030500; P:regulation of bone mineralization; ISO:RGD. DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD. DR GO; GO:0006986; P:response to unfolded protein; ISO:RGD. DR GO; GO:0001501; P:skeletal system development; ISO:RGD. DR GO; GO:0043588; P:skin development; ISO:RGD. DR GO; GO:0035989; P:tendon development; ISO:RGD. DR GO; GO:0097084; P:vascular associated smooth muscle cell development; ISO:RGD. DR GO; GO:0014829; P:vascular associated smooth muscle contraction; ISO:RGD. DR CDD; cd00054; EGF_CA; 2. DR CDD; cd16077; TSP-5cc; 1. DR FunFam; 2.10.25.10:FF:000346; Cartilage oligomeric matrix protein; 1. DR FunFam; 4.10.1080.10:FF:000004; Cartilage oligomeric matrix protein; 1. DR FunFam; 2.10.25.10:FF:000025; Thrombospondin 3; 1. DR FunFam; 2.10.25.10:FF:000027; Thrombospondin 3; 1. DR FunFam; 2.60.120.200:FF:000002; Thrombospondin 3; 1. DR FunFam; 4.10.1080.10:FF:000001; Thrombospondin 3; 1. DR FunFam; 2.10.25.10:FF:000170; thrombospondin-3 isoform X1; 1. DR FunFam; 1.20.5.10:FF:000001; thrombospondin-3 isoform X2; 1. DR Gene3D; 1.20.5.10; -; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 2.10.25.10; Laminin; 4. DR Gene3D; 4.10.1080.10; TSP type-3 repeat; 2. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR000742; EGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR049883; NOTCH1_EGF-like. DR InterPro; IPR003367; Thrombospondin_3-like_rpt. DR InterPro; IPR017897; Thrombospondin_3_rpt. DR InterPro; IPR008859; Thrombospondin_C. DR InterPro; IPR039081; TSP-5_CC. DR InterPro; IPR024665; TSP/COMP_CC. DR InterPro; IPR046970; TSP/COMP_CC_sf. DR InterPro; IPR028974; TSP_type-3_rpt. DR PANTHER; PTHR10199:SF88; CARTILAGE OLIGOMERIC MATRIX PROTEIN; 1. DR PANTHER; PTHR10199; THROMBOSPONDIN; 1. DR Pfam; PF11598; COMP; 1. DR Pfam; PF07645; EGF_CA; 2. DR Pfam; PF02412; TSP_3; 6. DR Pfam; PF05735; TSP_C; 1. DR SMART; SM00181; EGF; 4. DR SMART; SM00179; EGF_CA; 2. DR SUPFAM; SSF58006; Assembly domain of cartilage oligomeric matrix protein; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF103647; TSP type-3 repeat; 3. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 3. DR PROSITE; PS01187; EGF_CA; 2. DR PROSITE; PS51234; TSP3; 8. DR PROSITE; PS51236; TSP_CTER; 1. DR PDBsum; 1FBM; -. DR PDBsum; 1VDF; -. DR PDBsum; 6SF6; -. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Calcium; Cell adhesion; Disulfide bond; KW EGF-like domain; Extracellular matrix; Glycoprotein; Heparin-binding; KW Phosphoprotein; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..755 FT /note="Cartilage oligomeric matrix protein" FT /id="PRO_0000035859" FT DOMAIN 85..124 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 125..177 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 178..220 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 223..265 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REPEAT 266..298 FT /note="TSP type-3 1" FT REPEAT 299..334 FT /note="TSP type-3 2" FT REPEAT 335..357 FT /note="TSP type-3 3" FT REPEAT 358..393 FT /note="TSP type-3 4" FT REPEAT 394..416 FT /note="TSP type-3 5" FT REPEAT 417..454 FT /note="TSP type-3 6" FT REPEAT 455..490 FT /note="TSP type-3 7" FT REPEAT 491..526 FT /note="TSP type-3 8" FT DOMAIN 530..744 FT /note="TSP C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00635" FT REGION 21..84 FT /note="COMP N-terminal" FT REGION 295..501 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 525..755 FT /note="Mediates cell survival and induction of the IAP FT family of survival proteins" FT /evidence="ECO:0000250" FT COMPBIAS 332..344 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 350..365 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 412..424 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 456..465 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 394 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9R0G6" FT CARBOHYD 119 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 740 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 68 FT /note="Interchain (with C-71)" FT /evidence="ECO:0000269|PubMed:8864111, FT ECO:0007744|PDB:1FBM, ECO:0007744|PDB:1VDF" FT DISULFID 71 FT /note="Interchain (with C-68)" FT /evidence="ECO:0000269|PubMed:8864111, FT ECO:0007744|PDB:1FBM, ECO:0007744|PDB:1VDF" FT DISULFID 89..100 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 94..109 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 112..123 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 129..140 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 134..149 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 152..176 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 182..195 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 189..204 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 207..219 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 227..241 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 235..251 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 253..264 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 280..285 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 290..310 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 326..346 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 349..369 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 385..405 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 408..428 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 446..466 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 482..502 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 518..739 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT HELIX 30..66 FT /evidence="ECO:0007829|PDB:1VDF" FT TURN 69..71 FT /evidence="ECO:0007829|PDB:1FBM" SQ SEQUENCE 755 AA; 82664 MW; AB48888FE093C598 CRC64; MSPTACVLVL ALAALRATGQ GQIPLGGDLA PQMLRELQET NAALQDVREL LRHRVKEITF LKNTVMECDA CGMQPARTPG LSVRPVALCA PGSCFPGVVC TETATGARCG PCPPGYTGNG SHCTDVNECN AHPCFPRVRC INTSPGFHCE ACPPGFSGPT HEGVGLTFAK TNKQVCTDIN ECETGQHNCV PNSVCVNTRG SFQCGPCQPG FVGDQRSGCQ RRGQHFCPDG SPSPCHEKAD CILERDGSRS CVCAVGWAGN GLLCGRDTDL DGFPDEKLRC SERQCRKDNC VTVPNSGQED VDRDRIGDAC DPDADGDGVP NEQDNCPLVR NPDQRNSDKD KWGDACDNCR SQKNDDQKDT DRDGQGDACD DDIDGDRIRN VADNCPRVPN FDQSDSDGDG VGDACDNCPQ KDNPDQRDVD HDFVGDACDS DQDQDGDGHQ DSRDNCPTVP NSAQQDSDHD GKGDACDDDD DNDGVPDSRD NCRLVPNPGQ EDNDRDGVGD ACQGDFDADK VIDKIDVCPE NAEVTLTDFR AFQTVVLDPE GDAQIDPNWV VLNQGMEIVQ TMNSDPGLAV GYTAFNGVDF EGTFHVNTAT DDDYAGFIFG YQDSSSFYVV MWKQMEQTYW QANPFRAVAE PGIQLKAVKS STGPGEQLRN ALWHTGDTAS QVRLLWKDPR NVGWKDKTSY RWFLQHRPQV GYIRVRFYEG PELVADSNVV LDTAMRGGRL GVFCFSQENI IWANLRYRCN DTIPEDYERH RLRRA //