COMP_RAT
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 03-AUG-2022, entry version 156.
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 -!- SIMILARITY: Belongs to the thrombospondin family. {ECO:0000305}.
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DR EMBL; X72914; CAA51419.1; -; mRNA.
DR PIR; A44315; A44315.
DR RefSeq; NP_036966.1; NM_012834.1.
DR PDB; 1FBM; X-ray; 2.70 A; A/B/C/D/E=28-72.
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 PDBsum; 1FBM; -.
DR PDBsum; 1VDF; -.
DR PDBsum; 6SF6; -.
DR AlphaFoldDB; P35444; -.
DR SMR; P35444; -.
DR BioGRID; 247343; 2.
DR STRING; 10116.ENSRNOP00000067037; -.
DR GlyGen; P35444; 2 sites.
DR PaxDb; P35444; -.
DR PRIDE; P35444; -.
DR ABCD; P35444; 1 sequenced antibody.
DR GeneID; 25304; -.
DR KEGG; rno:25304; -.
DR CTD; 1311; -.
DR RGD; 2378; Comp.
DR eggNOG; ENOG502QRK8; Eukaryota.
DR InParanoid; P35444; -.
DR OrthoDB; 120983at2759; -.
DR PhylomeDB; P35444; -.
DR Reactome; R-RNO-216083; Integrin cell surface interactions.
DR Reactome; R-RNO-3000178; ECM proteoglycans.
DR EvolutionaryTrace; P35444; -.
DR PRO; PR:P35444; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
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: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:0010259; P:multicellular organism aging; 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; cd16077; TSP-5cc; 1.
DR Gene3D; 4.10.1080.10; -; 2.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR024665; Thbs/COMP_coiled-coil.
DR InterPro; IPR003367; Thrombospondin_3-like_rpt.
DR InterPro; IPR017897; Thrombospondin_3_rpt.
DR InterPro; IPR008859; Thrombospondin_C.
DR InterPro; IPR028492; TSP-5.
DR InterPro; IPR039081; TSP-5_cc.
DR InterPro; IPR028974; TSP_type-3_rpt.
DR PANTHER; PTHR10199:SF88; PTHR10199:SF88; 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; SSF103647; SSF103647; 3.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
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.
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 298..312
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..381
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..442
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"
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
