COMP_HUMAN
ID COMP_HUMAN Reviewed; 757 AA.
AC P49747; B4DKJ3; O14592; Q16388; Q16389; Q2NL86; Q8N4T2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Cartilage oligomeric matrix protein {ECO:0000305};
DE Short=COMP;
DE AltName: Full=Thrombospondin-5;
DE Short=TSP5;
DE Flags: Precursor;
GN Name=COMP {ECO:0000312|HGNC:HGNC:2227};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASP-50; TRP-51;
RP GLY-109; GLY-224 AND PRO-285.
RC TISSUE=Cartilage;
RX PubMed=7713493; DOI=10.1006/geno.1994.1649;
RA Newton G., Weremowicz S., Morton C.C., Copeland N.G., Gilbert D.J.,
RA Jenkins N.A., Lawler J.;
RT "Characterization of human and mouse cartilage oligomeric matrix protein.";
RL Genomics 24:435-439(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASP-50; TRP-51;
RP GLY-109; GLY-224 AND PRO-285.
RA Hashimoto Y., Mori H.;
RT "Human comp cDNA with 5 SNIPs.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 326-344, VARIANT EDM1 TYR-342, AND
RP VARIANT PSACH ARG-328.
RX PubMed=7670472; DOI=10.1038/ng0795-330;
RA Briggs M.D., Hoffman S.M.G., King L.M., Olsen A.S., Mohrenweiser H.,
RA Leroy J.G., Mortier G.R., Rimoin D.L., Lachman R.S., Gaines E.S.,
RA Cekleniak J.A., Knowlton R.G., Cohn D.H.;
RT "Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in
RT the cartilage oligomeric matrix protein gene.";
RL Nat. Genet. 10:330-336(1995).
RN [8]
RP PROTEIN SEQUENCE OF 80-89, SUBUNIT, CALCIUM-BINDING, AND CHARACTERIZATION
RP OF VARIANT PSACH ASP-469 DEL.
RX PubMed=10852928; DOI=10.1074/jbc.m909780199;
RA Chen H., Deere M., Hecht J.T., Lawler J.;
RT "Cartilage oligomeric matrix protein is a calcium-binding protein, and a
RT mutation in its type 3 repeats causes conformational changes.";
RL J. Biol. Chem. 275:26538-26544(2000).
RN [9]
RP PROTEIN SEQUENCE, CALCIUM-BINDING, INTERACTION WITH COLLAGEN I; COLLAGEN II
RP AND COLLAGEN IX, CHARACTERIZATION OF VARIANT PSACH ASP-469 DEL, AND
RP CHARACTERIZATION OF VARIANT EDM1 TYR-361.
RX PubMed=11084047; DOI=10.1074/jbc.m009512200;
RA Thur J., Rosenberg K., Nitsche D.P., Pihlajamaa T., Ala-Kokko L.,
RA Heinegaard D., Paulsson M., Maurer P.;
RT "Mutations in cartilage oligomeric matrix protein causing
RT pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of
RT calcium and collagen I, II, and IX.";
RL J. Biol. Chem. 276:6083-6092(2001).
RN [10]
RP INTERACTION WITH FN1.
RX PubMed=12225811; DOI=10.1016/s0945-053x(02)00015-x;
RA Di Cesare P.E., Chen F.S., Moergelin M., Carlson C.S., Leslie M.P.,
RA Perris R., Fang C.;
RT "Matrix-matrix interaction of cartilage oligomeric matrix protein and
RT fibronectin.";
RL Matrix Biol. 21:461-470(2002).
RN [11]
RP INTERACTION WITH MATN1; MATN3 AND MATN4.
RX PubMed=15075323; DOI=10.1074/jbc.m403778200;
RA Mann H.H., Oezbek S., Engel J., Paulsson M., Wagener R.;
RT "Interactions between the cartilage oligomeric matrix protein and
RT matrilins. Implications for matrix assembly and the pathogenesis of
RT chondrodysplasias.";
RL J. Biol. Chem. 279:25294-25298(2004).
RN [12]
RP FUNCTION, AND INTERACTION WITH ITGB3 AND ITGA5.
RX PubMed=16051604; DOI=10.1074/jbc.m504778200;
RA Chen F.-H., Thomas A.O., Hecht J.T., Goldring M.B., Lawler J.;
RT "Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte
RT attachment through interaction with integrins.";
RL J. Biol. Chem. 280:32655-32661(2005).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16542502; DOI=10.1186/ar1922;
RA Koelling S., Clauditz T.S., Kaste M., Miosge N.;
RT "Cartilage oligomeric matrix protein is involved in human limb development
RT and in the pathogenesis of osteoarthritis.";
RL Arthritis Res. Ther. 8:R56-R56(2006).
RN [14]
RP INTERACTION WITH ADAMTS12.
RX PubMed=16611630; DOI=10.1074/jbc.m513433200;
RA Liu C.-J., Kong W., Xu K., Luan Y., Ilalov K., Sehgal B., Yu S.,
RA Howell R.D., Di Cesare P.E.;
RT "ADAMTS-12 associates with and degrades cartilage oligomeric matrix
RT protein.";
RL J. Biol. Chem. 281:15800-15808(2006).
RN [15]
RP INTERACTION WITH ACAN; HEPARIN; HEPARAN SULFATE AND CHONDROITIN SULFATE.
RX PubMed=17588949; DOI=10.1074/jbc.m611390200;
RA Chen F.-H., Herndon M.E., Patel N., Hecht J.T., Tuan R.S., Lawler J.;
RT "Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with
RT aggrecan.";
RL J. Biol. Chem. 282:24591-24598(2007).
RN [16]
RP FUNCTION, AND DOMAINS.
RX PubMed=17993464; DOI=10.1074/jbc.m704035200;
RA Gagarina V., Carlberg A.L., Pereira-Mouries L., Hall D.J.;
RT "Cartilage oligomeric matrix protein protects cells against death by
RT elevating members of the IAP family of survival proteins.";
RL J. Biol. Chem. 283:648-659(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.15 ANGSTROMS) OF 225-757 IN COMPLEX WITH CALCIUM
RP IONS, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-742.
RX PubMed=19276170; DOI=10.1096/fj.08-128090;
RA Tan K., Duquette M., Joachimiak A., Lawler J.;
RT "The crystal structure of the signature domain of cartilage oligomeric
RT matrix protein: implications for collagen, glycosaminoglycan and integrin
RT binding.";
RL FASEB J. 23:2490-2501(2009).
RN [19]
RP VARIANTS PSACH SER-459 DEL; TYR-468 AND TYR-472.
RX PubMed=7670471; DOI=10.1038/ng0795-325;
RA Hecht J.T., Nelson L.D., Crowder E., Wang Y., Elder F.F.B., Harrison W.R.,
RA Francomano C.A., Prange C.K., Lennon G.G., Deere M., Lawler J.;
RT "Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause
RT pseudoachondroplasia.";
RL Nat. Genet. 10:325-329(1995).
RN [20]
RP VARIANT EDM1 LYS-523.
RX PubMed=9021009;
RX DOI=10.1002/(sici)1096-8628(19970211)68:4<396::aid-ajmg4>3.0.co;2-k;
RA Ballo R., Briggs M.D., Cohn D.H., Knowlton R.G., Beighton P.H.,
RA Ramesar R.S.;
RT "Multiple epiphyseal dysplasia, ribbing type: a novel point mutation in the
RT COMP gene in a South African family.";
RL Am. J. Med. Genet. 68:396-400(1997).
RN [21]
RP VARIANT EDM1 SER-371, AND VARIANT PSACH 513-VAL--LYS-516 DEL.
RX PubMed=9184241; DOI=10.1111/j.1399-0004.1997.tb02458.x;
RA Susic S., McGrory J., Ahier J., Cole W.G.;
RT "Multiple epiphyseal dysplasia and pseudoachondroplasia due to novel
RT mutations in the calmodulin-like repeats of cartilage oligomeric matrix
RT protein.";
RL Clin. Genet. 51:219-224(1997).
RN [22]
RP VARIANTS PSACH, AND VARIANTS EDM1 SER-453 AND ARG-585.
RX PubMed=9463320; DOI=10.1086/301713;
RA Briggs M.D., Mortier G.R., Cole W.G., King L.M., Golik S.S.,
RA Bonaventure J., Nuytinck L., de Paepe A., Leroy J.G., Biesecker L.,
RA Lipson M., Wilcox W.R., Lachman R.S., Rimoin D.L., Knowlton R.G.,
RA Cohn D.H.;
RT "Diverse mutations in the gene for cartilage oligomeric matrix protein in
RT the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.";
RL Am. J. Hum. Genet. 62:311-319(1998).
RN [23]
RP VARIANTS PSACH AND EDM1.
RX PubMed=9921895; DOI=10.1007/s004390050883;
RA Ikegawa S., Ohashi H., Nishimura G., Kim K.C., Sannohe A., Kimizuka M.,
RA Fukushima Y., Nagai T., Nakamura Y.;
RT "Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations
RT in pseudoachondroplasia and multiple epiphyseal dysplasia.";
RL Hum. Genet. 103:633-638(1998).
RN [24]
RP VARIANTS PSACH ARG-328; ASP-372 DEL; 391-PRO--ASP-394 DELINS VAL; ARG-440;
RP SER-459 DEL; TYR-468; ASP-469 DEL AND TYR-472, AND VARIANTS EDM1 TYR-342;
RP TYR-361; 367-ARG-GLY-368 DEL AND TYR-408.
RX PubMed=9452026; DOI=10.1002/humu.1380110105;
RA Loughlin J., Irven C., Mustafa Z., Briggs M.D., Carr A., Lynch S.-A.,
RA Knowlton R.G., Cohn D.H., Sykes B.;
RT "Identification of five novel mutations in cartilage oligomeric matrix
RT protein gene in pseudoachondroplasia and multiple epiphyseal dysplasia.";
RL Hum. Mutat. Suppl. 1:S10-S17(1998).
RN [25]
RP VARIANT PSACH GLY-482.
RX PubMed=9452063; DOI=10.1002/humu.1380110142;
RA Susic S., Ahier J., Cole W.G.;
RT "Pseudoachondroplasia due to the substitution of the highly conserved
RT Asp482 by Gly in the seventh calmodulin-like repeat of cartilage oligomeric
RT matrix protein.";
RL Hum. Mutat. Suppl. 1:S125-S127(1998).
RN [26]
RP VARIANT PSACH ARG-348.
RX PubMed=11746045; DOI=10.1002/ajmg.10062;
RA Unger S., Koerkkoe J., Krakow D., Lachman R.S., Rimoin D.L., Cohn D.H.;
RT "Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal
RT dysplasia congenita.";
RL Am. J. Med. Genet. 104:140-146(2001).
RN [27]
RP VARIANT PSACH ASP-719.
RX PubMed=11746044; DOI=10.1002/ajmg.10067;
RA Mabuchi A., Haga N., Ikeda T., Manabe N., Ohashi H., Takatori Y.,
RA Nakamura K., Ikegawa S.;
RT "Novel mutation in exon 18 of the cartilage oligomeric matrix protein gene
RT causes a severe pseudoachondroplasia.";
RL Am. J. Med. Genet. 104:135-139(2001).
RN [28]
RP VARIANTS EDM1 ARG-276; ALA-420 AND MET-585.
RX PubMed=11565064; DOI=10.1086/324023;
RA Czarny-Ratajczak M., Lohiniva J., Rogala P., Kozlowski K., Peraelae M.,
RA Carter L., Spector T.D., Kolodziej L., Seppaenen U., Glazar R.,
RA Krolewski J., Latos-Bielenska A., Ala-Kokko L.;
RT "A mutation in COL9A1 causes multiple epiphyseal dysplasia: further
RT evidence for locus heterogeneity.";
RL Am. J. Hum. Genet. 69:969-980(2001).
RN [29]
RP VARIANTS PSACH SER-234; GLY-290; ARG-299; TYR-326; 341-GLU-ASP-342 DEL;
RP 350-ASN--ASP-372 DEL; VAL-378; ARG-387; 402-GLY--GLY-404 DELINS VAL-CYS;
RP ARG-440; ASN-446; SER-448; ASP-473 DEL; HIS-473; ASN-475; GLY-482; GLY-507;
RP GLY-511; GLY-515; ILE-529; ARG-585 AND SER-719, VARIANTS EDM1 GLU-167;
RP ARG-276; LEU-298; ASP-311; GLY-317; GLY-326; PHE-348; SER-371; TYR-371;
RP ASN-374; ASN-376; ASN-385; ASP-385 DEL; TYR-385; HIS-397; ARG-404; TYR-410;
RP LYS-415; GLU-427; 430-CYS--SER-432 DELINS LEU-TRP-CYS; GLU-457 DEL; ASP-473
RP INS; ASP-501; LYS-523; MET-585; PRO-718 AND TRP-718, AND VARIANT ARG-756.
RX PubMed=21922596; DOI=10.1002/humu.21611;
RA Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J.,
RA Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A.,
RA Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R.,
RA Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D.;
RT "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year
RT comprehensive analysis of the known disease genes identify novel and
RT recurrent mutations and provides an accurate assessment of their relative
RT contribution.";
RL Hum. Mutat. 33:144-157(2012).
RN [30]
RP VARIANTS CTS2 GLU-66 AND TRP-718, CHARACTERIZATION OF VARIANTS CTS2 GLU-66
RP AND TRP-718, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=32686688; DOI=10.1038/s41467-020-17378-z;
RA Li C., Wang N., Schaeffer A.A., Liu X., Zhao Z., Elliott G., Garrett L.,
RA Choi N.T., Wang Y., Wang Y., Wang C., Wang J., Chan D., Su P., Cui S.,
RA Yang Y., Gao B.;
RT "Mutations in COMP cause familial carpal tunnel syndrome.";
RL Nat. Commun. 11:3642-3642(2020).
RN [31]
RP ERRATUM OF PUBMED:32747625.
RX PubMed=32747625; DOI=10.1038/s41467-020-17845-7;
RA Li C., Wang N., Schaeffer A.A., Liu X., Zhao Z., Elliott G., Garrett L.,
RA Choi N.T., Wang Y., Wang Y., Wang C., Wang J., Chan D., Su P., Cui S.,
RA Yang Y., Gao B.;
RT "Author Correction: Mutations in COMP cause familial carpal tunnel
RT syndrome.";
RL Nat. Commun. 11:3931-3931(2020).
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 (PubMed:16542502, PubMed:16051604). Could
CC play a role in the pathogenesis of osteoarthritis (PubMed:16542502).
CC Potent suppressor of apoptosis in both primary chondrocytes and
CC transformed cells. Suppresses apoptosis by blocking the activation of
CC caspase-3 and by inducing the IAP family of survival proteins (BIRC3,
CC BIRC2, BIRC5 and XIAP) (PubMed:17993464). Essential for maintaining a
CC vascular smooth muscle cells (VSMCs) contractile/differentiated
CC phenotype under physiological and pathological stimuli. Maintains this
CC phenotype of VSMCs by interacting with ITGA7 (By similarity).
CC {ECO:0000250|UniProtKB:P35444, ECO:0000269|PubMed:16051604,
CC ECO:0000269|PubMed:16542502, ECO:0000269|PubMed:17993464}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:10852928, ECO:0000269|PubMed:11084047,
CC ECO:0000269|PubMed:19276170};
CC Note=Binds 11-14 calcium ions per subunit.
CC {ECO:0000269|PubMed:19276170};
CC -!- SUBUNIT: Pentamer; disulfide-linked (PubMed:32686688). Exists in a more
CC compact conformation in the presence of calcium and shows a more
CC extended conformation in the absence of calcium (PubMed:19276170).
CC Interacts with ITGB3, ITGA5 and FN1. Binding to FN1 requires the
CC presence of divalent cations (Ca(2+), Mg(2+) or Mn(2+)). The greatest
CC amount of binding is seen in the presence of Mn(2+) (PubMed:16051604,
CC PubMed:12225811). Interacts with MATN1, MATN3, MATN4 and ACAN
CC (PubMed:15075323, PubMed:17588949). Binds heparin, heparan sulfate and
CC chondroitin sulfate. EDTA dimishes significantly its binding to ACAN
CC and abolishes its binding to MATN3, MATN4 and chondroitin sulfate
CC (PubMed:17588949). Interacts with collagen I, II and IX, and
CC interaction with these collagens is dependent on the presence of zinc
CC ions (PubMed:11084047). Interacts with ADAMTS12 (PubMed:16611630).
CC Interacts with ITGA7 (By similarity). {ECO:0000250|UniProtKB:P35444,
CC ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:12225811,
CC ECO:0000269|PubMed:15075323, ECO:0000269|PubMed:16051604,
CC ECO:0000269|PubMed:16611630, ECO:0000269|PubMed:17588949,
CC ECO:0000269|PubMed:19276170, ECO:0000269|PubMed:32686688}.
CC -!- INTERACTION:
CC P49747; P58397: ADAMTS12; NbExp=3; IntAct=EBI-2531022, EBI-9028051;
CC P49747; P29972: AQP1; NbExp=3; IntAct=EBI-2531022, EBI-745213;
CC P49747; O00244: ATOX1; NbExp=3; IntAct=EBI-2531022, EBI-10179267;
CC P49747; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2531022, EBI-3867333;
CC P49747; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2531022, EBI-16439278;
CC P49747; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-2531022, EBI-1210753;
CC P49747; P32242: OTX1; NbExp=7; IntAct=EBI-2531022, EBI-740446;
CC P49747; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-2531022, EBI-744081;
CC P49747; P13608: ACAN; Xeno; NbExp=2; IntAct=EBI-2531022, EBI-6259246;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:32686688}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49747-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49747-2; Sequence=VSP_055758;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in the chondrocyte
CC extracellular matrix, and is also found in bone, tendon, ligament and
CC synovium and blood vessels. Increased amounts are produced during late
CC stages of osteoarthritis in the area adjacent to the main defect.
CC {ECO:0000269|PubMed:16542502, ECO:0000269|PubMed:32686688}.
CC -!- DEVELOPMENTAL STAGE: Present during the earliest stages of limb
CC maturation and is later found in regions where the joints develop.
CC {ECO:0000269|PubMed:16542502}.
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:0000269|PubMed:17993464}.
CC -!- DOMAIN: The TSP C-terminal domain mediates interaction with FN1 and
CC ACAN. {ECO:0000269|PubMed:17993464}.
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:0000269|PubMed:17993464}.
CC -!- DISEASE: Multiple epiphyseal dysplasia 1 (EDM1) [MIM:132400]: A
CC generalized skeletal dysplasia associated with significant morbidity.
CC Joint pain, joint deformity, waddling gait, and short stature are the
CC main clinical signs and symptoms. Radiological examination of the
CC skeleton shows delayed, irregular mineralization of the epiphyseal
CC ossification centers and of the centers of the carpal and tarsal bones.
CC Multiple epiphyseal dysplasia is broadly categorized into the more
CC severe Fairbank and the milder Ribbing types. The Fairbank type is
CC characterized by shortness of stature, short and stubby fingers, small
CC epiphyses in several joints, including the knee, ankle, hand, and hip.
CC The Ribbing type is confined predominantly to the hip joints and is
CC characterized by hands that are normal and stature that is normal or
CC near-normal. {ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:11565064,
CC ECO:0000269|PubMed:21922596, ECO:0000269|PubMed:7670472,
CC ECO:0000269|PubMed:9021009, ECO:0000269|PubMed:9184241,
CC ECO:0000269|PubMed:9452026, ECO:0000269|PubMed:9463320,
CC ECO:0000269|PubMed:9921895}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Pseudoachondroplasia (PSACH) [MIM:177170]: A skeletal
CC dysplasia usually manifesting in the second year of life and
CC characterized by moderate to severe disproportionate short stature,
CC deformity of the lower limbs, brachydactyly, ligamentous laxity, and
CC degenerative joint disease. {ECO:0000269|PubMed:10852928,
CC ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:11746044,
CC ECO:0000269|PubMed:11746045, ECO:0000269|PubMed:21922596,
CC ECO:0000269|PubMed:7670471, ECO:0000269|PubMed:7670472,
CC ECO:0000269|PubMed:9184241, ECO:0000269|PubMed:9452026,
CC ECO:0000269|PubMed:9452063, ECO:0000269|PubMed:9463320,
CC ECO:0000269|PubMed:9921895}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Carpal tunnel syndrome 2 (CTS2) [MIM:619161]: An autosomal
CC dominant form of carpal tunnel syndrome, a condition characterized by
CC entrapment of the median nerve within the carpal tunnel. Symptoms
CC include burning pain and paresthesias involving the ventral surface of
CC the hand and fingers which may radiate proximally. Impairment of
CC sensation in the distribution of the median nerve and thenar muscle
CC atrophy may occur. This condition may be associated with repetitive
CC occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid
CC arthritis. {ECO:0000269|PubMed:32686688}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the thrombospondin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB86501.1; Type=Erroneous gene model prediction; Evidence={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; L32137; AAA57253.1; -; mRNA.
DR EMBL; AB086984; BAC53888.1; -; mRNA.
DR EMBL; AK296586; BAG59205.1; -; mRNA.
DR EMBL; AC003107; AAB86501.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471106; EAW84737.1; -; Genomic_DNA.
DR EMBL; BC110847; AAI10848.1; -; mRNA.
DR EMBL; BC125092; AAI25093.1; -; mRNA.
DR EMBL; S79499; AAB35269.1; -; Genomic_DNA.
DR EMBL; S79500; AAB35270.1; -; Genomic_DNA.
DR CCDS; CCDS12385.1; -. [P49747-1]
DR RefSeq; NP_000086.2; NM_000095.2. [P49747-1]
DR PDB; 3FBY; X-ray; 3.15 A; A/B/C=225-757.
DR PDBsum; 3FBY; -.
DR AlphaFoldDB; P49747; -.
DR SMR; P49747; -.
DR BioGRID; 107706; 12.
DR ComplexPortal; CPX-1791; Thrombospondin 5 complex.
DR IntAct; P49747; 18.
DR STRING; 9606.ENSP00000222271; -.
DR DrugBank; DB01373; Calcium.
DR GlyConnect; 1076; 7 N-Linked glycans (2 sites).
DR GlyGen; P49747; 2 sites, 8 N-linked glycans (2 sites).
DR iPTMnet; P49747; -.
DR PhosphoSitePlus; P49747; -.
DR BioMuta; COMP; -.
DR DMDM; 209572601; -.
DR jPOST; P49747; -.
DR MassIVE; P49747; -.
DR PaxDb; P49747; -.
DR PeptideAtlas; P49747; -.
DR PRIDE; P49747; -.
DR ProteomicsDB; 4464; -.
DR ProteomicsDB; 56060; -. [P49747-1]
DR Antibodypedia; 15160; 398 antibodies from 30 providers.
DR DNASU; 1311; -.
DR Ensembl; ENST00000222271.7; ENSP00000222271.2; ENSG00000105664.11. [P49747-1]
DR Ensembl; ENST00000425807.1; ENSP00000403792.1; ENSG00000105664.11. [P49747-2]
DR GeneID; 1311; -.
DR KEGG; hsa:1311; -.
DR MANE-Select; ENST00000222271.7; ENSP00000222271.2; NM_000095.3; NP_000086.2.
DR UCSC; uc002nke.4; human. [P49747-1]
DR CTD; 1311; -.
DR DisGeNET; 1311; -.
DR GeneCards; COMP; -.
DR GeneReviews; COMP; -.
DR HGNC; HGNC:2227; COMP.
DR HPA; ENSG00000105664; Tissue enhanced (adipose tissue, skin).
DR MalaCards; COMP; -.
DR MIM; 132400; phenotype.
DR MIM; 177170; phenotype.
DR MIM; 600310; gene.
DR MIM; 619161; phenotype.
DR neXtProt; NX_P49747; -.
DR OpenTargets; ENSG00000105664; -.
DR Orphanet; 93308; Multiple epiphyseal dysplasia type 1.
DR Orphanet; 750; Pseudoachondroplasia.
DR PharmGKB; PA26744; -.
DR VEuPathDB; HostDB:ENSG00000105664; -.
DR eggNOG; ENOG502QRK8; Eukaryota.
DR GeneTree; ENSGT00940000162169; -.
DR InParanoid; P49747; -.
DR OMA; RSQRFCP; -.
DR OrthoDB; 120983at2759; -.
DR PhylomeDB; P49747; -.
DR TreeFam; TF324917; -.
DR PathwayCommons; P49747; -.
DR Reactome; R-HSA-216083; Integrin cell surface interactions.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR SignaLink; P49747; -.
DR BioGRID-ORCS; 1311; 12 hits in 1066 CRISPR screens.
DR ChiTaRS; COMP; human.
DR EvolutionaryTrace; P49747; -.
DR GeneWiki; Cartilage_oligomeric_matrix_protein; -.
DR GenomeRNAi; 1311; -.
DR Pharos; P49747; Tbio.
DR PRO; PR:P49747; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P49747; protein.
DR Bgee; ENSG00000105664; Expressed in tibia and 135 other tissues.
DR ExpressionAtlas; P49747; baseline and differential.
DR Genevisible; P49747; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0036122; F:BMP binding; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB.
DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:ProtInc.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IEA:Ensembl.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0043394; F:proteoglycan binding; IDA:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:1990079; P:cartilage homeostasis; IDA:UniProtKB.
DR GO; GO:0002063; P:chondrocyte development; IEA:Ensembl.
DR GO; GO:0035988; P:chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0003417; P:growth plate cartilage development; IEA:Ensembl.
DR GO; GO:0060173; P:limb development; IDA:UniProtKB.
DR GO; GO:0010259; P:multicellular organism aging; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0050881; P:musculoskeletal movement; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:1900047; P:negative regulation of hemostasis; IEA:Ensembl.
DR GO; GO:0070527; P:platelet aggregation; IEA:Ensembl.
DR GO; GO:1902732; P:positive regulation of chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IEA:Ensembl.
DR GO; GO:0009306; P:protein secretion; IEA:Ensembl.
DR GO; GO:0030500; P:regulation of bone mineralization; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0043588; P:skin development; IEA:Ensembl.
DR GO; GO:0035989; P:tendon development; IEA:Ensembl.
DR GO; GO:0097084; P:vascular associated smooth muscle cell development; IEA:Ensembl.
DR GO; GO:0014829; P:vascular associated smooth muscle contraction; IEA:Ensembl.
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; 5.
DR Pfam; PF05735; TSP_C; 1.
DR SMART; SM00181; EGF; 4.
DR SMART; SM00179; EGF_CA; 3.
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; Alternative splicing; Apoptosis; Calcium; Cell adhesion;
KW Direct protein sequencing; Disease variant; Disulfide bond; Dwarfism;
KW EGF-like domain; Extracellular matrix; Glycoprotein; Heparin-binding;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..757
FT /note="Cartilage oligomeric matrix protein"
FT /id="PRO_0000035857"
FT DOMAIN 87..126
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 127..179
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 180..222
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 225..267
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 268..300
FT /note="TSP type-3 1"
FT REPEAT 301..336
FT /note="TSP type-3 2"
FT REPEAT 337..359
FT /note="TSP type-3 3"
FT REPEAT 360..395
FT /note="TSP type-3 4"
FT REPEAT 396..418
FT /note="TSP type-3 5"
FT REPEAT 419..456
FT /note="TSP type-3 6"
FT REPEAT 457..492
FT /note="TSP type-3 7"
FT REPEAT 493..528
FT /note="TSP type-3 8"
FT DOMAIN 532..746
FT /note="TSP C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00635"
FT REGION 22..86
FT /note="COMP N-terminal"
FT REGION 298..503
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 527..757
FT /note="Mediates cell survival and induction of the IAP
FT family of survival proteins"
FT MOTIF 367..369
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 303..322
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 335..383
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..444
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..477
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 742
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19276170"
FT DISULFID 69
FT /note="Interchain"
FT /evidence="ECO:0000305|PubMed:19276170"
FT DISULFID 72
FT /note="Interchain"
FT /evidence="ECO:0000305|PubMed:19276170"
FT DISULFID 91..102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 96..111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 114..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 131..142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 136..151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 154..178
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 184..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 191..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 209..221
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 229..243
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 237..253
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 255..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 282..287
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 292..312
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 328..348
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 351..371
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 387..407
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 410..430
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 448..468
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 484..504
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT DISULFID 520..741
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:19276170"
FT VAR_SEQ 129..181
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055758"
FT VARIANT 50
FT /note="E -> D"
FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2"
FT /id="VAR_016254"
FT VARIANT 51
FT /note="L -> W"
FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2"
FT /id="VAR_016255"
FT VARIANT 66
FT /note="V -> E (in CTS2; reduced secretion in tendon cells;
FT no effect on secretion in chondrocytes; disrupted
FT pentamerization; induced ER stress)"
FT /evidence="ECO:0000269|PubMed:32686688"
FT /id="VAR_085230"
FT VARIANT 109
FT /note="A -> G"
FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2"
FT /id="VAR_016257"
FT VARIANT 167
FT /note="G -> E (in EDM1; dbSNP:rs763887855)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066789"
FT VARIANT 224
FT /note="R -> G"
FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2"
FT /id="VAR_016258"
FT VARIANT 234
FT /note="P -> S (in PSACH; dbSNP:rs557483957)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066790"
FT VARIANT 276
FT /note="P -> R (in EDM1; dbSNP:rs1311845746)"
FT /evidence="ECO:0000269|PubMed:11565064,
FT ECO:0000269|PubMed:21922596"
FT /id="VAR_026239"
FT VARIANT 285
FT /note="R -> P"
FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2"
FT /id="VAR_016261"
FT VARIANT 290
FT /note="D -> G (in PSACH; dbSNP:rs1568556118)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066791"
FT VARIANT 290
FT /note="D -> N (in PSACH; mild form)"
FT /id="VAR_007614"
FT VARIANT 298
FT /note="S -> L (in EDM1; phenotypic features overlapping
FT with mild PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066792"
FT VARIANT 299
FT /note="G -> R (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_007615"
FT VARIANT 311
FT /note="A -> D (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066793"
FT VARIANT 317
FT /note="D -> G (in EDM1; atypical form)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066794"
FT VARIANT 326
FT /note="D -> G (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066795"
FT VARIANT 326
FT /note="D -> Y (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066796"
FT VARIANT 328
FT /note="C -> R (in PSACH; mild form; dbSNP:rs137852653)"
FT /evidence="ECO:0000269|PubMed:7670472,
FT ECO:0000269|PubMed:9452026"
FT /id="VAR_007616"
FT VARIANT 341..342
FT /note="Missing (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066797"
FT VARIANT 342
FT /note="D -> Y (in EDM1; Fairbank type; dbSNP:rs137852652)"
FT /evidence="ECO:0000269|PubMed:7670472,
FT ECO:0000269|PubMed:9452026"
FT /id="VAR_007617"
FT VARIANT 348
FT /note="C -> F (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066798"
FT VARIANT 348
FT /note="C -> R (in PSACH; dbSNP:rs137852656)"
FT /evidence="ECO:0000269|PubMed:11746045"
FT /id="VAR_017102"
FT VARIANT 349
FT /note="D -> V (in PSACH; mild form)"
FT /id="VAR_007618"
FT VARIANT 350..372
FT /note="Missing (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066799"
FT VARIANT 361
FT /note="D -> V (in EDM1; Fairbank type)"
FT /id="VAR_007619"
FT VARIANT 361
FT /note="D -> Y (in EDM1; binds less calcium)"
FT /evidence="ECO:0000269|PubMed:11084047,
FT ECO:0000269|PubMed:9452026"
FT /id="VAR_007620"
FT VARIANT 367..368
FT /note="Missing (in EDM1)"
FT /evidence="ECO:0000269|PubMed:9452026"
FT /id="VAR_007621"
FT VARIANT 371
FT /note="C -> S (in EDM1; Fairbank type)"
FT /evidence="ECO:0000269|PubMed:21922596,
FT ECO:0000269|PubMed:9184241"
FT /id="VAR_007622"
FT VARIANT 371
FT /note="C -> Y (in EDM1; dbSNP:rs1057521130)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066800"
FT VARIANT 372
FT /note="Missing (in PSACH)"
FT /evidence="ECO:0000269|PubMed:9452026"
FT /id="VAR_007623"
FT VARIANT 374
FT /note="D -> N (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066801"
FT VARIANT 374
FT /note="Missing (in PSACH; mild form)"
FT /id="VAR_007624"
FT VARIANT 376
FT /note="D -> N (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066802"
FT VARIANT 378
FT /note="D -> V (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066803"
FT VARIANT 381
FT /note="R -> C (in dbSNP:rs3179763)"
FT /id="VAR_046796"
FT VARIANT 385
FT /note="D -> N (in EDM1; atypical form)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066804"
FT VARIANT 385
FT /note="D -> Y (in EDM1; atypical form; dbSNP:rs1601054715)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066805"
FT VARIANT 385
FT /note="Missing (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066806"
FT VARIANT 387
FT /note="C -> G (in PSACH; mild form)"
FT /id="VAR_007625"
FT VARIANT 387
FT /note="C -> R (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066807"
FT VARIANT 391..394
FT /note="PNSD -> V (in PSACH)"
FT /evidence="ECO:0000269|PubMed:9452026"
FT /id="VAR_007626"
FT VARIANT 397
FT /note="D -> H (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066808"
FT VARIANT 402..404
FT /note="GIG -> VC (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066809"
FT VARIANT 404
FT /note="G -> R (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066810"
FT VARIANT 408
FT /note="D -> Y (in EDM1)"
FT /evidence="ECO:0000269|PubMed:9452026"
FT /id="VAR_007627"
FT VARIANT 410
FT /note="C -> Y (in EDM1; phenotype overlapping with mild
FT PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066811"
FT VARIANT 415
FT /note="N -> K (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066812"
FT VARIANT 420
FT /note="D -> A (in EDM1)"
FT /evidence="ECO:0000269|PubMed:11565064"
FT /id="VAR_026240"
FT VARIANT 427
FT /note="G -> E (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066813"
FT VARIANT 430..432
FT /note="CDS -> LWC (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066814"
FT VARIANT 440
FT /note="G -> E (in PSACH; mild form)"
FT /id="VAR_007628"
FT VARIANT 440
FT /note="G -> R (in PSACH; dbSNP:rs1601053997)"
FT /evidence="ECO:0000269|PubMed:21922596,
FT ECO:0000269|PubMed:9452026"
FT /id="VAR_007629"
FT VARIANT 446
FT /note="D -> N (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066815"
FT VARIANT 448
FT /note="C -> S (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066816"
FT VARIANT 453
FT /note="N -> S (in EDM1; Fairbank type; dbSNP:rs28936668)"
FT /evidence="ECO:0000269|PubMed:9463320"
FT /id="VAR_007630"
FT VARIANT 457
FT /note="Missing (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066817"
FT VARIANT 459
FT /note="Missing (in PSACH; severe form)"
FT /evidence="ECO:0000269|PubMed:7670471,
FT ECO:0000269|PubMed:9452026"
FT /id="VAR_007631"
FT VARIANT 468
FT /note="C -> Y (in PSACH; severe form; dbSNP:rs137852651)"
FT /evidence="ECO:0000269|PubMed:7670471,
FT ECO:0000269|PubMed:9452026"
FT /id="VAR_007632"
FT VARIANT 469
FT /note="Missing (in PSACH; severe form; MUT3 mutant; most
FT common mutation; binds less calcium and causes misfolding
FT of the protein; greatly reduced interaction with ACAN;
FT reduced interaction with collagen)"
FT /evidence="ECO:0000269|PubMed:10852928,
FT ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:9452026"
FT /id="VAR_007633"
FT VARIANT 472
FT /note="D -> Y (in PSACH; severe form; dbSNP:rs137852650)"
FT /evidence="ECO:0000269|PubMed:7670471,
FT ECO:0000269|PubMed:9452026"
FT /id="VAR_007634"
FT VARIANT 473
FT /note="D -> DD (in EDM1)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066818"
FT VARIANT 473
FT /note="D -> G (in PSACH; severe form; dbSNP:rs28936669)"
FT /id="VAR_007635"
FT VARIANT 473
FT /note="D -> H (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066819"
FT VARIANT 473
FT /note="Missing (in PSACH; severe form; dbSNP:rs193922900)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_007636"
FT VARIANT 475
FT /note="D -> N (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066820"
FT VARIANT 482
FT /note="D -> G (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596,
FT ECO:0000269|PubMed:9452063"
FT /id="VAR_007637"
FT VARIANT 501
FT /note="G -> D (in EDM1; dbSNP:rs1555791425)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066821"
FT VARIANT 507
FT /note="D -> G (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066822"
FT VARIANT 511
FT /note="D -> G (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066823"
FT VARIANT 513..516
FT /note="Missing (in PSACH; mild form)"
FT /evidence="ECO:0000269|PubMed:9184241"
FT /id="VAR_007638"
FT VARIANT 515
FT /note="D -> G (in PSACH)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066824"
FT VARIANT 518
FT /note="D -> N (in PSACH; mild form; dbSNP:rs1359984033)"
FT /id="VAR_007639"
FT VARIANT 523
FT /note="N -> K (in EDM1; Ribbing type; dbSNP:rs137852654)"
FT /evidence="ECO:0000269|PubMed:21922596,
FT ECO:0000269|PubMed:9021009"
FT /id="VAR_007640"
FT VARIANT 529
FT /note="T -> I (in PSACH; dbSNP:rs312262903)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066825"
FT VARIANT 585
FT /note="T -> M (in PSACH; mild form and EDM1;
FT dbSNP:rs312262900)"
FT /evidence="ECO:0000269|PubMed:11565064,
FT ECO:0000269|PubMed:21922596"
FT /id="VAR_007641"
FT VARIANT 585
FT /note="T -> R (in EDM1 and PSACH; dbSNP:rs312262900)"
FT /evidence="ECO:0000269|PubMed:21922596,
FT ECO:0000269|PubMed:9463320"
FT /id="VAR_007642"
FT VARIANT 718
FT /note="R -> P (in EDM1; dbSNP:rs149551600)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066826"
FT VARIANT 718
FT /note="R -> W (in EDM1 and CTS2; reduced secretion in
FT tendon cells and chondrocytes; dbSNP:rs28936368)"
FT /evidence="ECO:0000269|PubMed:21922596,
FT ECO:0000269|PubMed:32686688"
FT /id="VAR_066827"
FT VARIANT 719
FT /note="G -> D (in PSACH; severe; dbSNP:rs137852655)"
FT /evidence="ECO:0000269|PubMed:11746044"
FT /id="VAR_017103"
FT VARIANT 719
FT /note="G -> S (in PSACH; dbSNP:rs312262904)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066828"
FT VARIANT 756
FT /note="Q -> R (in a patient with multiple epiphyseal
FT dysplasia; dbSNP:rs61752496)"
FT /evidence="ECO:0000269|PubMed:21922596"
FT /id="VAR_066829"
FT CONFLICT 256
FT /note="A -> R (in Ref. 1; AAA57253 and 2; BAC53888)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="D -> Y (in Ref. 7; AAB35270)"
FT /evidence="ECO:0000305"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 259..265
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 291..295
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:3FBY"
FT TURN 314..317
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 364..367
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 369..371
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 405..407
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:3FBY"
FT TURN 428..430
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 443..445
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 462..464
FT /evidence="ECO:0007829|PDB:3FBY"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 470..473
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 495..500
FT /evidence="ECO:0007829|PDB:3FBY"
FT TURN 503..506
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 511..513
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 515..517
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 532..540
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 551..553
FT /evidence="ECO:0007829|PDB:3FBY"
FT TURN 555..557
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 560..562
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 567..588
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 596..605
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 608..617
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 625..627
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 636..641
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 648..655
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 656..658
FT /evidence="ECO:0007829|PDB:3FBY"
FT TURN 661..663
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 664..669
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 681..689
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 690..692
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 694..701
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 704..708
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 716..728
FT /evidence="ECO:0007829|PDB:3FBY"
FT STRAND 732..741
FT /evidence="ECO:0007829|PDB:3FBY"
FT HELIX 748..754
FT /evidence="ECO:0007829|PDB:3FBY"
SQ SEQUENCE 757 AA; 82860 MW; A0B73AADB39FBC7B CRC64;
MVPDTACVLL LTLAALGASG QGQSPLGSDL GPQMLRELQE TNAALQDVRE LLRQQVREIT
FLKNTVMECD ACGMQQSVRT GLPSVRPLLH CAPGFCFPGV ACIQTESGAR CGPCPAGFTG
NGSHCTDVNE CNAHPCFPRV RCINTSPGFR CEACPPGYSG PTHQGVGLAF AKANKQVCTD
INECETGQHN CVPNSVCINT RGSFQCGPCQ PGFVGDQASG CQRRAQRFCP DGSPSECHEH
ADCVLERDGS RSCVCAVGWA GNGILCGRDT DLDGFPDEKL RCPERQCRKD NCVTVPNSGQ
EDVDRDGIGD ACDPDADGDG VPNEKDNCPL VRNPDQRNTD EDKWGDACDN CRSQKNDDQK
DTDQDGRGDA CDDDIDGDRI RNQADNCPRV PNSDQKDSDG DGIGDACDNC PQKSNPDQAD
VDHDFVGDAC DSDQDQDGDG HQDSRDNCPT VPNSAQEDSD HDGQGDACDD DDDNDGVPDS
RDNCRLVPNP GQEDADRDGV GDVCQDDFDA DKVVDKIDVC PENAEVTLTD FRAFQTVVLD
PEGDAQIDPN WVVLNQGREI VQTMNSDPGL AVGYTAFNGV DFEGTFHVNT VTDDDYAGFI
FGYQDSSSFY VVMWKQMEQT YWQANPFRAV AEPGIQLKAV KSSTGPGEQL RNALWHTGDT
ESQVRLLWKD PRNVGWKDKK SYRWFLQHRP QVGYIRVRFY EGPELVADSN VVLDTTMRGG
RLGVFCFSQE NIIWANLRYR CNDTIPEDYE THQLRQA
