CO9A3_HUMAN
ID CO9A3_HUMAN Reviewed; 684 AA.
AC Q14050; Q13681; Q9H4G9; Q9UPE2;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Collagen alpha-3(IX) chain;
DE Flags: Precursor;
GN Name=COL9A3;
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], AND VARIANT GLU-435.
RC TISSUE=Cartilage;
RX PubMed=8586434; DOI=10.1006/geno.1995.9870;
RA Brewton R.G., Wood B.M., Ren Z.-X., Gong Y., Tiller G.E., Warman M.L.,
RA Lee B., Horton W.A., Olsen B.R., Baker J.R., Mayne R.;
RT "Molecular cloning of the alpha 3 chain of human type IX collagen: linkage
RT of the gene COL9A3 to chromosome 20q13.3.";
RL Genomics 30:329-336(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS 563-GLY--PRO-565 DEL AND
RP 564-PRO--GLY-566 DEL.
RX PubMed=10428822; DOI=10.1074/jbc.274.32.22469;
RA Paassilta P., Pihlajamaa T., Annunen S., Brewton R.G., Wood B.M.,
RA Johnson C.C., Liu J., Gong Y., Warman M.L., Prockop D.J., Mayne R.,
RA Ala-Kokko L.;
RT "Complete sequence of the 23-kilobase human COL9A3 gene. Detection of Gly-
RT X-Y triplet deletions that represent neutral variants.";
RL J. Biol. Chem. 274:22469-22475(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 522-667.
RC TISSUE=Cartilage;
RX PubMed=9164858; DOI=10.1042/bj3240209;
RA Peraelae M., Savontaus M., Metsaeranta M., Vuorio E.;
RT "Developmental regulation of mRNA species for types II, IX and XI collagens
RT during mouse embryogenesis.";
RL Biochem. J. 324:209-216(1997).
RN [6]
RP INVOLVEMENT IN EDM3.
RX PubMed=10090888; DOI=10.1086/302328;
RA Paassilta P., Lohiniva J., Annunen S., Bonaventure J., Le Merrer M.,
RA Pai L., Ala-Kokko L.;
RT "COL9A3: A third locus for multiple epiphyseal dysplasia.";
RL Am. J. Hum. Genet. 64:1036-1044(1999).
RN [7]
RP ERRATUM OF PUBMED:10090888.
RA Paassilta P., Lohiniva J., Annunen S., Bonaventure J., Le Merrer M.,
RA Pai L., Ala-Kokko L.;
RL Am. J. Hum. Genet. 65:1214-1214(1999).
RN [8]
RP INVOLVEMENT IN SUSCEPTIBILITY TO IDD.
RX PubMed=11308397; DOI=10.1001/jama.285.14.1843;
RA Paassilta P., Lohiniva J., Goring H.H., Perala M., Raina S.S.,
RA Karppinen J., Hakala M., Palm T., Kroger H., Kaitila I., Vanharanta H.,
RA Ott J., Ala-Kokko L.;
RT "Identification of a novel common genetic risk factor for lumbar disk
RT disease.";
RL JAMA 285:1843-1849(2001).
RN [9]
RP VARIANTS GLN-103; TRP-103; LEU-296; GLN-402 AND GLU-435.
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 [10]
RP VARIANT EDM3 ASP-35.
RX PubMed=25381065; DOI=10.1186/1471-2474-15-371;
RA Jeong C., Lee J.Y., Kim J., Chae H., Park H.I., Kim M., Kim O.H., Kim P.,
RA Lee Y.K., Jung J.;
RT "Novel COL9A3 mutation in a family diagnosed with multiple epiphyseal
RT dysplasia: a case report.";
RL BMC Musculoskelet. Disord. 15:371-371(2014).
CC -!- FUNCTION: Structural component of hyaline cartilage and vitreous of the
CC eye.
CC -!- SUBUNIT: Heterotrimer of an alpha 1(IX), an alpha 2(IX) and an alpha
CC 3(IX) chain.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- PTM: Covalently linked to the telopeptides of type II collagen by
CC lysine-derived cross-links.
CC -!- PTM: Prolines at the third position of the tripeptide repeating unit
CC (G-X-Y) are hydroxylated in some or all of the chains.
CC -!- DISEASE: Multiple epiphyseal dysplasia 3 (EDM3) [MIM:600969]: 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:10090888,
CC ECO:0000269|PubMed:25381065}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Intervertebral disc disease (IDD) [MIM:603932]: A common
CC musculo-skeletal disorder caused by degeneration of intervertebral
CC disks of the lumbar spine. It results in low-back pain and unilateral
CC leg pain. {ECO:0000269|PubMed:11308397, ECO:0000269|PubMed:25381065}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry. Susceptibility to intervertebral disk
CC disease is conferred by variant p.Arg103Trp (PubMed:11308397).
CC {ECO:0000269|PubMed:11308397}.
CC -!- SIMILARITY: Belongs to the fibril-associated collagens with interrupted
CC helices (FACIT) family. {ECO:0000305}.
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DR EMBL; L41162; AAC41947.1; -; mRNA.
DR EMBL; AF026802; AAD47357.1; -; Genomic_DNA.
DR EMBL; AF026801; AAD47357.1; JOINED; Genomic_DNA.
DR EMBL; AL035669; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011705; AAH11705.1; -; mRNA.
DR EMBL; X91013; CAA62495.1; -; mRNA.
DR CCDS; CCDS13505.1; -.
DR RefSeq; NP_001844.3; NM_001853.3.
DR PDB; 5CTD; X-ray; 1.60 A; C=517-553.
DR PDB; 5CTI; X-ray; 1.90 A; C=517-553.
DR PDB; 5CVA; X-ray; 2.10 A; C/F=517-553.
DR PDB; 5CVB; X-ray; 2.25 A; C/F=517-553.
DR PDBsum; 5CTD; -.
DR PDBsum; 5CTI; -.
DR PDBsum; 5CVA; -.
DR PDBsum; 5CVB; -.
DR AlphaFoldDB; Q14050; -.
DR SMR; Q14050; -.
DR BioGRID; 107696; 6.
DR ComplexPortal; CPX-1748; Collagen type IX trimer.
DR IntAct; Q14050; 2.
DR STRING; 9606.ENSP00000341640; -.
DR GlyGen; Q14050; 1 site.
DR iPTMnet; Q14050; -.
DR PhosphoSitePlus; Q14050; -.
DR BioMuta; COL9A3; -.
DR DMDM; 20137327; -.
DR EPD; Q14050; -.
DR jPOST; Q14050; -.
DR MassIVE; Q14050; -.
DR MaxQB; Q14050; -.
DR PaxDb; Q14050; -.
DR PeptideAtlas; Q14050; -.
DR PRIDE; Q14050; -.
DR ProteomicsDB; 59803; -.
DR Antibodypedia; 29570; 179 antibodies from 24 providers.
DR DNASU; 1299; -.
DR Ensembl; ENST00000649368.1; ENSP00000496793.1; ENSG00000092758.18.
DR GeneID; 1299; -.
DR KEGG; hsa:1299; -.
DR MANE-Select; ENST00000649368.1; ENSP00000496793.1; NM_001853.4; NP_001844.3.
DR UCSC; uc002ydm.3; human.
DR CTD; 1299; -.
DR DisGeNET; 1299; -.
DR GeneCards; COL9A3; -.
DR GeneReviews; COL9A3; -.
DR HGNC; HGNC:2219; COL9A3.
DR HPA; ENSG00000092758; Tissue enhanced (brain, choroid plexus, salivary gland, thyroid gland).
DR MalaCards; COL9A3; -.
DR MIM; 120270; gene.
DR MIM; 600969; phenotype.
DR MIM; 603932; phenotype.
DR neXtProt; NX_Q14050; -.
DR OpenTargets; ENSG00000092758; -.
DR Orphanet; 250984; Autosomal recessive Stickler syndrome.
DR Orphanet; 166002; Multiple epiphyseal dysplasia due to collagen 9 anomaly.
DR PharmGKB; PA26735; -.
DR VEuPathDB; HostDB:ENSG00000092758; -.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00940000163687; -.
DR HOGENOM; CLU_001074_18_2_1; -.
DR InParanoid; Q14050; -.
DR OMA; MINEQIA; -.
DR OrthoDB; 1029126at2759; -.
DR PhylomeDB; Q14050; -.
DR PathwayCommons; Q14050; -.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR Reactome; R-HSA-186797; Signaling by PDGF.
DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-HSA-216083; Integrin cell surface interactions.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR Reactome; R-HSA-8948216; Collagen chain trimerization.
DR SignaLink; Q14050; -.
DR SIGNOR; Q14050; -.
DR BioGRID-ORCS; 1299; 15 hits in 1067 CRISPR screens.
DR ChiTaRS; COL9A3; human.
DR GeneWiki; COL9A3; -.
DR GenomeRNAi; 1299; -.
DR Pharos; Q14050; Tbio.
DR PRO; PR:Q14050; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q14050; protein.
DR Bgee; ENSG00000092758; Expressed in tibia and 148 other tissues.
DR ExpressionAtlas; Q14050; baseline and differential.
DR Genevisible; Q14050; HS.
DR GO; GO:0005604; C:basement membrane; IBA:GO_Central.
DR GO; GO:0005594; C:collagen type IX trimer; IDA:BHF-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005201; F:extracellular matrix structural constituent; IBA:GO_Central.
DR GO; GO:0030020; F:extracellular matrix structural constituent conferring tensile strength; IC:BHF-UCL.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0008585; P:female gonad development; IBA:GO_Central.
DR GO; GO:0008584; P:male gonad development; IBA:GO_Central.
DR InterPro; IPR008160; Collagen.
DR Pfam; PF01391; Collagen; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Collagen; Disease variant; Dwarfism; Extracellular matrix;
KW Glycoprotein; Hydroxylation; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..684
FT /note="Collagen alpha-3(IX) chain"
FT /id="PRO_0000005848"
FT REGION 26..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 29..519
FT /note="Triple-helical region 3 (COL3)"
FT REGION 520..550
FT /note="Nonhelical region 3 (NC3)"
FT REGION 548..665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 551..630
FT /note="Triple-helical region 2 (COL2)"
FT REGION 631..632
FT /note="Nonhelical region 2 (NC2)"
FT REGION 633..661
FT /note="Triple-helical region 1 (COL1)"
FT REGION 662..684
FT /note="Nonhelical region 1 (NC1)"
FT MOTIF 423..425
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 601..603
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 54..68
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..163
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 176..190
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..574
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 483
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 35
FT /note="G -> D (in EDM3; dbSNP:rs1390736361)"
FT /evidence="ECO:0000269|PubMed:25381065"
FT /id="VAR_072736"
FT VARIANT 94
FT /note="P -> S (in dbSNP:rs35908728)"
FT /id="VAR_048808"
FT VARIANT 103
FT /note="R -> Q (in dbSNP:rs142639450)"
FT /evidence="ECO:0000269|PubMed:11565064"
FT /id="VAR_026467"
FT VARIANT 103
FT /note="R -> W (associated with an increased risk for
FT intervertebral disk disease; dbSNP:rs61734651)"
FT /evidence="ECO:0000269|PubMed:11565064"
FT /id="VAR_026468"
FT VARIANT 296
FT /note="P -> L (in dbSNP:rs45628843)"
FT /evidence="ECO:0000269|PubMed:11565064"
FT /id="VAR_026469"
FT VARIANT 402
FT /note="R -> Q (in dbSNP:rs373519549)"
FT /evidence="ECO:0000269|PubMed:11565064"
FT /id="VAR_026470"
FT VARIANT 435
FT /note="A -> E (in dbSNP:rs751557)"
FT /evidence="ECO:0000269|PubMed:11565064,
FT ECO:0000269|PubMed:8586434"
FT /id="VAR_026471"
FT VARIANT 563..565
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:10428822"
FT /id="VAR_012660"
FT VARIANT 564..566
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:10428822"
FT /id="VAR_012661"
FT CONFLICT 18
FT /note="E -> Q (in Ref. 1; AAC41947 and 2; AAD47357)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="P -> R (in Ref. 1; AAC41947)"
FT /evidence="ECO:0000305"
FT CONFLICT 144
FT /note="S -> P (in Ref. 1; AAC41947)"
FT /evidence="ECO:0000305"
FT CONFLICT 524
FT /note="R -> H (in Ref. 5; CAA62495)"
FT /evidence="ECO:0000305"
FT CONFLICT 576
FT /note="A -> T (in Ref. 5; CAA62495)"
FT /evidence="ECO:0000305"
FT HELIX 522..543
FT /evidence="ECO:0007829|PDB:5CTD"
SQ SEQUENCE 684 AA; 63616 MW; 892F035CF6E06733 CRC64;
MAGPRACAPL LLLLLLGELL AAAGAQRVGL PGPPGPPGPP GKPGQDGIDG EAGPPGLPGP
PGPKGAPGKP GKPGEAGLPG LPGVDGLTGR DGPPGPKGAP GERGSLGPPG PPGLGGKGLP
GPPGEAGVSG PPGGIGLRGP PGPSGLPGLP GPPGPPGPPG HPGVLPEGAT DLQCPSICPP
GPPGPPGMPG FKGPTGYKGE QGEVGKDGEK GDPGPPGPAG LPGSVGLQGP RGLRGLPGPL
GPPGDRGPIG FRGPPGIPGA PGKAGDRGER GPEGFRGPKG DLGRPGPKGT PGVAGPSGEP
GMPGKDGQNG VPGLDGQKGE AGRNGAPGEK GPNGLPGLPG RAGSKGEKGE RGRAGELGEA
GPSGEPGVPG DAGMPGERGE AGHRGSAGAL GPQGPPGAPG VRGFQGQKGS MGDPGLPGPQ
GLRGDVGDRG PGGAAGPKGD QGIAGSDGLP GDKGELGPSG LVGPKGESGS RGELGPKGTQ
GPNGTSGVQG VPGPPGPLGL QGVPGVPGIT GKPGVPGKEA SEQRIRELCG GMISEQIAQL
AAHLRKPLAP GSIGRPGPAG PPGPPGPPGS IGHPGARGPP GYRGPTGELG DPGPRGNQGD
RGDKGAAGAG LDGPEGDQGP QGPQGVPGTS KDGQDGAPGE PGPPGDPGLP GAIGAQGTPG
ICDTSACQGA VLGGVGEKSG SRSS
