ID CO9A2_HUMAN Reviewed; 689 AA. AC Q14055; B2RMP9; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 2. DT 02-OCT-2024, entry version 207. DE RecName: Full=Collagen alpha-2(IX) chain {ECO:0000305}; DE Flags: Precursor; GN Name=COL9A2 {ECO:0000312|HGNC:HGNC:2218}; 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 [GENOMIC DNA]. RC TISSUE=Foreskin; RX PubMed=9707347; DOI=10.1016/s0945-053x(98)90063-4; RA Pihlajamaa T., Vuoristo M.M., Annunen S., Peraelae M., Prockop D.J., RA Ala-Kokko L.; RT "Human COL9A1 and COL9A2 genes. Two genes of 90 and 15 kb code for similar RT polypeptides of the same collagen molecule."; RL Matrix Biol. 17:237-241(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 50-668. RC TISSUE=Cartilage; RX PubMed=8454052; DOI=10.1016/0014-5793(93)80062-y; RA Peraelae M., Haenninen M., Haestbacka J., Elima K., Vuorio E.; RT "Molecular cloning of the human alpha 2(IX) collagen cDNA and assignment of RT the human COL9A2 gene to chromosome 1."; RL FEBS Lett. 319:177-180(1993). RN [6] RP INVOLVEMENT IN EDM2. RX PubMed=10364514; DOI=10.1086/302440; RA Holden P., Canty E.G., Mortier G.R., Zabel B., Spranger J., Carr A., RA Grant M.E., Loughlin J.A., Briggs M.D.; RT "Identification of novel pro-alpha2(IX) collagen gene mutations in two RT families with distinctive oligo-epiphyseal forms of multiple epiphyseal RT dysplasia."; RL Am. J. Hum. Genet. 65:31-38(1999). RN [7] RP INVOLVEMENT IN STL5. RX PubMed=21671392; DOI=10.1002/ajmg.a.34071; RA Baker S., Booth C., Fillman C., Shapiro M., Blair M.P., Hyland J.C., RA Ala-Kokko L.; RT "A loss of function mutation in the COL9A2 gene causes autosomal recessive RT Stickler syndrome."; RL Am. J. Med. Genet. A 155:1668-1672(2011). RN [8] RP INVOLVEMENT IN STL5. RX PubMed=31090205; DOI=10.1002/ajmg.a.61191; RA Nixon T.R.W., Alexander P., Richards A., McNinch A., Bearcroft P.W.P., RA Cobben J., Snead M.P.; RT "Homozygous Type IX collagen variants (COL9A1, COL9A2, and COL9A3) causing RT recessive Stickler syndrome-Expanding the phenotype."; RL Am. J. Med. Genet. A 179:1498-1506(2019). RN [9] RP INVOLVEMENT IN STL5. RX PubMed=33356723; DOI=10.1080/13816810.2020.1861309; RA Kjellstroem U., Martell S., Brobeck C., Andreasson S.; RT "Autosomal recessive Stickler syndrome associated with homozygous mutations RT in the COL9A2 gene."; RL Ophthalmic Genet. 42:161-169(2021). RN [10] RP VARIANT IDD TRP-326, AND VARIANT ARG-326. RX PubMed=10411504; DOI=10.1126/science.285.5426.409; RA Annunen S., Paassilta P., Lohiniva J., Peraelae M., Pihlajamaa T., RA Karppinen J., Tervonen O., Kroeger H., Laehde S., Vanharanta H., RA Ryhaenen L., Goering H.H.H., Ott J., Prockop D.J., Ala-Kokko L.; RT "An allele of COL9A2 associated with intervertebral disc disease."; RL Science 285:409-412(1999). RN [11] RP VARIANTS MET-246; ARG-326 AND VAL-335. 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 [12] RP VARIANT 326-GLN--PRO-689 DEL. RX PubMed=28887846; DOI=10.1002/humu.23335; RA Zhou X.L., He L.X., Yu L.J., Wang Y., Wang X.J., Wang E.D., Yang T.; RT "Mutations in KARS cause early-onset hearing loss and leukoencephalopathy: RT Potential pathogenic mechanism."; RL Hum. Mutat. 38:1740-1750(2017). 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 (By similarity). The chains are linked to each other by CC interchain disulfide bonds (By similarity). Trimers are also cross- CC linked via hydroxylysines (By similarity). CC {ECO:0000250|UniProtKB:C0HLN2}. CC -!- INTERACTION: CC Q14055; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-714971, EBI-16439278; CC Q14055; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-714971, EBI-741480; CC Q14055; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-714971, EBI-947187; 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 2 (EDM2) [MIM:600204]: 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:10364514}. Note=The disease is caused CC by variants 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:10411504}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Stickler syndrome 5 (STL5) [MIM:614284]: An autosomal CC recessive form of Stickler syndrome, an inherited disorder that CC associates ocular signs with more or less complete forms of Pierre CC Robin sequence, bone disorders and sensorineural deafness. STL5 is CC characterized by high myopia, vitreoretinal degeneration, retinal CC detachment, mild to moderate sensorineural hearing loss, short stature CC in childhood, and absence of cleft palate and Pierre Robin sequence. CC {ECO:0000269|PubMed:21671392, ECO:0000269|PubMed:31090205, CC ECO:0000269|PubMed:33356723}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the fibril-associated collagens with interrupted CC helices (FACIT) 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; AF019406; AAC33512.1; -; Genomic_DNA. DR EMBL; AL050341; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07229.1; -; Genomic_DNA. DR EMBL; BC136326; AAI36327.1; -; mRNA. DR EMBL; BC136327; AAI36328.1; -; mRNA. DR EMBL; M95610; AAA80977.1; -; mRNA. DR CCDS; CCDS450.1; -. DR PIR; S32436; S32436. DR RefSeq; NP_001843.1; NM_001852.3. DR RefSeq; XP_006710428.1; XM_006710365.3. DR PDB; 5CTD; X-ray; 1.60 A; B=517-552. DR PDB; 5CTI; X-ray; 1.90 A; B=517-552. DR PDB; 5CVA; X-ray; 2.10 A; B/E=517-552. DR PDB; 5CVB; X-ray; 2.25 A; B/E=517-552. DR PDBsum; 5CTD; -. DR PDBsum; 5CTI; -. DR PDBsum; 5CVA; -. DR PDBsum; 5CVB; -. DR AlphaFoldDB; Q14055; -. DR SMR; Q14055; -. DR BioGRID; 107695; 14. DR ComplexPortal; CPX-1748; Collagen type IX trimer. DR IntAct; Q14055; 10. DR STRING; 9606.ENSP00000361834; -. DR GlyCosmos; Q14055; 2 sites, No reported glycans. DR GlyGen; Q14055; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q14055; -. DR PhosphoSitePlus; Q14055; -. DR BioMuta; COL9A2; -. DR DMDM; 20137328; -. DR jPOST; Q14055; -. DR MassIVE; Q14055; -. DR PaxDb; 9606-ENSP00000361834; -. DR PeptideAtlas; Q14055; -. DR ProteomicsDB; 59804; -. DR Pumba; Q14055; -. DR TopDownProteomics; Q14055; -. DR Antibodypedia; 64754; 35 antibodies from 13 providers. DR DNASU; 1298; -. DR Ensembl; ENST00000372748.8; ENSP00000361834.3; ENSG00000049089.15. DR GeneID; 1298; -. DR KEGG; hsa:1298; -. DR MANE-Select; ENST00000372748.8; ENSP00000361834.3; NM_001852.4; NP_001843.1. DR UCSC; uc001cfh.2; human. DR AGR; HGNC:2218; -. DR CTD; 1298; -. DR DisGeNET; 1298; -. DR GeneCards; COL9A2; -. DR GeneReviews; COL9A2; -. DR HGNC; HGNC:2218; COL9A2. DR HPA; ENSG00000049089; Group enriched (brain, pituitary gland). DR MalaCards; COL9A2; -. DR MIM; 120260; gene. DR MIM; 600204; phenotype. DR MIM; 603932; phenotype. DR MIM; 614284; phenotype. DR neXtProt; NX_Q14055; -. DR OpenTargets; ENSG00000049089; -. DR Orphanet; 250984; Autosomal recessive Stickler syndrome. DR Orphanet; 166002; Multiple epiphyseal dysplasia due to collagen 9 anomaly. DR PharmGKB; PA26734; -. DR VEuPathDB; HostDB:ENSG00000049089; -. DR eggNOG; KOG3544; Eukaryota. DR GeneTree; ENSGT00940000161290; -. DR HOGENOM; CLU_001074_18_2_1; -. DR InParanoid; Q14055; -. DR OMA; MIGGPGQ; -. DR OrthoDB; 2970370at2759; -. DR PhylomeDB; Q14055; -. DR PathwayCommons; Q14055; -. 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; Q14055; -. DR SIGNOR; Q14055; -. DR BioGRID-ORCS; 1298; 11 hits in 1144 CRISPR screens. DR ChiTaRS; COL9A2; human. DR GeneWiki; COL9A2; -. DR GenomeRNAi; 1298; -. DR Pharos; Q14055; Tbio. DR PRO; PR:Q14055; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q14055; protein. DR Bgee; ENSG00000049089; Expressed in C1 segment of cervical spinal cord and 137 other cell types or tissues. DR ExpressionAtlas; Q14055; baseline and differential. 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:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0030020; F:extracellular matrix structural constituent conferring tensile strength; IBA:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR InterPro; IPR008160; Collagen. DR InterPro; IPR050149; Collagen_superfamily. DR PANTHER; PTHR24023; COLLAGEN ALPHA; 1. DR PANTHER; PTHR24023:SF958; ZGC:113232; 1. DR Pfam; PF01391; Collagen; 8. PE 1: Evidence at protein level; KW 3D-structure; Collagen; Deafness; Disease variant; Disulfide bond; KW Dwarfism; Extracellular matrix; Glycoprotein; Hydroxylation; Proteoglycan; KW Proteomics identification; Reference proteome; Repeat; Secreted; Signal; KW Stickler syndrome. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..689 FT /note="Collagen alpha-2(IX) chain" FT /id="PRO_0000005837" FT REGION 26..518 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 27..163 FT /note="Triple-helical region 4 (COL4)" FT REGION 164..180 FT /note="Nonhelical region 4 (NC4)" FT REGION 181..519 FT /note="Triple-helical region 3 (COL3)" FT REGION 520..549 FT /note="Nonhelical region 3 (NC3)" FT REGION 550..632 FT /note="Triple-helical region 2 (COL2)" FT REGION 554..663 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 633..634 FT /note="Nonhelical region 2 (NC2)" FT REGION 635..664 FT /note="Triple-helical region 1 (COL1)" FT REGION 665..689 FT /note="Nonhelical region 1 (NC1)" FT COMPBIAS 30..44 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 103..128 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 143..158 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 556..571 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 160 FT /note="4-hydroxyproline" FT /evidence="ECO:0000250|UniProtKB:P12108" FT MOD_RES 183 FT /note="5-hydroxylysine" FT /evidence="ECO:0000250|UniProtKB:P12108" FT CARBOHYD 169 FT /note="O-linked (Xyl...) (glycosaminoglycan) serine" FT /evidence="ECO:0000250|UniProtKB:P12108" FT CARBOHYD 183 FT /note="O-linked (Gal...) hydroxylysine" FT /evidence="ECO:0000250|UniProtKB:P12108" FT DISULFID 174 FT /note="Interchain" FT /evidence="ECO:0000255" FT DISULFID 178 FT /note="Interchain" FT /evidence="ECO:0000255" FT VARIANT 246 FT /note="T -> M (in dbSNP:rs2228565)" FT /evidence="ECO:0000269|PubMed:11565064" FT /id="VAR_026465" FT VARIANT 326..689 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:28887846" FT /id="VAR_079749" FT VARIANT 326 FT /note="Q -> R (in dbSNP:rs2228564)" FT /evidence="ECO:0000269|PubMed:10411504, FT ECO:0000269|PubMed:11565064" FT /id="VAR_012659" FT VARIANT 326 FT /note="Q -> W (in IDD; requires 2 nucleotide substitutions; FT dbSNP:rs137853213)" FT /evidence="ECO:0000269|PubMed:10411504" FT /id="VAR_012658" FT VARIANT 335 FT /note="L -> V (in dbSNP:rs2228567)" FT /evidence="ECO:0000269|PubMed:11565064" FT /id="VAR_026466" FT VARIANT 581 FT /note="V -> I (in dbSNP:rs3737821)" FT /id="VAR_020014" FT HELIX 523..549 FT /evidence="ECO:0007829|PDB:5CTD" SQ SEQUENCE 689 AA; 65131 MW; EB6106E02F6FA862 CRC64; MAAATASPRS LLVLLQVVVL ALAQIRGPPG ERGPPGPPGP PGVPGSDGID GDNGPPGKAG PPGPKGEPGK AGPDGPDGKP GIDGLTGAKG EPGPMGIPGV KGQPGLPGPP GLPGPGFAGP PGPPGPVGLP GEIGIRGPKG DPGPDGPSGP PGPPGKPGRP GTIQGLEGSA DFLCPTNCPP GMKGPPGLQG VKGHAGKRGI LGDPGHQGKP GPKGDVGASG EQGIPGPPGP QGIRGYPGMA GPKGETGPHG YKGMVGAIGA TGPPGEEGPR GPPGRAGEKG DEGSPGIRGP QGITGPKGAT GPPGINGKDG TPGTPGMKGS AGQAGQPGSP GHQGLAGVPG QPGTKGGPGD QGEPGPQGLP GFSGPPGKEG EPGPRGEIGP QGIMGQKGDQ GERGPVGQPG PQGRQGPKGE QGPPGIPGPQ GLPGVKGDKG SPGKTGPRGK VGDPGVAGLP GEKGEKGESG EPGPKGQQGV RGEPGYPGPS GDAGAPGVQG YPGPPGPRGL AGNRGVPGQP GRQGVEGRDA TDQHIVDVAL KMLQEQLAEV AVSAKREALG AVGMMGPPGP PGPPGYPGKQ GPHGHPGPRG VPGIVGAVGQ IGNTGPKGKR GEKGDPGEVG RGHPGMPGPP GIPGLPGRPG QAINGKDGDR GSPGAPGEAG RPGLPGPVGL PGFCEPAACL GASAYASARL TEPGSIKGP //