CO9A2_HUMAN
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 03-AUG-2022, entry version 195.
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 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 [9]
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 [10]
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}. 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}.
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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; 11.
DR ComplexPortal; CPX-1748; Collagen type IX trimer.
DR IntAct; Q14055; 8.
DR STRING; 9606.ENSP00000361834; -.
DR GlyGen; Q14055; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q14055; -.
DR PhosphoSitePlus; Q14055; -.
DR BioMuta; COL9A2; -.
DR DMDM; 20137328; -.
DR EPD; Q14055; -.
DR jPOST; Q14055; -.
DR MassIVE; Q14055; -.
DR PaxDb; Q14055; -.
DR PeptideAtlas; Q14055; -.
DR PRIDE; Q14055; -.
DR ProteomicsDB; 59804; -.
DR TopDownProteomics; Q14055; -.
DR Antibodypedia; 64754; 29 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 CTD; 1298; -.
DR DisGeNET; 1298; -.
DR GeneCards; COL9A2; -.
DR GeneReviews; COL9A2; -.
DR HGNC; HGNC:2218; COL9A2.
DR HPA; ENSG00000049089; Tissue enhanced (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; DKCSKFQ; -.
DR OrthoDB; 1051097at2759; -.
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 1066 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 135 other tissues.
DR ExpressionAtlas; Q14055; baseline and differential.
DR Genevisible; Q14055; HS.
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:0001501; P:skeletal system development; TAS:ProtInc.
DR InterPro; IPR008160; Collagen.
DR Pfam; PF01391; Collagen; 9.
PE 1: Evidence at protein level;
KW 3D-structure; Collagen; Deafness; Disease variant; Disulfide bond;
KW Dwarfism; Extracellular matrix; Glycoprotein; Hydroxylation; Proteoglycan;
KW Reference proteome; Repeat; Secreted; Signal; 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
