COL2A1

Protein identityUniProt · HPA

UniProt accession

P02458

Gene

COL2A1

Ensembl

ENSG00000139219

Chromosome

12

Canonical length

1487 aa

Protein class

Cancer-related genes, Disease related genes, FDA approved drug targets, Human disease related genes, Predicted secreted proteins

Subcellular location

Nucleoplasm

Secretome location

Secreted to extracellular matrix

Quaternary structure

Homotrimer

OverviewNCBI Gene

This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Mutations in this gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia. There are two transcripts identified for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1487 residues, UniProt reviewed canonical sequence.

>P02458|COL2A1
     1  MIRLGAPQTL VLLTLLVAAV LRCQGQDVQE AGSCVQDGQR YNDKDVWKPE PCRICVCDTG
    61  TVLCDDIICE DVKDCLSPEI PFGECCPICP TDLATASGQP GPKGQKGEPG DIKDIVGPKG
   121  PPGPQGPAGE QGPRGDRGDK GEKGAPGPRG RDGEPGTPGN PGPPGPPGPP GPPGLGGNFA
   181  AQMAGGFDEK AGGAQLGVMQ GPMGPMGPRG PPGPAGAPGP QGFQGNPGEP GEPGVSGPMG
   241  PRGPPGPPGK PGDDGEAGKP GKAGERGPPG PQGARGFPGT PGLPGVKGHR GYPGLDGAKG
   301  EAGAPGVKGE SGSPGENGSP GPMGPRGLPG ERGRTGPAGA AGARGNDGQP GPAGPPGPVG
   361  PAGGPGFPGA PGAKGEAGPT GARGPEGAQG PRGEPGTPGS PGPAGASGNP GTDGIPGAKG
   421  SAGAPGIAGA PGFPGPRGPP GPQGATGPLG PKGQTGEPGI AGFKGEQGPK GEPGPAGPQG
   481  APGPAGEEGK RGARGEPGGV GPIGPPGERG APGNRGFPGQ DGLAGPKGAP GERGPSGLAG
   541  PKGANGDPGR PGEPGLPGAR GLTGRPGDAG PQGKVGPSGA PGEDGRPGPP GPQGARGQPG
   601  VMGFPGPKGA NGEPGKAGEK GLPGAPGLRG LPGKDGETGA AGPPGPAGPA GERGEQGAPG
   661  PSGFQGLPGP PGPPGEGGKP GDQGVPGEAG APGLVGPRGE RGFPGERGSP GAQGLQGPRG
   721  LPGTPGTDGP KGASGPAGPP GAQGPPGLQG MPGERGAAGI AGPKGDRGDV GEKGPEGAPG
   781  KDGGRGLTGP IGPPGPAGAN GEKGEVGPPG PAGSAGARGA PGERGETGPP GPAGFAGPPG
   841  ADGQPGAKGE QGEAGQKGDA GAPGPQGPSG APGPQGPTGV TGPKGARGAQ GPPGATGFPG
   901  AAGRVGPPGS NGNPGPPGPP GPSGKDGPKG ARGDSGPPGR AGEPGLQGPA GPPGEKGEPG
   961  DDGPSGAEGP PGPQGLAGQR GIVGLPGQRG ERGFPGLPGP SGEPGKQGAP GASGDRGPPG
  1021  PVGPPGLTGP AGEPGREGSP GADGPPGRDG AAGVKGDRGE TGAVGAPGAP GPPGSPGPAG
  1081  PTGKQGDRGE AGAQGPMGPS GPAGARGIQG PQGPRGDKGE AGEPGERGLK GHRGFTGLQG
  1141  LPGPPGPSGD QGASGPAGPS GPRGPPGPVG PSGKDGANGI PGPIGPPGPR GRSGETGPAG
  1201  PPGNPGPPGP PGPPGPGIDM SAFAGLGPRE KGPDPLQYMR ADQAAGGLRQ HDAEVDATLK
  1261  SLNNQIESIR SPEGSRKNPA RTCRDLKLCH PEWKSGDYWI DPNQGCTLDA MKVFCNMETG
  1321  ETCVYPNPAN VPKKNWWSSK SKEKKHIWFG ETINGGFHFS YGDDNLAPNT ANVQMTFLRL
  1381  LSTEGSQNIT YHCKNSIAYL DEAAGNLKKA LLIQGSNDVE IRAEGNSRFT YTALKDGCTK
  1441  HTGKWGKTVI EYRSQKTSRL PIIDIAPMDI GGPEQEFGVD IGPVCFL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against COL2A1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.66

Highest tissue expression

18 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about COL2A1.

Disease | AllUniProt

Conditions COL2A1 is implicated in, by any mechanism.

• Spondyloepiphyseal dysplasia congenital type (SEDC) MIM:183900
• Spondyloepiphyseal dysplasia, Stanescu type (SEDSTN) MIM:616583
• Spondyloepimetaphyseal dysplasia, Strudwick type (SEMDSTWK) MIM:184250
• Achondrogenesis 2 (ACG2) MIM:200610
• Legg-Calve-Perthes disease (LCPD) MIM:150600
• Kniest dysplasia (KD) MIM:156550
• Avascular necrosis of femoral head, primary, 1 (ANFH1) MIM:608805
• Osteoarthritis with mild chondrodysplasia (OSCDP) MIM:604864
• Platyspondylic lethal skeletal dysplasia Torrance type (PLSD-T) MIM:151210
• Multiple epiphyseal dysplasia with myopia and conductive deafness (EDMMD) MIM:132450
• Spondyloperipheral dysplasia (SPD) MIM:271700
• Stickler syndrome 1 (STL1) MIM:108300
• Stickler syndrome 1 non-syndromic ocular (STL1O) MIM:609508
• Rhegmatogenous retinal detachment autosomal dominant (DRRD) MIM:609508
• Czech dysplasia (CZECHD) MIM:609162
• Vitreoretinopathy with phalangeal epiphyseal dysplasia (VPED) MIM:619248
• Spondylometaphyseal dysplasia, Algerian type (SMDALG) MIM:184253

Disease | GeneticClinVar

1,121 pathogenic / likely-pathogenic of 3,530 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Stickler syndrome type 1
• COL2A1-related disorder
• Spondyloepiphyseal dysplasia congenita
• Achondrogenesis type II
• Stickler syndrome

Disease | ImmuneIEDB

Conditions an epitope on COL2A1 was assayed in.

• rheumatoid arthritis B and T cell
• osteoarthritis B cell
• relapsing polychondritis B and T cell
• systemic lupus erythematosus B cell
• reactive arthritis T cell
• ankylosing spondylitis T cell
• granulomatosis with polyangiitis B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against COL2A1 are reported. Each links to that disease's full target list.

• Arthritis, Rheumatoid 67
• Arthritis 34
• Lupus Erythematosus, Systemic 6
• Arthritis, Juvenile 5
• Hypersensitivity, Delayed 3
• Spondylitis, Ankylosing 3

Showing 6 of 10 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for COL2A1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.13

gnomAD pLI

1

gnomAD missense Z

3.29

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anterior head development
• cartilage condensation
• cartilage development
• cartilage development involved in endochondral bone morphogenesis
• cellular response to BMP stimulus
• central nervous system development
• chondrocyte differentiation
• collagen fibril organization
• embryonic skeletal joint morphogenesis
• endochondral ossification
• extrinsic apoptotic signaling pathway in absence of ligand
• heart morphogenesis
• inner ear morphogenesis
• limb bud formation
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• notochord development
• otic vesicle development
• proteoglycan metabolic process
• regulation of gene expression
• roof of mouth development
• sensory perception of sound
• skeletal system development
• tissue homeostasis
• visual perception

Molecular functions

• extracellular matrix structural constituent
• extracellular matrix structural constituent conferring tensile strength
• metal ion binding
• MHC class II protein binding
• platelet-derived growth factor binding
• protein homodimerization activity
• proteoglycan binding

Cellular components

• basement membrane
• collagen type II trimer
• collagen type XI trimer
• endoplasmic reticulum lumen
• extracellular matrix
• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Fibrillar collagen, C-terminal
• VWFC domain
• Collagen triple helix repeat
• Collagen superfamily
• von Willebrand factor type C domain
• Collagen triple helix repeat (20 copies)
• Fibrillar collagen C-terminal domain

KeywordsUniProt

• Calcium
• Cataract
• Collagen
• Deafness
• Disulfide bond
• Dwarfism
• Extracellular matrix
• Glycoprotein
• Hydroxylation
• Metal-binding
• Repeat
• Secreted
• Signal
• Stickler syndrome