COMP

Protein identityUniProt · HPA

UniProt accession

P49747

Gene

COMP

Ensembl

ENSG00000105664

Chromosome

19

Canonical length

757 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfides. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Contraction or expansion of a 5 aa aspartate repeat and other mutations can cause pseudochondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

757 residues, UniProt reviewed canonical sequence.

>P49747|COMP
     1  MVPDTACVLL LTLAALGASG QGQSPLGSDL GPQMLRELQE TNAALQDVRE LLRQQVREIT
    61  FLKNTVMECD ACGMQQSVRT GLPSVRPLLH CAPGFCFPGV ACIQTESGAR CGPCPAGFTG
   121  NGSHCTDVNE CNAHPCFPRV RCINTSPGFR CEACPPGYSG PTHQGVGLAF AKANKQVCTD
   181  INECETGQHN CVPNSVCINT RGSFQCGPCQ PGFVGDQASG CQRRAQRFCP DGSPSECHEH
   241  ADCVLERDGS RSCVCAVGWA GNGILCGRDT DLDGFPDEKL RCPERQCRKD NCVTVPNSGQ
   301  EDVDRDGIGD ACDPDADGDG VPNEKDNCPL VRNPDQRNTD EDKWGDACDN CRSQKNDDQK
   361  DTDQDGRGDA CDDDIDGDRI RNQADNCPRV PNSDQKDSDG DGIGDACDNC PQKSNPDQAD
   421  VDHDFVGDAC DSDQDQDGDG HQDSRDNCPT VPNSAQEDSD HDGQGDACDD DDDNDGVPDS
   481  RDNCRLVPNP GQEDADRDGV GDVCQDDFDA DKVVDKIDVC PENAEVTLTD FRAFQTVVLD
   541  PEGDAQIDPN WVVLNQGREI VQTMNSDPGL AVGYTAFNGV DFEGTFHVNT VTDDDYAGFI
   601  FGYQDSSSFY VVMWKQMEQT YWQANPFRAV AEPGIQLKAV KSSTGPGEQL RNALWHTGDT
   661  ESQVRLLWKD PRNVGWKDKK SYRWFLQHRP QVGYIRVRFY EGPELVADSN VVLDTTMRGG
   721  RLGVFCFSQE NIIWANLRYR CNDTIPEDYE THQLRQA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against COMP 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)

0.31

Highest tissue expression

334 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about COMP.

Disease | AllUniProt

Conditions COMP is implicated in, by any mechanism.

• Multiple epiphyseal dysplasia 1 (EDM1) MIM:132400
• Pseudoachondroplasia (PSACH) MIM:177170
• Carpal tunnel syndrome 2 (CTS2) MIM:619161

Disease | GeneticClinVar

174 pathogenic / likely-pathogenic of 892 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome
• Multiple epiphyseal dysplasia type 1
• COMP-related disorder
• Multiple epiphyseal dysplasia
• Carpal tunnel syndrome 2

Disease | ImmuneIEDB

Conditions an epitope on COMP was assayed in.

• rheumatoid arthritis B cell

Disease | AutoantibodyPubMed

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

Showing 0 of 1 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for COMP 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)

0.77

gnomAD pLI

0

gnomAD missense Z

1.78

DepMap mean gene effect

-0.06

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

• animal organ morphogenesis
• apoptotic process
• artery morphogenesis
• BMP signaling pathway
• bone mineralization
• cartilage homeostasis
• cellular senescence
• chondrocyte development
• chondrocyte proliferation
• collagen fibril organization
• growth plate cartilage development
• limb development
• multicellular organism growth
• musculoskeletal movement
• negative regulation of apoptotic process
• platelet aggregation
• positive regulation of chondrocyte proliferation
• protein homooligomerization
• protein processing
• protein secretion
• regulation of bone mineralization
• regulation of gene expression
• response to unfolded protein
• skeletal system development
• skin development
• tendon development
• vascular associated smooth muscle cell development
• vascular associated smooth muscle contraction
• negative regulation of hemostasis

Molecular functions

• BMP binding
• calcium ion binding
• collagen binding
• extracellular matrix structural constituent
• heparan sulfate proteoglycan binding
• heparin binding
• integrin binding
• protease binding
• proteoglycan binding

Cellular components

• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• EGF-like domain
• EGF-like calcium-binding domain
• Thrombospondin, type 3-like repeat
• Thrombospondin, C-terminal
• Growth factor receptor cysteine-rich domain superfamily
• Concanavalin A-like lectin/glucanase domain superfamily
• Thrombospondin, type 3 repeat
• EGF-like calcium-binding, conserved site
• Thrombospondin/cartilage oligomeric matrix protein, coiled-coil domain
• TSP type-3 repeat
• TSP/COMP, coiled-coil domain superfamily
• NOTCH1, EGF-like calcium-binding domain
• Thrombospondin type 3 repeat
• Thrombospondin C-terminal region
• Calcium-binding EGF domain
• Cartilage oligomeric matrix protein
• Thrombospondin-5, coiled coil domain

KeywordsUniProt

• Apoptosis
• Calcium
• Cell adhesion
• Disulfide bond
• Dwarfism
• EGF-like domain
• Extracellular matrix
• Glycoprotein
• Heparin-binding
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of COMP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ACAN
• ADAMTS12
• FN1
• II
• ITGA5
• ITGA7
• ITGB3
• IX
• MATN1
• MATN3
• MATN4
• ADAMTS7