COL18A1

Protein identityUniProt · HPA

UniProt accession

P39060

Gene

COL18A1

Ensembl

ENSG00000182871

Chromosome

21

Canonical length

1754 aa

Protein class

Cancer-related genes, 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

Quaternary structure

Homotrimer

OverviewNCBI Gene

This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. A long isoform of the protein has an N-terminal domain that is homologous to the extracellular part of frizzled receptors. Proteolytic processing at several endogenous cleavage sites in the C-terminal domain results in production of endostatin, a potent antiangiogenic protein that is able to inhibit angiogenesis and tumor growth. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities, so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Canonical amino-acid sequenceUniProt

1754 residues, UniProt reviewed canonical sequence.

>P39060|COL18A1
     1  MAPYPCGCHI LLLLFCCLAA ARANLLNLNW LWFNNEDTSH AATTIPEPQG PLPVQPTADT
    61  TTHVTPRNGS TEPATAPGSP EPPSELLEDG QDTPTSAESP DAPEENIAGV GAEILNVAKG
   121  IRSFVQLWND TVPTESLARA ETLVLETPVG PLALAGPSST PQENGTTLWP SRGIPSSPGA
   181  HTTEAGTLPA PTPSPPSLGR PWAPLTGPSV PPPSSGRASL SSLLGGAPPW GSLQDPDSQG
   241  LSPAAAAPSQ QLQRPDVRLR TPLLHPLVMG SLGKHAAPSA FSSGLPGALS QVAVTTLTRD
   301  SGAWVSHVAN SVGPGLANNS ALLGADPEAP AGRCLPLPPS LPVCGHLGIS RFWLPNHLHH
   361  ESGEQVRAGA RAWGGLLQTH CHPFLAWFFC LLLVPPCGSV PPPAPPPCCQ FCEALQDACW
   421  SRLGGGRLPV ACASLPTQED GYCVLIGPAA ERISEEVGLL QLLGDPPPQQ VTQTDDPDVG
   481  LAYVFGPDAN SGQVARYHFP SLFFRDFSLL FHIRPATEGP GVLFAITDSA QAMVLLGVKL
   541  SGVQDGHQDI SLLYTEPGAG QTHTAASFRL PAFVGQWTHL ALSVAGGFVA LYVDCEEFQR
   601  MPLARSSRGL ELEPGAGLFV AQAGGADPDK FQGVIAELKV RRDPQVSPMH CLDEEGDDSD
   661  GASGDSGSGL GDARELLREE TGAALKPRLP APPPVTTPPL AGGSSTEDSR SEEVEEQTTV
   721  ASLGAQTLPG SDSVSTWDGS VRTPGGRVKE GGLKGQKGEP GVPGPPGRAG PPGSPCLPGP
   781  PGLPCPVSPL GPAGPALQTV PGPQGPPGPP GRDGTPGRDG EPGDPGEDGK PGDTGPQGFP
   841  GTPGDVGPKG DKGDPGVGER GPPGPQGPPG PPGPSFRHDK LTFIDMEGSG FGGDLEALRG
   901  PRGFPGPPGP PGVPGLPGEP GRFGVNSSDV PGPAGLPGVP GREGPPGFPG LPGPPGPPGR
   961  EGPPGRTGQK GSLGEAGAPG HKGSKGAPGP AGARGESGLA GAPGPAGPPG PPGPPGPPGP
  1021  GLPAGFDDME GSGGPFWSTA RSADGPQGPP GLPGLKGDPG VPGLPGAKGE VGADGVPGFP
  1081  GLPGREGIAG PQGPKGDRGS RGEKGDPGKD GVGQPGLPGP PGPPGPVVYV SEQDGSVLSV
  1141  PGPEGRPGFA GFPGPAGPKG NLGSKGERGS PGPKGEKGEP GSIFSPDGGA LGPAQKGAKG
  1201  EPGFRGPPGP YGRPGYKGEI GFPGRPGRPG MNGLKGEKGE PGDASLGFGM RGMPGPPGPP
  1261  GPPGPPGTPV YDSNVFAESS RPGPPGLPGN QGPPGPKGAK GEVGPPGPPG QFPFDFLQLE
  1321  AEMKGEKGDR GDAGQKGERG EPGGGGFFGS SLPGPPGPPG PPGPRGYPGI PGPKGESIRG
  1381  QPGPPGPQGP PGIGYEGRQG PPGPPGPPGP PSFPGPHRQT ISVPGPPGPP GPPGPPGTMG
  1441  ASSGVRLWAT RQAMLGQVHE VPEGWLIFVA EQEELYVRVQ NGFRKVQLEA RTPLPRGTDN
  1501  EVAALQPPVV QLHDSNPYPR REHPHPTARP WRADDILASP PRLPEPQPYP GAPHHSSYVH
  1561  LRPARPTSPP AHSHRDFQPV LHLVALNSPL SGGMRGIRGA DFQCFQQARA VGLAGTFRAF
  1621  LSSRLQDLYS IVRRADRAAV PIVNLKDELL FPSWEALFSG SEGPLKPGAR IFSFDGKDVL
  1681  RHPTWPQKSV WHGSDPNGRR LTESYCETWR TEAPSATGQA SSLLGGRLLG QSAASCHHAY
  1741  IVLCIENSFM TASK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against COL18A1 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)

0.57

Highest tissue expression

547 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about COL18A1.

Disease | AllUniProt

Conditions COL18A1 is implicated in, by any mechanism.

• Knobloch syndrome 1 (KNO1) MIM:267750
• Glaucoma, primary closed-angle (GLCC) MIM:618880

Disease | GeneticClinVar

210 pathogenic / likely-pathogenic of 3,244 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Knobloch syndrome
• Knobloch syndrome 1
• Retinal dystrophy
• Hereditary glaucoma, primary closed-angle
• early onset and severe retinal dystrophy

Disease | AutoantibodyPubMed

Conditions in which antibodies against COL18A1 are reported. Each links to that disease's full target list.

• Anti-Glomerular Basement Membrane Disease 15
• Glomerulonephritis 8

Showing 2 of 3 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for COL18A1 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. 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)

0.54

gnomAD pLI

0

gnomAD missense Z

-0.8

DepMap mean gene effect

-0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• animal organ morphogenesis
• cell adhesion
• endothelial cell morphogenesis
• negative regulation of cell population proliferation
• response to hydrostatic pressure
• response to xenobiotic stimulus
• skeletal system development
• visual perception

Molecular functions

• extracellular matrix structural constituent conferring tensile strength
• metal ion binding

Cellular components

• basement membrane
• collagen trimer
• endoplasmic reticulum lumen
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Collagen triple helix repeat
• Collagenase NC10/endostatin
• Concanavalin A-like lectin/glucanase domain superfamily
• C-type lectin-like/link domain superfamily
• C-type lectin fold
• Frizzled domain
• Frizzled cysteine-rich domain superfamily
• Collagen type XV/XVIII, trimerization domain
• Thrombospondin-like, N-terminal domain
• Collagen superfamily
• Collagen triple helix repeat (20 copies)
• Fz domain
• Collagenase NC10 and Endostatin
• Collagen trimerization domain
• Domain of unknown function DUF959, collagen XVIII, N-terminal
• Collagen alpha-1(XVIII) chain, frizzled domain
• Domain of Unknown Function (DUF959)

KeywordsUniProt

• Alternative promoter usage
• Basement membrane
• Cell adhesion
• Collagen
• Disulfide bond
• Extracellular matrix
• Glaucoma
• Glycoprotein
• Hydroxylation
• Metal-binding
• Phosphoprotein
• Proteoglycan
• Repeat
• Secreted
• Signal
• Zinc

InteractionsUniProt · HPA

Protein binding partners of COL18A1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FBLN1
• FBLN2
• HSPG2
• NID1