COL4A1

Protein identityUniProt · HPA

UniProt accession

P02462

Gene

COL4A1

Ensembl

ENSG00000187498

Chromosome

13

Canonical length

1669 aa

Protein class

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

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

This gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Canonical amino-acid sequenceUniProt

1669 residues, UniProt reviewed canonical sequence.

>P02462|COL4A1
     1  MGPRLSVWLL LLPAALLLHE EHSRAAAKGG CAGSGCGKCD CHGVKGQKGE RGLPGLQGVI
    61  GFPGMQGPEG PQGPPGQKGD TGEPGLPGTK GTRGPPGASG YPGNPGLPGI PGQDGPPGPP
   121  GIPGCNGTKG ERGPLGPPGL PGFAGNPGPP GLPGMKGDPG EILGHVPGML LKGERGFPGI
   181  PGTPGPPGLP GLQGPVGPPG FTGPPGPPGP PGPPGEKGQM GLSFQGPKGD KGDQGVSGPP
   241  GVPGQAQVQE KGDFATKGEK GQKGEPGFQG MPGVGEKGEP GKPGPRGKPG KDGDKGEKGS
   301  PGFPGEPGYP GLIGRQGPQG EKGEAGPPGP PGIVIGTGPL GEKGERGYPG TPGPRGEPGP
   361  KGFPGLPGQP GPPGLPVPGQ AGAPGFPGER GEKGDRGFPG TSLPGPSGRD GLPGPPGSPG
   421  PPGQPGYTNG IVECQPGPPG DQGPPGIPGQ PGFIGEIGEK GQKGESCLIC DIDGYRGPPG
   481  PQGPPGEIGF PGQPGAKGDR GLPGRDGVAG VPGPQGTPGL IGQPGAKGEP GEFYFDLRLK
   541  GDKGDPGFPG QPGMPGRAGS PGRDGHPGLP GPKGSPGSVG LKGERGPPGG VGFPGSRGDT
   601  GPPGPPGYGP AGPIGDKGQA GFPGGPGSPG LPGPKGEPGK IVPLPGPPGA EGLPGSPGFP
   661  GPQGDRGFPG TPGRPGLPGE KGAVGQPGIG FPGPPGPKGV DGLPGDMGPP GTPGRPGFNG
   721  LPGNPGVQGQ KGEPGVGLPG LKGLPGLPGI PGTPGEKGSI GVPGVPGEHG AIGPPGLQGI
   781  RGEPGPPGLP GSVGSPGVPG IGPPGARGPP GGQGPPGLSG PPGIKGEKGF PGFPGLDMPG
   841  PKGDKGAQGL PGITGQSGLP GLPGQQGAPG IPGFPGSKGE MGVMGTPGQP GSPGPVGAPG
   901  LPGEKGDHGF PGSSGPRGDP GLKGDKGDVG LPGKPGSMDK VDMGSMKGQK GDQGEKGQIG
   961  PIGEKGSRGD PGTPGVPGKD GQAGQPGQPG PKGDPGISGT PGAPGLPGPK GSVGGMGLPG
  1021  TPGEKGVPGI PGPQGSPGLP GDKGAKGEKG QAGPPGIGIP GLRGEKGDQG IAGFPGSPGE
  1081  KGEKGSIGIP GMPGSPGLKG SPGSVGYPGS PGLPGEKGDK GLPGLDGIPG VKGEAGLPGT
  1141  PGPTGPAGQK GEPGSDGIPG SAGEKGEPGL PGRGFPGFPG AKGDKGSKGE VGFPGLAGSP
  1201  GIPGSKGEQG FMGPPGPQGQ PGLPGSPGHA TEGPKGDRGP QGQPGLPGLP GPMGPPGLPG
  1261  IDGVKGDKGN PGWPGAPGVP GPKGDPGFQG MPGIGGSPGI TGSKGDMGPP GVPGFQGPKG
  1321  LPGLQGIKGD QGDQGVPGAK GLPGPPGPPG PYDIIKGEPG LPGPEGPPGL KGLQGLPGPK
  1381  GQQGVTGLVG IPGPPGIPGF DGAPGQKGEM GPAGPTGPRG FPGPPGPDGL PGSMGPPGTP
  1441  SVDHGFLVTR HSQTIDDPQC PSGTKILYHG YSLLYVQGNE RAHGQDLGTA GSCLRKFSTM
  1501  PFLFCNINNV CNFASRNDYS YWLSTPEPMP MSMAPITGEN IRPFISRCAV CEAPAMVMAV
  1561  HSQTIQIPPC PSGWSSLWIG YSFVMHTSAG AEGSGQALAS PGSCLEEFRS APFIECHGRG
  1621  TCNYYANAYS FWLATIERSE MFKKPTPSTL KAGELRTHVS RCQVCMRRT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against COL4A1 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)

0.67

Highest tissue expression

846 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about COL4A1.

Disease | AllUniProt

Conditions COL4A1 is implicated in, by any mechanism.

• Hereditary angiopathy with nephropathy aneurysms and muscle cramps (HANAC) MIM:611773
• Brain small vessel disease 1 with or without ocular anomalies (BSVD1) MIM:175780
• Intracerebral hemorrhage (ICH) MIM:614519
• Tortuosity of retinal arteries (RATOR) MIM:180000
• Schizencephaly (SCHZC) MIM:269160
• Microangiopathy and leukoencephalopathy, pontine, autosomal dominant (PADMAL) MIM:618564

Disease | GeneticClinVar

404 pathogenic / likely-pathogenic of 2,916 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Brain small vessel disease 1 with or without ocular anomalies
• Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
• Microangiopathy and leukoencephalopathy, pontine, autosomal dominant
• Hemorrhage, intracerebral, susceptibility to
• Retinal arterial tortuosity

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

3.02

DepMap mean gene effect

-0.03

DepMap dependency class

selective

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

• basement membrane organization
• blood vessel morphogenesis
• brain development
• branching involved in blood vessel morphogenesis
• cellular response to amino acid stimulus
• collagen fibril organization
• collagen-activated tyrosine kinase receptor signaling pathway
• epithelial cell differentiation
• neuromuscular junction development
• renal tubule morphogenesis
• retinal blood vessel morphogenesis

Molecular functions

• extracellular matrix structural constituent
• extracellular matrix structural constituent conferring tensile strength
• platelet-derived growth factor binding

Cellular components

• basement membrane
• collagen type IV trimer
• endoplasmic reticulum lumen
• extracellular matrix
• extracellular region

Protein domainsUniProt · Pfam · InterPro

• Collagen IV, non-collagenous
• Collagen triple helix repeat
• C-type lectin fold
• Collagen IV, non-collagenous domain superfamily
• Collagen superfamily
• Collagen triple helix repeat (20 copies)
• C-terminal tandem repeated domain in type 4 procollagen

KeywordsUniProt

• Angiogenesis
• Basement membrane
• Collagen
• Disulfide bond
• Extracellular matrix
• Glycoprotein
• Hydroxylation
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of COL4A1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EFEMP2