COL4A3

Protein identityUniProt · HPA

UniProt accession

Q01955

Gene

COL4A3

Ensembl

ENSG00000169031

Chromosome

2

Canonical length

1670 aa

Protein class

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

Subcellular location

Endoplasmic reticulum,Vesicles

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3. In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein. A specific kinase phosphorylates amino acids in this same C-terminal region and the expression of this kinase is upregulated during pathogenesis. This gene is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to this syndrome are also located within the exons that encode this C-terminal region. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jun 2010]

Canonical amino-acid sequenceUniProt

1670 residues, UniProt reviewed canonical sequence.

>Q01955|COL4A3
     1  MSARTAPRPQ VLLLPLLLVL LAAAPAASKG CVCKDKGQCF CDGAKGEKGE KGFPGPPGSP
    61  GQKGFTGPEG LPGPQGPKGF PGLPGLTGSK GVRGISGLPG FSGSPGLPGT PGNTGPYGLV
   121  GVPGCSGSKG EQGFPGLPGT LGYPGIPGAA GLKGQKGAPA KEEDIELDAK GDPGLPGAPG
   181  PQGLPGPPGF PGPVGPPGPP GFFGFPGAMG PRGPKGHMGE RVIGHKGERG VKGLTGPPGP
   241  PGTVIVTLTG PDNRTDLKGE KGDKGAMGEP GPPGPSGLPG ESYGSEKGAP GDPGLQGKPG
   301  KDGVPGFPGS EGVKGNRGFP GLMGEDGIKG QKGDIGPPGF RGPTEYYDTY QEKGDEGTPG
   361  PPGPRGARGP QGPSGPPGVP GSPGSSRPGL RGAPGWPGLK GSKGERGRPG KDAMGTPGSP
   421  GCAGSPGLPG SPGPPGPPGD IVFRKGPPGD HGLPGYLGSP GIPGVDGPKG EPGLLCTQCP
   481  YIPGPPGLPG LPGLHGVKGI PGRQGAAGLK GSPGSPGNTG LPGFPGFPGA QGDPGLKGEK
   541  GETLQPEGQV GVPGDPGLRG QPGRKGLDGI PGTPGVKGLP GPKGELALSG EKGDQGPPGD
   601  PGSPGSPGPA GPAGPPGYGP QGEPGLQGTQ GVPGAPGPPG EAGPRGELSV STPVPGPPGP
   661  PGPPGHPGPQ GPPGIPGSLG KCGDPGLPGP DGEPGIPGIG FPGPPGPKGD QGFPGTKGSL
   721  GCPGKMGEPG LPGKPGLPGA KGEPAVAMPG GPGTPGFPGE RGNSGEHGEI GLPGLPGLPG
   781  TPGNEGLDGP RGDPGQPGPP GEQGPPGRCI EGPRGAQGLP GLNGLKGQQG RRGKTGPKGD
   841  PGIPGLDRSG FPGETGSPGI PGHQGEMGPL GQRGYPGNPG ILGPPGEDGV IGMMGFPGAI
   901  GPPGPPGNPG TPGQRGSPGI PGVKGQRGTP GAKGEQGDKG NPGPSEISHV IGDKGEPGLK
   961  GFAGNPGEKG NRGVPGMPGL KGLKGLPGPA GPPGPRGDLG STGNPGEPGL RGIPGSMGNM
  1021  GMPGSKGKRG TLGFPGRAGR PGLPGIHGLQ GDKGEPGYSE GTRPGPPGPT GDPGLPGDMG
  1081  KKGEMGQPGP PGHLGPAGPE GAPGSPGSPG LPGKPGPHGD LGFKGIKGLL GPPGIRGPPG
  1141  LPGFPGSPGP MGIRGDQGRD GIPGPAGEKG ETGLLRAPPG PRGNPGAQGA KGDRGAPGFP
  1201  GLPGRKGAMG DAGPRGPTGI EGFPGPPGLP GAIIPGQTGN RGPPGSRGSP GAPGPPGPPG
  1261  SHVIGIKGDK GSMGHPGPKG PPGTAGDMGP PGRLGAPGTP GLPGPRGDPG FQGFPGVKGE
  1321  KGNPGFLGSI GPPGPIGPKG PPGVRGDPGT LKIISLPGSP GPPGTPGEPG MQGEPGPPGP
  1381  PGNLGPCGPR GKPGKDGKPG TPGPAGEKGN KGSKGEPGPA GSDGLPGLKG KRGDSGSPAT
  1441  WTTRGFVFTR HSQTTAIPSC PEGTVPLYSG FSFLFVQGNQ RAHGQDLGTL GSCLQRFTTM
  1501  PFLFCNVNDV CNFASRNDYS YWLSTPALMP MNMAPITGRA LEPYISRCTV CEGPAIAIAV
  1561  HSQTTDIPPC PHGWISLWKG FSFIMFTSAG SEGTGQALAS PGSCLEEFRA SPFLECHGRG
  1621  TCNYYSNSYS FWLASLNPER MFRKPIPSTV KAGELEKIIS RCQVCMKKRH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against COL4A3 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

34 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about COL4A3.

Disease | AllUniProt

Conditions COL4A3 is implicated in, by any mechanism.

• Hematuria, benign familial, 2 (BFH2) MIM:620320
• Alport syndrome 3A, autosomal dominant (ATS3A) MIM:104200
• Alport syndrome 3B, autosomal recessive (ATS3B) MIM:620536

Disease | GeneticClinVar

886 pathogenic / likely-pathogenic of 3,465 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal dominant Alport syndrome
• Alport syndrome
• Alport syndrome 3b, autosomal recessive
• Autosomal recessive Alport syndrome
• Hematuria, benign familial, 2

Disease | ImmuneIEDB

Conditions an epitope on COL4A3 was assayed in.

• Goodpasture syndrome B and T cell
• autoimmune vasculitis B cell

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)

0.52

gnomAD pLI

0

gnomAD missense Z

1.99

DepMap mean gene effect

0.05

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

• cell adhesion
• cell surface receptor signaling pathway
• collagen fibril organization
• collagen-activated tyrosine kinase receptor signaling pathway
• endothelial cell apoptotic process
• glomerular basement membrane development
• negative regulation of angiogenesis
• negative regulation of cell population proliferation
• negative regulation of vascular endothelial cell proliferation
• sensory perception of sound

Molecular functions

• extracellular matrix structural constituent conferring tensile strength
• integrin binding
• metalloendopeptidase inhibitor activity
• structural molecule activity

Cellular components

• basement membrane
• collagen type IV trimer
• endoplasmic reticulum
• 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 and Collagen-like Structural Proteins
• Collagen triple helix repeat (20 copies)
• C-terminal tandem repeated domain in type 4 procollagen

KeywordsUniProt

• Alport syndrome
• Basement membrane
• Cell adhesion
• Collagen
• Deafness
• Disulfide bond
• Extracellular matrix
• Glycoprotein
• Hydroxylation
• Phosphoprotein
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of COL4A3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ITGB3