MGP Database

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MGP000620

UniProt Annotations

Entry Information
Gene Namecollagen, type IV, alpha 4
Protein EntryCO4A4_HUMAN
UniProt IDP53420
SpeciesHuman
Comments
Comment typeDescription
DiseaseAlport syndrome, autosomal recessive (APSAR) [MIM:203780]: A syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness. {ECO:0000269|PubMed:7987396, ECO:0000269|PubMed:9792860}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseHematuria, benign familial (BFH) [MIM:141200]: An autosomal dominant condition characterized by non-progressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane. {ECO:0000269|PubMed:11961012, ECO:0000269|PubMed:12631110, ECO:0000269|PubMed:8787673}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainAlpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G- X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.
FunctionType IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.
PtmProlines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
PtmThe trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues. {ECO:0000250}.
PtmType IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.
SimilarityBelongs to the type IV collagen family. {ECO:0000255|PROSITE-ProRule:PRU00736}.
SimilarityContains 1 collagen IV NC1 (C-terminal non- collagenous) domain. {ECO:0000255|PROSITE-ProRule:PRU00736}.
Subcellular LocationSecreted, extracellular space, extracellular matrix, basement membrane {ECO:0000255|PROSITE-ProRule:PRU00736}. Note=Colocalizes with COL4A4 and COL4A5 in GBM, tubular basement membrane (TBM) and synaptic basal lamina (BL). {ECO:0000250}.
SubunitThere are six type IV collagen isoforms, alpha 1(IV)- alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1- NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite protomer, respectively. Associates with LAMB2 at the neuromuscular junction and in GBM (By similarity). {ECO:0000250}.
Tissue SpecificityAlpha 3 and alpha 4 type IV collagens are colocalized and present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney and fetal lung. PubMed:8083201 reports similar levels of expression of alpha 3 and alpha 4 type IV collagens in kidney, but PubMed:7523402 reports that in kidney levels of alpha 3 type IV collagen are significantly lower than those of alpha 4 type IV collagen. Highest levels of expression of alpha 4 type IV collagen are detected in kidney, calvaria, neuroretina and cardiac muscle. Lower levels of expression are observed in brain, lung and thymus, and no expression is detected in choroid plexus, liver, adrenal, pancreas, ileum or skin. {ECO:0000269|PubMed:7523402, ECO:0000269|PubMed:8083201}.
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