FUNCTION Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.SUBUNIT There 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).SUBCELLULAR LOCATION Colocalizes with COL4A4 and COL4A5 in GBM, tubular basement membrane (TBM) and synaptic basal lamina (BL).TISSUE SPECIFICITY Expressed in Bruch's membrane, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, inner limiting membrane and around the blood vessels of the retina (at protein level) (PubMed:29777959). Alpha 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.DEVELOPMENTAL STAGE At 6 weeks post-conception (WPC) expressed in the hyaloid artery and lens capsule (at protein level) (PubMed:29777959). Expressed between 6 and 19 WPC in the choroid and Bruch's membrane with faint expression in the retinal pigment epithelium, outer neuroblastic zone, inner plexiform layer, and the inner neuroblastic zone (at protein level) (PubMed:29777959).DOMAIN Alpha 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.PTM Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.PTM Type 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.PTM The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the type IV collagen family.