6mpx

== Disease ==

[https://www.uniprot.org/uniprot/CO4A1_HUMAN CO4A1_HUMAN] Defects in COL4A1 are a cause of brain small vessel disease with hemorrhage (BSVDH) [MIM:[https://omim.org/entry/607595 607595]. Brain small vessel diseases underlie 20 to 30 percent of ischemic strokes and a larger proportion of intracerebral hemorrhages. Inheritance is autosomal dominant.<ref>PMID:16598045</ref> <ref>PMID:17696175</ref> <ref>PMID:17379824</ref> <ref>PMID:20385946</ref> <ref>PMID:19477666</ref> Defects in COL4A1 are the cause of hereditary angiopathy with nephropathy aneurysms and muscle cramps (HANAC) [MIM:[https://omim.org/entry/611773 611773]. The clinical renal manifestations include hematuria and bilateral large cysts. Histologic analysis revealed complex basement membrane defects in kidney and skin. The systemic angiopathy appears to affect both small vessels and large arteries.<ref>PMID:18160688</ref> <ref>PMID:20818663</ref> Defects in COL4A1 are a cause of familial porencephaly (POREN1) [MIM:[https://omim.org/entry/175780 175780]. Porencephaly is a term used for any cavitation or cerebrospinal fluid-filled cyst in the brain. Porencephaly type 1 is usually unilateral and results from focal destructive lesions such as fetal vascular occlusion or birth trauma. Type 2, or schizencephalic porencephaly, is usually symmetric and represents a primary defect or arrest in the development of the cerebral ventricles.<ref>PMID:15905400</ref> <ref>PMID:16107487</ref> <ref>PMID:19194877</ref> [https://www.uniprot.org/uniprot/CO4A2_HUMAN CO4A2_HUMAN] Defects in COL4A2 are the cause of porencephaly type 2 (POREN2) [MIM:[https://omim.org/entry/614483 614483]. POREN2 is a neurologic disorder characterized by a fluid-filled cysts or cavities within the cerebral hemispheres. Affected individuals typically have hemiplegia, seizures, and intellectual disability. Porencephaly type 2, or schizencephalic porencephaly, is usually symmetric and represents a primary defect in the development of the cerebral ventricles.<ref>PMID:22209246</ref> Defects in COL4A2 are a cause of susceptibility to intracerebral hemorrhage (ICH) [MIM:[https://omim.org/entry/614519 614519]. ICH is a pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.<ref>PMID:22209247</ref>

== Function ==

[https://www.uniprot.org/uniprot/CO4A1_HUMAN CO4A1_HUMAN] 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.<ref>PMID:10811134</ref> <ref>PMID:16481288</ref> <ref>PMID:16151532</ref> <ref>PMID:18775695</ref> Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation. Inhibits expression of hypoxia-inducible factor 1alpha and ERK1/2 and p38 MAPK activation. Ligand for alpha1/beta1 integrin.<ref>PMID:10811134</ref> <ref>PMID:16481288</ref> <ref>PMID:16151532</ref> <ref>PMID:18775695</ref> [https://www.uniprot.org/uniprot/CO4A2_HUMAN CO4A2_HUMAN] 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.<ref>PMID:10625665</ref> <ref>PMID:12876280</ref> <ref>PMID:15899827</ref> Canstatin, a cleavage product corresponding to the collagen alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity. It inhibits proliferation and migration of endothelial cells, reduces mitochondrial membrane potential, and induces apoptosis. Specifically induces Fas-dependent apoptosis and activates procaspase-8 and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins.<ref>PMID:10625665</ref> <ref>PMID:12876280</ref> <ref>PMID:15899827</ref>