COL4A1

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.

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.

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.

Involvement in disease

Hereditary angiopathy with nephropathy aneurysms and muscle cramps

HANAC

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Brain small vessel disease 1 with or without ocular anomalies

BSVD1

An autosomal dominant cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD1 features include cerebral hemorrage, unilateral fluid-filled cysts or cavities within the cerebral hemispheres, leukoencephalopathy, hemiplegia, seizures, intellectual disability, and facial paresis. Affected individuals may manifest variable visual defects and ocular anomalies.

None

The disease is caused by variants affecting the gene represented in this entry.

Intracerebral hemorrhage

ICH

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.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Tortuosity of retinal arteries

RATOR

A disease characterized by marked tortuosity of second- and third-order retinal arteries with normal first-order arteries and venous system. Most patients manifest variable degrees of symptomatic transient vision loss due to retinal hemorrhage following minor stress or trauma.

None

The disease is caused by variants affecting the gene represented in this entry.

Schizencephaly

SCHZC

Extremely rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro-spinal fluid.

None

The disease is caused by variants affecting the gene represented in this entry.

Microangiopathy and leukoencephalopathy, pontine, autosomal dominant

PADMAL

A form of cerebral small vessel disease characterized by the recurrence of ischemic strokes starting in the thirties or forties, and associated with progressive imbalance and cognitive impairment. MRI examination shows ischemic lacunas in the pons and cerebral hemispheres, and diffuse leukoencephalopathy affecting various brain regions.

None

The disease is caused by variants affecting the gene represented in this entry. Causative mutations affect a binding site for miR-29 microRNA located within the 3'UTR of COL4A1 and lead to an up-regulation of this gene.

Post-translational modifications

Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated. The modified lysines can be O-glycosylated.

Contains 4-hydroxyproline (Probable). Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains (By similarity).

Contains 3-hydroxyproline. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline.

Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding (PubMed:2844531). 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.

The trimeric structure of the NC1 domains is stabilized by covalent bonds (sulfilimine cross-links) between Lys and Met residues (PubMed:12011424). These cross-links are important for the mechanical stability of the basement membrane (By similarity).

Proteolytic processing produces the C-terminal NC1 peptide, arresten.

Sequence similarities

Belongs to the type IV collagen family.

Tissue specificity

Highly expressed in placenta.

Cellular localization

• Secreted
• Extracellular space
• Extracellular matrix
• Basement membrane

Alternative names

• Collagen alpha-1(IV) chain
• COL4A1

Database links

• entrezGene:1287
• entrezGene:1285
• entrezGene:1284
• entrezGene:1282
• entrezGene:1286
• omim:120070
• omim:120090
• omim:120131
• omim:303630
• omim:120130
• swissprot:P02462
• swissprot:P08572
• swissprot:P29400
• swissprot:P53420
• swissprot:Q01955

Target type

Proteins

Primary research area

Oncology

Other research areas

• Cardiovascular

Molecular weight

160611Da