Collagen, type IV, alpha 4 explained

Collagen alpha-4(IV) chain is a protein that in humans is encoded by the COL4A4 gene.^{[1] [2]}

This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. 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. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3' UTR.

Disease Database

LOVD Alport gene variant databases (COL4A4, COL4A3, COL4A5)

Further reading

• Hinek A . Nature and the multiple functions of the 67-kD elastin-/laminin binding protein . Cell Adhes. Commun. . 2 . 3 . 185–93 . 1995 . 7827955 . 10.3109/15419069409004436 .
• Hudson BG, Reeders ST, Tryggvason K . Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis . J. Biol. Chem. . 268 . 35 . 26033–6 . 1994 . 10.1016/S0021-9258(19)74270-7 . 8253711 . free .
• Lemmink HH, Schröder CH, Monnens LA, Smeets HJ . The clinical spectrum of type IV collagen mutations . Hum. Mutat. . 9 . 6 . 477–99 . 1997 . 9195222 . 10.1002/(SICI)1098-1004(1997)9:6<477::AID-HUMU1>3.0.CO;2-# . 2066/25010 . 196601220 . free .
• Ständer M, Naumann U, Wick W, Weller M . Transforming growth factor-beta and p-21: multiple molecular targets of decorin-mediated suppression of neoplastic growth . Cell Tissue Res. . 296 . 2 . 221–7 . 1999 . 10382266 . 10.1007/s004410051283 . 20282995 .
• Kurpakus Wheater M, Kernacki KA, Hazlett LD . Corneal cell proteins and ocular surface pathology . Biotechnic & Histochemistry . 74 . 3 . 146–59 . 1999 . 10416788 . 10.3109/10520299909047967.
• Pescucci C, Longo I, Bruttini M . Type-IV collagen related diseases . J. Nephrol. . 16 . 2 . 314–6 . 2003 . 12768082 . etal.
• Torra R, Tazón-Vega B, Ars E, Ballarín J . Collagen type IV (alpha3-alpha4) nephropathy: from isolated haematuria to renal failure . Nephrol. Dial. Transplant. . 19 . 10 . 2429–32 . 2005 . 15280517 . 10.1093/ndt/gfh435 . free .
• Rana K, Wang YY, Buzza M . The genetics of thin basement membrane nephropathy . Semin. Nephrol. . 25 . 3 . 163–70 . 2005 . 15880327 . 10.1016/j.semnephrol.2005.01.008 . etal.
• Maziers N, Dahan K, Pirson Y . [From Alport syndrome to benign familial hematuria: clinical and genetic aspect] . Nephrol. Ther. . 1 . 2 . 90–100 . 2006 . 16895672 . 10.1016/j.nephro.2005.03.005 .
• Kamagata Y, Mattei MG, Ninomiya Y . Isolation and sequencing of cDNAs and genomic DNAs encoding the alpha 4 chain of basement membrane collagen type IV and assignment of the gene to the distal long arm of human chromosome 2 . J. Biol. Chem. . 267 . 33 . 23753–8 . 1992 . 10.1016/S0021-9258(18)35902-7 . 1429714 . free .
• Gupta S, Batchu RB, Datta K . Purification, partial characterization of rat kidney hyaluronic acid binding protein and its localization on the cell surface . Eur. J. Cell Biol. . 56 . 1 . 58–67 . 1992 . 1724753 .
• Sanes JR, Engvall E, Butkowski R, Hunter DD . Molecular heterogeneity of basal laminae: isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere . J. Cell Biol. . 111 . 4 . 1685–99 . 1990 . 2211832 . 10.1083/jcb.111.4.1685 . 2116223 .
• Gunwar S, Saus J, Noelken ME, Hudson BG . Glomerular basement membrane. Identification of a fourth chain, alpha 4, of type IV collagen . J. Biol. Chem. . 265 . 10 . 5466–9 . 1990 . 10.1016/S0021-9258(19)39384-6 . 2318822 . free .
• Hernandez MR, Igoe F, Neufeld AH . Extracellular matrix of the human optic nerve head . Am. J. Ophthalmol. . 102 . 2 . 139–48 . 1986 . 2426947 . 10.1016/0002-9394(86)90134-0 .
• Murata K, Motayama T, Kotake C . Collagen types in various layers of the human aorta and their changes with the atherosclerotic process . Atherosclerosis . 60 . 3 . 251–62 . 1986 . 3089234 . 10.1016/0021-9150(86)90172-3 .
• Glant TT, Hadházy C, Mikecz K, Sipos A . Appearance and persistence of fibronectin in cartilage. Specific interaction of fibronectin with collagen type II . Histochemistry . 82 . 2 . 149–58 . 1985 . 3997552 . 10.1007/bf00708199. 19401258 .
• Uscanga L, Kennedy RH, Stocker S . Immunolocalization of collagen types, laminin and fibronectin in the normal human pancreas . Digestion . 30 . 3 . 158–64 . 1984 . 6389236 . 10.1159/000199100 . etal.
• Sundarraj N, Willson J . Monoclonal antibody to human basement membrane collagen type IV . Immunology . 47 . 1 . 133–40 . 1982 . 6811420 . 1555500 .
• Hahn E, Wick G, Pencev D, Timpl R . Distribution of basement membrane proteins in normal and fibrotic human liver: collagen type IV, laminin, and fibronectin . Gut . 21 . 1 . 63–71 . 1980 . 6988303 . 10.1136/gut.21.1.63 . 1419572 .

Notes and References

1. Mariyama M, Zheng K, Yang-Feng TL, Reeders ST . Colocalization of the genes for the alpha 3(IV) and alpha 4(IV) chains of type IV collagen to chromosome 2 bands q35-q37 . Genomics . 13 . 3 . 809–13 . Aug 1992 . 1639407 . 10.1016/0888-7543(92)90157-N . free .
2. Web site: Entrez Gene: COL4A4 collagen, type IV, alpha 4.