Collagen, type I, alpha 1

COL1A1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3GXE, 1Q7D, 2LLP, 3EJH
Identifiers
Aliases	COL1A1 , EDSC, OI1, OI2, OI3, OI4, collagen type I alpha 1, collagen type I alpha 1 chain, EDSARTH1, CAFYD
External IDs	OMIM: 120150; MGI: 88467; HomoloGene: 73874; GeneCards: COL1A1; OMA:COL1A1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q21.33 Start 50,184,101 bp [1] End 50,201,632 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 59.01 cM|11 D Start 94,827,050 bp [2] End 94,843,868 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium skin of hip periodontal fiber gallbladder tendon of biceps brachii mucosa of paranasal sinus tibia cartilage tissue skin of thigh parietal pleura Top expressed in body of femur ankle tibiofemoral joint molar umbilical cord efferent ductule skin of back fossa ascending aorta calvaria More reference expression data BioGPS More reference expression data
Gene ontology Molecular function metal ion binding identical protein binding platelet-derived growth factor binding extracellular matrix structural constituent protein binding protease binding extracellular matrix structural constituent conferring tensile strength Cellular component endoplasmic reticulum lumen cytoplasm Golgi apparatus endoplasmic reticulum collagen secretory granule extracellular matrix extracellular space collagen type I trimer extracellular region collagen-containing extracellular matrix Biological process cellular response to tumor necrosis factor blood coagulation tooth eruption response to mechanical stimulus response to corticosteroid negative regulation of cell-substrate adhesion response to steroid hormone extracellular matrix organization osteoblast differentiation collagen fibril organization skin morphogenesis bone trabecula formation wound healing skin development intramembranous ossification positive regulation of cell migration tooth mineralization cellular response to epidermal growth factor stimulus cellular response to fibroblast growth factor stimulus response to estradiol collagen catabolic process response to cAMP cellular response to vitamin E response to fluoride cartilage development involved in endochondral bone morphogenesis hearing response to peptide hormone cellular response to retinoic acid cellular response to transforming growth factor beta stimulus regulation of immune response cellular response to fluoride positive regulation of transcription, DNA-templated leukocyte migration collagen biosynthetic process protein heterotrimerization cellular response to amino acid stimulus endochondral ossification response to hyperoxia face morphogenesis protein transport response to nutrient platelet activation visual perception positive regulation of epithelial to mesenchymal transition response to hydrogen peroxide embryonic skeletal system development skeletal system morphogenesis ossification response to nutrient levels positive regulation of canonical Wnt signaling pathway protein localization to nucleus cellular response to mechanical stimulus skeletal system development blood vessel development collagen-activated tyrosine kinase receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1277 12842 Ensembl ENSG00000108821 ENSMUSG00000001506 UniProt P02452 P11087 RefSeq (mRNA) NM_000088 NM_007742 RefSeq (protein) NP_000079 NP_031768 Location (UCSC) Chr 17: 50.18 – 50.2 Mb Chr 11: 94.83 – 94.84 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Collagen, type I, alpha 1, also known as alpha-1 type I collagen, is a protein that in humans is encoded by the COL1A1 gene. COL1A1 encodes the major component of type I collagen, the fibrillar collagen found in most connective tissues, including cartilage.

Function

Collagen is a protein that strengthens and supports many tissues in the body, including cartilage, bone, tendon, skin and the white part of the eye (sclera). The COL1A1 gene produces a component of type I collagen, called the pro-alpha1(I) chain. This chain combines with another pro-alpha1(I) chain and also with a pro-alpha2(I) chain (produced by the COL1A2 gene) to make a molecule of type I procollagen. These triple-stranded, rope-like procollagen molecules must be processed by enzymes outside the cell. Once these molecules are processed, they arrange themselves into long, thin fibrils that cross-link to one another in the spaces around cells. The cross-links result in the formation of very strong mature type I collagen fibers. Collagenous function includes rigidity and elasticity.

Gene

The COL1A1 gene is located on the long (q) arm of chromosome 17 between positions 21.3 and 22.1, from base pair 50183289 to base pair 50201632.

Clinical significance

Mutations in the COL1A1 gene are associated with the following conditions:

• Ehlers–Danlos syndrome, vascular type: In rare cases, specific heterozygous arginine-to-cysteine substitution mutations in COL1A1 that are also associated with vascular fragility and mimic COL3A1-vEDS
• Ehlers–Danlos syndrome, arthrochalasia type: It is caused by mutations in the COL1A1 gene. The mutations in the COL1A1 gene that cause this disorder instruct the cell to leave out a part of the pro-alpha1(I) chain that contains a segment used to attach one molecule to another. When this part of the protein is missing, the structure of type I collagen is compromised. Tissues that are rich in type I collagen, such as the skin, bones, and tendons, are affected by this change. Ehlers–Danlos type IV is most attributed to abnormalities in the reticular fibers (collagen Type III).
• Ehlers–Danlos syndrome, classical type: In rare cases, a mutation in the COL1A1 gene has been shown to cause the classical type of Ehlers–Danlos syndrome. This mutation substitutes the amino acid cysteine for the amino acid arginine at position 134 in the protein made by the gene. (The mutation can also be written as Arg134Cys.) The altered protein interacts abnormally with other collagen-building proteins, disrupting the structure of type I collagen fibrils and trapping collagen in the cell. Researchers believe that these changes in collagen cause the signs and symptoms of the disorder. Ehlers–Danlos type IV is most attributed to abnormalities in the reticular fibers (collagen Type III). Without the hydroxylation of lysine, by the enzyme lysyl hydroxylase, the final collagen structure cannot form.
• Osteogenesis imperfecta, type I: Osteogenesis imperfecta is the most common disorder caused by mutations in this gene. Mutations that inactivate one of the two copies of the COL1A1 gene cause osteogenesis imperfecta type I. The mutated copy of the gene does not produce any pro-alpha1(I) collagen chains. Because only one copy of the gene is directing the cell to make pro-alpha1(I) chains, cells from people with this disorder make only half of the normal amount of type I collagen, which results in bone fragility and other symptoms.
• Osteogenesis imperfecta, type II: Many different types of mutations in the COL1A1 gene can cause osteogenesis imperfecta type II. These mutations range from missing pieces of the COL1A1 gene to amino acid substitutions, in which the amino acid glycine is replaced by another amino acid in the protein strand. Sometimes one end of the gene (called the C-terminus) is altered, which interferes with the association of the protein strands. All of these changes prevent the normal production of mature type I collagen, which results in this severe condition, type II osteogenesis imperfecta.
• Osteogenesis imperfecta, type III: Mutations in the COL1A1 gene may result in the production of a protein that is missing segments, making it unusable for collagen production. Other mutations cause the amino acid glycine to be replaced by a different amino acid in the pro-alpha1(I) chain, which inhibits the essential interaction between protein chains. Type I collagen production is inhibited by the inability of the altered procollagen strands to associate and form the triple-stranded, ropelike structure of mature collagen. These alterations negatively affect tissues that are rich in type I collagen, such as the skin, bones, teeth, and tendons, leading to the signs and symptoms of type III osteogenesis imperfecta.
• Osteogenesis imperfecta, type IV: Several different types of mutations in the COL1A1 gene cause osteogenesis imperfecta type IV. These mutations may involve missing pieces of the COL1A1 gene or changes in base pairs (the building blocks of DNA). These gene alterations result in a protein that is missing segments or has amino acid substitutions; specifically, the amino acid glycine is replaced by another amino acid. All of these changes interfere with the formation of the mature triple-stranded collagen molecule and prevent the production of mature type I collagen, which results in type IV osteogenesis imperfecta.
• Osteoporosis: Osteoporosis is a condition that makes bones progressively more brittle and prone to fracturing. A particular variation (polymorphism) in the COL1A1 gene appears to increase the risk of developing osteoporosis. A specific variation at Sp1 binding site is shown to be associated with increased risk of low bone mass and vertebral fracture, because of the changes the COL1A1 protein produced from one copy of the gene. Several studies have shown that women with this particular genetic variation at Sp1 site are more likely to have signs of osteoporosis than are women without the variation.
• Predisposition to hernias. ^[5]
• Predisposition to degenerative disc disease, and disc herniation. ^[6]

References

1. GRCh38: Ensembl release 89: ENSG00000108821 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001506 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Sezer S, Şimşek N, Celik HT, Erden G, Ozturk G, Düzgün AP, et al. (Aug 2014). "Association of collagen type I alpha 1 gene polymorphism with inguinal hernia - PubMed". Hernia. 18 (4): 507–512. doi:10.1007/s10029-013-1147-y. PMID   23925543. S2CID   22999363.
6. Kawaguchi Y (2018). "Genetic background of degenerative disc disease in the lumbar spine". Spine Surgery and Related Research. 2 (2): 98–112. doi:10.22603/ssrr.2017-0007. PMC   6698496 . PMID   31440655.

Further reading

• Alvarez-Hernandez D, Naves M, Diaz-Lopez JB, Gomez C, Santamaria I, Cannata-Andia JB (Jun 2003). "Influence of polymorphisms in VDR and COLIA1 genes on the risk of osteoporotic fractures in aged men". Kidney International. Supplement. 63 (85): S14 –S18. doi: 10.1046/j.1523-1755.63.s85.5.x . PMID   12753258.
• Bou-Gharios G, Ponticos M, Rajkumar V, Abraham D (Jun 2004). "Extra-cellular matrix in vascular networks". Cell Proliferation. 37 (3): 207–220. doi:10.1111/j.1365-2184.2004.00306.x. PMC   6496925 . PMID   15144498.
• Chamberlain JR, Schwarze U, Wang PR, Hirata RK, Hankenson KD, Pace JM, et al. (Feb 2004). "Gene targeting in stem cells from individuals with osteogenesis imperfecta". Science. 303 (5661). New York, N.Y.: 1198–1201. Bibcode:2004Sci...303.1198C. doi:10.1126/science.1088757. PMID   14976317. S2CID   13212242.
• Forlino A, Marini JC (2000). "Osteogenesis imperfecta: prospects for molecular therapeutics". Molecular Genetics and Metabolism. 71 (1–2): 225–232. doi:10.1006/mgme.2000.3039. PMID   11001814.
• Karsenty G, Park RW (1995). "Regulation of type I collagen genes expression". International Reviews of Immunology. 12 (2–4): 177–185. doi:10.3109/08830189509056711. PMID   7650420.
• Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH (Oct 1996). "Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene". Nature Genetics. 14 (2): 203–205. doi:10.1038/ng1096-203. PMID   8841196. S2CID   20896127.
• Keen RW, Woodford-Richens KL, Grant SF, Ralston SH, Lanchbury JS, Spector TD (Feb 1999). "Association of polymorphism at the type I collagen (COL1A1) locus with reduced bone mineral density, increased fracture risk, and increased collagen turnover". Arthritis and Rheumatism. 42 (2): 285–290. doi: 10.1002/1529-0131(199902)42:2<285::AID-ANR10>3.0.CO;2-3 . PMID   10025922.
• Kocher MS, Shapiro F (1998). "Osteogenesis imperfecta". The Journal of the American Academy of Orthopaedic Surgeons. 6 (4): 225–236. doi:10.5435/00124635-199807000-00004. PMID   9682085.
• Mann V, Ralston SH (Jun 2003). "Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture". Bone. 32 (6): 711–717. doi:10.1016/S8756-3282(03)00087-5. PMID   12810179.
• Nuytinck L, Freund M, Lagae L, Pierard GE, Hermanns-Le T, De Paepe A (Apr 2000). "Classical Ehlers-Danlos syndrome caused by a mutation in type I collagen". American Journal of Human Genetics. 66 (4): 1398–1402. doi:10.1086/302859. PMC   1288203 . PMID   10739762.
• Persikov AV, Pillitteri RJ, Amin P, Schwarze U, Byers PH, Brodsky B (Oct 2004). "Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders". Human Mutation. 24 (4): 330–337. doi: 10.1002/humu.20091 . PMID   15365990. S2CID   34854398.
• Ralston SH (Jun 2002). "Genetic control of susceptibility to osteoporosis". The Journal of Clinical Endocrinology and Metabolism. 87 (6): 2460–2466. doi: 10.1210/jc.87.6.2460 . PMID   12050200.
• Byers PH, Wallis GA, Willing MC (Jul 1991). "Osteogenesis imperfecta: translation of mutation to phenotype". Journal of Medical Genetics. 28 (7): 433–442. doi:10.1136/jmg.28.7.433. PMC   1016951 . PMID   1895312.
• Kuivaniemi H, Tromp G, Prockop DJ (Apr 1991). "Mutations in collagen genes: causes of rare and some common diseases in humans". FASEB Journal. 5 (7): 2052–2060. doi: 10.1096/fasebj.5.7.2010058 . PMID   2010058. S2CID   24461341.
• Kuivaniemi H, Tromp G, Prockop DJ (1997). "Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels". Human Mutation. 9 (4): 300–315. doi: 10.1002/(SICI)1098-1004(1997)9:4<300::AID-HUMU2>3.0.CO;2-9 . PMID   9101290. S2CID   6890740.
• Rossert J, Terraz C, Dupont S (2001). "Regulation of type I collagen genes expression". Nephrology, Dialysis, Transplantation. 15 (Suppl 6): 66–68. doi: 10.1093/ndt/15.suppl_6.66 . PMID   11143996.

External links

• GeneReviews/NCBI/NIH/UW entry on Osteogenesis Imperfecta
• Online Mendelian Inheritance in Man (OMIM): 120150
• EntrezGene 1277
• COL1A1 GeneCard
• Database of human type I and type III collagen mutations
• Overview of all the structural information available in the PDB for UniProt : P02452 (Collagen alpha-1(I) chain) at the PDBe-KB .