Cyanocobalamin (T3D0673)

General Function:

Oxidoreductase activity, oxidizing metal ions, nad or nadp as acceptor

Specific Function:

Involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state. Necessary for utilization of methylgroups from the folate cycle, thereby affecting transgenerational epigenetic inheritance. Folate pathway donates methyl groups necessary for cellular methylation and affects different pathways such as DNA methylation, possibly explaining the transgenerational epigenetic inheritance effects.

Gene Name:

MTRR

Uniprot ID:

Q9UBK8

Molecular Weight:

80409.22 Da

References

1. O'Leary VB, Mills JL, Pangilinan F, Kirke PN, Cox C, Conley M, Weiler A, Peng K, Shane B, Scott JM, Parle-McDermott A, Molloy AM, Brody LC: Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. Mol Genet Metab. 2005 Jul;85(3):220-7. Epub 2005 Mar 17. [15979034 ]
2. Gueant-Rodriguez RM, Juilliere Y, Candito M, Adjalla CE, Gibelin P, Herbeth B, Van Obberghen E, Gueant JL: Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population. Thromb Haemost. 2005 Sep;94(3):510-5. [16268464 ]
3. Miriuka SG, Langman LJ, Evrovski J, Miner SE, D'Mello N, Delgado DH, Wong BY, Ross HJ, Cole DE: Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. Transpl Int. 2005 Jan;18(1):29-35. [15612980 ]
4. Berkun Y, Abou Atta I, Rubinow A, Orbach H, Levartovsky D, Aamar S, Arbel O, Dresner-Pollak R, Friedman G, Ben-Yehuda A: 2756GG genotype of methionine synthase reductase gene is more prevalent in rheumatoid arthritis patients treated with methotrexate and is associated with methotrexate-induced nodulosis. J Rheumatol. 2007 Aug;34(8):1664-9. Epub 2007 Jul 1. [17611986 ]
5. van der Linden IJ, den Heijer M, Afman LA, Gellekink H, Vermeulen SH, Kluijtmans LA, Blom HJ: The methionine synthase reductase 66A>G polymorphism is a maternal risk factor for spina bifida. J Mol Med (Berl). 2006 Dec;84(12):1047-54. Epub 2006 Oct 6. [17024475 ]

General Function:

Metal ion binding

Specific Function:

Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.

Gene Name:

TCN2

Uniprot ID:

P20062

Molecular Weight:

47534.54 Da

References

1. Al-Alami JR, Tanner SM, Tayeh MK, de la Chapelle A, El-Shanti H: Homozygous AMN mutation in hereditary selective intestinal malabsorption of vitamin B12 in Jordan. Saudi Med J. 2005 Jul;26(7):1061-4. [16047053 ]
2. Chen X, Remacha AF, Sarda MP, Carmel R: Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holo-transcobalamin II. Am J Clin Nutr. 2005 Jan;81(1):110-4. [15640468 ]
3. Alessio AC, Hoehr NF, Siqueira LH, Bydlowski SP, Annichino-Bizzacchi JM: Polymorphism C776G in the transcobalamin II gene and homocysteine, folate and vitamin B12 concentrations. Association with MTHFR C677T and A1298C and MTRR A66G polymorphisms in healthy children. Thromb Res. 2007;119(5):571-7. Epub 2006 Jul 3. [16820193 ]
4. Bowen RA, Drake SK, Vanjani R, Huey ED, Grafman J, Horne MK 3rd: Markedly increased vitamin B12 concentrations attributable to IgG-IgM-vitamin B12 immune complexes. Clin Chem. 2006 Nov;52(11):2107-14. [17068171 ]
5. Bosco P, Gueant-Rodriguez RM, Anello G, Spada R, Romano A, Fajardo A, Caraci F, Ferri R, Gueant JL: Association of homocysteine (but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66 A>G and TCN2 776 C>G) with ischaemic cerebrovascular disease in Sicily. Thromb Haemost. 2006 Aug;96(2):154-9. [16894458 ]

General Function:

Cobalamin binding

Specific Function:

May be involved in the binding and intracellular trafficking of cobalamin (vitamin B12).

Gene Name:

MMACHC

Uniprot ID:

Q9Y4U1

Molecular Weight:

31728.095 Da

References

1. Chandler RJ, Aswani V, Tsai MS, Falk M, Wehrli N, Stabler S, Allen R, Sedensky M, Kazazian HH, Venditti CP: Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism. Mol Genet Metab. 2006 Sep-Oct;89(1-2):64-73. Epub 2006 Jul 14. [16843692 ]
2. Ben-Omran TI, Wong H, Blaser S, Feigenbaum A: Late-onset cobalamin-C disorder: a challenging diagnosis. Am J Med Genet A. 2007 May 1;143A(9):979-84. [17431913 ]
3. Morel CF, Lerner-Ellis JP, Rosenblatt DS: Combined methylmalonic aciduria and homocystinuria (cblC): phenotype-genotype correlations and ethnic-specific observations. Mol Genet Metab. 2006 Aug;88(4):315-21. Epub 2006 May 22. [16714133 ]
4. Lerner-Ellis JP, Tirone JC, Pawelek PD, Dore C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS: Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Nat Genet. 2006 Jan;38(1):93-100. Epub 2005 Nov 27. [16311595 ]

General Function:

Hydrolase activity

Specific Function:

Probable GTPase. May function as chaperone. May be involved in the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis.

Gene Name:

MMAA

Uniprot ID:

Q8IVH4

Molecular Weight:

46537.865 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
3. Lerner-Ellis JP, Dobson CM, Wai T, Watkins D, Tirone JC, Leclerc D, Dore C, Lepage P, Gravel RA, Rosenblatt DS: Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism. Hum Mutat. 2004 Dec;24(6):509-16. [15523652 ]
4. Dobson CM, Gradinger A, Longo N, Wu X, Leclerc D, Lerner-Ellis J, Lemieux M, Belair C, Watkins D, Rosenblatt DS, Gravel RA: Homozygous nonsense mutation in the MCEE gene and siRNA suppression of methylmalonyl-CoA epimerase expression: a novel cause of mild methylmalonic aciduria. Mol Genet Metab. 2006 Aug;88(4):327-33. Epub 2006 May 11. [16697227 ]

General Function:

Modified amino acid binding

Specific Function:

Involved in the degradation of several amino acids, odd-chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle. MCM has different functions in other species.

Gene Name:

MUT

Uniprot ID:

P22033

Molecular Weight:

83133.755 Da

References

1. Worgan LC, Niles K, Tirone JC, Hofmann A, Verner A, Sammak A, Kucic T, Lepage P, Rosenblatt DS: Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype. Hum Mutat. 2006 Jan;27(1):31-43. [16281286 ]
2. Brooks AJ, Vlasie M, Banerjee R, Brunold TC: Co-C bond activation in methylmalonyl-CoA mutase by stabilization of the post-homolysis product Co2+ cobalamin. J Am Chem Soc. 2005 Nov 30;127(47):16522-8. [16305240 ]
3. Kozlowski PM, Andruniow T, Jarzecki AA, Zgierski MZ, Spiro TG: DFT analysis of co-alkyl and co-adenosyl vibrational modes in B12-cofactors. Inorg Chem. 2006 Jul 10;45(14):5585-90. [16813422 ]
4. Moras E, Hosack A, Watkins D, Rosenblatt DS: Mitochondrial vitamin B12-binding proteins in patients with inborn errors of cobalamin metabolism. Mol Genet Metab. 2007 Feb;90(2):140-7. Epub 2006 Sep 29. [17011224 ]

General Function:

Transporter activity

Specific Function:

Cotransporter which plays a role in lipoprotein, vitamin and iron metabolism, by facilitating their uptake. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the GIF-cobalamin complex. The binding of all ligands requires calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. Interaction with LRP2 mediates its trafficking throughout vesicles and facilitates the uptake of specific ligands like GC, hemoglobin, ALB, TF and SCGB1A1. Interaction with AMN controls its trafficking to the plasma membrane and facilitates endocytosis of ligands. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface.

Gene Name:

CUBN

Uniprot ID:

O60494

Molecular Weight:

398732.93 Da

References

1. Fedosov SN, Fedosova NU, Berglund L, Moestrup SK, Nexo E, Petersen TE: Composite organization of the cobalamin binding and cubilin recognition sites of intrinsic factor. Biochemistry. 2005 Mar 8;44(9):3604-14. [15736970 ]
2. He Q, Madsen M, Kilkenney A, Gregory B, Christensen EI, Vorum H, Hojrup P, Schaffer AA, Kirkness EF, Tanner SM, de la Chapelle A, Giger U, Moestrup SK, Fyfe JC: Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood. 2005 Aug 15;106(4):1447-53. Epub 2005 Apr 21. [15845892 ]
3. Moestrup SK: New insights into carrier binding and epithelial uptake of the erythropoietic nutrients cobalamin and folate. Curr Opin Hematol. 2006 May;13(3):119-23. [16567952 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.

Gene Name:

CA1

Uniprot ID:

P00915

Molecular Weight:

28870.0 Da

References

1. Ekinci D, Beydemir S, Kufrevioglu OI: In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. J Enzyme Inhib Med Chem. 2007 Dec;22(6):745-50. doi: 10.1080/14756360601176048 . [18237030 ]
2. Ul-Hassan M, Scozzafava A, Chohan ZH, Supuran CT: Carbonic anhydrase inhibitors: metal complexes of a sulfanilamide derived Schiff base and their interaction with isozymes I, II and IV. J Enzyme Inhib. 2001 Dec;16(6):499-505. [12164389 ]

General Function:

Zinc ion binding

Specific Function:

Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.

Gene Name:

CA2

Uniprot ID:

P00918

Molecular Weight:

29245.895 Da

References

1. Ekinci D, Beydemir S, Kufrevioglu OI: In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. J Enzyme Inhib Med Chem. 2007 Dec;22(6):745-50. doi: 10.1080/14756360601176048 . [18237030 ]
2. Ul-Hassan M, Scozzafava A, Chohan ZH, Supuran CT: Carbonic anhydrase inhibitors: metal complexes of a sulfanilamide derived Schiff base and their interaction with isozymes I, II and IV. J Enzyme Inhib. 2001 Dec;16(6):499-505. [12164389 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.

Gene Name:

CA4

Uniprot ID:

P22748

Molecular Weight:

35032.075 Da

References

1. Ekinci D, Beydemir S, Kufrevioglu OI: In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. J Enzyme Inhib Med Chem. 2007 Dec;22(6):745-50. doi: 10.1080/14756360601176048 . [18237030 ]
2. Ul-Hassan M, Scozzafava A, Chohan ZH, Supuran CT: Carbonic anhydrase inhibitors: metal complexes of a sulfanilamide derived Schiff base and their interaction with isozymes I, II and IV. J Enzyme Inhib. 2001 Dec;16(6):499-505. [12164389 ]

General Function:

Cob(i)yrinic acid a,c-diamide adenosyltransferase activity

Specific Function:

Not Available

Gene Name:

MMAB

Uniprot ID:

Q96EY8

Molecular Weight:

27387.975 Da

References

1. Zhang J, Dobson CM, Wu X, Lerner-Ellis J, Rosenblatt DS, Gravel RA: Impact of cblB mutations on the function of ATP:cob(I)alamin adenosyltransferase in disorders of vitamin B12 metabolism. Mol Genet Metab. 2006 Apr;87(4):315-22. Epub 2006 Jan 24. [16439175 ]
2. Lerner-Ellis JP, Gradinger AB, Watkins D, Tirone JC, Villeneuve A, Dobson CM, Montpetit A, Lepage P, Gravel RA, Rosenblatt DS: Mutation and biochemical analysis of patients belonging to the cblB complementation class of vitamin B12-dependent methylmalonic aciduria. Mol Genet Metab. 2006 Mar;87(3):219-25. Epub 2006 Jan 10. [16410054 ]

General Function:

Protein complex binding

Specific Function:

Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.

Gene Name:

MTHFR

Uniprot ID:

P42898

Molecular Weight:

74595.895 Da

References

1. Nakamura T, Saionji K, Hiejima Y, Hirayama H, Tago K, Takano H, Tajiri M, Hayashi K, Kawabata M, Funamizu M, Makita Y, Hata A: Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients. Am J Kidney Dis. 2002 May;39(5):1032-9. [11979347 ]
2. Erdogan MO, Yildiz SH, Solak M, Eser O, Cosar E, Eser B, Koken R, Buyukbas S: C677T polymorphism of the methylenetetrahydrofolate reductase gene does not affect folic acid, vitamin B12, and homocysteine serum levels in Turkish children with neural tube defects. Genet Mol Res. 2010 Jun 22;9(2):1197-203. doi: 10.4238/vol9-2gmr816. [20589617 ]

General Function:

Cobalamin binding

Specific Function:

Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach.

Gene Name:

TCN1

Uniprot ID:

P20061

Molecular Weight:

48206.32 Da

References

1. Carmel R: Haptocorrin (transcobalamin I) and cobalamin deficiencies. Clin Chem. 2007 Feb;53(2):367-8; author reply 368-9. [17259255 ]
2. Al-Alami JR, Tanner SM, Tayeh MK, de la Chapelle A, El-Shanti H: Homozygous AMN mutation in hereditary selective intestinal malabsorption of vitamin B12 in Jordan. Saudi Med J. 2005 Jul;26(7):1061-4. [16047053 ]

General Function:

Pyridoxal phosphate binding

Specific Function:

Not Available

Gene Name:

ALAS2

Uniprot ID:

P22557

Molecular Weight:

64632.86 Da

References

1. Wikipedia. Mercury poisoning. Last Updated 8 March 2009. [Link]

General Function:

Pyridoxal phosphate binding

Specific Function:

Not Available

Gene Name:

ALAS1

Uniprot ID:

P13196

Molecular Weight:

70580.325 Da

References

1. Wikipedia. Mercury poisoning. Last Updated 8 March 2009. [Link]

General Function:

Used for biological information storage.

Specific Function:

DNA contains the instructions needed for an organism to develop, survive and reproduce.

Molecular Weight:

2.15 x 10¹² Da

References

1. ATSDR - Agency for Toxic Substances and Disease Registry (2004). Toxicological profile for cobalt. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]

General Function:

Protein homodimerization activity

Specific Function:

Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.

Gene Name:

XPA

Uniprot ID:

P23025

Molecular Weight:

31367.71 Da

References

1. Hartwig A, Asmuss M, Ehleben I, Herzer U, Kostelac D, Pelzer A, Schwerdtle T, Burkle A: Interference by toxic metal ions with DNA repair processes and cell cycle control: molecular mechanisms. Environ Health Perspect. 2002 Oct;110 Suppl 5:797-9. [12426134 ]

General Function:

Antigen binding

Specific Function:

Ig alpha is the major immunoglobulin class in body secretions. It may serve both to defend against local infection and to prevent access of foreign antigens to the general immunologic system.

Gene Name:

IGHA1

Uniprot ID:

P01876

Molecular Weight:

37654.29 Da

References

1. Bencko V, Wagner V, Wagnerova M, Reichrtova E: Immuno-biochemical findings in groups of individuals occupationally and non-occupationally exposed to emissions containing nickel and cobalt. J Hyg Epidemiol Microbiol Immunol. 1983;27(4):387-94. [6663071 ]

General Function:

Antigen binding

Specific Function:

Ig alpha is the major immunoglobulin class in body secretions. It may serve both to defend against local infection and to prevent access of foreign antigens to the general immunologic system.

Gene Name:

IGHA2

Uniprot ID:

P01877

Molecular Weight:

36526.005 Da

References

1. Bencko V, Wagner V, Wagnerova M, Reichrtova E: Immuno-biochemical findings in groups of individuals occupationally and non-occupationally exposed to emissions containing nickel and cobalt. J Hyg Epidemiol Microbiol Immunol. 1983;27(4):387-94. [6663071 ]

General Function:

Immunoglobulin receptor binding

Specific Function:

Not Available

Gene Name:

IGHE

Uniprot ID:

P01854

Molecular Weight:

47018.665 Da

References

1. Shirakawa T, Kusaka Y, Fujimura N, Goto S, Morimoto K: The existence of specific antibodies to cobalt in hard metal asthma. Clin Allergy. 1988 Sep;18(5):451-60. [3233723 ]

General Function:

Zinc ion binding

Specific Function:

Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites.

Gene Name:

PARP1

Uniprot ID:

P09874

Molecular Weight:

113082.945 Da

References

1. Hartwig A, Asmuss M, Ehleben I, Herzer U, Kostelac D, Pelzer A, Schwerdtle T, Burkle A: Interference by toxic metal ions with DNA repair processes and cell cycle control: molecular mechanisms. Environ Health Perspect. 2002 Oct;110 Suppl 5:797-9. [12426134 ]

General Function:

Receptor binding

Specific Function:

Necessary for efficient absorption of vitamin B12. May direct the production of trunk mesoderm during development by modulating a bone morphogenetic protein (BMP) signaling pathway in the underlying visceral endoderm (By similarity).

Gene Name:

AMN

Uniprot ID:

Q9BXJ7

Molecular Weight:

47753.91 Da

References

1. Al-Alami JR, Tanner SM, Tayeh MK, de la Chapelle A, El-Shanti H: Homozygous AMN mutation in hereditary selective intestinal malabsorption of vitamin B12 in Jordan. Saudi Med J. 2005 Jul;26(7):1061-4. [16047053 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.

Gene Name:

CACNA1C

Uniprot ID:

Q13936

Molecular Weight:

248974.1 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity involved sa node cell action potential

Specific Function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).

Gene Name:

CACNA1D

Uniprot ID:

Q01668

Molecular Weight:

245138.75 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).

Gene Name:

CACNA1F

Uniprot ID:

O60840

Molecular Weight:

220675.9 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.

Gene Name:

CACNA1S

Uniprot ID:

Q13698

Molecular Weight:

212348.1 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.

Gene Name:

CACNB1

Uniprot ID:

Q02641

Molecular Weight:

65712.995 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.

Gene Name:

CACNB2

Uniprot ID:

Q08289

Molecular Weight:

73579.925 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.

Gene Name:

CACNB3

Uniprot ID:

P54284

Molecular Weight:

54531.425 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.

Gene Name:

CACNB4

Uniprot ID:

O00305

Molecular Weight:

58168.625 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.

Gene Name:

CACNA1B

Uniprot ID:

Q00975

Molecular Weight:

262493.84 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin-IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA).

Gene Name:

CACNA1A

Uniprot ID:

O00555

Molecular Weight:

282362.39 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents. R-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by nickel, and partially by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), omega-conotoxin-GVIA (omega-CTx-GVIA), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1E subunit could be involved in the modulation of firing patterns of neurons which is important for information processing.

Gene Name:

CACNA1E

Uniprot ID:

Q15878

Molecular Weight:

261729.05 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex.

Gene Name:

CACNG1

Uniprot ID:

Q06432

Molecular Weight:

25028.105 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.

Gene Name:

CACNG2

Uniprot ID:

Q9Y698

Molecular Weight:

35965.44 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity).

Gene Name:

CACNG3

Uniprot ID:

O60359

Molecular Weight:

35548.14 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.

Gene Name:

CACNG4

Uniprot ID:

Q9UBN1

Molecular Weight:

36578.39 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Regulates the gating properties of AMPA-selective glutamate receptors (AMPARs). Modulates their gating properties by accelerating their rates of activation, deactivation and desensitization. Displays subunit-specific AMPA receptor regulation. Shows specificity for GRIA1, GRIA4 and the long isoform of GRIA2. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity).

Gene Name:

CACNG5

Uniprot ID:

Q9UF02

Molecular Weight:

30902.44 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Thought to stabilize the calcium channel in an inactivated (closed) state.

Gene Name:

CACNG6

Uniprot ID:

Q9BXT2

Molecular Weight:

28128.745 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Displays subunit-specific AMPA receptor regulation. Shows specificity only for GRIA1 and GRIA2. Thought to stabilize the calcium channel in an inactivated (closed) state.

Gene Name:

CACNG7

Uniprot ID:

P62955

Molecular Weight:

31002.29 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.

Gene Name:

CACNG8

Uniprot ID:

Q8WXS5

Molecular Weight:

43312.44 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated ion channel activity

Specific Function:

Thought to stabilize the calcium channel in an inactivated (closed) state. Modulates calcium current when coexpressed with CACNA1G (By similarity).

Gene Name:

TMEM37

Uniprot ID:

Q8WXS4

Molecular Weight:

20931.565 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling (By similarity).

Gene Name:

CACNA2D1

Uniprot ID:

P54289

Molecular Weight:

124566.93 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosis.

Gene Name:

CACNA2D2

Uniprot ID:

Q9NY47

Molecular Weight:

129816.095 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated ion channel activity

Specific Function:

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity).

Gene Name:

CACNA2D3

Uniprot ID:

Q8IZS8

Molecular Weight:

123010.22 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Voltage-gated calcium channel activity

Specific Function:

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.

Gene Name:

CACNA2D4

Uniprot ID:

Q7Z3S7

Molecular Weight:

127936.93 Da

References

1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]

General Function:

Zinc ion binding

Specific Function:

Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).

Gene Name:

MTR

Uniprot ID:

Q99707

Molecular Weight:

140525.91 Da