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Record Information
Version2.0
Creation Date2009-03-22 21:24:53 UTC
Update Date2014-12-24 20:22:31 UTC
Accession NumberT3D0673
Identification
Common NameCyanocobalamin
ClassSmall Molecule
DescriptionCyanocobalamin (commonly known as Vitamin B12) is the most chemically complex of all the vitamins. Cyanocobalamin's structure is based on a corrin ring, which, although similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion is Co (cobalt). Cyanocobalamin cannot be made by plants or by animals, as the only type of organisms that have the enzymes required for the synthesis of cyanocobalamin are bacteria and archaea. Higher plants do not concentrate cyanocobalamin from the soil and so are a poor source of the substance as compared with animal tissues. Cyanocobalamin is naturally found in foods including meat (especially liver and shellfish), eggs, and milk products. [HMDB]
Compound Type
  • Anti-Anemic Agent
  • Cobalt Compound
  • Drug
  • Essential Vitamin
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Nutraceutical
  • Pollutant
  • Vitamin
  • Vitamin B Complex
Chemical Structure
Thumb
Synonyms
Synonym
Anacobin
Bedodeka
Bedoz
Berubigen
Betalin
Betalin 12 Crystalline
Betaline-12
Betolvex
Bevidox
Bevidox concentrate
Biocobalamine
Byladoce
Cabadon M
Cobadoce forte
Cobalin
Cobavite
Cobione
Cobolin-M
Copharvit 5000
Covit
Crystamin
Crystamine
Crystimin
Crystwel
Cyano-B12
Cyanobalamin concentrate
Cyanocob(III)alamin
Cyanocobalamine
Cyanocobalmin
Cyanoject
Cycobemin
Cycolamin
Cykobemin
Cykobeminet
Cyomin
Cyredin
Cytacon
Cytakon
Cytamen
Cytobion
Depinar
Dicopac
Dimethylbenzimidazoylcobamide
Distivit
Docemine
Docibin
Docivit
Dodecabee
Dodecavite
Dodex
Duodecibin
Embiol
Emociclina
Eritrone
Erycytol
Erythrotin
Euhaemon
Extrinsic factor
Factor II
Fermin
Fresmin
Hemomin
Hepagon
Hepavis
Hepcovite
Hylugel plus
Macrabin
Megabion
Megalovel
Milbedoce
Millevit
Nagravon
Nascobal
Neuroforte-R
Normocytin
Novidroxin
Pernaemon
Pernaevit
Pernipuron
Plecyamin
Poyamin
Primabalt
Rebramin
Redamina
Redisol
Rhodacryst
Rubesol
Rubramin
Rubramin PC
Rubripca
Rubrocitol
Sytobex
Vibalt
Vibisone
Virubra
Vita-rubra
Vitabee 12
Vitamin B12
Vitamin B12 complex
Vitamin B12 Preparation
Vitarubin
Vitral
Chemical FormulaC63H88CoN14O14P
Average Molecular Mass1355.365 g/mol
Monoisotopic Mass1354.567 g/mol
CAS Registry Number68-19-9
IUPAC Name(10S,12R,13S,17R,23R,24R,25R,30S,35S,36S,40S,41S,42R,46R)-30,35,40-tris(2-carbamoylethyl)-24,36,41-tris(carbamoylmethyl)-1-cyano-46-hydroxy-12-(hydroxymethyl)-5,6,17,23,28,31,31,36,38,41,42-undecamethyl-15,20-dioxo-11,14,16-trioxa-2λ⁵,9,19,26,43λ⁵,44λ⁵,45λ⁵-heptaaza-15λ⁵-phospha-1-cobaltadodecacyclo[27.14.1.1¹,³⁴.1²,⁹.1¹⁰,¹³.0¹,²⁶.0³,⁸.0²³,²⁷.0²⁵,⁴².0³²,⁴⁴.0³⁹,⁴³.0³⁷,⁴⁵]heptatetraconta-2(47),3,5,7,27,29(44),32,34(45),37,39(43)-decaene-2,43,44,45-tetrakis(ylium)-1,1,1-triuid-15-olate
Traditional Name(10S,12R,13S,17R,23R,24R,25R,30S,35S,36S,40S,41S,42R,46R)-30,35,40-tris(2-carbamoylethyl)-24,36,41-tris(carbamoylmethyl)-1-cyano-46-hydroxy-12-(hydroxymethyl)-5,6,17,23,28,31,31,36,38,41,42-undecamethyl-15,20-dioxo-11,14,16-trioxa-2λ⁵,9,19,26,43λ⁵,44λ⁵,45λ⁵-heptaaza-15λ⁵-phospha-1-cobaltadodecacyclo[27.14.1.1¹,³⁴.1²,⁹.1¹⁰,¹³.0¹,²⁶.0³,⁸.0²³,²⁷.0²⁵,⁴².0³²,⁴⁴.0³⁹,⁴³.0³⁷,⁴⁵]heptatetraconta-2(47),3,5,7,27,29(44),32,34(45),37,39(43)-decaene-2,43,44,45-tetrakis(ylium)-1,1,1-triuid-15-olate
SMILES[C@H]1([C@@H]2[C@H]([C@@H](N3C4=CC(=C(C)C=C4[N+]([Co-3]456(N7C8=C(C9=[N+]4C(C([C@@H]9CCC(N)=O)(C)C)=CC4=[N+]5C(=C(C5=[N+]6[C@@]([C@]7([C@@H]([C@@]8(C)CCC(=O)NC[C@@]([H])(C)OP([O-])(=O)O2)CC(N)=O)[H])([C@@]([C@@H]5CCC(N)=O)(C)CC(N)=O)C)C)[C@@]([C@@H]4CCC(N)=O)(C)CC(N)=O)C)C#N)=C3)C)O1)O)CO
InChI IdentifierInChI=1S/C62H90N13O14P.CN.Co/c1-29-20-39-40(21-30(29)2)75(28-70-39)57-52(84)53(41(27-76)87-57)89-90(85,86)88-31(3)26-69-49(83)18-19-59(8)37(22-46(66)80)56-62(11)61(10,25-48(68)82)36(14-17-45(65)79)51(74-62)33(5)55-60(9,24-47(67)81)34(12-15-43(63)77)38(71-55)23-42-58(6,7)35(13-16-44(64)78)50(72-42)32(4)54(59)73-56;1-2;/h20-21,23,28,31,34-37,41,52-53,56-57,76,84H,12-19,22,24-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);;/q;;+2/p-2/t31-,34-,35-,36-,37+,41-,52-,53-,56-,57+,59-,60+,61+,62+;;/m1../s1
InChI KeyInChIKey=RMRCNWBMXRMIRW-WZHZPDAFSA-L
Chemical Taxonomy
Description belongs to the class of organic compounds known as glutamic acid and derivatives. Glutamic acid and derivatives are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentGlutamic acid and derivatives
Alternative Parents
Substituents
  • Glutamic acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Hippuric acid or derivatives
  • Pterin
  • Aminobenzamide
  • Aminobenzoic acid or derivatives
  • Pteridine
  • Benzamide
  • Benzoic acid or derivatives
  • Aniline or substituted anilines
  • Benzoyl
  • Phenylalkylamine
  • Hydroxypyrimidine
  • Secondary aliphatic/aromatic amine
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Amino acid
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Organoheterocyclic compound
  • Azacycle
  • Carboxylic acid
  • Secondary amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Amine
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Adrenal Cortex
  • Adrenal Gland
  • Adrenal Medulla
  • All Tissues
  • Bladder
  • Brain
  • Epidermis
  • Fibroblasts
  • Gonads
  • Intestine
  • Kidney
  • Liver
  • Muscle
  • Nerve Cells
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Testes
  • Thyroid Gland
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceDark red solid.
Experimental Properties
PropertyValue
Melting Point> 300°C
Boiling PointNot Available
Solubility1.25E+004 mg/L
LogPNot Available
Predicted Properties
PropertyValueSource
logP-14ChemAxon
pKa (Strongest Acidic)1.82ChemAxon
pKa (Strongest Basic)-0.55ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area440.79 ŲChemAxon
Rotatable Bond Count16ChemAxon
Refractivity344.12 m³·mol⁻¹ChemAxon
Polarizability134.61 ųChemAxon
Number of Rings12ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-08g0-0029000000-77072081600b65a1c4d3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-029l-0039000000-38d31a7c52468bf044e6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-0090000000-932c5dd7c708f3803c27JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0w2i-0029000000-79a52bb6630feb8682a4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kr-2098000000-8f39892e9be557c444a4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9043000000-9ef3360537c06103842fJSpectraViewer
Toxicity Profile
Route of ExposureInhalation (26) ; oral (26) ; dermal (26) Readily absorbed in the lower half of the ileum.
Mechanism of ToxicityVitamin B12 is used in the body in two forms: Methylcobalamin and 5-deoxyadenosyl cobalamin. The enzyme methionine synthase needs methylcobalamin as a cofactor. This enzyme is involved in the conversion of the amino acid homocysteine into methionine. Methionine in turn is required for DNA methylation. 5-Deoxyadenosyl cobalamin is a cofactor needed by the enzyme that converts L-methylmalonyl-CoA to succinyl-CoA. This conversion is an important step in the extraction of energy from proteins and fats. Furthermore, succinyl CoA is necessary for the production of hemoglobin, the substances that carries oxygen in red blood cells.
MetabolismCobalt is absorbed though the lungs, gastrointestinal tract, and skin. Since it is a component of the vitamin B12 (cyanocobalamin), it is distributed to most tissues of the body. It is transported in the blood, often bound to albumin, with the highest levels being found in the liver and kidney. Cobalt is excreted mainly in the urine and faeces. (26) Half Life: Approximately 6 days (400 days in the liver).
Toxicity ValuesORL-MUS LD50 > 8000 mg/kg
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (29)
Uses/SourcesCyanocobalamin is a form of vitamin B12. (30) It is used for treatment of pernicious anemia (due to lack of or inhibition of intrinsic factor) and for prevention and treatment of vitamin B 12 deficiency.
Minimum Risk LevelChronic Inhalation: 0.0001 mg/m3 (28) Intermediate Oral: 0.01 mg/kg/day (28)
Health EffectsExposure to high amount of cobalt can cause heart, lung, kidney, and liver damage. Skin contact is known to result in contact dermatitis. Cobalt may also have mutagenic and carcinogenic effects. (26, 27)
SymptomsAnaphylactic reaction (skin rash, itching, wheezing)-after parenteral administration. Cobalt inhalation can cause asthma-like breathing problems. Skin contact is known to result in contact dermatitis, which is characterized by irritation and rashes. Ingesting large amounts of cobalt may cause nausea and vomiting. (31)
TreatmentTreatment of cobalt poisoning is symptomatic. (26)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00115
HMDB IDHMDB00607
PubChem Compound ID44176380
ChEMBL IDCHEMBL2110563
ChemSpider ID4575342
KEGG IDC02823
UniProt IDNot Available
OMIM ID
ChEBI ID17439
BioCyc IDCPD-315
CTD IDD014805
Stitch IDCyanocobalamin
PDB IDNot Available
ACToR ID8316
Wikipedia LinkCyanocobalamin
References
Synthesis Reference

Robert H. Allen, “Preparation of samples for vitamin B12 and/or folate assay and assay.” U.S. Patent US4451571, issued October, 1982.

MSDSLink
General References
  1. Amirtharaj GJ, Natarajan SK, Mukhopadhya A, Zachariah UG, Hegde SK, Kurian G, Balasubramanian KA, Ramachandran A: Fatty acids influence binding of cobalt to serum albumin in patients with fatty liver. Biochim Biophys Acta. 2008 May;1782(5):349-54. doi: 10.1016/j.bbadis.2008.02.006. Epub 2008 Feb 29. [18346470 ]
  2. Wickramasinghe SN: Morphology, biology and biochemistry of cobalamin- and folate-deficient bone marrow cells. Baillieres Clin Haematol. 1995 Sep;8(3):441-59. [8534956 ]
  3. Sharabi A, Cohen E, Sulkes J, Garty M: Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route. Br J Clin Pharmacol. 2003 Dec;56(6):635-8. [14616423 ]
  4. Hall AH, Rumack BH: Hydroxycobalamin/sodium thiosulfate as a cyanide antidote. J Emerg Med. 1987;5(2):115-21. [3295013 ]
  5. Andres E, Noel E, Goichot B: Metformin-associated vitamin B12 deficiency. Arch Intern Med. 2002 Oct 28;162(19):2251-2. [12390080 ]
  6. Gilligan MA: Metformin and vitamin B12 deficiency. Arch Intern Med. 2002 Feb 25;162(4):484-5. [11863489 ]
  7. Cupp MS, Zhang D, Cupp EW: Horn fly (Diptera: Muscidae) saliva targets thrombin action in hemostasis. J Med Entomol. 2000 May;37(3):416-21. [15535586 ]
  8. Waters RS, Bryden NA, Patterson KY, Veillon C, Anderson RA: EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res. 2001 Dec;83(3):207-21. [11794513 ]
  9. Reznichenko AM, Fesenko VP, Shestopalov DV, Tatarchuk PA: [Changes in cell immunity indexes under the influence of thymalin, thyroxine and fibronectin in patients with hyperplastic diseases of thyroid gland before and after the surgery]. Klin Khir. 2001 Dec;(12):31-3. [11944270 ]
  10. Hermann K, Rittweger R, Ring J: Urinary excretion of angiotensin I, II, arginine vasopressin and oxytocin in patients with anaphylactoid reactions. Clin Exp Allergy. 1992 Sep;22(9):845-53. [1422942 ]
  11. Nilsson-Ehle H, Jagenburg R, Landahl S, Lindstedt G, Swolin B, Westin J: Cyanocobalamin absorption in the elderly: results for healthy subjects and for subjects with low serum cobalamin concentration. Clin Chem. 1986 Jul;32(7):1368-71. [3719947 ]
  12. Sesso RM, Iunes Y, Melo AC: Myeloneuropathy following nitrous oxide anesthaesia in a patient with macrocytic anaemia. Neuroradiology. 1999 Aug;41(8):588-90. [10447571 ]
  13. No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age. Circulation. 2003 Mar 4;107(8):1117-22. [12615788 ]
  14. Oh Y, Beukers MW, Pham HM, Smanik PA, Smith MC, Rosenfeld RG: Altered affinity of insulin-like growth factor II (IGF-II) for receptors and IGF-binding proteins, resulting from limited modifications of the IGF-II molecule. Biochem J. 1991 Aug 15;278 ( Pt 1):249-54. [1715685 ]
  15. Hoffer LJ, Saboohi F, Golden M, Barre PE: Cobalamin dose regimen for maximum homocysteine reduction in end-stage renal disease. Metabolism. 2005 Jun;54(6):835-40. [15931623 ]
  16. Hohlagschwandtner M, Unfried G, Heinze G, Huber JC, Nagele F, Tempfer C: Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage. Fertil Steril. 2003 May;79(5):1141-8. [12738509 ]
  17. Pittock SJ, Payne TA, Harper CM: Reversible myelopathy in a 34-year-old man with vitamin B12 deficiency. Mayo Clin Proc. 2002 Mar;77(3):291-4. [11888035 ]
  18. Houeto P, Buneaux F, Galliot-Guilley M, Baud FJ, Levillain P: Determination of hydroxocobalamin and cyanocobalamin by derivative spectrophotometry in cyanide poisoning. J Anal Toxicol. 1994 May-Jun;18(3):154-8. [8065126 ]
  19. Manier JW, Beltaos E: Benign gastric ulcer in a patient with pernicious anemia. Gastroenterology. 1975 Sep;69(3):744-5. [1158091 ]
  20. Mayer G, Kroger M, Meier-Ewert K: Effects of vitamin B12 on performance and circadian rhythm in normal subjects. Neuropsychopharmacology. 1996 Nov;15(5):456-64. [8914118 ]
  21. Lao JI, Montoriol C, Morer I, Beyer K: Genetic contribution to aging: deleterious and helpful genes define life expectancy. Ann N Y Acad Sci. 2005 Dec;1057:50-63. [16399887 ]
  22. Baumann H, Muller-Eberhard U: Synthesis of hemopexin and cysteine protease inhibitor is coordinately regulated by HSF-II and interferon-beta 2 in rat hepatoma cells. Biochem Biophys Res Commun. 1987 Aug 14;146(3):1218-28. [3304291 ]
  23. Houeto P, Hoffman JR, Imbert M, Levillain P, Baud FJ: Relation of blood cyanide to plasma cyanocobalamin concentration after a fixed dose of hydroxocobalamin in cyanide poisoning. Lancet. 1995 Sep 2;346(8975):605-8. [7651005 ]
  24. van Asselt DZ, van den Broek WJ, Lamers CB, Corstens FH, Hoefnagels WH: Free and protein-bound cobalamin absorption in healthy middle-aged and older subjects. J Am Geriatr Soc. 1996 Aug;44(8):949-53. [8708306 ]
  25. Wu H, Bruley DF: Homologous human blood protein separation using immobilized metal affinity chromatography: protein C separation from prothrombin with application to the separation of factor IX and prothrombin. Biotechnol Prog. 1999 Sep-Oct;15(5):928-31. [10514264 ]
  26. 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]
  27. Wikipedia. Cobalt. Last Updated 21 March 2009. [Link]
  28. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  29. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  30. Wikipedia. Vitamin B12. Last Updated 3 June 2009. [Link]
  31. U.S. National Library of Medicine, MedlinePlus: Cobalt poisoning. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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]
15. DNA
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