Haptocorrin

TCN1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 4KKI, 4KKJ
Identifiers
Aliases	TCN1 , HC, TC-1, TC1, TCI, transcobalamin 1
External IDs	OMIM: 189905; HomoloGene: 47985; GeneCards: TCN1; OMA:TCN1 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q12.1 Start 59,852,800 bp [1] End 59,866,489 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pancreatic ductal cell olfactory zone of nasal mucosa trachea parotid gland gallbladder bone marrow bone marrow cell nasal epithelium trabecular bone testicle n/a More reference expression data BioGPS n/a
Gene ontology Molecular function cobalamin binding Cellular component extracellular region extracellular space specific granule lumen tertiary granule lumen Biological process cobalamin metabolic process cobalt ion transport ion transport cobalamin transport neutrophil degranulation transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6947 n/a Ensembl ENSG00000134827 n/a UniProt P20061 n/a RefSeq (mRNA) NM_001062 n/a RefSeq (protein) NP_001053 n/a Location (UCSC) Chr 11: 59.85 – 59.87 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Haptocorrin (HC) (also known as transcobalamin-1 (TC-1), or cobalophilin) is a transcobalamin ^[3] glycoprotein. ^[4] that in humans is encoded by the TCN1 gene. ^[3] It is essential to protect the acid-sensitive vitamin B₁₂ from degradation while in the stomach. It is also present in the serum where it binds most circulating vitamin B₁₂, rendering it unavailable for uptake by cells (this is conjectured to be a circulating storage function).

Function

Digestive

HC is produced by the salivary glands of the oral cavity in response to ingestion of food. ^[4] Vitamin B₁₂ is highly structural susceptible to denaturation by the acidic environment of the stomach. Haptocorrin has a high affinity for the molecular structure of vitamin B₁₂ ^[5] forming a haptocorrin–B₁₂ complex that is impervious to stomach acid, enabling it to reach the more alkaline duodenum intact. In the duodenum, pancreatic proteases (a component of pancreatic juice) cleave haptocorrin, releasing vitamin B₁₂.^{[ citation needed ]} Intrinsic factor (IF) that is secreted by parietal cells of the stomach now binds B₁₂ released from haptocorrin to subsequently enable cubilin receptors of the ileum to take up B₁₂–IF complexes by endocytosis-mediated absorption before B₁₂ is finally released into circulation. Without IF, only 1% of vitamin B₁₂ is ultimately absorbed. ^[6]

Serum

HC is present in blood serum where it binds 80-90% of circulating B₁₂, rendering it unavailable for cellular uptake by transcobalamin II. This is conjectured to be a circulating storage function. ^[7]

Several serious, even life-threatening diseases cause elevated serum HC, measured as abnormally high serum vitamin B₁₂ while at the same time manifesting as a vitamin deficiency because of insufficient vitamin bound to transcobalamin II. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000134827 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Entrez Gene: transcobalamin I (vitamin B₁₂ binding protein".
4. Pettit JD, Moss P (2006). Essential Haematology 5e (Essential). Blackwell Publishing Professional. p. 44. ISBN   1-4051-3649-9.
5. Morkbak AL, Poulsen SS, Nexo E (2007). "Haptocorrin in humans". Clinical Chemistry and Laboratory Medicine. 45 (12): 1751–9. doi:10.1515/CCLM.2007.343. PMID   17990953. S2CID   24204285.
6. Viola-Villegas N, Rabideau AE, Bartholomä M, Zubieta J, Doyle RP (Aug 2009). "Targeting the cubilin receptor through the vitamin B(12) uptake pathway: cytotoxicity and mechanistic insight through fluorescent Re(I) delivery". Journal of Medicinal Chemistry. 52 (16): 5253–61. doi:10.1021/jm900777v. PMID   19627091.
7. McCorvie TJ, Ferreira D, Yue WW, Froese DS (May 2023). "The complex machinery of human cobalamin metabolism". J Inherit Metab Dis. 46 (3): 406–20. doi: 10.1002/jimd.12593 . PMID   36680553.
8. Ermens AA, Vlasveld LT, Lindemans J (November 2003). "Significance of elevated cobalamin (vitamin B12) levels in blood". Clin Biochem. 36 (8): 585–90. doi:10.1016/j.clinbiochem.2003.08.004. PMID   14636871.

Further reading

• Guéant-Rodriguez RM, Juilliére Y, Candito M, Adjalla CE, Gibelin P, Herbeth B, Van Obberghen E, Gueánt JL (Sep 2005). "Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population". Thrombosis and Haemostasis. 94 (3): 510–5. doi:10.1160/TH05-04-0262. PMID   16268464. S2CID   33572371.
• Garrod MG, Allen LH, Haan MN, Green R, Miller JW (May 2010). "Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics". European Journal of Clinical Nutrition. 64 (5): 503–9. doi:10.1038/ejcn.2010.20. PMC   2864787 . PMID   20216556.
• McGeachie M, Ramoni RL, Mychaleckyj JC, Furie KL, Dreyfuss JM, Liu Y, Herrington D, Guo X, Lima JA, Post W, Rotter JI, Rich S, Sale M, Ramoni MF (Dec 2009). "Integrative predictive model of coronary artery calcification in atherosclerosis". Circulation. 120 (24): 2448–54. doi:10.1161/CIRCULATIONAHA.109.865501. PMC   2810344 . PMID   19948975.
• Matteini AM, Walston JD, Bandeen-Roche K, Arking DE, Allen RH, Fried LP, Chakravarti A, Stabler SP, Fallin MD (Jan 2010). "Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty". The Journal of Nutrition, Health & Aging. 14 (1): 73–7. doi:10.1007/s12603-010-0013-1. PMC   3042247 . PMID   20082058.
• Lee KM, Lan Q, Kricker A, Purdue MP, Grulich AE, Vajdic CM, Turner J, Whitby D, Kang D, Chanock S, Rothman N, Armstrong BK (Dec 2007). "One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia". Human Genetics. 122 (5): 525–33. doi:10.1007/s00439-007-0431-2. PMID   17891500. S2CID   21487646.
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD (2005). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". Journal of Proteome Research. 4 (6): 2070–80. doi:10.1021/pr0502065. PMC   1850943 . PMID   16335952.
• Fintelman-Rodrigues N, Corrêa JC, Santos JM, Pimentel MM, Santos-Rebouças CB (2009). "Investigation of CBS, MTR, RFC-1 and TC polymorphisms as maternal risk factors for Down syndrome". Disease Markers. 26 (4): 155–61. doi: 10.1155/2009/504625 . PMC   3833707 . PMID   19729796.
• Wang SS, Maurer MJ, Morton LM, Habermann TM, Davis S, Cozen W, Lynch CF, Severson RK, Rothman N, Chanock SJ, Hartge P, Cerhan JR (Mar 2009). "Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma and follicular lymphoma". Leukemia. 23 (3): 596–602. doi:10.1038/leu.2008.240. PMC   3066015 . PMID   18830263.
• Fedosov SN, Fedosova NU, Kräutler B, Nexø E, Petersen TE (May 2007). "Mechanisms of discrimination between cobalamins and their natural analogues during their binding to the specific B12-transporting proteins". Biochemistry. 46 (21): 6446–58. doi:10.1021/bi062063l. PMID   17487979.
• Carmel R, Parker J, Kelman Z (Nov 2009). "Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels". British Journal of Haematology. 147 (3): 386–91. doi: 10.1111/j.1365-2141.2009.07855.x . PMID   19686235. S2CID   20530258.
• Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD (Nov 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC   2775832 . PMID   19913121.
• Collin SM, Metcalfe C, Refsum H, Lewis SJ, Smith GD, Cox A, Davis M, Marsden G, Johnston C, Lane JA, Donovan JL, Neal DE, Hamdy FC, Smith AD, Martin RM (Nov 2010). "Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer". Cancer Epidemiology, Biomarkers & Prevention. 19 (11): 2833–8. doi: 10.1158/1055-9965.EPI-10-0582 . PMID   20852008.
• Haggarty P, Campbell DM, Duthie S, Andrews K, Hoad G, Piyathilake C, Fraser I, McNeill G (Jun 2008). "Folic acid use in pregnancy and embryo selection". BJOG. 115 (7): 851–6. doi:10.1111/j.1471-0528.2008.01737.x. PMID   18485163. S2CID   27260053.
• Tanaka T, Scheet P, Giusti B, Bandinelli S, Piras MG, Usala G, Lai S, Mulas A, Corsi AM, Vestrini A, Sofi F, Gori AM, Abbate R, Guralnik J, Singleton A, Abecasis GR, Schlessinger D, Uda M, Ferrucci L (Apr 2009). "Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations". American Journal of Human Genetics. 84 (4): 477–82. doi:10.1016/j.ajhg.2009.02.011. PMC   2667971 . PMID   19303062.
• Geisel J, Hübner U, Bodis M, Schorr H, Knapp JP, Obeid R, Herrmann W (Nov 2003). "The role of genetic factors in the development of hyperhomocysteinemia". Clinical Chemistry and Laboratory Medicine. 41 (11): 1427–34. doi:10.1515/CCLM.2003.219. PMID   14656021. S2CID   24720114.
• Martinelli M, Scapoli L, Palmieri A, Pezzetti F, Baciliero U, Padula E, Carinci P, Morselli PG, Carinci F (Mar 2006). "Study of four genes belonging to the folate pathway: transcobalamin 2 is involved in the onset of non-syndromic cleft lip with or without cleft palate". Human Mutation. 27 (3): 294. doi: 10.1002/humu.9411 . PMID   16470748. S2CID   39925478.
• von Castel-Dunwoody KM, Kauwell GP, Shelnutt KP, Vaughn JD, Griffin ER, Maneval DR, Theriaque DW, Bailey LB (Jun 2005). "Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism". The American Journal of Clinical Nutrition. 81 (6): 1436–41. doi: 10.1093/ajcn/81.6.1436 . PMID   15941899.
• Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS (Dec 2005). "Transcriptome analysis of human gastric cancer". Mammalian Genome. 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID   16341674. S2CID   69278.
• Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA (Jun 2006). "Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry". Journal of Proteome Research. 5 (6): 1493–503. doi:10.1021/pr050492k. PMID   16740002.
• Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S (Oct 2010). "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care. 33 (10): 2250–3. doi:10.2337/dc10-0452. PMC   2945168 . PMID   20628086.