Haptocorrin

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}}

'''Haptocorrin''' (HC) (also known as '''transcobalamin-1''' ('''TC-1'''), or '''cobalophilin'''<!-- see OMIM for ref. -->) is a transcobalamin<ref name="entrez" /> glycoprotein<ref name="isbn1-4051-3649-9" /> that in humans is encoded by the {{gene|TCN1}} gene.<ref name="entrez">{{cite web | title = Entrez Gene: transcobalamin I (vitamin B₁₂ binding protein| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6947| access-date = }}</ref> 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.<ref name="isbn1-4051-3649-9">{{cite book | vauthors = Pettit JD, Moss P | title = Essential Haematology 5e (Essential) | pages = 44 | year = 2006 | isbn = 978-1-4051-3649-5 | publisher = Blackwell Publishing Professional }}</ref> 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<ref name="pmid17990953">{{cite journal | vauthors = Morkbak AL, Poulsen SS, Nexo E | title = Haptocorrin in humans | journal = Clinical Chemistry and Laboratory Medicine | volume = 45 | issue = 12 | pages = 1751–1759 | year = 2007 | pmid = 17990953 | doi = 10.1515/CCLM.2007.343 | s2cid = 24204285 }}</ref> 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|date=June 2025}} 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.<ref name="pmid19627091">{{cite journal | vauthors = Viola-Villegas N, Rabideau AE, Bartholomä M, Zubieta J, Doyle RP | title = Targeting the cubilin receptor through the vitamin B(12) uptake pathway: cytotoxicity and mechanistic insight through fluorescent Re(I) delivery | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 16 | pages = 5253–5261 | date = Aug 2009 | pmid = 19627091 | doi = 10.1021/jm900777v }}</ref>

=== 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.<ref name="McCorvie2023">{{cite journal |vauthors=McCorvie TJ, Ferreira D, Yue WW, Froese DS |title=The complex machinery of human cobalamin metabolism |journal=Journal of Inherited Metabolic Disease |volume=46 |issue=3 |pages=406–420 |date=May 2023 |pmid=36680553 |doi=10.1002/jimd.12593 |url=|doi-access=free }}</ref>

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.<ref name="Ermens2003">{{cite journal |vauthors=Ermens AA, Vlasveld LT, Lindemans J |title=Significance of elevated cobalamin (vitamin B12) levels in blood |journal=Clinical Biochemistry |volume=36 |issue=8 |pages=585–590 |date=November 2003 |pmid=14636871 |doi=10.1016/j.clinbiochem.2003.08.004 |url=}}</ref>

== References == {{reflist|33em}} {{-}}

== Further reading == {{refbegin|33em}} * {{cite journal | vauthors = Guéant-Rodriguez RM, Juilliére Y, Candito M, Adjalla CE, Gibelin P, Herbeth B, Van Obberghen E, Gueánt JL | title = Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population | journal = Thrombosis and Haemostasis | volume = 94 | issue = 3 | pages = 510–515 | date = Sep 2005 | pmid = 16268464 | doi = 10.1160/TH05-04-0262 | s2cid = 33572371 }} * {{cite journal | vauthors = Garrod MG, Allen LH, Haan MN, Green R, Miller JW | title = Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics | journal = European Journal of Clinical Nutrition | volume = 64 | issue = 5 | pages = 503–509 | date = May 2010 | pmid = 20216556 | pmc = 2864787 | doi = 10.1038/ejcn.2010.20 }} * {{cite journal | vauthors = 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 | title = Integrative predictive model of coronary artery calcification in atherosclerosis | journal = Circulation | volume = 120 | issue = 24 | pages = 2448–2454 | date = Dec 2009 | pmid = 19948975 | pmc = 2810344 | doi = 10.1161/CIRCULATIONAHA.109.865501 }} * {{cite journal | vauthors = Matteini AM, Walston JD, Bandeen-Roche K, Arking DE, Allen RH, Fried LP, Chakravarti A, Stabler SP, Fallin MD | author-link3 = Karen Bandeen-Roche | title = Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty | journal = The Journal of Nutrition, Health & Aging | volume = 14 | issue = 1 | pages = 73–77 | date = Jan 2010 | pmid = 20082058 | pmc = 3042247 | doi = 10.1007/s12603-010-0013-1 }} * {{cite journal | vauthors = Lee KM, Lan Q, Kricker A, Purdue MP, Grulich AE, Vajdic CM, Turner J, Whitby D, Kang D, Chanock S, Rothman N, Armstrong BK | title = One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia | journal = Human Genetics | volume = 122 | issue = 5 | pages = 525–533 | date = Dec 2007 | pmid = 17891500 | doi = 10.1007/s00439-007-0431-2 | s2cid = 21487646 | url = https://zenodo.org/record/1232733 }} * {{cite journal | vauthors = Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD | title = Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry | journal = Journal of Proteome Research | year = 2005 | volume = 4 | issue = 6 | pages = 2070–2080 | pmid = 16335952 | pmc = 1850943 | doi = 10.1021/pr0502065 }} * {{cite journal | vauthors = Fintelman-Rodrigues N, Corrêa JC, Santos JM, Pimentel MM, Santos-Rebouças CB | title = Investigation of CBS, MTR, RFC-1 and TC polymorphisms as maternal risk factors for Down syndrome | journal = Disease Markers | volume = 26 | issue = 4 | pages = 155–161 | year = 2009 | pmid = 19729796 | doi = 10.1155/2009/504625| pmc = 3833707 | doi-access = free }} * {{cite journal | vauthors = Wang SS, Maurer MJ, Morton LM, Habermann TM, Davis S, Cozen W, Lynch CF, Severson RK, Rothman N, Chanock SJ, Hartge P, Cerhan JR | title = Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma and follicular lymphoma | journal = Leukemia | volume = 23 | issue = 3 | pages = 596–602 | date = Mar 2009 | pmid = 18830263 | pmc = 3066015 | doi = 10.1038/leu.2008.240 }} * {{cite journal | vauthors = Fedosov SN, Fedosova NU, Kräutler B, Nexø E, Petersen TE | title = Mechanisms of discrimination between cobalamins and their natural analogues during their binding to the specific B12-transporting proteins | journal = Biochemistry | volume = 46 | issue = 21 | pages = 6446–6458 | date = May 2007 | pmid = 17487979 | doi = 10.1021/bi062063l }} * {{cite journal | vauthors = Carmel R, Parker J, Kelman Z | title = Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels | journal = British Journal of Haematology | volume = 147 | issue = 3 | pages = 386–391 | date = Nov 2009 | pmid = 19686235 | doi = 10.1111/j.1365-2141.2009.07855.x | s2cid = 20530258 | doi-access = free }} * {{cite journal | vauthors = 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 | title = Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip | journal = American Journal of Human Genetics | volume = 85 | issue = 5 | pages = 628–642 | date = Nov 2009 | pmid = 19913121 | pmc = 2775832 | doi = 10.1016/j.ajhg.2009.10.014 }} * {{cite journal | vauthors = 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 | title = Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 19 | issue = 11 | pages = 2833–2838 | date = Nov 2010 | pmid = 20852008 | doi = 10.1158/1055-9965.EPI-10-0582 | doi-access = free }} * {{cite journal | vauthors = Haggarty P, Campbell DM, Duthie S, Andrews K, Hoad G, Piyathilake C, Fraser I, McNeill G | title = Folic acid use in pregnancy and embryo selection | journal = BJOG | volume = 115 | issue = 7 | pages = 851–856 | date = Jun 2008 | pmid = 18485163 | doi = 10.1111/j.1471-0528.2008.01737.x | s2cid = 27260053 }} * {{cite journal | vauthors = 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 | title = Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations | journal = American Journal of Human Genetics | volume = 84 | issue = 4 | pages = 477–482 | date = Apr 2009 | pmid = 19303062 | pmc = 2667971 | doi = 10.1016/j.ajhg.2009.02.011 }} * {{cite journal | vauthors = Geisel J, Hübner U, Bodis M, Schorr H, Knapp JP, Obeid R, Herrmann W | title = The role of genetic factors in the development of hyperhomocysteinemia | journal = Clinical Chemistry and Laboratory Medicine | volume = 41 | issue = 11 | pages = 1427–1434 | date = Nov 2003 | pmid = 14656021 | doi = 10.1515/CCLM.2003.219 | s2cid = 24720114 }} * {{cite journal | vauthors = Martinelli M, Scapoli L, Palmieri A, Pezzetti F, Baciliero U, Padula E, Carinci P, Morselli PG, Carinci F | title = 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 | journal = Human Mutation | volume = 27 | issue = 3 | pages = 294 | date = Mar 2006 | pmid = 16470748 | doi = 10.1002/humu.9411 | s2cid = 39925478 | doi-access = free }} * {{cite journal | vauthors = von Castel-Dunwoody KM, Kauwell GP, Shelnutt KP, Vaughn JD, Griffin ER, Maneval DR, Theriaque DW, Bailey LB | title = Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism | journal = The American Journal of Clinical Nutrition | volume = 81 | issue = 6 | pages = 1436–1441 | date = Jun 2005 | pmid = 15941899 | doi = 10.1093/ajcn/81.6.1436| doi-access = free }} * {{cite journal | vauthors = 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 | title = Transcriptome analysis of human gastric cancer | journal = Mammalian Genome | volume = 16 | issue = 12 | pages = 942–954 | date = Dec 2005 | pmid = 16341674 | doi = 10.1007/s00335-005-0075-2 | s2cid = 69278 }} * {{cite journal | vauthors = Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA | title = Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry | journal = Journal of Proteome Research | volume = 5 | issue = 6 | pages = 1493–1503 | date = Jun 2006 | pmid = 16740002 | doi = 10.1021/pr050492k }} * {{cite journal | vauthors = Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S | title = Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study | journal = Diabetes Care | volume = 33 | issue = 10 | pages = 2250–2253 | date = Oct 2010 | pmid = 20628086 | pmc = 2945168 | doi = 10.2337/dc10-0452 }} {{refend}}

Category:Digestive system