Haptocorrin

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).

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

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]