TCN1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005576 extracellular region	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference that TCN1 acts in the extracellular region. Correct: haptocorrin is a secreted protein acting in saliva, gastric juice, plasma and other extracellular fluids, so extracellular region is an appropriate and core localization. GO:0005576 is the exact extracellular CC term also carried elsewhere in the GOA. Reason: TCN1 is a secreted cobalamin-binding glycoprotein; extracellular region is the correct cellular component and is corroborated by the UniProt "Secreted" subcellular location, proteomic detection in plasma/saliva/colostrum, and Reactome. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt SUBCELLULAR LOCATION: Secreted.
GO:0015889 cobalamin transport	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference that TCN1 is involved in cobalamin transport. This is the correct core biological process: haptocorrin binds dietary/plasma cobalamin (and corrinoid analogues) and participates in B12 transport, protecting acid-labile cobalamin in the stomach and carrying most plasma B12. Reason: Cobalamin transport is the established core biological process of the cobalamin transport protein family; TCN1 binds and carries cobalamin in secretions and plasma. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt Binds vitamin B12 with femtomolar affinity and protects it PMID:23846701 a similar overall structure but a different selectivity for corrinoids.
GO:0031419 cobalamin binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference of cobalamin binding. This is the core molecular function of TCN1/haptocorrin, directly demonstrated by the crystal structures of human HC bound to cyanocobalamin and cobinamide and by defined cobalamin-binding residues in UniProt. GO:0031419 is the exact current MF term in the GOA. Reason: Cobalamin binding is directly established experimentally (X-ray structures, defined binding site, femtomolar affinity) and is the central molecular function of the protein. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt Binds vitamin B12 with femtomolar affinity and protects it PMID:23846701 a similar overall structure but a different selectivity for corrinoids.
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	Summary: Electronic mapping from the UniProt Swiss-Prot subcellular location ("Secreted") to extracellular region. Consistent with the curated secreted localization; correct. Reason: The SubCell "Secreted" -> extracellular region mapping is accurate for this secreted glycoprotein and agrees with the IBA, HDA and Reactome CC annotations. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt SUBCELLULAR LOCATION: Secreted.
GO:0015889 cobalamin transport	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping (IPR002157, cobalamin-binding protein) to cobalamin transport. TCN1 belongs to this family and does participate in cobalamin transport, so the mapping is appropriate. Reason: The cobalamin-binding-protein InterPro signature correctly maps to the family's cobalamin transport process, consistent with the experimental and IBA evidence. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt Belongs to the eukaryotic cobalamin transport proteins
GO:0031419 cobalamin binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping (IPR002157) to cobalamin binding. Correct and specific: the signature captures the cobalamin-binding fold and TCN1 is experimentally shown to bind cobalamin. Reason: InterPro cobalamin-binding-protein signature maps precisely to the demonstrated core molecular function. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt Belongs to the eukaryotic cobalamin transport proteins
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: IPI annotation to the uninformative "protein binding" term, supported by a single high-throughput yeast two-hybrid interaction with junctophilin-3 (JPH3, Q8WXH2) from a neurodegenerative-disease interactome screen. The interaction is recorded in UniProt/IntAct but has no functional follow-up and does not describe an informative molecular function for this secreted cobalamin-binding protein. There is no established biology linking secreted haptocorrin to the intracellular junctophilin. Reason: Bare "protein binding" is uninformative and this rests on one large-scale Y2H hit (JPH3) without functional characterization; per curation policy the experimental IPI is retained but flagged as an over-annotation rather than removed. It should not be treated as a core function. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt P20061; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2557232, EBI-1055254;
GO:0015889 cobalamin transport	TAS Reactome:R-HSA-9758881	ACCEPT	Summary: Reactome TAS annotation placing TCN1 in "Uptake of dietary cobalamins into enterocytes". Haptocorrin binds dietary RCbl in saliva/stomach, protecting it, so participation in the cobalamin transport process is correct. Reason: Reactome captures TCN1's role in the gastrointestinal step of cobalamin transport; consistent with the core BP. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt from the acidic environment of the stomach.
GO:0015889 cobalamin transport	TAS Reactome:R-HSA-9758890	ACCEPT	Summary: Reactome TAS annotation placing TCN1 in "Transport of RCbl within the body". Haptocorrin carries the majority of circulating plasma cobalamin and scavenges corrinoids for hepatobiliary clearance, so involvement in body-wide cobalamin transport is correct. Reason: Duplicate cobalamin transport annotation from a different Reactome pathway; correct and core. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt Binds vitamin B12 with femtomolar affinity and protects it
GO:0140355 cargo receptor ligand activity	EXP PMID:22547309 Vitamin B12 transport from food to the body's cells--a sophi...	KEEP AS NON CORE	Summary: Reactome-assigned EXP annotation to "cargo receptor ligand activity", reflecting that cobalamin-loaded haptocorrin acts as a ligand whose complex is captured and endocytosed (in the liver via the asialoglycoprotein receptor). This is a defensible molecular-function framing of receptor-mediated clearance, but it is a downstream consequence of cobalamin binding rather than the protein's central function; the cited reference is an abstract-only review of the multistep B12 transport pathway. Reason: TCN1's ligand/cargo behaviour follows from its cobalamin binding; the annotation is not wrong but is secondary to the core cobalamin-binding/transport functions and relies on a review rather than a direct TCN1 assay, so it is kept as non-core. Supporting Evidence: PMID:22547309 for specific uptake and transport of this molecule has evolved.
GO:0140313 molecular sequestering activity	EXP PMID:23846701 Structural basis for universal corrinoid recognition by the ...	KEEP AS NON CORE	Summary: Reactome-assigned EXP annotation to "molecular sequestering activity", supported by the crystal structure showing broad-specificity binding of cobalamin and cobinamide. This captures haptocorrin's role in binding/sequestering cobalamin (protecting it) and scavenging inactive corrinoid analogues. It is essentially a restatement of the cobalamin-binding function in sequestering terms. Reason: Sequestering is a valid characterization of HC's broad corrinoid binding, but it is a facet of the core cobalamin-binding molecular function rather than an independent core activity; retained as non-core. Supporting Evidence: PMID:23846701 a similar overall structure but a different selectivity for corrinoids.
GO:0140313 molecular sequestering activity	EXP PMID:27411955 Structural basis of transcobalamin recognition by human CD32...	KEEP AS NON CORE	Summary: Reactome-assigned EXP annotation to "molecular sequestering activity". This paper (holo-transcobalamin/CD320 structure) explicitly notes haptocorrin's role as a high-affinity plasma Cbl-binding scavenger that, unlike transcobalamin, is not recognized by the cellular uptake receptor CD320. Supports HC's sequestering/ scavenging role but is a facet of cobalamin binding. Reason: Duplicate molecular sequestering annotation; correctly reflects HC's scavenging role but is secondary to cobalamin binding, so kept as non-core. Supporting Evidence: PMID:27411955 Even haptocorrin (HC), a high affinity Cbl-binding protein that shares significant sequence and structural similarities with TC and is also circulating in the plasma, is not recognized by CD320.
GO:0035580 specific granule lumen	TAS Reactome:R-HSA-6798749	ACCEPT	Summary: Reactome TAS annotation to specific (secondary) granule lumen. TCN1 is a major constituent of neutrophil secondary/specific granules and is released by neutrophil degranulation, so this localization is correct. Reason: TCN1/haptocorrin is a well-established secondary (specific) granule protein of neutrophils; the granule-lumen localization is supported by UniProt tissue specificity and the original cloning paper. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt in response to ingestion of food. Major constituent of secondary PMID:2777761 It is a major protein constituent of secondary granules in
GO:1904724 tertiary granule lumen	TAS Reactome:R-HSA-6798745	KEEP AS NON CORE	Summary: Reactome TAS annotation to tertiary granule lumen, from the neutrophil degranulation pathway. TCN1 is primarily a specific/secondary granule protein; Reactome models it among granule-lumen proteins exocytosed during degranulation. Retained as a non-core localization since the primary granule assignment is the specific granule. Reason: Granule-lumen localization is consistent with TCN1 being a neutrophil granule protein released by degranulation, but the tertiary-granule assignment is secondary to its established specific-granule localization; kept as non-core. Supporting Evidence: PMID:2777761 It is a major protein constituent of secondary granules in
GO:0005576 extracellular region	HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu...	ACCEPT	Summary: High-throughput proteomic detection (HDA) of TCN1 in the extracellular fluid, here in the aqueous phase of human colostrum. Consistent with the secreted localization; supports extracellular region. Reason: Proteomic identification of TCN1 in an extracellular body fluid corroborates the secreted/extracellular localization. Supporting Evidence: PMID:16502470 identification of minor proteins in the aqueous phase
GO:0005576 extracellular region	TAS Reactome:R-HSA-3132753	ACCEPT	Summary: Reactome TAS annotation (Pancreatic proteases degrade TCN1:RCbl) placing TCN1 in the extracellular region, where the haptocorrin:cobalamin complex is degraded by pancreatic proteases in the small intestine. Correct localization. Reason: Consistent with the secreted/extracellular localization of haptocorrin acting in the gastrointestinal lumen. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt SUBCELLULAR LOCATION: Secreted.
GO:0005576 extracellular region	TAS Reactome:R-HSA-3132759	ACCEPT	Summary: Reactome TAS annotation (TCN1 binds RCbl) placing TCN1 in the extracellular region, where secreted haptocorrin binds free/protein-released RCbl in saliva and stomach. Correct localization. Reason: Consistent with the secreted/extracellular localization; this is where TCN1 binds and protects dietary cobalamin. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt Produced by the salivary glands of the oral cavity,
GO:0005576 extracellular region	TAS Reactome:R-HSA-3245898	ACCEPT	Summary: Reactome TAS annotation (TCN1 binds corrinoids in the circulation) placing TCN1 in the extracellular region (plasma), where haptocorrin binds inactive corrinoid analogues for hepatobiliary clearance. Correct localization. Reason: Consistent with secreted/plasma localization; corroborated by Reactome's scavenging/ broad-corrinoid-specificity model of TCN1. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt SUBCELLULAR LOCATION: Secreted.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798745	ACCEPT	Summary: Reactome TAS annotation (Exocytosis of tertiary granule lumen proteins) placing released TCN1 in the extracellular region following neutrophil degranulation. Consistent with the secreted/extracellular localization. Reason: TCN1 released by degranulation resides in the extracellular region; correct CC. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt SUBCELLULAR LOCATION: Secreted.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798749	ACCEPT	Summary: Reactome TAS annotation (Exocytosis of specific granule lumen proteins) placing released TCN1 in the extracellular region following neutrophil degranulation. Consistent with the secreted/extracellular localization. Reason: TCN1 released from specific granules by degranulation resides in the extracellular region; correct CC. Supporting Evidence: file:human/TCN1/TCN1-uniprot.txt SUBCELLULAR LOCATION: Secreted.
GO:0015889 cobalamin transport	TAS PMID:2777761 Structure of the cDNA encoding transcobalamin I, a neutrophi...	ACCEPT	Summary: TAS annotation to cobalamin transport from the original TCN1 cDNA cloning paper, which describes TCI as a member of the R-binder family of vitamin B12 binding proteins and a major secondary-granule protein. Supports the core cobalamin transport/binding role. Reason: Author-stated (TAS) assignment consistent with TCN1's established role as an R-binder vitamin B12 binding protein; core biological process. Supporting Evidence: PMID:2777761 member of the R binder family of vitamin B12 binding

Gene Description

Existing Annotations Review

Core Functions

Binds cobalamin (vitamin B12) with femtomolar affinity and broad corrinoid specificity, binding both cobalamin and biologically inactive cobalamin analogues; this is the central molecular function of secreted haptocorrin.

References

📚 Additional Documentation

Notes

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