TCN2

Protein identityUniProt · HPA

UniProt accession

P20062

Gene

TCN2

Ensembl

ENSG00000185339

Chromosome

22

Canonical length

427 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Cytosol

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This plasma protein binds cobalamin and mediates the transport of cobalamin into cells. This protein and other mammalian cobalamin-binding proteins, such as transcobalamin I and gastric intrisic factor, may have evolved by duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

427 residues, UniProt reviewed canonical sequence.

>P20062|TCN2
     1  MRHLGAFLFL LGVLGALTEM CEIPEMDSHL VEKLGQHLLP WMDRLSLEHL NPSIYVGLRL
    61  SSLQAGTKED LYLHSLKLGY QQCLLGSAFS EDDGDCQGKP SMGQLALYLL ALRANCEFVR
   121  GHKGDRLVSQ LKWFLEDEKR AIGHDHKGHP HTSYYQYGLG ILALCLHQKR VHDSVVDKLL
   181  YAVEPFHQGH HSVDTAAMAG LAFTCLKRSN FNPGRRQRIT MAIRTVREEI LKAQTPEGHF
   241  GNVYSTPLAL QFLMTSPMRG AELGTACLKA RVALLASLQD GAFQNALMIS QLLPVLNHKT
   301  YIDLIFPDCL APRVMLEPAA ETIPQTQEII SVTLQVLSLL PPYRQSISVL AGSTVEDVLK
   361  KAHELGGFTY ETQASLSGPY LTSVMGKAAG EREFWQLLRD PNTPLLQGIA DYRPKDGETI
   421  ELRLVSW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TCN2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

108 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TCN2.

Disease | AllUniProt

Conditions TCN2 is implicated in, by any mechanism.

• Transcobalamin II deficiency (TCN2D) MIM:275350

Disease | GeneticClinVar

70 pathogenic / likely-pathogenic of 797 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Transcobalamin II deficiency
• TCN2-related disorder
• Inborn genetic diseases
• Pancytopenia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.93

gnomAD pLI

0

gnomAD missense Z

-2.12

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cobalamin transport
• cobalt ion transport

Molecular functions

• cargo receptor ligand activity
• cobalamin binding
• metal ion binding
• molecular carrier activity

Cellular components

• external side of plasma membrane
• extracellular region
• extracellular space
• lysosomal lumen
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Cobalamin (vitamin B12)-binding protein
• Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid
• Eukaryotic Cobalamin Transport
• Eukaryotic cobalamin-binding protein

KeywordsUniProt

• Cobalt
• Cobalt transport
• Disulfide bond
• Ion transport
• Metal-binding
• Secreted
• Signal
• Transport

InteractionsUniProt · HPA

Protein binding partners of TCN2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD320