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Protein

Transcobalamin-2

Gene

TCN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei104Cobalamin1 Publication1
Metal bindingi190Cobalt (cobalamin axial ligand)1
Binding sitei242Cobalamin1 Publication1
Binding sitei245Cobalamin1 Publication1
Binding sitei291Cobalamin1 Publication1

GO - Molecular functioni

  • cobalamin binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • cobalamin metabolic process Source: Reactome
  • cobalamin transport Source: ProtInc
  • cobalt ion transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Cobalt transport, Ion transport, Transport

Keywords - Ligandi

Cobalt, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100036-MONOMER.
ReactomeiR-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.
R-HSA-3359454. Defective TCN2 causes hereditary megaloblastic anemia.
R-HSA-3359485. Defective CD320 causes methylmalonic aciduria.
SABIO-RKP20062.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcobalamin-2
Short name:
TC-2
Alternative name(s):
Transcobalamin II
Short name:
TC II
Short name:
TCII
Gene namesi
Name:TCN2
Synonyms:TC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:11653. TCN2.

Subcellular locationi

GO - Cellular componenti

  • endosome Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: ProtInc
  • lysosomal lumen Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Transcobalamin II deficiency (TCN2 deficiency)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionResults in various forms of anemia.
See also OMIM:275350

Organism-specific databases

DisGeNETi6948.
MalaCardsiTCN2.
MIMi275350. phenotype.
OpenTargetsiENSG00000185339.
Orphaneti859. Transcobalamin deficiency.
PharmGKBiPA36404.

Chemistry databases

DrugBankiDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

Polymorphism and mutation databases

BioMutaiTCN2.
DMDMi224471876.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 181 PublicationAdd BLAST18
ChainiPRO_000000556419 – 427Transcobalamin-2Add BLAST409

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi21 ↔ 2671 Publication
Disulfide bondi116 ↔ 3091 Publication
Disulfide bondi165 ↔ 2051 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiP20062.
PaxDbiP20062.
PeptideAtlasiP20062.
PRIDEiP20062.

Expressioni

Gene expression databases

BgeeiENSG00000185339.
CleanExiHS_TCN2.
ExpressionAtlasiP20062. baseline and differential.
GenevisibleiP20062. HS.

Organism-specific databases

HPAiHPA000837.

Interactioni

Protein-protein interaction databases

BioGridi112808. 5 interactors.
IntActiP20062. 2 interactors.
STRINGi9606.ENSP00000215838.

Structurei

Secondary structure

1427
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi28 – 38Combined sources11
Helixi39 – 43Combined sources5
Turni47 – 49Combined sources3
Helixi52 – 59Combined sources8
Beta strandi61 – 64Combined sources4
Helixi67 – 85Combined sources19
Helixi102 – 114Combined sources13
Helixi121 – 142Combined sources22
Beta strandi144 – 146Combined sources3
Helixi154 – 166Combined sources13
Helixi173 – 183Combined sources11
Beta strandi184 – 186Combined sources3
Helixi193 – 208Combined sources16
Helixi213 – 215Combined sources3
Helixi216 – 232Combined sources17
Beta strandi240 – 242Combined sources3
Turni243 – 245Combined sources3
Helixi246 – 253Combined sources8
Helixi263 – 279Combined sources17
Helixi286 – 296Combined sources11
Helixi301 – 304Combined sources4
Beta strandi329 – 336Combined sources8
Beta strandi338 – 341Combined sources4
Beta strandi343 – 350Combined sources8
Helixi355 – 365Combined sources11
Beta strandi370 – 373Combined sources4
Beta strandi380 – 384Combined sources5
Beta strandi393 – 399Combined sources7
Turni400 – 402Combined sources3
Turni409 – 411Combined sources3
Beta strandi419 – 426Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BB5X-ray3.20A/B19-427[»]
4ZRPX-ray2.10A/B19-427[»]
4ZRQX-ray2.60A/B19-427[»]
ProteinModelPortaliP20062.
SMRiP20062.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20062.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni152 – 156Cobalamin binding5
Regioni190 – 194Cobalamin binding5
Regioni395 – 397Cobalamin binding3

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IDZK. Eukaryota.
ENOG410XSU1. LUCA.
GeneTreeiENSGT00530000063370.
HOGENOMiHOG000074060.
HOVERGENiHBG001328.
InParanoidiP20062.
KOiK14619.
OMAiGEREFWQ.
OrthoDBiEOG091G095C.
PhylomeDBiP20062.
TreeFamiTF333092.

Family and domain databases

InterProiIPR002157. Cbl-bd_transpt_euk.
IPR027954. DUF4430.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PANTHERiPTHR10559. PTHR10559. 1 hit.
PfamiPF01122. Cobalamin_bind. 1 hit.
PF14478. DUF4430. 1 hit.
[Graphical view]
SUPFAMiSSF48239. SSF48239. 1 hit.
PROSITEiPS00468. COBALAMIN_BINDING. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P20062-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRHLGAFLFL LGVLGALTEM CEIPEMDSHL VEKLGQHLLP WMDRLSLEHL
60 70 80 90 100
NPSIYVGLRL SSLQAGTKED LYLHSLKLGY QQCLLGSAFS EDDGDCQGKP
110 120 130 140 150
SMGQLALYLL ALRANCEFVR GHKGDRLVSQ LKWFLEDEKR AIGHDHKGHP
160 170 180 190 200
HTSYYQYGLG ILALCLHQKR VHDSVVDKLL YAVEPFHQGH HSVDTAAMAG
210 220 230 240 250
LAFTCLKRSN FNPGRRQRIT MAIRTVREEI LKAQTPEGHF GNVYSTPLAL
260 270 280 290 300
QFLMTSPMRG AELGTACLKA RVALLASLQD GAFQNALMIS QLLPVLNHKT
310 320 330 340 350
YIDLIFPDCL APRVMLEPAA ETIPQTQEII SVTLQVLSLL PPYRQSISVL
360 370 380 390 400
AGSTVEDVLK KAHELGGFTY ETQASLSGPY LTSVMGKAAG EREFWQLLRD
410 420
PNTPLLQGIA DYRPKDGETI ELRLVSW
Length:427
Mass (Da):47,535
Last modified:March 3, 2009 - v3
Checksum:iFD04A110941989DB
GO
Isoform 2 (identifier: P20062-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     116-143: CEFVRGHKGDRLVSQLKWFLEDEKRAIG → W

Note: No experimental confirmation available.
Show »
Length:400
Mass (Da):44,421
Checksum:i38C59B8CF61DC15D
GO

Polymorphismi

Pro/Arg-259 polymorphism affects TCN2 plasma concentration and may interfere in vitamin B(12) cellular availability and homocysteine metabolism (PubMed:11159542).1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05453923I → V.Corresponds to variant rs9606756dbSNPEnsembl.1
Natural variantiVAR_05454089F → L.Corresponds to variant rs35915865dbSNPEnsembl.1
Natural variantiVAR_001638198M → T.1 Publication1
Natural variantiVAR_054541215R → W.Corresponds to variant rs35838082dbSNPEnsembl.1
Natural variantiVAR_001639219I → L.1 Publication1
Natural variantiVAR_054542227R → Q.1 PublicationCorresponds to variant rs17849434dbSNPEnsembl.1
Natural variantiVAR_001640259R → P.3 PublicationsCorresponds to variant rs1801198dbSNPEnsembl.1
Natural variantiVAR_054543348S → F.Corresponds to variant rs9621049dbSNPEnsembl.1
Natural variantiVAR_001641376L → S.1 PublicationCorresponds to variant rs1131603dbSNPEnsembl.1
Natural variantiVAR_054544399R → Q.Corresponds to variant rs4820889dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043711116 – 143CEFVR…KRAIG → W in isoform 2. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60396 mRNA. Translation: AAA61054.1.
L02647 mRNA. Translation: AAA61056.1.
L02648 mRNA. Translation: AAA61057.1.
AF047576 Genomic DNA. Translation: AAC05491.1.
CR456591 mRNA. Translation: CAG30477.1.
AC005006 Genomic DNA. No translation available.
BC001176 mRNA. Translation: AAH01176.1.
BC011239 mRNA. Translation: AAH11239.1.
CCDSiCCDS13881.1. [P20062-1]
CCDS54519.1. [P20062-2]
PIRiA39744.
RefSeqiNP_000346.2. NM_000355.3. [P20062-1]
NP_001171655.1. NM_001184726.1. [P20062-2]
UniGeneiHs.417948.

Genome annotation databases

EnsembliENST00000215838; ENSP00000215838; ENSG00000185339. [P20062-1]
ENST00000407817; ENSP00000384914; ENSG00000185339. [P20062-2]
GeneIDi6948.
KEGGihsa:6948.
UCSCiuc003aip.3. human. [P20062-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

TCN2base

TCN2 mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60396 mRNA. Translation: AAA61054.1.
L02647 mRNA. Translation: AAA61056.1.
L02648 mRNA. Translation: AAA61057.1.
AF047576 Genomic DNA. Translation: AAC05491.1.
CR456591 mRNA. Translation: CAG30477.1.
AC005006 Genomic DNA. No translation available.
BC001176 mRNA. Translation: AAH01176.1.
BC011239 mRNA. Translation: AAH11239.1.
CCDSiCCDS13881.1. [P20062-1]
CCDS54519.1. [P20062-2]
PIRiA39744.
RefSeqiNP_000346.2. NM_000355.3. [P20062-1]
NP_001171655.1. NM_001184726.1. [P20062-2]
UniGeneiHs.417948.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BB5X-ray3.20A/B19-427[»]
4ZRPX-ray2.10A/B19-427[»]
4ZRQX-ray2.60A/B19-427[»]
ProteinModelPortaliP20062.
SMRiP20062.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112808. 5 interactors.
IntActiP20062. 2 interactors.
STRINGi9606.ENSP00000215838.

Chemistry databases

DrugBankiDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

Polymorphism and mutation databases

BioMutaiTCN2.
DMDMi224471876.

Proteomic databases

EPDiP20062.
PaxDbiP20062.
PeptideAtlasiP20062.
PRIDEiP20062.

Protocols and materials databases

DNASUi6948.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000215838; ENSP00000215838; ENSG00000185339. [P20062-1]
ENST00000407817; ENSP00000384914; ENSG00000185339. [P20062-2]
GeneIDi6948.
KEGGihsa:6948.
UCSCiuc003aip.3. human. [P20062-1]

Organism-specific databases

CTDi6948.
DisGeNETi6948.
GeneCardsiTCN2.
HGNCiHGNC:11653. TCN2.
HPAiHPA000837.
MalaCardsiTCN2.
MIMi275350. phenotype.
613441. gene.
neXtProtiNX_P20062.
OpenTargetsiENSG00000185339.
Orphaneti859. Transcobalamin deficiency.
PharmGKBiPA36404.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IDZK. Eukaryota.
ENOG410XSU1. LUCA.
GeneTreeiENSGT00530000063370.
HOGENOMiHOG000074060.
HOVERGENiHBG001328.
InParanoidiP20062.
KOiK14619.
OMAiGEREFWQ.
OrthoDBiEOG091G095C.
PhylomeDBiP20062.
TreeFamiTF333092.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100036-MONOMER.
ReactomeiR-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.
R-HSA-3359454. Defective TCN2 causes hereditary megaloblastic anemia.
R-HSA-3359485. Defective CD320 causes methylmalonic aciduria.
SABIO-RKP20062.

Miscellaneous databases

EvolutionaryTraceiP20062.
GenomeRNAii6948.
PROiP20062.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185339.
CleanExiHS_TCN2.
ExpressionAtlasiP20062. baseline and differential.
GenevisibleiP20062. HS.

Family and domain databases

InterProiIPR002157. Cbl-bd_transpt_euk.
IPR027954. DUF4430.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PANTHERiPTHR10559. PTHR10559. 1 hit.
PfamiPF01122. Cobalamin_bind. 1 hit.
PF14478. DUF4430. 1 hit.
[Graphical view]
SUPFAMiSSF48239. SSF48239. 1 hit.
PROSITEiPS00468. COBALAMIN_BINDING. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTCO2_HUMAN
AccessioniPrimary (citable) accession number: P20062
Secondary accession number(s): Q96FD4
, Q9BVI8, Q9UCI5, Q9UCI6, Q9UDM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: March 3, 2009
Last modified: November 2, 2016
This is version 172 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.