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Protein

Transcobalamin-2

Gene

TCN2

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

Functioni

Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei104Cobalamin2 Publications1
Metal bindingi190Cobalt (cobalamin axial ligand)1
Binding sitei242Cobalamin1 Publication1
Binding sitei245Cobalamin2 Publications1
Binding sitei291Cobalamin1 Publication1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Biological processCobalt transport, Ion transport, Transport
LigandCobalt, Metal-binding

Enzyme and pathway databases

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-RKiP20062

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

EuPathDBiHostDB:ENSG00000185339.8
HGNCiHGNC:11653 TCN2
MIMi613441 gene
neXtProtiNX_P20062

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 ↔ 267Combined sources2 Publications
Disulfide bondi83 ↔ 96Combined sources1 Publication
Disulfide bondi116 ↔ 309Combined sources2 Publications
Disulfide bondi165 ↔ 205Combined sources2 Publications

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP20062
PeptideAtlasiP20062
PRIDEiP20062
ProteomicsDBi53720
53721 [P20062-2]

Expressioni

Gene expression databases

BgeeiENSG00000185339 Expressed in 136 organ(s), highest expression level in esophagus
CleanExiHS_TCN2
ExpressionAtlasiP20062 baseline and differential
GenevisibleiP20062 HS

Organism-specific databases

HPAiHPA000837

Interactioni

Subunit structurei

Interacts with CD320 (via LDL-receptor class A domains).1 Publication

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

3D structure databases

ProteinModelPortaliP20062
SMRiP20062
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20062

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni152 – 156Cobalamin binding1 Publication5
Regioni190 – 194Cobalamin binding1 Publication5
Regioni395 – 397Cobalamin binding1 Publication3

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR002157 Cbl-bd_prot
IPR027954 DUF4430
IPR008930 Terpenoid_cyclase/PrenylTrfase
PfamiView protein in Pfam
PF01122 Cobalamin_bind, 1 hit
PF14478 DUF4430, 1 hit
SUPFAMiSSF48239 SSF48239, 1 hit
PROSITEiView protein in PROSITE
PS00468 COBALAMIN_BINDING, 1 hit

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B5MBX2B5MBX2_HUMAN
Transcobalamin-2
TCN2
423Annotation score:
F8WE86F8WE86_HUMAN
Transcobalamin-2
TCN2
402Annotation score:

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 dbSNP:rs9606756EnsemblClinVar.1
Natural variantiVAR_05454089F → L. Corresponds to variant dbSNP:rs35915865EnsemblClinVar.1
Natural variantiVAR_001638198M → T1 Publication1
Natural variantiVAR_054541215R → W. Corresponds to variant dbSNP:rs35838082EnsemblClinVar.1
Natural variantiVAR_001639219I → L1 Publication1
Natural variantiVAR_054542227R → Q1 PublicationCorresponds to variant dbSNP:rs17849434Ensembl.1
Natural variantiVAR_001640259R → P3 PublicationsCorresponds to variant dbSNP:rs1801198EnsemblClinVar.1
Natural variantiVAR_054543348S → F. Corresponds to variant dbSNP:rs9621049EnsemblClinVar.1
Natural variantiVAR_001641376L → S1 PublicationCorresponds to variant dbSNP:rs1131603EnsemblClinVar.1
Natural variantiVAR_054544399R → Q. Corresponds to variant dbSNP:rs4820889EnsemblClinVar.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

Similar proteinsi

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[»]
5NO0X-ray1.57A325-427[»]
5NP4X-ray1.43A325-427[»]
5NRPX-ray1.57A325-427[»]
5NSAX-ray1.27A325-427[»]
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

PaxDbiP20062
PeptideAtlasiP20062
PRIDEiP20062
ProteomicsDBi53720
53721 [P20062-2]

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
EuPathDBiHostDB:ENSG00000185339.8
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

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-RKiP20062

Miscellaneous databases

ChiTaRSiTCN2 human
EvolutionaryTraceiP20062
GenomeRNAii6948
PROiPR:P20062
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185339 Expressed in 136 organ(s), highest expression level in esophagus
CleanExiHS_TCN2
ExpressionAtlasiP20062 baseline and differential
GenevisibleiP20062 HS

Family and domain databases

InterProiView protein in InterPro
IPR002157 Cbl-bd_prot
IPR027954 DUF4430
IPR008930 Terpenoid_cyclase/PrenylTrfase
PfamiView protein in Pfam
PF01122 Cobalamin_bind, 1 hit
PF14478 DUF4430, 1 hit
SUPFAMiSSF48239 SSF48239, 1 hit
PROSITEiView protein in PROSITE
PS00468 COBALAMIN_BINDING, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTCO2_HUMAN
AccessioniPrimary (citable) accession number: P20062
Secondary accession number(s): Q96FD4
, Q9BVI8, Q9UCI5, Q9UCI6, Q9UDM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: March 3, 2009
Last modified: September 12, 2018
This is version 184 of the entry and version 3 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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