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P20062 (TCO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcobalamin-2

Short name=TC-2
Alternative name(s):
Transcobalamin II
Short name=TC II
Short name=TCII
Gene names
Name:TCN2
Synonyms:TC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subcellular location

Secreted.

Polymorphism

Pro/Arg-259 polymorphism affects TCN2 plasma concentration and may interfere in vitamin B12 cellular availability and homocysteine metabolism.

Involvement in disease

Transcobalamin II deficiency (TCN2 deficiency) [MIM:275350]: Results in various forms of anemia.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the eukaryotic cobalamin transport proteins family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P20062-1)

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.
Isoform 2 (identifier: P20062-2)

The sequence of this isoform differs from the canonical sequence as follows:
     116-143: CEFVRGHKGDRLVSQLKWFLEDEKRAIG → W
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.7
Chain19 – 427409Transcobalamin-2
PRO_0000005564

Regions

Region152 – 1565Cobalamin binding
Region190 – 1945Cobalamin binding
Region395 – 3973Cobalamin binding

Sites

Metal binding1901Cobalt (cobalamin axial ligand)
Binding site1041Cobalamin
Binding site2421Cobalamin
Binding site2451Cobalamin
Binding site2911Cobalamin

Amino acid modifications

Disulfide bond21 ↔ 267 Ref.9
Disulfide bond116 ↔ 309 Ref.9
Disulfide bond165 ↔ 205 Ref.9

Natural variations

Alternative sequence116 – 14328CEFVR…KRAIG → W in isoform 2.
VSP_043711
Natural variant231I → V.
Corresponds to variant rs9606756 [ dbSNP | Ensembl ].
VAR_054539
Natural variant891F → L.
Corresponds to variant rs35915865 [ dbSNP | Ensembl ].
VAR_054540
Natural variant1981M → T. Ref.1
VAR_001638
Natural variant2151R → W.
Corresponds to variant rs35838082 [ dbSNP | Ensembl ].
VAR_054541
Natural variant2191I → L. Ref.1
VAR_001639
Natural variant2271R → Q. Ref.6
Corresponds to variant rs17849434 [ dbSNP | Ensembl ].
VAR_054542
Natural variant2591R → P. Ref.1 Ref.4 Ref.10
Corresponds to variant rs1801198 [ dbSNP | Ensembl ].
VAR_001640
Natural variant3481S → F.
Corresponds to variant rs9621049 [ dbSNP | Ensembl ].
VAR_054543
Natural variant3761L → S. Ref.1
Corresponds to variant rs1131603 [ dbSNP | Ensembl ].
VAR_001641
Natural variant3991R → Q.
Corresponds to variant rs4820889 [ dbSNP | Ensembl ].
VAR_054544

Secondary structure

.......................................................... 427
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 3, 2009. Version 3.
Checksum: FD04A110941989DB

FASTA42747,535
        10         20         30         40         50         60 
MRHLGAFLFL LGVLGALTEM CEIPEMDSHL VEKLGQHLLP WMDRLSLEHL NPSIYVGLRL 

        70         80         90        100        110        120 
SSLQAGTKED LYLHSLKLGY QQCLLGSAFS EDDGDCQGKP SMGQLALYLL ALRANCEFVR 

       130        140        150        160        170        180 
GHKGDRLVSQ LKWFLEDEKR AIGHDHKGHP HTSYYQYGLG ILALCLHQKR VHDSVVDKLL 

       190        200        210        220        230        240 
YAVEPFHQGH HSVDTAAMAG LAFTCLKRSN FNPGRRQRIT MAIRTVREEI LKAQTPEGHF 

       250        260        270        280        290        300 
GNVYSTPLAL QFLMTSPMRG AELGTACLKA RVALLASLQD GAFQNALMIS QLLPVLNHKT 

       310        320        330        340        350        360 
YIDLIFPDCL APRVMLEPAA ETIPQTQEII SVTLQVLSLL PPYRQSISVL AGSTVEDVLK 

       370        380        390        400        410        420 
KAHELGGFTY ETQASLSGPY LTSVMGKAAG EREFWQLLRD PNTPLLQGIA DYRPKDGETI 


ELRLVSW 

« Hide

Isoform 2 [UniParc].

Checksum: 38C59B8CF61DC15D
Show »

FASTA40044,421

References

« Hide 'large scale' references
[1]"The cDNA sequence and the deduced amino acid sequence of human transcobalamin II show homology with rat intrinsic factor and human transcobalamin I."
Platica O., Janeczko R., Quadros E.V., Regec A., Romain R., Rothenberg S.P.
J. Biol. Chem. 266:7860-7863(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-198; LEU-219; PRO-259 AND SER-376.
[2]"Isolation and sequence analysis of variant forms of human transcobalamin II."
Li N., Seetharam S., Lindemans J., Alpers D.H., Arwert F., Seetharam B.
Biochim. Biophys. Acta 1172:21-30(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"The cloning and characterization of the human transcobalamin II gene."
Regec A., Quadros E.V., Platica O., Rothenberg S.P.
Blood 85:2711-2719(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT PRO-259.
[5]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT GLN-227.
Tissue: Brain and Eye.
[7]"Purification and molecular characterization of human transcobalamin II."
Quadros E.V., Rothenberg S.P., Pan Y.C.E., Stein S.
J. Biol. Chem. 261:15455-15460(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 19-37.
[8]"Functional human transcobalamin II isoproteins are secreted by insect cells using the baculovirus expression system."
Quadros E.V., Sai P., Rothenberg S.P.
Blood 81:1239-1245(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-26.
[9]"Structural basis for mammalian vitamin B12 transport by transcobalamin."
Wuerges J., Garau G., Geremia S., Fedosov S.N., Petersen T.E., Randaccio L.
Proc. Natl. Acad. Sci. U.S.A. 103:4386-4391(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 19-427 IN COMPLEX WITH COBALAMIN, DISULFIDE BONDS.
[10]"Transcobalamin codon 259 polymorphism in HT-29 and Caco-2 cells and in Caucasians: relation to transcobalamin and homocysteine concentration in blood."
Namour F., Olivier J., Abdelmouttaleb I., Adjalla C., Debard R., Salvat C., Gueant J.
Blood 97:1092-1098(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PRO-259.
+Additional computationally mapped references.

Web resources

TCN2base

TCN2 mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS13881.1. [P20062-1]
CCDS54519.1. [P20062-2]
PIRA39744.
RefSeqNP_000346.2. NM_000355.3. [P20062-1]
NP_001171655.1. NM_001184726.1. [P20062-2]
UniGeneHs.417948.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BB5X-ray3.20A/B19-427[»]
ProteinModelPortalP20062.
SMRP20062. Positions 19-427.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112808. 3 interactions.
IntActP20062. 2 interactions.
STRING9606.ENSP00000215838.

Chemistry

DrugBankDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

PTM databases

PhosphoSiteP20062.

Polymorphism databases

DMDM224471876.

Proteomic databases

PaxDbP20062.
PRIDEP20062.

Protocols and materials databases

DNASU6948.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000215838; ENSP00000215838; ENSG00000185339. [P20062-1]
ENST00000407817; ENSP00000384914; ENSG00000185339. [P20062-2]
GeneID6948.
KEGGhsa:6948.
UCSCuc003aip.2. human. [P20062-1]
uc003air.2. human. [P20062-2]

Organism-specific databases

CTD6948.
GeneCardsGC22P031002.
HGNCHGNC:11653. TCN2.
HPAHPA000837.
MIM275350. phenotype.
613441. gene.
neXtProtNX_P20062.
Orphanet859. Transcobalamin deficiency.
PharmGKBPA36404.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47054.
HOGENOMHOG000074060.
HOVERGENHBG001328.
InParanoidP20062.
KOK14619.
OMAGHKGDRL.
OrthoDBEOG79GT6F.
PhylomeDBP20062.
TreeFamTF333092.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressP20062.
BgeeP20062.
CleanExHS_TCN2.
GenevestigatorP20062.

Family and domain databases

InterProIPR002157. Cbl-bd_transpt_euk.
IPR027954. DUF4430.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PANTHERPTHR10559. PTHR10559. 1 hit.
PfamPF01122. Cobalamin_bind. 1 hit.
PF14478. DUF4430. 1 hit.
[Graphical view]
SUPFAMSSF48239. SSF48239. 1 hit.
PROSITEPS00468. COBALAMIN_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP20062.
GenomeRNAi6948.
NextBio27203.
PROP20062.
SOURCESearch...

Entry information

Entry nameTCO2_HUMAN
AccessionPrimary (citable) accession number: P20062
Secondary accession number(s): Q96FD4 expand/collapse secondary AC list , Q9BVI8, Q9UCI5, Q9UCI6, Q9UDM0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: March 3, 2009
Last modified: July 9, 2014
This is version 150 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM