P20062 (TCO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Cobalt transport Ion transport Transport
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Cobalt Metal-binding
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cobalamin metabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome cobalamin transport Traceable author statement Ref.7. Source: ProtInc cobalt ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Traceable author statement Ref.1. Source: ProtInc
Molecular_function	cobalamin binding Inferred from direct assay Ref.9. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Ref.7

Chain

19 – 427

409

Transcobalamin-2

PRO_0000005564

Regions

Region

152 – 156

5

Cobalamin binding

Region

190 – 194

5

Cobalamin binding

Region

395 – 397

3

Cobalamin binding

Sites

Metal binding

190

1

Cobalt (cobalamin axial ligand)

Binding site

104

1

Cobalamin

Binding site

242

1

Cobalamin

Binding site

245

1

Cobalamin

Binding site

291

1

Cobalamin

Amino acid modifications

Disulfide bond

21 ↔ 267

Ref.9

Disulfide bond

116 ↔ 309

Ref.9

Disulfide bond

165 ↔ 205

Ref.9

Natural variations

Alternative sequence

116 – 143

28

CEFVR…KRAIG → W in isoform 2.

VSP_043711

Natural variant

23

1

I → V.
Corresponds to variant rs9606756 [ dbSNP | Ensembl ].

VAR_054539

Natural variant

89

1

F → L.
Corresponds to variant rs35915865 [ dbSNP | Ensembl ].

VAR_054540

Natural variant

198

1

M → T. Ref.1

VAR_001638

Natural variant

215

1

R → W.
Corresponds to variant rs35838082 [ dbSNP | Ensembl ].

VAR_054541

Natural variant

219

1

I → L. Ref.1

VAR_001639

Natural variant

227

1

R → Q. Ref.6
Corresponds to variant rs17849434 [ dbSNP | Ensembl ].

VAR_054542

Natural variant

259

1

R → P. Ref.1 Ref.4 Ref.10
Corresponds to variant rs1801198 [ dbSNP | Ensembl ].

VAR_001640

Natural variant

348

1

S → F.
Corresponds to variant rs9621049 [ dbSNP | Ensembl ].

VAR_054543

Natural variant

376

1

L → S. Ref.1
Corresponds to variant rs1131603 [ dbSNP | Ensembl ].

VAR_001641

Natural variant

399

1

R → Q.
Corresponds to variant rs4820889 [ dbSNP | Ensembl ].

VAR_054544

Secondary structure

1

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427

Helix Strand Turn

Details...

Helix

28 – 38

11

Helix

39 – 43

5

Turn

47 – 49

3

Helix

52 – 59

8

Beta strand

61 – 64

4

Helix

67 – 84

18

Helix

102 – 114

13

Helix

122 – 142

21

Helix

154 – 166

13

Helix

173 – 183

11

Helix

192 – 207

16

Turn

208 – 210

3

Helix

213 – 215

3

Helix

216 – 232

17

Beta strand

240 – 242

3

Turn

243 – 245

3

Helix

246 – 253

8

Helix

262 – 278

17

Turn

279 – 281

3

Helix

286 – 292

7

Helix

295 – 297

3

Helix

301 – 304

4

Beta strand

329 – 336

8

Beta strand

338 – 341

4

Beta strand

343 – 350

8

Helix

355 – 365

11

Beta strand

370 – 373

4

Beta strand

380 – 384

5

Beta strand

391 – 399

9

Turn

400 – 402

3

Turn

409 – 411

3

Beta strand

418 – 426

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 3, 2009. Version 3. Checksum: FD04A110941989DB	FASTA	427	47,535
	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
	Isoform 2 [UniParc]. Checksum: 38C59B8CF61DC15D	FASTA	400	44,421
	10 20 30 40 50 60 MRHLGAFLFL LGVLGALTEM CEIPEMDSHL VEKLGQHLLP WMDRLSLEHL NPSIYVGLRL 70 80 90 100 110 120 SSLQAGTKED LYLHSLKLGY QQCLLGSAFS EDDGDCQGKP SMGQLALYLL ALRANWHDHK 130 140 150 160 170 180 GHPHTSYYQY GLGILALCLH QKRVHDSVVD KLLYAVEPFH QGHHSVDTAA MAGLAFTCLK 190 200 210 220 230 240 RSNFNPGRRQ RITMAIRTVR EEILKAQTPE GHFGNVYSTP LALQFLMTSP MRGAELGTAC 250 260 270 280 290 300 LKARVALLAS LQDGAFQNAL MISQLLPVLN HKTYIDLIFP DCLAPRVMLE PAAETIPQTQ 310 320 330 340 350 360 EIISVTLQVL SLLPPYRQSI SVLAGSTVED VLKKAHELGG FTYETQASLS GPYLTSVMGK 370 380 390 400 AAGEREFWQL LRDPNTPLLQ GIADYRPKDG ETIELRLVSW

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00219465.
IPI00386630.

PIR

A39744.

RefSeq

NP_000346.2. NM_000355.3.
NP_001171655.1. NM_001184726.1.

UniGene

Hs.417948.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BB5	X-ray	3.20	A/B	19-427	[»]

ProteinModelPortal

P20062.

ModBase

Search...

Protein-protein interaction databases

IntAct

P20062. 2 interactions.

STRING

9606.ENSP00000215838.

PTM databases

PhosphoSite

P20062.

Polymorphism databases

DMDM

224471876.

Proteomic databases

PaxDb

P20062.

PRIDE

P20062.

Protocols and materials databases

DNASU

6948.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000215838; ENSP00000215838; ENSG00000185339.
ENST00000407817; ENSP00000384914; ENSG00000185339.

GeneID

6948.

KEGG

hsa:6948.

UCSC

uc003aip.2. human.

Organism-specific databases

CTD

6948.

GeneCards

GC22P031002.

HGNC

HGNC:11653. TCN2.

HPA

HPA000837.

MIM

275350. phenotype.
613441. gene.

neXtProt

NX_P20062.

Orphanet

859. Transcobalamin II deficiency.

PharmGKB

PA36404.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47054.

HOGENOM

HOG000074060.

HOVERGEN

HBG001328.

InParanoid

P20062.

KO

K14619.

OMA

KAQTPEG.

OrthoDB

EOG4VDPZJ.

PhylomeDB

P20062.

Gene expression databases

ArrayExpress

P20062.

Bgee

P20062.

CleanEx

HS_TCN2.

Genevestigator

P20062.

GermOnline

ENSG00000185339. Homo sapiens.

Family and domain databases

InterPro

IPR002157. Cbl-bd_transpt_euk.
[Graphical view]

PANTHER

PTHR10559. PTHR10559. 1 hit.

Pfam

PF01122. Cobalamin_bind. 1 hit.
[Graphical view]

PROSITE

PS00468. COBALAMIN_BINDING. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

EvolutionaryTrace

P20062.

GenomeRNAi

6948.

NextBio

27203.

SOURCE

Search...

Entry information

Entry name

TCO2_HUMAN

Accession

Primary (citable) accession number: P20062
Secondary accession number(s): Q96FD4 , Q9BVI8, Q9UCI5, Q9UCI6, Q9UDM0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	March 3, 2009
Last modified:	May 1, 2013
This is version 138 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.