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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 B(12) cellular availability and homocysteine metabolism.
Involvement in disease	Defects in TCN2 are the cause of transcobalamin II deficiency (TCN2 deficiency) [MIM:275350]. This results in various forms of anemia.
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	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. Source: ProtInc cobalt ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular space Traceable author statement. 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...

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

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

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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)
	P20062 [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

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: 1708393] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 8439564] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 7742531] [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: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], 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: 10591208] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-227. Tissue: 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: 3782074] [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: 8443384] [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: 16537422] [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: 11159542] [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.

IPI

IPI00219465.

PIR

A39744.

RefSeq

NP_000346.2. NM_000355.3.

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.

SMR

P20062. Positions 19-427.

ModBase

Search...

Protein-protein interaction databases

IntAct

P20062. 2 interactions.

STRING

P20062.

Polymorphism databases

DMDM

224471876.

Proteomic databases

PRIDE

P20062.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000215838; ENSP00000215838; ENSG00000185339.

GeneID

6948.

KEGG

hsa:6948.

UCSC

uc003aip.1. human.

Organism-specific databases

CTD

6948.

GeneCards

GC22P031002.

H-InvDB

HIX0016376.

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

prNOG17185.

GeneTree

ENSGT00530000063370.

HOGENOM

HBG125088.

HOVERGEN

HBG001328.

InParanoid

P20062.

OMA

HTSYYQY.

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]

KO

K14619.

PANTHER

PTHR10559. Cobalamin_bd. 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.

NextBio

27203.

SOURCE

Search...

Entry information

Entry name

TCO2_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	March 3, 2009
Last modified:	January 25, 2012
This is version 126 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.