Q9NPD8 (UBE2T_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-conjugating enzyme E2 T
EC=6.3.2.19

Alternative name(s):
Cell proliferation-inducing gene 50 protein
Ubiquitin carrier protein T
Ubiquitin-protein ligase T

Gene names

Name:	UBE2T
ORF Names:	HSPC150, PIG50

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	197 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA repair: acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCL and FANCI. May contribute to ubiquitination and degradation of BRCA1. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with FANCL and BRCA1. Ref.9 Ref.10 Ref.11 Ref.13 Ref.17
Subcellular location	Nucleus. Note: Accumulates to chromatin. Ref.10 Ref.13
Induction	Down-regulated following hypoxia. Up-regulated in breast cancers. Ref.18
Post-translational modification	Auto-ubiquitinated. Effects of auto-monoubiquitination at Lys-91 and Lys-182 are unclear: according to a report, monoubiquitination inactivates E2 enzyme activity (Ref.9). In contrast, according to another report, autoubiquitination does not affect E2 enzyme activity (Ref.11).
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from mutant phenotype Ref.9. Source: UniProtKB protein K11-linked ubiquitination Inferred from direct assay Ref.15. Source: UniProtKB protein K27-linked ubiquitination Inferred from direct assay Ref.15. Source: UniProtKB protein K29-linked ubiquitination Inferred from direct assay Ref.15. Source: UniProtKB protein K48-linked ubiquitination Inferred from direct assay Ref.15. Source: UniProtKB protein K6-linked ubiquitination Inferred from direct assay Ref.15. Source: UniProtKB protein K63-linked ubiquitination Inferred from direct assay Ref.15. Source: UniProtKB protein autoubiquitination Inferred from direct assay Ref.9Ref.11. Source: UniProtKB protein monoubiquitination Inferred from direct assay Ref.9Ref.10Ref.11. Source: UniProtKB
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW chromatin binding Inferred from direct assay Ref.10. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.9Ref.10Ref.11Ref.15. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 197

197

Ubiquitin-conjugating enzyme E2 T

PRO_0000082509

Sites

Active site

86

1

Glycyl thioester intermediate

Amino acid modifications

Cross-link

91

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9 Ref.11

Cross-link

182

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.11

Experimental info

Mutagenesis

63

1

F → A: Decreased binding to FANCL. Ref.17

Mutagenesis

86

1

C → A: Loss of E2 enzyme activity. Ref.9 Ref.10 Ref.11 Ref.13 Ref.14

Mutagenesis

91

1

K → R: Decreased monoubiquitination. Ref.11

Mutagenesis

182 – 191

10

Missing: Decreased monoubiquitination. Ref.11

Secondary structure

1

.

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197

Helix Strand Turn

Details...

Helix

1 – 16

16

Beta strand

22 – 29

8

Beta strand

33 – 39

7

Turn

45 – 48

4

Beta strand

50 – 56

7

Turn

59 – 62

4

Beta strand

67 – 72

6

Helix

88 – 90

3

Turn

93 – 95

3

Helix

104 – 116

13

Helix

126 – 134

9

Helix

136 – 150

15

Sequences

	Sequence		Length	Mass (Da)
	Q9NPD8 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 6C02D774A7FA928A	FASTA	197	22,521
	10 20 30 40 50 60 MQRASRLKRE LHMLATEPPP GITCWQDKDQ MDDLRAQILG GANTPYEKGV FKLEVIIPER 70 80 90 100 110 120 YPFEPPQIRF LTPIYHPNID SAGRICLDVL KLPPKGAWRP SLNIATVLTS IQLLMSEPNP 130 140 150 160 170 180 DDPLMADISS EFKYNKPAFL KNARQWTEKH ARQKQKADEE EMLDNLPEAG DSRVHNSTQK 190 RKASQLVGIE KKFHPDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Ubiquitin-conjugating enzyme isolog." Okaze H., Hayashi A., Kozuma S., Saito T. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Adrenal gland.
[3]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Carcinoma.
[5]	"Identification of a human cell proliferation inducing gene." Kim J.W. Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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]. Tissue: Lung.
[9]	"UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation." Machida Y.J., Machida Y., Chen Y., Gurtan A.M., Kupfer G.M., D'Andrea A.D., Dutta A. Mol. Cell 23:589-596(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FANCL, UBIQUITINATION AT LYS-91, MUTAGENESIS OF CYS-86.
[10]	"UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination." Alpi A., Langevin F., Mosedale G., Machida Y.J., Dutta A., Patel K.J. Mol. Cell. Biol. 27:8421-8430(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FANCL, MUTAGENESIS OF CYS-86.
[11]	"Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI." Alpi A.F., Pace P.E., Babu M.M., Patel K.J. Mol. Cell 32:767-777(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FANCL, UBIQUITINATION AT LYS-91 AND LYS-182, MUTAGENESIS OF CYS-86; LYS-91 AND 182-LYS--LYS-191.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[13]	"Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme E2T overexpression in human breast cancer cells." Ueki T., Park J.H., Nishidate T., Kijima K., Hirata K., Nakamura Y., Katagiri T. Cancer Res. 69:8752-8760(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-86, INTERACTION WITH BRCA1.
[14]	"FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL." Longerich S., San Filippo J., Liu D., Sung P. J. Biol. Chem. 284:23182-23186(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-86.
[15]	"The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred lysines." David Y., Ziv T., Admon A., Navon A. J. Biol. Chem. 285:8595-8604(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia pathway." Hodson C., Cole A.R., Lewis L.P., Miles J.A., Purkiss A., Walden H. J. Biol. Chem. 286:32628-32637(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FANCL, MUTAGENESIS OF PHE-63.
[18]	"Hypoxia disrupts the Fanconi anemia pathway and sensitizes cells to chemotherapy through regulation of UBE2T." Ramaekers C.H., van den Beucken T., Meng A., Kassam S., Thoms J., Bristow R.G., Wouters B.G. Radiother. Oncol. 101:190-197(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[19]	"Ubiquitin-conjugating enzyme HSPC150." Walker J.R., Avvakumov G.V., Newman E.M., Mackenzie F., Kozieradzki I., Sundstrom M., Arrowsmith C., Edwards A., Bochkarev A., Dhe-Paganon S. Submitted (FEB-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-167.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB032931 mRNA. Translation: BAA93711.1.
AF160215 mRNA. Translation: AAF67016.1.
AF161499 mRNA. Translation: AAF29114.1.
AK000504 mRNA. Translation: BAA91211.1.
AY542309 mRNA. Translation: AAT08178.1.
AL356953 Genomic DNA. Translation: CAI15933.1.
CH471067 Genomic DNA. Translation: EAW91411.1.
BC004152 mRNA. Translation: AAH04152.1.
BC019284 mRNA. Translation: AAH19284.1.

IPI

IPI00023087.

RefSeq

NP_054895.1. NM_014176.3.

UniGene

Hs.5199.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YH2	X-ray	2.00	A	1-167	[»]

ProteinModelPortal

Q9NPD8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NPD8. 10 interactions.

STRING

9606.ENSP00000356243.

PTM databases

PhosphoSite

Q9NPD8.

Polymorphism databases

DMDM

73622065.

Proteomic databases

PaxDb

Q9NPD8.

PRIDE

Q9NPD8.

Protocols and materials databases

DNASU

29089.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000367274; ENSP00000356243; ENSG00000077152.

GeneID

29089.

KEGG

hsa:29089.

UCSC

uc001gxx.4. human.

Organism-specific databases

CTD

29089.

GeneCards

GC01M202300.

HGNC

HGNC:25009. UBE2T.

HPA

HPA002831.

MIM

610538. gene.

neXtProt

NX_Q9NPD8.

PharmGKB

PA142670655.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5078.

HOGENOM

HOG000233455.

HOVERGEN

HBG063308.

InParanoid

Q9NPD8.

KO

K13960.

OMA

GITCWQE.

OrthoDB

EOG40GCRT.

PhylomeDB

Q9NPD8.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

UniPathway

UPA00143.

Gene expression databases

Bgee

Q9NPD8.

CleanEx

HS_UBE2T.

Genevestigator

Q9NPD8.

GermOnline

ENSG00000077152. Homo sapiens.

Family and domain databases

Gene3D

3.10.110.10. 1 hit.

InterPro

IPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]

Pfam

PF00179. UQ_con. 1 hit.
[Graphical view]

SUPFAM

SSF54495. UBQ-conjugat/RWD-like. 1 hit.

PROSITE

PS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

UBE2T. human.

EvolutionaryTrace

Q9NPD8.

GenomeRNAi

29089.

NextBio

52094.

SOURCE

Search...

Entry information

Entry name

UBE2T_HUMAN

Accession

Primary (citable) accession number: Q9NPD8
Secondary accession number(s): Q2TU36

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 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.