Reviewed, UniProtKB/Swiss-Prot O00762 (UBE2C_HUMAN)

Names and origin

Protein names

Recommended name:
    Ubiquitin-conjugating enzyme E2 C
    EC=6.3.2.19
Alternative name(s):
    Ubiquitin-protein ligase C
    Ubiquitin carrier protein C
    UbcH10

Gene names

Name:	UBE2C
Synonyms:	UBCH10

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	179 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	Catalyzes the covalent attachment of ubiquitin to other proteins. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by initiating 'Lys-11'-linked polyubiquitin chains on APC/C substrates, leading to the degradation of APC/C substrates by the proteasome and promoting mitotic exit. Ref.5 Ref.6 Ref.9 Ref.10
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine. Ref.6
Pathway	Protein modification; protein ubiquitination. Ref.6
Subunit structure	Component of the APC/C complex.
Post-translational modification	Autoubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Its degradation plays a central role in APC/C regulation, allowing cyclin-A accumulation before S phase entry. APC/C substrates inhibit the autoubiquitination of UBE2C/UBCH10 but not its E2 function, hence APC/C remaining active until its substrates have been destroyed.
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Ubl conjugation pathway
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Ref.10 Inferred from direct assay. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW cyclin catabolic process Ref.1 Inferred from direct assay. Source: UniProtKB exit from mitosis Ref.10 Inferred from mutant phenotype. Source: UniProtKB free ubiquitin chain polymerization Ref.10 Inferred from direct assay. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome phosphoinositide-mediated signaling Non-traceable author statement. Source: UniProtKB positive regulation of exit from mitosis Ref.1 Inferred from mutant phenotype. Source: UniProtKB positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome protein K11-linked ubiquitination Ref.6 Ref.10 Inferred from direct assay. Source: UniProtKB regulation of protein metabolic process Inferred from electronic annotation. Source: InterPro spindle organization Non-traceable author statement. Source: UniProtKB
Cellular component	anaphase-promoting complex Ref.6 Ref.10 Inferred from direct assay. Source: UniProtKB cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.10 Inferred from physical interaction. Source: UniProtKB ubiquitin-protein ligase activity Ref.6 Ref.9 Ref.10 Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 179

178

Ubiquitin-conjugating enzyme E2 C

PRO_0000082560

Sites

Active site

114

1

Glycyl thioester intermediate

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Natural variations

Natural variant

25

1

G → D

VAR_007694

Experimental info

Mutagenesis

114

1

C → S: Loss of function; inhibition of cyclin-B degradation. Ref.5 Ref.1

Secondary structure

1

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179

Helix Strand Turn

Details...

Helix

31 – 45

15

Beta strand

50 – 55

6

Beta strand

58 – 68

11

Beta strand

78 – 84

7

Turn

87 – 91

5

Beta strand

95 – 100

6

Helix

116 – 118

3

Turn

119 – 121

3

Helix

128 – 140

13

Helix

150 – 155

6

Helix

159 – 171

13

Sequences

	Sequence		Length	Mass (Da)
	O00762-1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 0B6F58A1F0665D9A	FASTA	179	19,652
	10 20 30 40 50 60 MASQNRDPAA TSVAAARKGA EPSGGAARGP VGKRLQQELM TLMMSGDKGI SAFPESDNLF 70 80 90 100 110 120 KWVGTIHGAA GTVYEDLRYK LSLEFPSGYP YNAPTVKFLT PCYHPNVDTQ GNICLDILKE 130 140 150 160 170 KWSALYDVRT ILLSIQSLLG EPNIDSPLNT HAAELWKNPT AFKKYLQETY SKQVTSQEP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase." Townsley F.M., Aristarkhov A., Beck S., Hershko A., Ruderman J.V. Proc. Natl. Acad. Sci. U.S.A. 94:2362-2367(1997) [PubMed: 9122200] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF CYS-114.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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]. Tissue: Lymph and Uterus.
[5]	"Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry." Rape M., Kirschner M.W. Nature 432:588-595(2004) [PubMed: 15558010] [Abstract] Cited for: FUNCTION, UBIQUITINATION, MUTAGENESIS OF CYS-114.
[6]	"Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex." Jin L., Williamson A., Banerjee S., Philipp I., Rape M. Cell 133:653-665(2008) [PubMed: 18485873] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
[9]	"UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit." Garnett M.J., Mansfeld J., Godwin C., Matsusaka T., Wu J., Russell P., Pines J., Venkitaraman A.R. Nat. Cell Biol. 11:1363-1369(2009) [PubMed: 19820702] [Abstract] Cited for: FUNCTION.
[10]	"Identification of a physiological E2 module for the human anaphase-promoting complex." Williamson A., Wickliffe K.E., Mellone B.G., Song L., Karpen G.H., Rape M. Proc. Natl. Acad. Sci. U.S.A. 106:18213-18218(2009) [PubMed: 19822757] [Abstract] Cited for: FUNCTION.
[11]	"Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10." Lin Y., Hwang W.C., Basavappa R. J. Biol. Chem. 277:21913-21921(2002) [PubMed: 11927573] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U73379 mRNA. Translation: AAB53362.1.
BT007300 mRNA. Translation: AAP35964.1.
AL050348 Genomic DNA. No translation available.
BC007656 mRNA. Translation: AAH07656.1.
BC016292 mRNA. Translation: AAH16292.1.
BC050736 mRNA. Translation: AAH50736.1.

IPI

IPI00013002.

RefSeq

NP_008950.1.
NP_861515.1.
NP_861516.1.
NP_861517.1.

UniGene

Hs.93002

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I7K	X-ray	1.95	A/B	1-179	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O00762. 4 interactions.

STRING

O00762.

Proteomic databases

PRIDE

O00762.

Genome annotation databases

Ensembl

ENST00000356455; ENSP00000348838; ENSG00000175063; Homo sapiens. [Genome view]

GeneID

11065.

KEGG

hsa:11065.

UCSC

uc002xpm.1. human.

Organism-specific databases

CTD

11065.

GeneCards

GC20P043874.

H-InvDB

HIX0015862.

HGNC

HGNC:15937. UBE2C.

HPA

CAB011464.

MIM

605574. gene.

PharmGKB

PA38057.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13072.

HOGENOM

HBG756483.

HOVERGEN

O00762.

InParanoid

O00762.

OMA

KEKWSAV.

PhylomeDB

O00762.

Enzyme and pathway databases

BRENDA

6.3.2.19. 247.

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
REACT_8017. APC-Cdc20 mediated degradation of Nek2A.
REACT_9035. APC/C:Cdh1-mediated degradation of Skp2.

Gene expression databases

ArrayExpress

O00762.

Bgee

O00762.

CleanEx

HS_UBE2C.

Genevestigator

O00762.

GermOnline

ENSG00000175063. Homo sapiens.

Family and domain databases

InterPro

IPR015582. Ubiquitin-conj_enz_E2_H10.
IPR016135. UBQ-conjugat/RWD-like.
IPR000608. UBQ-conjugat_E2.
[Graphical view]

Gene3D

G3DSA:3.10.110.10. UBQ-conjugat_E2. 1 hit.

PANTHER

PTHR11621:SF26. UbcH10. 1 hit.

Pfam

PF00179. UQ_con. 1 hit.
[Graphical view]

SMART

SM00212. UBCc. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

NextBio

42051.

SOURCE

Search...

Entry information

Entry name

UBE2C_HUMAN

Accession

Primary (citable) accession number: O00762

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	July 1, 1997
Last modified:	January 19, 2010
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.