O00762 (UBE2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
UbcH10
Ubiquitin carrier protein C
Ubiquitin-protein ligase C

Gene names

Name:	UBE2C
Synonyms:	UBCH10

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	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	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination. 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.6 Ref.7 Ref.8 Ref.9 Ref.10
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine. Ref.7
Pathway	Protein modification; protein ubiquitination. Ref.7
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	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of anaphase-promoting complex activity Traceable author statement PubMed 17443180. Source: UniProtKB anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.9. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW cyclin catabolic process Inferred from direct assay Ref.1. Source: UniProtKB exit from mitosis Inferred from mutant phenotype Ref.9. Source: UniProtKB free ubiquitin chain polymerization Inferred from direct assay Ref.9. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic spindle assembly checkpoint Traceable author statement. Source: Reactome negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome phosphatidylinositol-mediated signaling Non-traceable author statement PubMed 15504738. Source: UniProtKB positive regulation of exit from mitosis Inferred from mutant phenotype Ref.1. Source: UniProtKB positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome protein K11-linked ubiquitination Inferred from direct assay Ref.7Ref.9Ref.10. Source: UniProtKB protein K48-linked ubiquitination Inferred from direct assay Ref.10. Source: UniProtKB spindle organization Non-traceable author statement PubMed 15504738. Source: UniProtKB
Cellular_component	anaphase-promoting complex Inferred from direct assay Ref.7Ref.9. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-protein ligase activity Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00762-1)

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: O00762-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O00762-3)

The sequence of this isoform differs from the canonical sequence as follows:
     44-72: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: O00762-4)

The sequence of this isoform differs from the canonical sequence as follows:
     73-140: VYEDLRYKLS...ILLSIQSLLG → AVGSIRTSST...LTLQLFLQMP

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.12

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.12

Modified residue

3

1

Phosphoserine Ref.12

Natural variations

Alternative sequence

1 – 39

39

Missing in isoform 2.

VSP_045647

Alternative sequence

44 – 72

29

Missing in isoform 3.

VSP_045648

Alternative sequence

73 – 140

68

VYEDL…QSLLG → AVGSIRTSSTVCLLSGPRET QDSSKPLVWGLGWDMRLLLE LTLQLFLQMP in isoform 4.

VSP_045649

Natural variant

25

1

G → D.

VAR_007694

Experimental info

Mutagenesis

114

1

C → S: Loss of function; inhibition of cyclin-B degradation. Ref.1 Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: 194F276AD75D5168	FASTA	140	15,765
	10 20 30 40 50 60 MTLMMSGDKG ISAFPESDNL FKWVGTIHGA AGTVYEDLRY KLSLEFPSGY PYNAPTVKFL 70 80 90 100 110 120 TPCYHPNVDT QGNICLDILK EKWSALYDVR TILLSIQSLL GEPNIDSPLN THAAELWKNP 130 140 TAFKKYLQET YSKQVTSQEP
	Isoform 3 [UniParc]. Checksum: 5410B7BA11DFC35E	FASTA	150	16,676
	10 20 30 40 50 60 MASQNRDPAA TSVAAARKGA EPSGGAARGP VGKRLQQELM TLMVYEDLRY KLSLEFPSGY 70 80 90 100 110 120 PYNAPTVKFL TPCYHPNVDT QGNICLDILK EKWSALYDVR TILLSIQSLL GEPNIDSPLN 130 140 150 THAAELWKNP TAFKKYLQET YSKQVTSQEP
	Isoform 4 [UniParc]. Checksum: D8F52001401888DA	FASTA	161	17,373
	10 20 30 40 50 60 MASQNRDPAA TSVAAARKGA EPSGGAARGP VGKRLQQELM TLMMSGDKGI SAFPESDNLF 70 80 90 100 110 120 KWVGTIHGAA GTAVGSIRTS STVCLLSGPR ETQDSSKPLV WGLGWDMRLL LELTLQLFLQ 130 140 150 160 MPEPNIDSPL NTHAAELWKN PTAFKKYLQE TYSKQVTSQE P

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] (ISOFORM 1).
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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; 2; 3 AND 4). Tissue: Lung adenocarcinoma, Lymph, Melanoma, Teratocarcinoma and Uterus.
[6]	"Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry." Rape M., Kirschner M.W. Nature 432:588-595(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, UBIQUITINATION, MUTAGENESIS OF CYS-114.
[7]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY.
[8]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"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.
[11]	"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].
[12]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE.
[13]	"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] [Europe PMC] [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.
CH471077 Genomic DNA. Translation: EAW75804.1.
CH471077 Genomic DNA. Translation: EAW75805.1.
CH471077 Genomic DNA. Translation: EAW75806.1.
CH471077 Genomic DNA. Translation: EAW75807.1.
BC007656 mRNA. Translation: AAH07656.1.
BC016292 mRNA. Translation: AAH16292.1.
BC050736 mRNA. Translation: AAH50736.1.
BI858659 mRNA. No translation available.
BM556795 mRNA. No translation available.
BU844974 mRNA. No translation available.

IPI

IPI00013002.
IPI00335561.
IPI00375615.

RefSeq

NP_008950.1. NM_007019.2.
NP_861515.1. NM_181799.1.
NP_861516.1. NM_181800.1.
NP_861517.1. NM_181801.2.
NP_861518.1. NM_181802.1.

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	[»]

ProteinModelPortal

O00762.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00762. 8 interactions.

STRING

9606.ENSP00000348838.

PTM databases

PhosphoSite

O00762.

Proteomic databases

PaxDb

O00762.

PRIDE

O00762.

Protocols and materials databases

DNASU

11065.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000335046; ENSP00000335674; ENSG00000175063.
ENST00000352551; ENSP00000333975; ENSG00000175063.
ENST00000356455; ENSP00000348838; ENSG00000175063.
ENST00000372568; ENSP00000361649; ENSG00000175063.
ENST00000405520; ENSP00000385878; ENSG00000175063.

GeneID

11065.

KEGG

hsa:11065.

UCSC

uc002xpl.3. human.

Organism-specific databases

CTD

11065.

GeneCards

GC20P044442.

HGNC

HGNC:15937. UBE2C.

HPA

CAB011464.
CAB035990.

MIM

605574. gene.

neXtProt

NX_O00762.

PharmGKB

PA38057.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5078.

HOGENOM

HOG000233454.

HOVERGEN

HBG063308.

InParanoid

O00762.

KO

K06688.

OMA

DNLFRWI.

OrthoDB

EOG4FN4JS.

PhylomeDB

O00762.

Enzyme and pathway databases

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
REACT_6900. Immune System.
REACT_8017. APC-Cdc20 mediated degradation of Nek2A.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

O00762.

Bgee

O00762.

CleanEx

HS_UBE2C.

Genevestigator

O00762.

GermOnline

ENSG00000175063. 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

EvolutionaryTrace

O00762.

GenomeRNAi

11065.

NextBio

42051.

SOURCE

Search...

Entry information

Entry name

UBE2C_HUMAN

Accession

Primary (citable) accession number: O00762
Secondary accession number(s): A6NP33, E1P5N7, G3XAB7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 137 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.