Q16763 (UBE2S_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
E2-EPF
Ubiquitin carrier protein S
Ubiquitin-conjugating enzyme E2-24 kDa
Ubiquitin-conjugating enzyme E2-EPF5
Ubiquitin-protein ligase S

Gene names

Name:	UBE2S
Synonyms:	E2EPF
ORF Names:	OK/SW-cl.73

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	222 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 'Lys-11'-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 specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit. Also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as a E2 enzyme for the APC/C in vivo. Also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination. Ref.5 Ref.7 Ref.8 Ref.9 Ref.10
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine. Ref.7 Ref.8
Pathway	Protein modification; protein ubiquitination. Ref.7 Ref.8
Subunit structure	Component of the APC/C complex. Interacts with CDC20, FZR1/CDH1 and VHL. Ref.5 Ref.8
Post-translational modification	Autoubiquitinated by the APC/C complex during G1, leading to its degradation by the proteasome.
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.

Ontologies

Keywords
Biological process	Cell cycle Cell division Ubl conjugation pathway
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of anaphase-promoting complex activity Inferred from direct assay Ref.7Ref.8. Source: UniProtKB anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.7Ref.8. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW exit from mitosis Inferred from direct assay Ref.7. Source: UniProtKB free ubiquitin chain polymerization Inferred from direct assay Ref.8. Source: UniProtKB protein K11-linked ubiquitination Inferred from direct assay Ref.8Ref.9Ref.10. Source: UniProtKB protein K27-linked ubiquitination Inferred from direct assay Ref.9. Source: UniProtKB protein K29-linked ubiquitination Inferred from direct assay Ref.9. Source: UniProtKB protein K6-linked ubiquitination Inferred from direct assay Ref.9. Source: UniProtKB protein K63-linked ubiquitination Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	anaphase-promoting complex Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-protein ligase activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 222

222

Ubiquitin-conjugating enzyme E2 S

PRO_0000082507

Sites

Active site

95

1

Glycyl thioester intermediate

Experimental info

Mutagenesis

95

1

C → S: Loss of function. Ref.8 Ref.10

Sequence conflict

216

1

K → KRAL in AAA58446. Ref.1

Secondary structure

1

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222

Helix Strand Turn

Details...

Helix

10 – 25

16

Beta strand

31 – 35

5

Beta strand

42 – 48

7

Turn

54 – 57

4

Beta strand

59 – 65

7

Turn

68 – 72

5

Beta strand

76 – 81

6

Beta strand

92 – 94

3

Helix

96 – 99

4

Turn

100 – 102

3

Helix

109 – 121

13

Helix

125 – 127

3

Helix

131 – 139

9

Helix

141 – 155

15

Sequences

	Sequence		Length	Mass (Da)
	Q16763 [UniParc]. Last modified October 10, 2002. Version 2. Checksum: 2842DC3DCD2AFCB5	FASTA	222	23,845
	10 20 30 40 50 60 MNSNVENLPP HIIRLVYKEV TTLTADPPDG IKVFPNEEDL TDLQVTIEGP EGTPYAGGLF 70 80 90 100 110 120 RMKLLLGKDF PASPPKGYFL TKIFHPNVGA NGEICVNVLK RDWTAELGIR HVLLTIKCLL 130 140 150 160 170 180 IHPNPESALN EEAGRLLLEN YEEYAARARL LTEIHGGAGG PSGRAEAGRA LASGTEASST 190 200 210 220 DPGAPGGPGG AEGPMAKKHA GERDKKLAAK KKTDKKRALR RL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of a novel human ubiquitin carrier protein. An antigenic domain specifically recognized by endemic pemphigus foliaceus autoantibodies is encoded in a secondary reading frame of this human epidermal transcript." Liu Z., Diaz L.A., Haas A.L., Giudice G.J. J. Biol. Chem. 267:15829-15835(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Foreskin.
[2]	"Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients." Shichijo S., Itoh K. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon adenocarcinoma.
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon and Skin.
[5]	"E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis." Jung C.R., Hwang K.S., Yoo J., Cho W.K., Kim J.M., Kim W.H., Im D.S. Nat. Med. 12:809-816(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH VHL.
[6]	"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.
[7]	"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, CATALYTIC ACTIVITY, PATHWAY.
[8]	"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, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH CDC20 AND FZR, UBIQUITINATION, MUTAGENESIS OF CYS-95.
[9]	"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.
[10]	"Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne." Bremm A., Freund S.M., Komander D. Nat. Struct. Mol. Biol. 17:939-947(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-95.
[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]	"Crystal structure of human ubiquitin-conjugating enzyme E2S." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 1-156.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M91670 mRNA. Translation: AAA58446.1.
AB062397 mRNA. Translation: BAB93484.1.
AC020922 Genomic DNA. No translation available.
BC004236 mRNA. Translation: AAH04236.1.
BC007554 mRNA. Translation: AAH07554.1.
BC065364 mRNA. Translation: AAH65364.1.

IPI

IPI00217949.

RefSeq

NP_055316.2. NM_014501.2.

UniGene

Hs.396393.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZDN	X-ray	1.93	A/B	1-156	[»]

ProteinModelPortal

Q16763.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16763. 4 interactions.

STRING

9606.ENSP00000264552.

PTM databases

PhosphoSite

Q16763.

Polymorphism databases

DMDM

23829978.

Proteomic databases

PaxDb

Q16763.

PeptideAtlas

Q16763.

PRIDE

Q16763.

Protocols and materials databases

DNASU

27338.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264552; ENSP00000264552; ENSG00000108106.

GeneID

27338.

KEGG

hsa:27338.

UCSC

uc002qkx.1. human.

Organism-specific databases

CTD

27338.

GeneCards

GC19M055912.

H-InvDB

HIX0039201.

HGNC

HGNC:17895. UBE2S.

HPA

CAB015228.

MIM

610309. gene.

neXtProt

NX_Q16763.

PharmGKB

PA134904441.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5078.

HOGENOM

HOG000233455.

HOVERGEN

HBG063308.

InParanoid

Q16763.

KO

K10583.

OMA

PDLGIKH.

OrthoDB

EOG4KPTBW.

PhylomeDB

Q16763.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

Bgee

Q16763.

CleanEx

HS_UBE2S.

Genevestigator

Q16763.

GermOnline

ENSG00000108106. 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

Q16763.

GenomeRNAi

27338.

NextBio

50400.

SOURCE

Search...

Entry information

Entry name

UBE2S_HUMAN

Accession

Primary (citable) accession number: Q16763
Secondary accession number(s): Q9BTC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 10, 2002
Last modified:	May 1, 2013
This is version 128 of the entry and version 2 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.