Reviewed, UniProtKB/Swiss-Prot P61088 (UBE2N_HUMAN)

Names and origin

Protein names

Recommended name:
    Ubiquitin-conjugating enzyme E2 N
    EC=6.3.2.19
Alternative name(s):
    Ubiquitin-protein ligase N
    Ubiquitin carrier protein N
    Ubc13
    Bendless-like ubiquitin-conjugating enzyme

Gene names

Name:	UBE2N
Synonyms:	BLU

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	152 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligase SHPRH in the poly-ubiquitination of PCNA 'Lys-164' upon genotoxic stress, which is required for DNA repair. Ref.6 Ref.7
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Heterodimer with UBE2V2. Interacts with RNF8, RNF168 and SHPRH. Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13
Post-translational modification	Conjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2.
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Isopeptide bond Ubl conjugation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Uncategorized	ubiquitin cycle Ref.5 Traceable author statement. Source: HGNC
Biological process	DNA double-strand break processing Inferred from mutant phenotype. Source: HGNC T cell receptor signaling pathway Inferred from mutant phenotype. Source: UniProtKB double-strand break repair via homologous recombination Inferred from mutant phenotype. Source: HGNC histone ubiquitination Inferred from mutant phenotype. Source: HGNC modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of DNA repair Inferred from mutant phenotype. Source: HGNC positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype. Source: HGNC positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype. Source: UniProtKB positive regulation of histone modification Inferred from mutant phenotype. Source: HGNC positive regulation of ubiquitin-protein ligase activity Inferred from mutant phenotype. Source: HGNC postreplication repair Inferred from mutant phenotype. Source: HGNC regulation of histone ubiquitination Inferred from mutant phenotype. Source: HGNC
Cellular component	UBC13-MMS2 complex Inferred from direct assay. Source: HGNC cytoplasm Traceable author statement. Source: UniProtKB nucleus Inferred from direct assay. Source: HGNC
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin binding Ref.5 Inferred from direct assay. Source: HGNC ubiquitin-protein ligase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RNF168	Q8IYW5	2	EBI-1052908,EBI-914207
UBE2V2	Q15819	1	EBI-1052908,EBI-714329

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 152

152

Ubiquitin-conjugating enzyme E2 N

PRO_0000082502

Sites

Active site

87

1

Glycyl thioester intermediate

Amino acid modifications

Cross-link

92

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)

Experimental info

Mutagenesis

87

1

C → A: Impairs interaction with SHPRH. Ref.9

Mutagenesis

92

1

K → R: No ISGylation. Ref.5 Ref.8

Mutagenesis

94

1

K → R: No effect on ISGylation. Ref.8

Secondary structure

1

.

.

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152

Helix Strand Turn

Details...

Helix

6 – 15

10

Beta strand

23 – 27

5

Beta strand

34 – 40

7

Turn

46 – 49

4

Beta strand

51 – 57

7

Turn

60 – 64

5

Beta strand

68 – 71

4

Helix

89 – 91

3

Helix

101 – 113

13

Helix

125 – 131

7

Helix

133 – 147

15

Sequences

	Sequence		Length	Mass (Da)
	P61088-1 [UniParc]. Last modified April 26, 2004. Version 1. Checksum: FACD84D883D77407	FASTA	152	17,138
	10 20 30 40 50 60 MAGLPRRIIK ETQRLLAEPV PGIKAEPDES NARYFHVVIA GPQDSPFEGG TFKLELFLPE 70 80 90 100 110 120 EYPMAAPKVR FMTKIYHPNV DKLGRICLDI LKDKWSPALQ IRTVLLSIQA LLSAPNPDDP 130 140 150 LANDVAEQWK TNEAQAIETA RAWTRLYAMN NI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of cDNA encoding a human ubiquitin-conjugating enzyme similar to the Drosophila bendless gene product." Yamaguchi T., Kim N.-S., Sekine S., Seino H., Osaka F., Yamao F., Kato S. J. Biochem. 120:494-497(1996) [PubMed: 8902611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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: Lung, Placenta and Uterus.
[4]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 15-24; 34-68; 86-92 AND 95-102, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[5]	"ISG15 modification of ubiquitin E2 Ubc13 disrupts its ability to form thioester bond with ubiquitin." Zou W., Papov V., Malakhova O., Kim K.I., Dao C., Li J., Zhang D.-E. Biochem. Biophys. Res. Commun. 336:61-68(2005) [PubMed: 16122702] [Abstract] Cited for: PROTEIN SEQUENCE OF 86-94, MUTAGENESIS OF LYS-92, ISGYLATION AT LYS-92, MASS SPECTROMETRY.
[6]	"Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair." Hofmann R.M., Pickart C.M. Cell 96:645-653(1999) [PubMed: 10089880] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBE2V2.
[7]	"The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains." Bothos J., Summers M.K., Venere M., Scolnick D.M., Halazonetis T.D. Oncogene 22:7101-7107(2003) [PubMed: 14562038] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBE2V2.
[8]	"ISG15 modification of Ubc13 suppresses its ubiquitin-conjugating activity." Takeuchi T., Yokosawa H. Biochem. Biophys. Res. Commun. 336:9-13(2005) [PubMed: 16112642] [Abstract] Cited for: MUTAGENESIS OF LYS-92 AND LYS-94, ISGYLATION AT LYS-92.
[9]	"Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination." Motegi A., Sood R., Moinova H., Markowitz S.D., Liu P.P., Myung K. J. Cell Biol. 175:703-708(2006) [PubMed: 17130289] [Abstract] Cited for: INTERACTION WITH SHPRH, MUTAGENESIS OF CYS-87.
[10]	"The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation." Plans V., Scheper J., Soler M., Loukili N., Okano Y., Thomson T.M. J. Cell. Biochem. 97:572-582(2006) [PubMed: 16215985] [Abstract] Cited for: INTERACTION WITH RNF8.
[11]	"Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen." Unk I., Hajdu I., Fatyol K., Szakal B., Blastyak A., Bermudez V., Hurwitz J., Prakash L., Prakash S., Haracska L. Proc. Natl. Acad. Sci. U.S.A. 103:18107-18112(2006) [PubMed: 17108083] [Abstract] Cited for: INTERACTION WITH SHPRH.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]	"The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage." Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K., Miller E.S., Nakada S., Ylanko J., Olivarius S., Mendez M., Oldreive C., Wildenhain J., Tagliaferro A., Pelletier L., Taubenheim N., Durandy A., Byrd P.J., Stankovic T., Taylor A.M.R., Durocher D. Cell 136:420-434(2009) [PubMed: 19203578] [Abstract] Cited for: INTERACTION WITH RNF168.
[14]	"Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13." Moraes T.F., Edwards R.A., McKenna S., Pastushok L., Xiao W., Glover J.N.M., Ellison M.J. Nat. Struct. Biol. 8:669-673(2001) [PubMed: 11473255] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH UBE2V2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

D83004 mRNA. Translation: BAA11675.1.
BT006873 mRNA. Translation: AAP35519.1.
BC000396 mRNA. Translation: AAH00396.1.
BC003365 mRNA. Translation: AAH03365.1.
BC108704 mRNA. Translation: AAI08705.1.

IPI

IPI00003949.

PIR

JC4894.

RefSeq

NP_003339.1.

UniGene

Hs.524630

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J7D	X-ray	1.85	B	1-152	[»]
2C2V	X-ray	2.90	B/E/H/K	2-152	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P61088. 7 interactions.

PTM databases

PhosphoSite

P61088.

2-D gel databases

OGP

Q16781.

REPRODUCTION-2DPAGE

IPI00003949.

Proteomic databases

PeptideAtlas

P61088.

PRIDE

P61088.

Genome annotation databases

Ensembl

ENSG00000177889. Homo sapiens. [Contig view]

GeneID

7334.

KEGG

hsa:7334.

Organism-specific databases

GeneCards

GC12M092304.

H-InvDB

HIX0010883.
HIX0056502.

HGNC

HGNC:12492. UBE2N.

HPA

HPA003962.

MIM

603679. gene.

PharmGKB

PA37141.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P61088.

HOVERGEN

P61088.

OMA

P61088. LGAPNPD.

Enzyme and pathway databases

BRENDA

6.3.2.19. 247.

Pathway_Interaction_DB

il1pathway. IL1-mediated signaling events.

Reactome

REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P61088.

Bgee

P61088.

CleanEx

HS_UBE2N.

GermOnline

ENSG00000177889. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.10.110.10. UBQ-conjugat_E2. 1 hit.

Pfam

PF00179. UQ_con. 1 hit.
[Graphical view]

ProDom

PD000461. UBQ_conjugat. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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

28704.

SOURCE

Search...

Entry information

Entry name

UBE2N_HUMAN

Accession

Primary (citable) accession number: P61088
Secondary accession number(s): Q16781, Q53Y81

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	April 26, 2004
Last modified:	June 16, 2009
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)