P61088 (UBE2N_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Bendless-like ubiquitin-conjugating enzyme
Ubc13
Ubiquitin carrier protein N
Ubiquitin-protein ligase N

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 further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination 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 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Ref.6 Ref.7 Ref.17 Ref.21
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Heterodimer with UBE2V2. Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts with RNF8 and RNF168. Interacts with RNF11. Interacts with the E3 ligases, HLTF and SHPRH; the interactions promote the 'Lys-63'-linked polyubiquitination of PCNA upon genotoxic stress and lead to DNA repair. Interacts with ARIH2 (via RING-type 2). Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.16 Ref.18 Ref.19
Subcellular location	Nucleus. Cytoplasm Ref.18.
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
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA double-strand break processing Inferred from mutant phenotype. Source: HGNC MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome T cell receptor signaling pathway Inferred from mutant phenotype. Source: UniProtKB Toll signaling pathway Traceable author statement. Source: Reactome double-strand break repair via homologous recombination Inferred from mutant phenotype. Source: HGNC histone ubiquitination Inferred from mutant phenotype. Source: HGNC innate immune response Traceable author statement. Source: Reactome nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome 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 protein K63-linked ubiquitination Inferred from direct assay Ref.25Ref.21. Source: UniProtKB regulation of histone ubiquitination Inferred from mutant phenotype. Source: HGNC toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular component	UBC13-MMS2 complex Inferred from direct assay. Source: HGNC UBC13-UEV1A complex Inferred from direct assay Ref.25. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay Ref.18. Source: UniProtKB ubiquitin ligase complex Inferred from direct assay Ref.25. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin binding Inferred from direct assay Ref.5. Source: HGNC ubiquitin-protein ligase activity Inferred from direct assay Ref.21. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RNF11	Q9Y3C5	3	EBI-1052908,EBI-396669
RNF168	Q8IYW5	2	EBI-1052908,EBI-914207
STUB1	Q9UNE7	3	EBI-1052908,EBI-357085
Stub1	Q9WUD1	2	EBI-1052908,EBI-773027	From a different organism.
TRAF6	Q9Y4K3	3	EBI-1052908,EBI-359276
UBE2V1	Q13404	9	EBI-1052908,EBI-1050671
UBE2V2	Q15819	3	EBI-1052908,EBI-714329
XIAP	P98170	2	EBI-1052908,EBI-517127
ZNRF1	Q8ND25	3	EBI-1052908,EBI-2129250

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 152

151

Ubiquitin-conjugating enzyme E2 N

PRO_0000082502

Sites

Active site

87

1

Glycyl thioester intermediate

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.15

Modified residue

10

1

N6-acetyllysine Ref.20

Modified residue

82

1

N6-acetyllysine Ref.20

Modified residue

94

1

N6-acetyllysine Ref.20

Cross-link

92

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.5 Ref.8

Experimental info

Mutagenesis

87

1

C → A: Loss of polyubiquitination of PCNA. Impairs interaction with SHPRH. Ref.9 Ref.12

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

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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 [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]	"Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation." Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G. J. Biol. Chem. 282:4102-4112(2007) [PubMed: 17135271] [Abstract] Cited for: MUTAGENESIS OF CYS-87.
[13]	"Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination." Unk I., Hajdu I., Fatyol K., Hurwitz J., Yoon J.-H., Prakash L., Prakash S., Haracska L. Proc. Natl. Acad. Sci. U.S.A. 105:3768-3773(2008) [PubMed: 18316726] [Abstract] Cited for: INTERACTION WITH HLTF.
[14]	"Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks." Motegi A., Liaw H.-J., Lee K.-Y., Roest H.P., Maas A., Wu X., Moinova H., Markowitz S.D., Ding H., Hoeijmakers J.H.J., Myung K. Proc. Natl. Acad. Sci. U.S.A. 105:12411-12416(2008) [PubMed: 18719106] [Abstract] Cited for: INTERACTION WITH HLTF.
[15]	"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. Tissue: Embryonic kidney.
[16]	"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.
[17]	"Regulation of endoplasmic reticulum-associated degradation by RNF5-dependent ubiquitination of JNK-associated membrane protein (JAMP)." Tcherpakov M., Delaunay A., Toth J., Kadoya T., Petroski M.D., Ronai Z.A. J. Biol. Chem. 284:12099-12109(2009) [PubMed: 19269966] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF JKAMP.
[18]	"The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 interacting domains." Marteijn J.A., van der Meer L.T., Smit J.J., Noordermeer S.M., Wissink W., Jansen P., Swarts H.G., Hibbert R.G., de Witte T., Sixma T.K., Jansen J.H., van der Reijden B.A. Leukemia 23:1480-1489(2009) [PubMed: 19340006] [Abstract] Cited for: INTERACTION WITH ARIH2, SUBCELLULAR LOCATION.
[19]	"Analysis of electrostatic contributions to the selectivity of interactions between RING-finger domains and ubiquitin-conjugating enzymes." Scheper J., Oliva B., Villa-Freixa J., Thomson T.M. Proteins 74:92-103(2009) [PubMed: 18615712] [Abstract] Cited for: INTERACTION WITH RNF11.
[20]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-10; LYS-82 AND LYS-94, MASS SPECTROMETRY.
[21]	"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: 20061386] [Abstract] Cited for: FUNCTION.
[22]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling." Cotta-Ramusino C., McDonald E.R. III, Hurov K., Sowa M.E., Harper J.W., Elledge S.J. Science 332:1313-1317(2011) [PubMed: 21659603] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
[24]	"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.
[25]	"Chaperoned ubiquitylation -- crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex." Zhang M., Windheim M., Roe S.M., Peggie M., Cohen P., Prodromou C., Pearl L.H. Mol. Cell 20:525-538(2005) [PubMed: 16307917] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 2-152 IN COMPLEX WITH STUB1 AND UBE2V1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_003348.3.

UniGene

Hs.524630.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3HCT	X-ray	2.10	B	1-152	[»]
3HCU	X-ray	2.60	B/D	1-152	[»]

ProteinModelPortal

P61088.

SMR

P61088. Positions 2-150.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29829N.

IntAct

P61088. 54 interactions.

MINT

MINT-5001139.

STRING

P61088.

PTM databases

PhosphoSite

P61088.

Polymorphism databases

DMDM

46577660.

2D gel databases

OGP

Q16781.

REPRODUCTION-2DPAGE

IPI00003949.

Proteomic databases

PeptideAtlas

P61088.

PRIDE

P61088.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000318066; ENSP00000316176; ENSG00000177889.

GeneID

7334.

KEGG

hsa:7334.

UCSC

uc001tcp.1. human.

Organism-specific databases

CTD

7334.

GeneCards

GC12M093735.

H-InvDB

HIX0010883.

HGNC

HGNC:12492. UBE2N.

HPA

HPA003962.

MIM

603679. gene.

neXtProt

NX_P61088.

PharmGKB

PA37141.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04881.

GeneTree

ENSGT00540000070023.

HOGENOM

HBG756483.

HOVERGEN

HBG063308.

InParanoid

P61088.

OMA

LGAPNPD.

OrthoDB

EOG4MCX1K.

PhylomeDB

P61088.

Enzyme and pathway databases

Pathway_Interaction_DB

il1pathway. IL1-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P61088.

Bgee

P61088.

CleanEx

HS_UBE2N.

Genevestigator

P61088.

GermOnline

ENSG00000177889. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.10.110.10. UBQ-conjugat_E2. 1 hit.

KO

K10580.

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

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:	January 25, 2012
This is version 103 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.