P62837 (UB2D2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-conjugating enzyme E2 D2
EC=6.3.2.19

Alternative name(s):
Ubiquitin carrier protein D2
Ubiquitin-conjugating enzyme E2(17)KB 2
Ubiquitin-conjugating enzyme E2-17 kDa 2
Ubiquitin-protein ligase D2

Gene names

Name:	UBE2D2
Synonyms:	UBC4, UBC5B, UBCH4, UBCH5B

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	147 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. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3. Ref.8 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex and with E3 ubiquitin-protein ligase PJA2 By similarity. Interacts with PDZRN3 By similarity. Interacts with CNOT4 (via RING domain). Ref.9 Ref.11
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	protein K48-linked ubiquitination Inferred from direct assay Ref.18. Source: UniProtKB ubiquitin-dependent protein catabolic process Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.11. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.14Ref.13Ref.18. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
OTUB1	Q96FW1	2	EBI-347677,EBI-1058491
RNF11	Q9Y3C5	4	EBI-347677,EBI-396669
RNF43	Q68DV7	2	EBI-347677,EBI-1647060
RNF5	Q99942	3	EBI-347677,EBI-348482
TRAF6	Q9Y4K3	2	EBI-347677,EBI-359276
XIAP	P98170	2	EBI-347677,EBI-517127
ZNRF1	Q8ND25	4	EBI-347677,EBI-2129250

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 147

147

Ubiquitin-conjugating enzyme E2 D2

PRO_0000082462

Sites

Active site

85

1

Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue

8

1

N6-acetyllysine Ref.16

Experimental info

Mutagenesis

63

1

K → A or E: Strongly reduced interaction with CNTO4. Ref.11

Mutagenesis

85

1

C → A: Loss of ability to promote FBXW2-mediated GCM1 ubiquitination. Inhibition of TNF-alpha-induced degradation of NFKBIA. Ref.8 Ref.13

Sequence conflict

128

1

K → Q in AAC41750. Ref.2

Secondary structure

1

.

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147

Helix Strand Turn

Details...

Helix

1 – 15

15

Beta strand

19 – 28

10

Beta strand

32 – 38

7

Turn

44 – 47

4

Beta strand

49 – 55

7

Turn

58 – 61

4

Beta strand

66 – 71

6

Helix

87 – 89

3

Turn

90 – 92

3

Helix

99 – 111

13

Helix

121 – 129

9

Helix

131 – 145

15

Sequences

	Sequence		Length	Mass (Da)
	P62837 [UniParc]. Last modified August 16, 2004. Version 1. Checksum: C942BE7853CBC355	FASTA	147	16,735
	10 20 30 40 50 60 MALKRIHKEL NDLARDPPAQ CSAGPVGDDM FHWQATIMGP NDSPYQGGVF FLTIHFPTDY 70 80 90 100 110 120 PFKPPKVAFT TRIYHPNINS NGSICLDILR SQWSPALTIS KVLLSICSLL CDPNPDDPLV 130 140 PEIARIYKTD REKYNRIARE WTQKYAM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a family of closely related human ubiquitin conjugating enzymes." Jensen J.P., Bates P.W., Yang M., Vierstra R.D., Weissman A.M. J. Biol. Chem. 270:30408-30414(1995) [PubMed: 8530467] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Reconstitution of p53-ubiquitinylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP)." Rolfe M., Beer-Romero P., Glass S., Eckstein J., Berdo I., Theodoras A., Pagano M., Draetta G. Proc. Natl. Acad. Sci. U.S.A. 92:3264-3268(1995) [PubMed: 7724550] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Humoral detection of leukaemia-associated antigens in presentation acute myeloid leukaemia." Guinn B.-A., Bland E.A., Lodi U., Liggins A.P., Tobal K., Petters S., Wells J.W., Banham A.H., Mufti G.J. Biochem. Biophys. Res. Commun. 335:1293-1304(2005) [PubMed: 16112646] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.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].
[6]	"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: Testis.
[7]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 73-90, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[8]	"Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IkappaBalpha." Gonen H., Bercovich B., Orian A., Carrano A., Takizawa C., Yamanaka K., Pagano M., Iwai K., Ciechanover A. J. Biol. Chem. 274:14823-14830(1999) [PubMed: 10329681] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-85.
[9]	"SCF(beta-TRCP) and phosphorylation dependent ubiquitination of I kappa B alpha catalyzed by Ubc3 and Ubc4." Strack P., Caligiuri M., Pelletier M., Boisclair M., Theodoras A., Beer-Romero P., Glass S., Parsons T., Copeland R.A., Auger K.R., Benfield P., Brizuela L., Rolfe M. Oncogene 19:3529-3536(2000) [PubMed: 10918611] [Abstract] Cited for: INTERACTION WITH SCF COMPLEX.
[10]	"Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo." Saville M.K., Sparks A., Xirodimas D.P., Wardrop J., Stevenson L.F., Bourdon J.C., Woods Y.L., Lane D.P. J. Biol. Chem. 279:42169-42181(2004) [PubMed: 15280377] [Abstract] Cited for: FUNCTION.
[11]	"An altered-specificity ubiquitin-conjugating enzyme/ubiquitin-protein ligase pair." Winkler G.S., Albert T.K., Dominguez C., Legtenberg Y.I., Boelens R., Timmers H.T. J. Mol. Biol. 337:157-165(2004) [PubMed: 15001359] [Abstract] Cited for: INTERACTION WITH CNOT4, MUTAGENESIS OF LYS-63.
[12]	"Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology." Windheim M., Peggie M., Cohen P. Biochem. J. 409:723-729(2008) [PubMed: 18042044] [Abstract] Cited for: FUNCTION.
[13]	"Ubiquitin-conjugating enzyme UBE2D2 is responsible for FBXW2 (F-box and WD repeat domain containing 2)-mediated human GCM1 (glial cell missing homolog 1) ubiquitination and degradation." Chiang M.H., Chen L.F., Chen H. Biol. Reprod. 79:914-920(2008) [PubMed: 18703417] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-85.
[14]	"Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor." Grou C.P., Carvalho A.F., Pinto M.P., Wiese S., Piechura H., Meyer H.E., Warscheid B., Sa-Miranda C., Azevedo J.E. J. Biol. Chem. 283:14190-14197(2008) [PubMed: 18359941] [Abstract] Cited for: FUNCTION.
[15]	"Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3." Zeng W., Xu M., Liu S., Sun L., Chen Z.J. Mol. Cell 36:315-325(2009) [PubMed: 19854139] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION.
[16]	"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-8, MASS SPECTROMETRY.
[17]	"Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity." Zeng W., Sun L., Jiang X., Chen X., Hou F., Adhikari A., Xu M., Chen Z.J. Cell 141:315-330(2010) [PubMed: 20403326] [Abstract] Cited for: FUNCTION.
[18]	"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.
[19]	"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].
[20]	"Solution structure of the ubiquitin-conjugating enzyme UbcH5B." Houben K., Dominguez C., van Schaik F.M., Timmers H.T., Bonvin A.M., Boelens R. J. Mol. Biol. 344:513-526(2004) [PubMed: 15522302] [Abstract] Cited for: STRUCTURE BY NMR.
[21]	"Crystal structure of UbcH5b~ubiquitin intermediate: insight into the formation of the self-assembled E2~Ub conjugates." Sakata E., Satoh T., Yamamoto S., Yamaguchi Y., Yagi-Utsumi M., Kurimoto E., Tanaka K., Wakatsuki S., Kato K. Structure 18:138-147(2010) [PubMed: 20152160] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U39317 mRNA. Translation: AAA91460.1.
L40146 Genomic DNA. Translation: AAC41750.1.
AY651263 mRNA. Translation: AAX35690.1.
AK001311 mRNA. Translation: BAG50891.1.
AK001428 mRNA. Translation: BAG50911.1.
CH471062 Genomic DNA. Translation: EAW62095.1.
CH471062 Genomic DNA. Translation: EAW62096.1.
BC033349 mRNA. Translation: AAH33349.1.

IPI

IPI00332376.

PIR

I59365.

RefSeq

NP_003330.1. NM_003339.2.
NP_862821.1. NM_181838.1.

UniGene

Hs.108332.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UR6	NMR	-	A	1-147	[»]
1W4U	NMR	-	A	1-147	[»]
2C4O	X-ray	1.94	A/B/C/D	1-147	[»]
2CLW	X-ray	1.94	A/B/C/D	1-147	[»]
2ESK	X-ray	1.36	A	1-147	[»]
2ESO	X-ray	1.50	A	1-147	[»]
2ESP	X-ray	1.52	A	1-147	[»]
2ESQ	X-ray	1.44	A	1-147	[»]
3A33	X-ray	2.20	A	1-147	[»]
3JVZ	X-ray	3.30	A/B	4-147	[»]
3JW0	X-ray	3.10	A/B	4-147	[»]
3L1Y	X-ray	1.60	A	1-147	[»]
3TGD	X-ray	1.80	A	1-147	[»]

ProteinModelPortal

P62837.

SMR

P62837. Positions 1-147.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29267N.

IntAct

P62837. 93 interactions.

MINT

MINT-1035011.

STRING

P62837.

PTM databases

PhosphoSite

P62837.

Polymorphism databases

DMDM

51338685.

Proteomic databases

PRIDE

P62837.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000398733; ENSP00000381717; ENSG00000131508.

GeneID

7322.

KEGG

hsa:7322.

UCSC

uc003ler.1. human.

Organism-specific databases

CTD

7322.

GeneCards

GC05P138920.

H-InvDB

HIX0005224.
HIX0028451.

HGNC

HGNC:12475. UBE2D2.

HPA

HPA003920.

MIM

602962. gene.

neXtProt

NX_P62837.

PharmGKB

PA37125.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG756483.

HOVERGEN

HBG063308.

OMA

KVNFTTR.

OrthoDB

EOG4RR6JK.

PhylomeDB

P62837.

Enzyme and pathway databases

Reactome

REACT_25177. RNF125 mediated ubiquitination of RIG-I, MDA5 and IPS-1.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P62837.

Bgee

P62837.

CleanEx

HS_UBE2D2.

Genevestigator

P62837.

GermOnline

ENSG00000131508. 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

K06689.

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

28630.

SOURCE

Search...

Entry information

Entry name

UB2D2_HUMAN

Accession

Primary (citable) accession number: P62837
Secondary accession number(s): D3DQC9, P51669, Q3MN78

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	August 16, 2004
Last modified:	January 25, 2012
This is version 94 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.