P68036 (UB2L3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-conjugating enzyme E2 L3
EC=6.3.2.19

Alternative name(s):
L-UBC
UbcH7
Ubiquitin carrier protein L3
Ubiquitin-conjugating enzyme E2-F1
Ubiquitin-protein ligase L3

Gene names

Name:	UBE2L3
Synonyms:	UBCE7, UBCH7

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	154 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PARK2 and ARIH1, that function like function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down-regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis. Ref.11 Ref.15 Ref.17 Ref.19 Ref.20 Ref.22 Ref.24
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with PARK2; involved in ubiquitination and degradation of misfolded proteins. Interacts with UBE3A; used by the papilloma virus HPV-16 E6 protein to ubiquitinate p53/TP53. Interacts with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B. Interacts with ARIH1. Interacts with ARIH2 (via RING-type 1). Interacts with NCOA1; they functionally interact to regulate progesterone receptor transcriptional activity. May interact with NR3C1. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.24
Subcellular location	Nucleus. Cytoplasm Ref.13 Ref.17.
Tissue specificity	Ubiquitous, with highest expression in testis.
Domain	In contrast to other ubiquitin-conjugating enzymes E2, residues essential for lysine reactivity are absent: Pro and a His residues are present instead of an Asp and an Asp residues in positions 88 and 119,respectively. Ref.24
Post-translational modification	Ubiquitinated. The alteration of UBE2L3 protein levels during the S-phase of the cell cycle is due to ubiquitin-dependent proteasomal degradation. Ref.20
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.
Caution	Ref.10 reported that UBE2L1, UBE2L2 and UBE2L4 are most likely pseudogenes and the only expressed member of this subfamily seems to be UBE2L3.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell proliferation Inferred from mutant phenotype Ref.20. Source: UniProtKB cellular response to glucocorticoid stimulus Inferred from direct assay Ref.17. Source: UniProtKB protein K11-linked ubiquitination Inferred from direct assay Ref.22. Source: UniProtKB regulation of S phase of mitotic cell cycle Inferred from mutant phenotype Ref.20. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from direct assay Ref.17. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-dependent protein catabolic process Traceable author statement Ref.1. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay Ref.13Ref.17. Source: UniProtKB nucleus Inferred from direct assay Ref.17Ref.13. Source: UniProtKB ubiquitin ligase complex Traceable author statement Ref.1. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transcription coactivator activity Inferred from direct assay Ref.15. Source: UniProtKB ubiquitin protein ligase binding Inferred from physical interaction Ref.13Ref.24. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.22Ref.24. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARIH2	O95376	3	EBI-711173,EBI-711158
RNF19B	Q6ZMZ0	2	EBI-711173,EBI-2466594

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 154

154

Ubiquitin-conjugating enzyme E2 L3

PRO_0000082476

Sites

Active site

86

1

Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue

9

1

N6-acetyllysine Ref.21

Modified residue

131

1

N6-acetyllysine Ref.21

Modified residue

138

1

N6-acetyllysine Ref.21

Experimental info

Mutagenesis

86

1

C → S: Loss of catalytic activity. Prevents ubiquitin-dependent proteasomal degradation of UBE2L3. Ref.11 Ref.20

Mutagenesis

88

1

P → D: Does not convert into a lysine reactive E2; when associated with D-119. Ref.24

Mutagenesis

119

1

H → D: Does not convert into a lysine reactive E2; when associated with D-88. Ref.24

Sequence conflict

23

1

R → C in AAG17922. Ref.4

Sequence conflict

118

1

E → K in AAG17922. Ref.4

Secondary structure

1

.

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154

Helix Strand Turn

Details...

Helix

7 – 11

5

Beta strand

15 – 17

3

Beta strand

23 – 25

3

Beta strand

30 – 39

10

Beta strand

43 – 45

3

Beta strand

51 – 56

6

Turn

59 – 63

5

Beta strand

67 – 72

6

Turn

88 – 90

3

Beta strand

91 – 94

4

Helix

101 – 113

13

Helix

123 – 130

8

Helix

137 – 144

8

Sequences

	Sequence		Length	Mass (Da)
	P68036 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: F5A30243BE3C9985	FASTA	154	17,862
	10 20 30 40 50 60 MAASRRLMKE LEEIRKCGMK NFRNIQVDEA NLLTWQGLIV PDNPPYDKGA FRIEINFPAE 70 80 90 100 110 120 YPFKPPKITF KTKIYHPNID EKGQVCLPVI SAENWKPATK TDQVIQSLIA LVNDPQPEHP 130 140 150 LRADLAEEYS KDRKKFCKNA EEFTKKYGEK RPVD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human ubiquitin conjugating enzyme, L-UBC, maps in the Alzheimer's disease locus on chromosome 14q24.3." Robinson P.A., Leek J.P., Thompson J., Carr I.M., Bailey A., Moynihan T.P., Coletta P.L., Lench N.J., Markham A.F. Mamm. Genome 6:725-731(1995) [PubMed: 8563171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5." Nuber U., Schwarz S., Kaiser P., Schneider R., Scheffner M. J. Biol. Chem. 271:2795-2800(1996) [PubMed: 8576257] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Fine-mapping, genomic organization, and transcript analysis of the human ubiquitin-conjugating enzyme gene UBE2L3." Moynihan T.P., Cole C.G., Dunham I., O'Neil L., Markham A.F., Robinson P.A. Genomics 51:124-127(1998) [PubMed: 9693040] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[4]	"Is retroposition a common way of spreading ubiquitin-conjugating enzyme genes throughout mammalian genomes?" Poloumienko A. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[5]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"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]. Tissue: Thalamus.
[7]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: Brain.
[9]	"Purification and characterization of a novel species of ubiquitin-carrier protein, E2, that is involved in degradation of non-'N-end rule' protein substrates." Blumenfeld N., Gonen H., Mayer A., Smith C.E., Siegel N.R., Schwartz A.L., Ciechanover A. J. Biol. Chem. 269:9574-9581(1994) [PubMed: 8144544] [Abstract] Cited for: PROTEIN SEQUENCE OF 53-67; 67-74 AND 101-122.
[10]	"Promoter analysis of the human ubiquitin-conjugating enzyme gene family UBE2L1-4, including UBE2L3 which encodes UbcH7." Ardley H.C., Moynihan T.P., Markham A.F., Robinson P.A. Biochim. Biophys. Acta 1491:57-64(2000) [PubMed: 10760570] [Abstract] Cited for: PROMOTER ANALYSIS.
[11]	"Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase." Shimura H., Hattori N., Kubo S., Mizuno Y., Asakawa S., Minoshima S., Shimizu N., Iwai K., Chiba T., Tanaka K., Suzuki T. Nat. Genet. 25:302-305(2000) [PubMed: 10888878] [Abstract] Cited for: FUNCTION, INTERACTION WITH PARK2, MUTAGENESIS OF CYS-86.
[12]	"A novel centrosomal ring-finger protein, dorfin, mediates ubiquitin ligase activity." Niwa J., Ishigaki S., Doyu M., Suzuki T., Tanaka K., Sobue G. Biochem. Biophys. Res. Commun. 281:706-713(2001) [PubMed: 11237715] [Abstract] Cited for: INTERACTION WITH RNF19A.
[13]	"Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7." Ardley H.C., Tan N.G.S., Rose S.A., Markham A.F., Robinson P.A. J. Biol. Chem. 276:19640-19647(2001) [PubMed: 11278816] [Abstract] Cited for: INTERACTION WITH ARIH1, SUBCELLULAR LOCATION.
[14]	"A novel RING finger protein, human enhancer of invasion 10, alters mitotic progression through regulation of cyclin B levels." Toby G.G., Gherraby W., Coleman T.R., Golemis E.A. Mol. Cell. Biol. 23:2109-2122(2003) [PubMed: 12612082] [Abstract] Cited for: INTERACTION WITH CCNB1IP1.
[15]	"The ubiquitin-conjugating enzyme UBCH7 acts as a coactivator for steroid hormone receptors." Verma S., Ismail A., Gao X., Fu G., Li X., O'Malley B.W., Nawaz Z. Mol. Cell. Biol. 24:8716-8726(2004) [PubMed: 15367689] [Abstract] Cited for: FUNCTION, INTERACTION WITH NCOA1.
[16]	"The p53-inducible E3 ubiquitin ligase p53RFP induces p53-dependent apoptosis." Huang J., Xu L.-G., Liu T., Zhai Z., Shu H.-B. FEBS Lett. 580:940-947(2006) [PubMed: 16427630] [Abstract] Cited for: INTERACTION WITH RNF144B.
[17]	"UbcH7 interacts with the glucocorticoid receptor and mediates receptor autoregulation." Garside H., Waters C., Berry A., Rice L., Ardley H.C., White A., Robinson P.A., Ray D. J. Endocrinol. 190:621-629(2006) [PubMed: 17003263] [Abstract] Cited for: FUNCTION, INTERACTION WITH NR3C1, SUBCELLULAR LOCATION.
[18]	"NK lytic-associated molecule, involved in NK cytotoxic function, is an E3 ligase." Fortier J.M., Kornbluth J. J. Immunol. 176:6454-6463(2006) [PubMed: 16709802] [Abstract] Cited for: INTERACTION WITH RNF19B.
[19]	"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: FUNCTION, INTERACTION WITH ARIH2.
[20]	"Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7." Whitcomb E.A., Dudek E.J., Liu Q., Taylor A. Mol. Biol. Cell 20:1-9(2009) [PubMed: 18946090] [Abstract] Cited for: FUNCTION, UBIQUITINATION, MUTAGENESIS OF CYS-86.
[21]	"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-9; LYS-131 AND LYS-138, MASS SPECTROMETRY.
[22]	"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.
[23]	"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].
[24]	"UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids." Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E. Nature 474:105-108(2011) [PubMed: 21532592] [Abstract] Cited for: FUNCTION, DOMAIN, INTERACTION WITH PARK2 AND ARIH1, MUTAGENESIS OF PRO-88 AND HIS-119.
[25]	"Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade." Huang L., Kinnucan E., Wang G., Beaudenon S., Howley P.M., Huibregtse J.M., Pavletich N.P. Science 286:1321-1326(1999) [PubMed: 10558980] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH UBE3A.
[26]	"Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases." Zheng N., Wang P., Jeffrey P.D., Pavletich N.P. Cell 102:533-539(2000) [PubMed: 10966114] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH 47-434 OF CBL AND ZAP70.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S81003 mRNA. Translation: AAB36017.1.
X92962 mRNA. Translation: CAA63538.1.
AJ000519 mRNA. Translation: CAA04156.1.
AF300336 Genomic DNA. Translation: AAG17922.1.
CR456606 mRNA. Translation: CAG30492.1.
AK311761 mRNA. Translation: BAG34704.1.
CH471095 Genomic DNA. Translation: EAW59459.1.
BC053368 mRNA. Translation: AAH53368.1.

IPI

IPI00021347.

RefSeq

NP_003338.1. NM_003347.2.

UniGene

Hs.108104.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C4Z	X-ray	2.60	D	1-154	[»]
1FBV	X-ray	2.90	C	1-154	[»]

ProteinModelPortal

P68036.

SMR

P68036. Positions 4-147.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6124N.

IntAct

P68036. 19 interactions.

MINT

MINT-5002693.

STRING

P68036.

PTM databases

PhosphoSite

P68036.

Polymorphism databases

DMDM

54039805.

2D gel databases

OGP

P51966.

UCD-2DPAGE

P68036.

Proteomic databases

PRIDE

P68036.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000342192; ENSP00000344259; ENSG00000185651.

GeneID

7332.

KEGG

hsa:7332.

UCSC

uc002zva.1. human.

Organism-specific databases

CTD

7332.

GeneCards

GC22P021903.

H-InvDB

HIX0027846.

HGNC

HGNC:12488. UBE2L3.

HPA

HPA045609.

MIM

603721. gene.

neXtProt

NX_P68036.

PharmGKB

PA37137.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5078.

GeneTree

ENSGT00630000089469.

HOVERGEN

HBG063308.

InParanoid

P68036.

KO

K04552.

PhylomeDB

P68036.

Enzyme and pathway databases

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.
bard1pathway. BARD1 signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P68036.

Bgee

P68036.

CleanEx

HS_UBE2L3.

Genevestigator

P68036.

GermOnline

ENSG00000185651. 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.

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

28696.

SOURCE

Search...

Entry information

Entry name

UB2L3_HUMAN

Accession

Primary (citable) accession number: P68036
Secondary accession number(s): B2R4A7 , P51966, P70653, Q9HAV1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	February 22, 2012
This is version 84 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.