O14933 (UB2L6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin/ISG15-conjugating enzyme E2 L6
EC=6.3.2.19

Alternative name(s):
Retinoic acid-induced gene B protein
Short name=RIG-B
UbcH8
Ubiquitin carrier protein L6
Ubiquitin-protein ligase L6

Gene names

Name:	UBE2L6
Synonyms:	UBCH8

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

General annotation (Comments)

Function	Catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Promotes ubiquitination and subsequent proteasomal degradation of FLT3. Ref.10 Ref.12 Ref.15
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with RNF19A, RNF19B and RNF144B. Interacts with FLT3 (tyrosine phosphorylated). Ref.11 Ref.13 Ref.14 Ref.15
Tissue specificity	Present in natural killer cells (at protein level). Ref.14
Induction	By IFNB1/IFN-beta. Ref.10
Post-translational modification	ISGylated. Ref.12
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.
Sequence caution	The sequence CAB64566.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Molecular function	Ligase
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ISG15-protein conjugation Inferred from electronic annotation. Source: Compara cytokine-mediated signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome modification-dependent protein catabolic process Inferred from electronic annotation. Source: Compara negative regulation of type I interferon production Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ISG15 ligase activity Inferred from electronic annotation. Source: Compara ubiquitin-protein ligase activity Traceable author statement Ref.9. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RNF19B	Q6ZMZ0	3	EBI-2129974,EBI-2466594
Rnf40	Q8CJB9	2	EBI-2129974,EBI-6110162	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O14933-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O14933-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 153

153

Ubiquitin/ISG15-conjugating enzyme E2 L6

PRO_0000082478

Sites

Active site

86

1

Glycyl thioester intermediate By similarity

Natural variations

Alternative sequence

1 – 66

66

Missing in isoform 2.

VSP_037344

Secondary structure

1

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153

Helix Strand Turn

Details...

Helix

4 – 16

13

Beta strand

22 – 27

6

Beta strand

34 – 39

6

Helix

46 – 48

3

Beta strand

49 – 56

8

Turn

59 – 62

4

Beta strand

67 – 72

6

Beta strand

81 – 83

3

Helix

88 – 90

3

Turn

92 – 94

3

Helix

101 – 113

13

Beta strand

117 – 119

3

Helix

123 – 131

9

Helix

133 – 147

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 16, 2009. Version 4. Checksum: D79768775344EFAE	FASTA	153	17,769
	10 20 30 40 50 60 MMASMRVVKE LEDLQKKPPP YLRNLSSDDA NVLVWHALLL PDQPPYHLKA FNLRISFPPE 70 80 90 100 110 120 YPFKPPMIKF TTKIYHPNVD ENGQICLPII SSENWKPCTK TCQVLEALNV LVNRPNIREP 130 140 150 LRMDLADLLT QNPELFRKNA EEFTLRFGVD RPS
	Isoform 2 [UniParc]. Checksum: CD4DEC38615607B1	FASTA	87	10,086
	10 20 30 40 50 60 MIKFTTKIYH PNVDENGQIC LPIISSENWK PCTKTCQVLE ALNVLVNRPN IREPLRMDLA 70 80 DLLTQNPELF RKNAEEFTLR FGVDRPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genomic organization of the human ubiquitin-conjugating enzyme gene, UBE2L6 on chromosome 11q12." Ardley H.C., Rose S.A., Tan N., Leek J.P., Markham A.F., Robinson P.A. Cytogenet. Cell Genet. 89:137-140(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]	"Human retinoic acid induced gene B (RIG-B) mRNA." Liu T., Mao M., Zhang J., Wu J., Zhang Q., Fu G., Shen Y., Zhou J., Yu Y., Wang Z., Chen S., Chen Z. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Thymus.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[6]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[9]	"Physical interaction between specific E2 and Hect E3 enzymes determines functional cooperativity." Kumar S., Kao W.H., Howley P.M. J. Biol. Chem. 272:13548-13554(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-153 (ISOFORM 1).
[10]	"The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-alpha/beta-induced ubiquitin-like protein." Zhao C., Beaudenon S.L., Kelley M.L., Waddell M.B., Yuan W., Schulman B.A., Huibregtse J.M., Krug R.M. Proc. Natl. Acad. Sci. U.S.A. 101:7578-7582(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 140-146, FUNCTION IN ISG15 ATTACHMENT, INDUCTION BY IFNB1.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RNF19A.
[12]	"Link between the ubiquitin conjugation system and the ISG15 conjugation system: ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme." Takeuchi T., Iwahara S., Saeki Y., Sasajima H., Yokosawa H. J. Biochem. 138:711-719(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ISGYLATION.
[13]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RNF144B.
[14]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RNF19B, TISSUE SPECIFICITY.
[15]	"Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for proteasomal degradation." Buchwald M., Pietschmann K., Muller J.P., Bohmer F.D., Heinzel T., Kramer O.H. Leukemia 24:1412-1421(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF FLT3, INTERACTION WITH FLT3.
[16]	"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].
[17]	"Crystal structure of Ubch8." Mizushima T., Suzuki M., Teshima N., Yamane T., Murata S., Tanaka K. Submitted (MAR-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 2-153.
[18]	"The structure of the UbcH8-ubiquitin complex shows a unique ubiquitin interaction site." Serniwka S.A., Shaw G.S. Biochemistry 48:12169-12179(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR IN COMPLEX WITH UBIQUITIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ243268 , AJ243269, AJ243270, AJ243271 Genomic DNA. Translation: CAB64566.1. Different initiation.
AF061736 mRNA. Translation: AAD17525.1.
AK315755 mRNA. Translation: BAG38109.1.
CR457126 mRNA. Translation: CAG33407.1.
AK226165 mRNA. No translation available.
AP002893 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW73757.1.
CH471076 Genomic DNA. Translation: EAW73759.1.
BC032491 mRNA. Translation: AAH32491.1.
AF031141 mRNA. Translation: AAB86433.1.

IPI

IPI00329563.
IPI00386520.

RefSeq

NP_004214.1. NM_004223.4.
NP_937826.1. NM_198183.2.

UniGene

Hs.425777.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WZV	X-ray	2.10	A/B	2-152	[»]
1WZW	X-ray	2.40	A	2-152	[»]
2KJH	NMR	-	A	2-153	[»]

ProteinModelPortal

O14933.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14933. 22 interactions.

MINT

MINT-240858.

STRING

9606.ENSP00000287156.

PTM databases

PhosphoSite

O14933.

Proteomic databases

PaxDb

O14933.

PRIDE

O14933.

Protocols and materials databases

DNASU

9246.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000287156; ENSP00000287156; ENSG00000156587.
ENST00000340573; ENSP00000341980; ENSG00000156587.

GeneID

9246.

KEGG

hsa:9246.

UCSC

uc001nkn.2. human.

Organism-specific databases

CTD

9246.

GeneCards

GC11M057319.

HGNC

HGNC:12490. UBE2L6.

HPA

HPA003328.

MIM

603890. gene.

neXtProt

NX_O14933.

PharmGKB

PA37139.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5078.

HOGENOM

HOG000233455.

HOVERGEN

HBG063308.

InParanoid

O14933.

KO

K04553.

OMA

PEKPPYN.

OrthoDB

EOG43BMQ6.

PhylomeDB

O14933.

Enzyme and pathway databases

Reactome

REACT_107772. Immune System.
REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

O14933.

Bgee

O14933.

CleanEx

HS_UBE2L6.

Genevestigator

O14933.

GermOnline

ENSG00000156587. 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

ChiTaRS

UBE2L6. human.

EvolutionaryTrace

O14933.

GenomeRNAi

9246.

NextBio

34661.

SOURCE

Search...

Entry information

Entry name

UB2L6_HUMAN

Accession

Primary (citable) accession number: O14933
Secondary accession number(s): A6NDM6 , A8MY53, Q8N5D8, Q9UEZ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	June 16, 2009
Last modified:	May 1, 2013
This is version 132 of the entry and version 4 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.