Reviewed, UniProtKB/Swiss-Prot O14933 (UB2L6_HUMAN)

Names and origin

Protein names

Recommended name:
    Ubiquitin/ISG15-conjugating enzyme E2 L6
    EC=6.3.2.19
Alternative name(s):
    Ubiquitin-protein ligase L6
    Ubiquitin carrier protein L6
    UbcH8
    Retinoic acid-induced gene B protein
      Short name=RIG-B

Gene names

Name:	UBE2L6
Synonyms:	UBCH8

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	153 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. Ref.10
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with RNF19A, RNF19B and RNF144B. Ref.11 Ref.12 Ref.13
Tissue specificity	Present in natural killer cells (at protein level). Ref.13
Induction	By interferon beta. Ref.10
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Molecular function	Ligase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW post-translational protein modification Inferred from electronic annotation. Source: InterPro regulation of protein metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB ubiquitin-protein ligase activity Ref.9 Traceable author statement. Source: ProtInc
Complete GO annotation...

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

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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

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. 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: 10894956] [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: 14702039] [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: 16554811] [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: 15489334] [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: 9153201] [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: 15131269] [Abstract] Cited for: PROTEIN SEQUENCE OF 140-146, FUNCTION IN ISG15 ATTACHMENT, INDUCTION BY INTERFERON BETA.
[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: 11237715] [Abstract] Cited for: INTERACTION WITH RNF19A.
[12]	"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.
[13]	"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, TISSUE SPECIFICITY.
[14]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

RefSeq

NP_004214.1.

UniGene

Hs.425777

3D structure databases

PDBPDBe

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

ModBase

Search...

Proteomic databases

PRIDE

O14933.

Genome annotation databases

Ensembl

ENSG00000156587. Homo sapiens. [Contig view]

GeneID

9246.

KEGG

hsa:9246.

Organism-specific databases

GeneCards

GC11M057075.

HGNC

HGNC:12490. UBE2L6.

HPA

HPA003328.

MIM

603890. gene.

PharmGKB

PA37139.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O14933.

OMA

O14933. EFTLQFG.

Enzyme and pathway databases

BRENDA

6.3.2.19. 247.

Gene expression databases

ArrayExpress

O14933.

Bgee

O14933.
Q8N5D8.

CleanEx

HS_UBE2L6.

GermOnline

ENSG00000156587. 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

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:	June 16, 2009
This is version 90 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)