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O14933

- UB2L6_HUMAN

UniProt

O14933 - UB2L6_HUMAN

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Protein

Ubiquitin/ISG15-conjugating enzyme E2 L6

Gene

UBE2L6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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 FLT3.3 Publications

Catalytic activityi

ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.PROSITE-ProRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei86 – 861Glycyl thioester intermediatePROSITE-ProRule annotation

GO - Molecular functioni

  1. ISG15 ligase activity Source: Ensembl
  2. ubiquitin-protein transferase activity Source: ProtInc

GO - Biological processi

  1. cellular protein modification process Source: ProtInc
  2. cytokine-mediated signaling pathway Source: Reactome
  3. innate immune response Source: Reactome
  4. ISG15-protein conjugation Source: Ensembl
  5. modification-dependent protein catabolic process Source: Ensembl
  6. negative regulation of type I interferon production Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_115831. ISG15 antiviral mechanism.
REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiO14933.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
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 namesi
Name:UBE2L6
Synonyms:UBCH8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:12490. UBE2L6.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37139.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 153153Ubiquitin/ISG15-conjugating enzyme E2 L6PRO_0000082478Add
BLAST

Post-translational modificationi

ISGylated.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiO14933.
PaxDbiO14933.
PRIDEiO14933.

PTM databases

PhosphoSiteiO14933.

Expressioni

Tissue specificityi

Present in natural killer cells (at protein level).1 Publication

Inductioni

By IFNB1/IFN-beta.1 Publication

Gene expression databases

BgeeiO14933.
CleanExiHS_UBE2L6.
ExpressionAtlasiO14933. baseline and differential.
GenevestigatoriO14933.

Organism-specific databases

HPAiHPA003328.

Interactioni

Subunit structurei

Interacts with RNF19A, RNF19B and RNF144B. Interacts with FLT3 (tyrosine phosphorylated).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ospGQ99PZ62EBI-2129974,EBI-9316527From a different organism.
RNF144BQ7Z4194EBI-2129974,EBI-2129982
RNF19BQ6ZMZ03EBI-2129974,EBI-2466594
Rnf40Q8CJB92EBI-2129974,EBI-6110162From a different organism.

Protein-protein interaction databases

BioGridi114672. 42 interactions.
DIPiDIP-41477N.
IntActiO14933. 27 interactions.
MINTiMINT-240858.
STRINGi9606.ENSP00000287156.

Structurei

Secondary structure

1
153
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 1613Combined sources
Beta strandi22 – 276Combined sources
Beta strandi34 – 396Combined sources
Helixi46 – 483Combined sources
Beta strandi49 – 568Combined sources
Turni59 – 624Combined sources
Beta strandi67 – 726Combined sources
Beta strandi81 – 833Combined sources
Helixi88 – 903Combined sources
Turni92 – 943Combined sources
Helixi101 – 11313Combined sources
Beta strandi117 – 1193Combined sources
Helixi123 – 1319Combined sources
Helixi133 – 14715Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WZVX-ray2.10A/B2-153[»]
1WZWX-ray2.40A2-153[»]
2KJHNMR-A2-153[»]
ProteinModelPortaliO14933.
SMRiO14933. Positions 3-152.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14933.

Family & Domainsi

Sequence similaritiesi

Belongs to the ubiquitin-conjugating enzyme family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5078.
GeneTreeiENSGT00760000119012.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiO14933.
KOiK04553.
OMAiPEKPPYN.
OrthoDBiEOG7GXPD8.
PhylomeDBiO14933.
TreeFamiTF313043.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O14933-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MMASMRVVKE LEDLQKKPPP YLRNLSSDDA NVLVWHALLL PDQPPYHLKA
60 70 80 90 100
FNLRISFPPE YPFKPPMIKF TTKIYHPNVD ENGQICLPII SSENWKPCTK
110 120 130 140 150
TCQVLEALNV LVNRPNIREP LRMDLADLLT QNPELFRKNA EEFTLRFGVD

RPS
Length:153
Mass (Da):17,769
Last modified:June 16, 2009 - v4
Checksum:iD79768775344EFAE
GO
Isoform 2 (identifier: O14933-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:87
Mass (Da):10,086
Checksum:iCD4DEC38615607B1
GO

Sequence cautioni

The sequence CAB64566.1 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6666Missing in isoform 2. 1 PublicationVSP_037344Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7960.1. [O14933-1]
CCDS7961.1. [O14933-2]
RefSeqiNP_004214.1. NM_004223.4. [O14933-1]
NP_937826.1. NM_198183.2. [O14933-2]
UniGeneiHs.425777.

Genome annotation databases

EnsembliENST00000287156; ENSP00000287156; ENSG00000156587. [O14933-1]
ENST00000340573; ENSP00000341980; ENSG00000156587. [O14933-2]
GeneIDi9246.
KEGGihsa:9246.
UCSCiuc001nkn.2. human. [O14933-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS7960.1. [O14933-1 ]
CCDS7961.1. [O14933-2 ]
RefSeqi NP_004214.1. NM_004223.4. [O14933-1 ]
NP_937826.1. NM_198183.2. [O14933-2 ]
UniGenei Hs.425777.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1WZV X-ray 2.10 A/B 2-153 [» ]
1WZW X-ray 2.40 A 2-153 [» ]
2KJH NMR - A 2-153 [» ]
ProteinModelPortali O14933.
SMRi O14933. Positions 3-152.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114672. 42 interactions.
DIPi DIP-41477N.
IntActi O14933. 27 interactions.
MINTi MINT-240858.
STRINGi 9606.ENSP00000287156.

PTM databases

PhosphoSitei O14933.

Proteomic databases

MaxQBi O14933.
PaxDbi O14933.
PRIDEi O14933.

Protocols and materials databases

DNASUi 9246.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000287156 ; ENSP00000287156 ; ENSG00000156587 . [O14933-1 ]
ENST00000340573 ; ENSP00000341980 ; ENSG00000156587 . [O14933-2 ]
GeneIDi 9246.
KEGGi hsa:9246.
UCSCi uc001nkn.2. human. [O14933-1 ]

Organism-specific databases

CTDi 9246.
GeneCardsi GC11M057319.
HGNCi HGNC:12490. UBE2L6.
HPAi HPA003328.
MIMi 603890. gene.
neXtProti NX_O14933.
PharmGKBi PA37139.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5078.
GeneTreei ENSGT00760000119012.
HOGENOMi HOG000233455.
HOVERGENi HBG063308.
InParanoidi O14933.
KOi K04553.
OMAi PEKPPYN.
OrthoDBi EOG7GXPD8.
PhylomeDBi O14933.
TreeFami TF313043.

Enzyme and pathway databases

UniPathwayi UPA00143 .
Reactomei REACT_115831. ISG15 antiviral mechanism.
REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinki O14933.

Miscellaneous databases

ChiTaRSi UBE2L6. human.
EvolutionaryTracei O14933.
GeneWikii UBE2L6.
GenomeRNAii 9246.
NextBioi 34661.
PROi O14933.
SOURCEi Search...

Gene expression databases

Bgeei O14933.
CleanExi HS_UBE2L6.
ExpressionAtlasi O14933. baseline and differential.
Genevestigatori O14933.

Family and domain databases

Gene3Di 3.10.110.10. 1 hit.
InterProi IPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view ]
Pfami PF00179. UQ_con. 1 hit.
[Graphical view ]
SUPFAMi SSF54495. SSF54495. 1 hit.
PROSITEi PS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. 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. 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.

Entry informationi

Entry nameiUB2L6_HUMAN
AccessioniPrimary (citable) accession number: O14933
Secondary accession number(s): A6NDM6
, A8MY53, Q8N5D8, Q9UEZ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 16, 2009
Last modified: November 26, 2014
This is version 147 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3