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Protein

Ubiquitin-conjugating enzyme E2 W

Gene

UBE2W

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

Functioni

Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:20061386). Specifically monoubiquitinates the N-terminus of various substrates, including ATXN3, MAPT/TAU, POLR2H/RPB8 and STUB1/CHIP, by recognizing backbone atoms of disordered N-termini (PubMed:23560854, PubMed:23696636, PubMed:25436519). Involved in degradation of misfolded chaperone substrates by mediating monoubiquitination of STUB1/CHIP, leading to recruitment of ATXN3 to monoubiquitinated STUB1/CHIP, and restriction of the length of ubiquitin chain attached to STUB1/CHIP substrates by ATXN3. After UV irradiation, but not after mitomycin-C (MMC) treatment, acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway (PubMed:19111657, PubMed:21229326). In vitro catalyzes 'Lys-11'-linked polyubiquitination. UBE2W-catalyzed ubiquitination occurs also in the presence of inactive RING/U-box type E3s, i.e. lacking the active site cysteine residues to form thioester bonds with ubiquitin, or even in the absence of E3, albeit at a slower rate (PubMed:25436519).6 Publications

Catalytic activityi

S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine.PROSITE-ProRule annotation1 Publication
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N-terminal-amino acid = [E1 ubiquitin-activating enzyme]-L-cysteine + N-terminal-ubiquitinyl-[acceptor protein].2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.PROSITE-ProRule annotation
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei91Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS11901-MONOMER.
BRENDAi2.3.2.B6. 2681.
2.3.2.B7. 2681.
ReactomeiR-HSA-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ96B02.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-conjugating enzyme E2 W (EC:2.3.2.231 Publication)
Alternative name(s):
E2 ubiquitin-conjugating enzyme W
N-terminal E2 ubiquitin-conjugating enzyme (EC:2.3.2.252 Publications)
N-terminus-conjugating E2
Ubiquitin carrier protein W
Ubiquitin-conjugating enzyme 16
Short name:
UBC-16
Ubiquitin-protein ligase W
Gene namesi
Name:UBE2W
Synonyms:UBC16
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104343.19.
HGNCiHGNC:25616. UBE2W.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi83H → N: Impaired substrate ubiquitination of both Tau and ATXN3. 1 Publication1
Mutagenesisi91C → A: Loss of predominant nuclear localization. 1 Publication1
Mutagenesisi132 – 145Missing : Loss of ubiquitination activity. 1 PublicationAdd BLAST14
Mutagenesisi144W → E: Loss of ubiquitination activity toward various substrates, including POLR2H, ATXN3, STUB1 and MAPT. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000104343.
PharmGKBiPA142670657.

Polymorphism and mutation databases

DMDMi74751754.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002326891 – 151Ubiquitin-conjugating enzyme E2 WAdd BLAST151

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Ubiquitinated in vitro in the presence of FANCL (By similarity). Autoubiquitinated at Met-1 (PubMed:23560854, PubMed:22496338).By similarity2 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ96B02.
PaxDbiQ96B02.
PeptideAtlasiQ96B02.
PRIDEiQ96B02.

PTM databases

iPTMnetiQ96B02.
PhosphoSitePlusiQ96B02.

Expressioni

Tissue specificityi

Widely expressed, with highest expression in brain, liver, pancreas and heart.1 Publication

Gene expression databases

BgeeiENSG00000104343.
CleanExiHS_UBE2W.
ExpressionAtlasiQ96B02. baseline and differential.
GenevisibleiQ96B02. HS.

Organism-specific databases

HPAiHPA045161.
HPA073181.

Interactioni

Subunit structurei

Homodimer. Interacts with FANCL (PubMed:19111657). Interacts with STUB1/CHIP (By similarity).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120572. 96 interactors.
DIPiDIP-52724N.
IntActiQ96B02. 71 interactors.
MINTiMINT-1428082.
STRINGi9606.ENSP00000454445.

Structurei

Secondary structure

1151
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 17Combined sources12
Beta strandi23 – 28Combined sources6
Beta strandi35 – 42Combined sources8
Turni48 – 51Combined sources4
Beta strandi53 – 60Combined sources8
Turni62 – 66Combined sources5
Beta strandi70 – 76Combined sources7
Beta strandi88 – 90Combined sources3
Helixi93 – 95Combined sources3
Turni96 – 98Combined sources3
Helixi105 – 115Combined sources11
Helixi128 – 133Combined sources6
Helixi134 – 137Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2A7LX-ray1.82A/B1-117[»]
2MT6NMR-A1-151[»]
ProteinModelPortaliQ96B02.
SMRiQ96B02.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96B02.

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0427. Eukaryota.
COG5078. LUCA.
GeneTreeiENSGT00900000140930.
HOGENOMiHOG000233453.
HOVERGENiHBG063308.
InParanoidiQ96B02.
KOiK10688.
PhylomeDBiQ96B02.
TreeFamiTF314582.

Family and domain databases

CDDicd00195. UBCc. 1 hit.
Gene3Di3.10.110.10. 1 hit.
InterProiView protein in InterPro
IPR000608. UBQ-conjugat_E2.
IPR016135. UBQ-conjugating_enzyme/RWD.
PfamiView protein in Pfam
PF00179. UQ_con. 1 hit.
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiView protein in PROSITE
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96B02-1) [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
MASMQKRLQK ELLALQNDPP PGMTLNEKSV QNSITQWIVD MEGAPGTLYE
60 70 80 90 100
GEKFQLLFKF SSRYPFDSPQ VMFTGENIPV HPHVYSNGHI CLSILTEDWS
110 120 130 140 150
PALSVQSVCL SIISMLSSCK EKRRPPDNSF YVRTCNKNPK KTKWWYHDDT

C
Length:151
Mass (Da):17,331
Last modified:December 1, 2001 - v1
Checksum:i276B585BBC4CEB71
GO
Isoform 2 (identifier: Q96B02-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     5-5: Q → QTTGRRVEVWFP

Show »
Length:162
Mass (Da):18,660
Checksum:iF41B440840AD0625
GO
Isoform 3 (identifier: Q96B02-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLSPRGVTRARQLLPLRLWPRRSWGDGSIM

Note: No experimental confirmation available.
Show »
Length:180
Mass (Da):20,689
Checksum:i3E0F0920D2F1AD9F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26N → S in BAB13883 (PubMed:14702039).Curated1
Sequence conflicti45P → S in BAA91954 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0429741M → MLSPRGVTRARQLLPLRLWP RRSWGDGSIM in isoform 3. 1 Publication1
Alternative sequenceiVSP_0179435Q → QTTGRRVEVWFP in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY948289 mRNA. Translation: AAY24555.1.
AK001873 mRNA. Translation: BAA91954.1.
AK021735 mRNA. Translation: BAB13883.1.
AK024050 mRNA. Translation: BAB14800.1.
AK295792 mRNA. Translation: BAG58613.1.
CR457275 mRNA. Translation: CAG33556.1.
CH471068 Genomic DNA. Translation: EAW87009.1.
CH471068 Genomic DNA. Translation: EAW87011.1.
AC022826 Genomic DNA. No translation available.
BC016326 mRNA. Translation: AAH16326.1.
CCDSiCCDS47874.2. [Q96B02-3]
RefSeqiNP_001001481.2. NM_001001481.2.
NP_001257944.1. NM_001271015.1.
NP_060769.4. NM_018299.4. [Q96B02-3]
UniGeneiHs.128841.

Genome annotation databases

EnsembliENST00000517608; ENSP00000428813; ENSG00000104343. [Q96B02-3]
ENST00000602593; ENSP00000473561; ENSG00000104343. [Q96B02-1]
GeneIDi55284.
KEGGihsa:55284.
UCSCiuc003xzv.4. human. [Q96B02-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiUBE2W_HUMAN
AccessioniPrimary (citable) accession number: Q96B02
Secondary accession number(s): B4DIV1
, Q1XBE0, Q9H823, Q9HAG6, Q9NV07
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: December 1, 2001
Last modified: November 22, 2017
This is version 151 of the entry and version 1 of the sequence. See 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, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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