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Protein

Ubiquitin-conjugating enzyme E2 K

Gene

UBE2K

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. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1.8 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

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 sitei92Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

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

GO - Biological processi

  • cellular response to interferon-beta Source: UniProtKB
  • free ubiquitin chain polymerization Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: Ensembl
  • positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
  • positive regulation of type I interferon-mediated signaling pathway Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  • protein K48-linked ubiquitination Source: UniProtKB
  • regulation of proteasomal ubiquitin-dependent protein catabolic process Source: Ensembl
  • ubiquitin-dependent protein catabolic process Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01274-MONOMER.
BRENDAi2.3.2.B6. 2681.
ReactomeiR-HSA-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP61086.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-conjugating enzyme E2 K (EC:2.3.2.231 Publication)
Alternative name(s):
E2 ubiquitin-conjugating enzyme K
Huntingtin-interacting protein 2
Short name:
HIP-2
Ubiquitin carrier protein
Ubiquitin-conjugating enzyme E2-25 kDa
Short name:
Ubiquitin-conjugating enzyme E2(25K)
Short name:
Ubiquitin-conjugating enzyme E2-25K
Ubiquitin-protein ligase
Gene namesi
Name:UBE2K
Synonyms:HIP2, LIG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:4914. UBE2K.

Subcellular locationi

  • Cytoplasm By similarity

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • filopodium tip Source: Ensembl
  • nucleus Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi94D → E: Decreased lysine reactivity and impaired formation of free polyubiquitin chains. 1 Publication1

Organism-specific databases

DisGeNETi3093.
OpenTargetsiENSG00000078140.
PharmGKBiPA162407874.

Polymorphism and mutation databases

BioMutaiUBE2K.
DMDMi46577658.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources3 Publications
ChainiPRO_00000824432 – 200Ubiquitin-conjugating enzyme E2 KAdd BLAST199

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei14N6-acetyllysine; alternateCombined sources1
Cross-linki14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Modified residuei159PhosphoserineCombined sources1

Post-translational modificationi

Sumoylation at Lys-14 impairs catalytic activity.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP61086.
MaxQBiP61086.
PaxDbiP61086.
PeptideAtlasiP61086.
PRIDEiP61086.
TopDownProteomicsiP61086-1. [P61086-1]

2D gel databases

OGPiP27924.

PTM databases

iPTMnetiP61086.
PhosphoSitePlusiP61086.
SwissPalmiP61086.

Expressioni

Tissue specificityi

Expressed in all tissues tested, including spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocytes, T-lymphocytes, monocytes, granulocytes and bone marrow mononuclear cells. Highly expressed in brain, with highest levels found in cortex and striatum and at lower levels in cerebellum and brainstem.3 Publications

Inductioni

By aggregated low-density lipoprotein.2 Publications

Gene expression databases

BgeeiENSG00000078140.
CleanExiHS_UBE2K.
ExpressionAtlasiP61086. baseline and differential.
GenevisibleiP61086. HS.

Organism-specific databases

HPAiCAB033212.
CAB033515.
HPA028869.

Interactioni

Subunit structurei

Interacts with RNF138/NARF. Interacts with BRCA1.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCNB1P146352EBI-473850,EBI-495332
DDI1Q8WTU03EBI-473850,EBI-748248
DTX3Q8N9I95EBI-473850,EBI-2340258
HTTP428583EBI-473850,EBI-466029
MIPOL1Q8TD105EBI-473850,EBI-2548751
ospGQ99PZ62EBI-473850,EBI-9316527From a different organism.
RELQ048643EBI-473850,EBI-307352
RNF138Q8WVD37EBI-473850,EBI-749039
RNF5Q999425EBI-473850,EBI-348482
SIAH1Q8IUQ44EBI-473850,EBI-747107
TRIM27P143736EBI-473850,EBI-719493
TRIM39Q9HCM93EBI-473850,EBI-739510

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109340. 90 interactors.
DIPiDIP-32524N.
IntActiP61086. 32 interactors.
MINTiMINT-5000019.
STRINGi9606.ENSP00000261427.

Structurei

Secondary structure

1200
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 17Combined sources12
Helixi20 – 23Combined sources4
Beta strandi26 – 31Combined sources6
Beta strandi33 – 35Combined sources3
Beta strandi36 – 44Combined sources9
Beta strandi47 – 49Combined sources3
Turni50 – 53Combined sources4
Beta strandi55 – 61Combined sources7
Turni64 – 68Combined sources5
Beta strandi72 – 77Combined sources6
Turni86 – 88Combined sources3
Helixi94 – 96Combined sources3
Turni97 – 99Combined sources3
Helixi106 – 118Combined sources13
Helixi128 – 136Combined sources9
Helixi138 – 153Combined sources16
Helixi160 – 170Combined sources11
Turni171 – 173Combined sources3
Helixi176 – 185Combined sources10
Turni186 – 188Combined sources3
Helixi190 – 199Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YLAX-ray2.40A/B1-200[»]
2O25X-ray2.60A/B1-200[»]
3E46X-ray1.86A1-200[»]
3F92X-ray2.23A13-200[»]
3K9OX-ray1.80A1-200[»]
3K9PX-ray2.80A1-200[»]
5DFLX-ray2.10A1-200[»]
ProteinModelPortaliP61086.
SMRiP61086.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61086.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini160 – 200UBAPROSITE-ProRule annotationAdd BLAST41

Sequence similaritiesi

Belongs to the ubiquitin-conjugating enzyme family.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0418. Eukaryota.
COG5078. LUCA.
GeneTreeiENSGT00670000098059.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiP61086.
KOiK04649.
OMAiHEMFILT.
OrthoDBiEOG091G0KVW.
PhylomeDBiP61086.
TreeFamiTF101127.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR015940. UBA.
IPR009060. UBA-like.
IPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00627. UBA. 1 hit.
PF00179. UQ_con. 1 hit.
[Graphical view]
SMARTiSM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF54495. SSF54495. 1 hit.
PROSITEiPS50030. UBA. 1 hit.
PS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: P61086-1) [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
MANIAVQRIK REFKEVLKSE ETSKNQIKVD LVDENFTELR GEIAGPPDTP
60 70 80 90 100
YEGGRYQLEI KIPETYPFNP PKVRFITKIW HPNISSVTGA ICLDILKDQW
110 120 130 140 150
AAAMTLRTVL LSLQALLAAA EPDDPQDAVV ANQYKQNPEM FKQTARLWAH
160 170 180 190 200
VYAGAPVSSP EYTKKIENLC AMGFDRNAVI VALSSKSWDV ETATELLLSN
Length:200
Mass (Da):22,407
Last modified:January 23, 2007 - v3
Checksum:iE40668099ED25828
GO
Isoform 2 (identifier: P61086-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     22-72: Missing.

Note: May be inactive.
Show »
Length:149
Mass (Da):16,618
Checksum:iF029A8438A8E88DB
GO
Isoform 3 (identifier: P61086-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     134-176: Missing.

Note: No experimental confirmation available.
Show »
Length:157
Mass (Da):17,447
Checksum:iE1083BBDA3B3DC65
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01179822 – 72Missing in isoform 2. 3 PublicationsAdd BLAST51
Alternative sequenceiVSP_046211134 – 176Missing in isoform 3. 1 PublicationAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58522 mRNA. Translation: AAC50633.1.
AB022435 mRNA. Translation: BAA78555.1.
AB022436 mRNA. Translation: BAA78556.1.
BX339118 mRNA. No translation available.
AK291454 mRNA. Translation: BAF84143.1.
AK315524 mRNA. Translation: BAG37905.1.
AC105287 Genomic DNA. No translation available.
AC108471 Genomic DNA. No translation available.
CH471069 Genomic DNA. Translation: EAW92948.1.
BC022804 mRNA. Translation: AAH22804.1.
BC050600 mRNA. Translation: AAH50600.1.
CCDSiCCDS33976.1. [P61086-1]
CCDS47043.1. [P61086-3]
CCDS47044.1. [P61086-2]
RefSeqiNP_001104582.1. NM_001111112.1. [P61086-3]
NP_001104583.1. NM_001111113.1. [P61086-2]
NP_005330.1. NM_005339.4. [P61086-1]
UniGeneiHs.50308.

Genome annotation databases

EnsembliENST00000261427; ENSP00000261427; ENSG00000078140. [P61086-1]
ENST00000445950; ENSP00000390483; ENSG00000078140. [P61086-3]
ENST00000503368; ENSP00000421203; ENSG00000078140. [P61086-2]
GeneIDi3093.
KEGGihsa:3093.
UCSCiuc003gus.5. human. [P61086-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58522 mRNA. Translation: AAC50633.1.
AB022435 mRNA. Translation: BAA78555.1.
AB022436 mRNA. Translation: BAA78556.1.
BX339118 mRNA. No translation available.
AK291454 mRNA. Translation: BAF84143.1.
AK315524 mRNA. Translation: BAG37905.1.
AC105287 Genomic DNA. No translation available.
AC108471 Genomic DNA. No translation available.
CH471069 Genomic DNA. Translation: EAW92948.1.
BC022804 mRNA. Translation: AAH22804.1.
BC050600 mRNA. Translation: AAH50600.1.
CCDSiCCDS33976.1. [P61086-1]
CCDS47043.1. [P61086-3]
CCDS47044.1. [P61086-2]
RefSeqiNP_001104582.1. NM_001111112.1. [P61086-3]
NP_001104583.1. NM_001111113.1. [P61086-2]
NP_005330.1. NM_005339.4. [P61086-1]
UniGeneiHs.50308.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YLAX-ray2.40A/B1-200[»]
2O25X-ray2.60A/B1-200[»]
3E46X-ray1.86A1-200[»]
3F92X-ray2.23A13-200[»]
3K9OX-ray1.80A1-200[»]
3K9PX-ray2.80A1-200[»]
5DFLX-ray2.10A1-200[»]
ProteinModelPortaliP61086.
SMRiP61086.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109340. 90 interactors.
DIPiDIP-32524N.
IntActiP61086. 32 interactors.
MINTiMINT-5000019.
STRINGi9606.ENSP00000261427.

PTM databases

iPTMnetiP61086.
PhosphoSitePlusiP61086.
SwissPalmiP61086.

Polymorphism and mutation databases

BioMutaiUBE2K.
DMDMi46577658.

2D gel databases

OGPiP27924.

Proteomic databases

EPDiP61086.
MaxQBiP61086.
PaxDbiP61086.
PeptideAtlasiP61086.
PRIDEiP61086.
TopDownProteomicsiP61086-1. [P61086-1]

Protocols and materials databases

DNASUi3093.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261427; ENSP00000261427; ENSG00000078140. [P61086-1]
ENST00000445950; ENSP00000390483; ENSG00000078140. [P61086-3]
ENST00000503368; ENSP00000421203; ENSG00000078140. [P61086-2]
GeneIDi3093.
KEGGihsa:3093.
UCSCiuc003gus.5. human. [P61086-1]

Organism-specific databases

CTDi3093.
DisGeNETi3093.
GeneCardsiUBE2K.
HGNCiHGNC:4914. UBE2K.
HPAiCAB033212.
CAB033515.
HPA028869.
MIMi602846. gene.
neXtProtiNX_P61086.
OpenTargetsiENSG00000078140.
PharmGKBiPA162407874.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0418. Eukaryota.
COG5078. LUCA.
GeneTreeiENSGT00670000098059.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiP61086.
KOiK04649.
OMAiHEMFILT.
OrthoDBiEOG091G0KVW.
PhylomeDBiP61086.
TreeFamiTF101127.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:HS01274-MONOMER.
BRENDAi2.3.2.B6. 2681.
ReactomeiR-HSA-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP61086.

Miscellaneous databases

ChiTaRSiUBE2K. human.
EvolutionaryTraceiP61086.
GeneWikiiHIP2.
GenomeRNAii3093.
PROiP61086.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000078140.
CleanExiHS_UBE2K.
ExpressionAtlasiP61086. baseline and differential.
GenevisibleiP61086. HS.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR015940. UBA.
IPR009060. UBA-like.
IPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00627. UBA. 1 hit.
PF00179. UQ_con. 1 hit.
[Graphical view]
SMARTiSM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF54495. SSF54495. 1 hit.
PROSITEiPS50030. UBA. 1 hit.
PS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBE2K_HUMAN
AccessioniPrimary (citable) accession number: P61086
Secondary accession number(s): A6NJC1
, A8K5Y9, B2RDF8, C9JGP1, O54806, P27924, Q16721, Q9CVV9, Q9Y2D3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 146 of the entry and version 3 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 4
    Human chromosome 4: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.