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Protein

Ubiquitin-conjugating enzyme E2 K

Gene

UBE2K

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.3.2.B6 2681
ReactomeiR-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiP61086
UniPathwayi
UPA00143

Protein family/group databases

MoonDBiP61086 Predicted

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

EuPathDBiHostDB:ENSG00000078140.13
HGNCiHGNC:4914 UBE2K
MIMi602846 gene
neXtProtiNX_P61086

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

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
ProteomicsDBi57262
57263 [P61086-2]
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 Expressed in 227 organ(s), highest expression level in postcentral gyrus
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109340, 96 interactors
DIPiDIP-32524N
IntActiP61086, 45 interactors
MINTiP61086
STRINGi9606.ENSP00000261427

Structurei

Secondary structure

1200
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

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

Family and domain databases

CDDicd00195 UBCc, 1 hit
Gene3Di3.10.110.10, 1 hit
InterProiView protein in InterPro
IPR015940 UBA
IPR009060 UBA-like_sf
IPR000608 UBQ-conjugat_E2
IPR023313 UBQ-conjugating_AS
IPR016135 UBQ-conjugating_enzyme/RWD
PfamiView protein in Pfam
PF00627 UBA, 1 hit
PF00179 UQ_con, 1 hit
SMARTiView protein in SMART
SM00165 UBA, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF54495 SSF54495, 1 hit
PROSITEiView protein in PROSITE
PS50030 UBA, 1 hit
PS00183 UBIQUITIN_CONJUGAT_1, 1 hit
PS50127 UBIQUITIN_CONJUGAT_2, 1 hit

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RDM7D6RDM7_HUMAN
Ubiquitin-conjugating enzyme E2 K
UBE2K
123Annotation score:
D6RFX1D6RFX1_HUMAN
Ubiquitin-conjugating enzyme E2 K
UBE2K
44Annotation score:

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

Similar proteinsi

Entry informationi

Entry nameiUBE2K_HUMAN
AccessioniPrimary (citable) accession number: P61086
Secondary accession number(s): A6NJC1
, A8K5Y9, B2RDF8, C9JGP1, O54806, P27924, Q16721, Q9CVV9, Q9Y2D3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 162 of the entry and version 3 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, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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