UBE2K_BOVIN
ID UBE2K_BOVIN Reviewed; 200 AA.
AC P61085; A5PK22; O54806; P27924; Q16721; Q9CVV9;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 K;
DE EC=2.3.2.23;
DE AltName: Full=E2 ubiquitin-conjugating enzyme K;
DE AltName: Full=Huntingtin-interacting protein 2;
DE Short=HIP-2;
DE AltName: Full=Ubiquitin carrier protein;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-25 kDa;
DE Short=Ubiquitin-conjugating enzyme E2(25K);
DE Short=Ubiquitin-conjugating enzyme E2-25K;
DE AltName: Full=Ubiquitin-protein ligase;
GN Name=UBE2K; Synonyms=HIP2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thymus;
RX PubMed=1714895; DOI=10.1016/s0021-9258(18)98465-6;
RA Chen Z., Niles E.G., Pickart C.M.;
RT "Isolation of a cDNA encoding a mammalian multiubiquitinating enzyme
RT (E225K) and overexpression of the functional enzyme in Escherichia coli.";
RL J. Biol. Chem. 266:15698-15704(1991).
RN [2]
RP SEQUENCE REVISION TO 23, AND MUTAGENESIS OF SER-86.
RX PubMed=9657692; DOI=10.1021/bi9800911;
RA Mastrandrea L.D., Kasperek E.M., Niles E.G., Pickart C.M.;
RT "Core domain mutation (S86Y) selectively inactivates polyubiquitin chain
RT synthesis catalyzed by E2-25K.";
RL Biochemistry 37:9784-9792(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION IN UBIQUITINATION OF NF-KAPPA-B.
RX PubMed=9535861; DOI=10.1074/jbc.273.15.8820;
RA Coux O., Goldberg A.L.;
RT "Enzymes catalyzing ubiquitination and proteolytic processing of the p105
RT precursor of nuclear factor kappaB1.";
RL J. Biol. Chem. 273:8820-8828(1998).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=1322903; DOI=10.2210/pdb1aar/pdb;
RA Cook W.J., Jeffrey L.C., Carson M., Chen Z., Pickart C.M.;
RT "Structure of a diubiquitin conjugate and a model for interaction with
RT ubiquitin conjugating enzyme (E2).";
RL J. Biol. Chem. 267:16467-16471(1992).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), AND SUMOYLATION AT LYS-14.
RX PubMed=15723079; DOI=10.1038/nsmb903;
RA Pichler A., Knipscheer P., Oberhofer E., van Dijk W.J., Koerner R.,
RA Olsen J.V., Jentsch S., Melchior F., Sixma T.K.;
RT "SUMO modification of the ubiquitin-conjugating enzyme E2-25K.";
RL Nat. Struct. Mol. Biol. 12:264-269(2005).
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. In vitro, in the presence or in
CC the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex,
CC catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does
CC not transfer ubiquitin directly to but elongates monoubiquitinated
CC substrate protein. Mediates the selective degradation of short-lived
CC and abnormal proteins, such as the endoplasmic reticulum-associated
CC degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates
CC huntingtin. May mediate foam cell formation by the suppression of
CC apoptosis of lipid-bearing macrophages through ubiquitination and
CC subsequence degradation of p53/TP53 (By similarity). Proposed to be
CC involved in ubiquitination and proteolytic processing of NF-kappa-B; in
CC vitro supports ubiquitination of NFKB1. {ECO:0000250|UniProtKB:P61086,
CC ECO:0000269|PubMed:9535861}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-
CC activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-
CC conjugating enzyme]-L-cysteine.; EC=2.3.2.23;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE-
CC ProRule:PRU10133};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC -!- SUBUNIT: Interacts with RNF138/NARF. Interacts with BRCA1.
CC {ECO:0000250|UniProtKB:P61086}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: Sumoylation at Lys-14 impairs catalytic activity.
CC {ECO:0000269|PubMed:15723079}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; S51016; AAB19536.1; -; mRNA.
DR EMBL; BC142324; AAI42325.1; -; mRNA.
DR PIR; A40797; A40797.
DR RefSeq; NP_776505.1; NM_174080.2.
DR PDB; 2BEP; X-ray; 1.80 A; A=1-155.
DR PDB; 2BF8; X-ray; 2.30 A; A=2-155.
DR PDBsum; 2BEP; -.
DR PDBsum; 2BF8; -.
DR AlphaFoldDB; P61085; -.
DR BMRB; P61085; -.
DR SMR; P61085; -.
DR STRING; 9913.ENSBTAP00000026871; -.
DR PaxDb; P61085; -.
DR PeptideAtlas; P61085; -.
DR PRIDE; P61085; -.
DR Ensembl; ENSBTAT00000026871; ENSBTAP00000026871; ENSBTAG00000020175.
DR GeneID; 281225; -.
DR KEGG; bta:281225; -.
DR CTD; 3093; -.
DR VEuPathDB; HostDB:ENSBTAG00000020175; -.
DR VGNC; VGNC:36587; UBE2K.
DR eggNOG; KOG0418; Eukaryota.
DR GeneTree; ENSGT00670000098059; -.
DR HOGENOM; CLU_030988_13_1_1; -.
DR InParanoid; P61085; -.
DR OMA; HHLKGSF; -.
DR OrthoDB; 1418652at2759; -.
DR TreeFam; TF101127; -.
DR Reactome; R-BTA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; P61085; -.
DR Proteomes; UP000009136; Chromosome 6.
DR Bgee; ENSBTAG00000020175; Expressed in occipital lobe and 105 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032433; C:filopodium tip; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; IEA:Ensembl.
DR GO; GO:0035458; P:cellular response to interferon-beta; IEA:Ensembl.
DR GO; GO:0010994; P:free ubiquitin chain polymerization; IEA:Ensembl.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR CDD; cd14390; UBA_II_E2_UBE2K; 1.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR042599; UBE2K_UBA.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00627; UBA; 1.
DR Pfam; PF00179; UQ_con; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS00183; UBC_1; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cytoplasm; Isopeptide bond;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P61086"
FT CHAIN 2..200
FT /note="Ubiquitin-conjugating enzyme E2 K"
FT /id="PRO_0000082442"
FT DOMAIN 4..154
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT DOMAIN 160..200
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ACT_SITE 92
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P61086"
FT MOD_RES 14
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P61086"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61086"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:P61086"
FT MUTAGEN 86
FT /note="S->Y: Inhibits ubiquitin transfer to macromolecular
FT acceptors."
FT /evidence="ECO:0000269|PubMed:9657692"
FT CONFLICT 23
FT /note="S -> T (in Ref. 1; AAB19536)"
FT /evidence="ECO:0000305"
FT HELIX 3..18
FT /evidence="ECO:0007829|PDB:2BEP"
FT HELIX 20..23
FT /evidence="ECO:0007829|PDB:2BEP"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:2BEP"
FT STRAND 33..44
FT /evidence="ECO:0007829|PDB:2BEP"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:2BEP"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:2BEP"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:2BEP"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:2BEP"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:2BEP"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:2BEP"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:2BEP"
FT HELIX 106..118
FT /evidence="ECO:0007829|PDB:2BEP"
FT HELIX 128..136
FT /evidence="ECO:0007829|PDB:2BEP"
FT HELIX 138..152
FT /evidence="ECO:0007829|PDB:2BEP"
SQ SEQUENCE 200 AA; 22407 MW; E40668099ED25828 CRC64;
MANIAVQRIK REFKEVLKSE ETSKNQIKVD LVDENFTELR GEIAGPPDTP YEGGRYQLEI
KIPETYPFNP PKVRFITKIW HPNISSVTGA ICLDILKDQW AAAMTLRTVL LSLQALLAAA
EPDDPQDAVV ANQYKQNPEM FKQTARLWAH VYAGAPVSSP EYTKKIENLC AMGFDRNAVI
VALSSKSWDV ETATELLLSN
