UBE2K_MOUSE
ID UBE2K_MOUSE Reviewed; 200 AA.
AC P61087; 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 165.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=10585161; DOI=10.1016/s0891-0618(99)00030-7;
RA Tanno Y., Mori T., Yokoya S., Kanazawa K., Honma Y., Nikaido T., Takeda J.,
RA Tojo M., Yamamoto T., Wanaka A.;
RT "Localization of huntingtin-interacting protein-2 (Hip-2) mRNA in the
RT developing mouse brain.";
RL J. Chem. Neuroanat. 17:99-107(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 85-200.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION IN UBIQUITINATION OF CASP12, AND DISRUPTION PHENOTYPE.
RX PubMed=18710920; DOI=10.1083/jcb.200711066;
RA Song S., Lee H., Kam T.I., Tai M.L., Lee J.Y., Noh J.Y., Shim S.M.,
RA Seo S.J., Kong Y.Y., Nakagawa T., Chung C.W., Choi D.Y., Oubrahim H.,
RA Jung Y.K.;
RT "E2-25K/Hip-2 regulates caspase-12 in ER stress-mediated Abeta
RT neurotoxicity.";
RL J. Cell Biol. 182:675-684(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Proposed to be involved in
CC ubiquitination and proteolytic processing of NF-kappa-B; in vitro
CC supports ubiquitination of NFKB1. Involved in stabilization of CASP12
CC during ER stress-mediated amyloid-beta neurotoxicity probably by
CC inhibiting proteasome activity; in vitro ubiquitinates CASP12.
CC {ECO:0000269|PubMed:18710920}.
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 {ECO:0000250|UniProtKB:P61085}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, with highest levels found
CC in the mitral cells of the olfactory bulb, the pyramidal cell layer of
CC the hippocampus and the Purkinje cells of the cerebellar cortex.
CC {ECO:0000269|PubMed:10585161}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all stages of brain development and
CC increases significantly between postnatal days 7 and 14.
CC {ECO:0000269|PubMed:10585161}.
CC -!- PTM: Sumoylation at Lys-14 impairs catalytic activity.
CC {ECO:0000250|UniProtKB:P61085}.
CC -!- DISRUPTION PHENOTYPE: Neurons are resistant to amyloid-beta
CC neurotoxicity. Significantly lower CASP12 expression in brain.
CC {ECO:0000269|PubMed:18710920}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; AB011081; BAA24927.1; -; mRNA.
DR EMBL; BC002013; AAH02013.1; -; mRNA.
DR EMBL; BC085311; AAH85311.1; -; mRNA.
DR EMBL; AK006316; BAB24523.1; -; mRNA.
DR CCDS; CCDS39098.1; -.
DR RefSeq; NP_058066.2; NM_016786.4.
DR AlphaFoldDB; P61087; -.
DR BMRB; P61087; -.
DR SMR; P61087; -.
DR BioGRID; 207286; 26.
DR IntAct; P61087; 13.
DR STRING; 10090.ENSMUSP00000122471; -.
DR iPTMnet; P61087; -.
DR PhosphoSitePlus; P61087; -.
DR SwissPalm; P61087; -.
DR REPRODUCTION-2DPAGE; P61087; -.
DR EPD; P61087; -.
DR jPOST; P61087; -.
DR PaxDb; P61087; -.
DR PeptideAtlas; P61087; -.
DR PRIDE; P61087; -.
DR ProteomicsDB; 298061; -.
DR Antibodypedia; 11733; 432 antibodies from 41 providers.
DR DNASU; 53323; -.
DR Ensembl; ENSMUST00000142407; ENSMUSP00000122471; ENSMUSG00000029203.
DR GeneID; 53323; -.
DR KEGG; mmu:53323; -.
DR UCSC; uc008xnu.1; mouse.
DR CTD; 3093; -.
DR MGI; MGI:1858216; Ube2k.
DR VEuPathDB; HostDB:ENSMUSG00000029203; -.
DR eggNOG; KOG0418; Eukaryota.
DR GeneTree; ENSGT00670000098059; -.
DR InParanoid; P61087; -.
DR OMA; HHLKGSF; -.
DR OrthoDB; 1418652at2759; -.
DR PhylomeDB; P61087; -.
DR TreeFam; TF101127; -.
DR Reactome; R-MMU-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 53323; 8 hits in 75 CRISPR screens.
DR ChiTaRS; Ube2k; mouse.
DR PRO; PR:P61087; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P61087; protein.
DR Bgee; ENSMUSG00000029203; Expressed in embryonic brain and 268 other tissues.
DR ExpressionAtlas; P61087; baseline and differential.
DR Genevisible; P61087; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0032433; C:filopodium tip; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; ISO: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; ISO:MGI.
DR GO; GO:0035458; P:cellular response to interferon-beta; ISO:MGI.
DR GO; GO:0010994; P:free ubiquitin chain polymerization; ISO:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; ISO:MGI.
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; IDA:MGI.
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 Acetylation; ATP-binding; Cytoplasm; Isopeptide bond; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW 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_0000082444"
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 ECO:0000255|PROSITE-ProRule:PRU10133"
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 /evidence="ECO:0000250|UniProtKB:P61085"
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 CONFLICT 163
FT /note="T -> P (in Ref. 1; BAA24927)"
FT /evidence="ECO:0000305"
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
