UBA6_MOUSE
ID UBA6_MOUSE Reviewed; 1053 AA.
AC Q8C7R4;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme 6;
DE Short=Ubiquitin-activating enzyme 6;
DE EC=6.2.1.45 {ECO:0000250|UniProtKB:P22314};
DE AltName: Full=Ubiquitin-activating enzyme E1-like protein 2;
DE Short=E1-L2;
GN Name=Uba6; Synonyms=Ube1l2;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Spinal cord;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH UBD, AND THIOESTER
RP FORMATION.
RX PubMed=17889673; DOI=10.1016/j.molcel.2007.08.020;
RA Chiu Y.-H., Sun Q., Chen Z.J.;
RT "E1-L2 activates both ubiquitin and FAT10.";
RL Mol. Cell 27:1014-1023(2007).
RN [4]
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).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-729, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Activates ubiquitin by first adenylating its C-terminal
CC glycine residue with ATP, and thereafter linking this residue to the
CC side chain of a cysteine residue in E1, yielding a ubiquitin-E1
CC thioester and free AMP. Specific for ubiquitin, does not activate
CC ubiquitin-like peptides. Differs from UBE1 in its specificity for
CC substrate E2 charging. Does not charge cell cycle E2s, such as CDC34
CC (By similarity). Essential for embryonic development. Required for
CC UBD/FAT10 conjugation. {ECO:0000250, ECO:0000269|PubMed:17889673}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
CC = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-
CC L-cysteine.; EC=6.2.1.45; Evidence={ECO:0000250|UniProtKB:P22314};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:P22314}.
CC -!- SUBUNIT: Forms a thioester with UBD in cells stimulated with tumor
CC necrosis factor-alpha (TNFa) and interferon-gamma (IFNg)
CC (PubMed:17889673). {ECO:0000269|PubMed:17889673}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality at early stage.
CC {ECO:0000269|PubMed:17889673}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family.
CC {ECO:0000305}.
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DR EMBL; AK049603; BAC33836.1; -; mRNA.
DR EMBL; BC063048; AAH63048.1; -; mRNA.
DR CCDS; CCDS19378.1; -.
DR RefSeq; NP_766300.1; NM_172712.2.
DR AlphaFoldDB; Q8C7R4; -.
DR SMR; Q8C7R4; -.
DR BioGRID; 231114; 12.
DR IntAct; Q8C7R4; 2.
DR MINT; Q8C7R4; -.
DR STRING; 10090.ENSMUSP00000035328; -.
DR iPTMnet; Q8C7R4; -.
DR PhosphoSitePlus; Q8C7R4; -.
DR SwissPalm; Q8C7R4; -.
DR EPD; Q8C7R4; -.
DR jPOST; Q8C7R4; -.
DR MaxQB; Q8C7R4; -.
DR PaxDb; Q8C7R4; -.
DR PeptideAtlas; Q8C7R4; -.
DR PRIDE; Q8C7R4; -.
DR ProteomicsDB; 298352; -.
DR Antibodypedia; 24140; 305 antibodies from 32 providers.
DR DNASU; 231380; -.
DR Ensembl; ENSMUST00000039373; ENSMUSP00000035328; ENSMUSG00000035898.
DR GeneID; 231380; -.
DR KEGG; mmu:231380; -.
DR UCSC; uc008xxj.2; mouse.
DR CTD; 55236; -.
DR MGI; MGI:1913894; Uba6.
DR VEuPathDB; HostDB:ENSMUSG00000035898; -.
DR eggNOG; KOG2012; Eukaryota.
DR GeneTree; ENSGT00940000158826; -.
DR InParanoid; Q8C7R4; -.
DR OMA; WSHCVEL; -.
DR OrthoDB; 91748at2759; -.
DR PhylomeDB; Q8C7R4; -.
DR TreeFam; TF300586; -.
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; 231380; 14 hits in 77 CRISPR screens.
DR ChiTaRS; Uba6; mouse.
DR PRO; PR:Q8C7R4; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8C7R4; protein.
DR Bgee; ENSMUSG00000035898; Expressed in ear vesicle and 224 other tissues.
DR ExpressionAtlas; Q8C7R4; baseline and differential.
DR Genevisible; Q8C7R4; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019780; F:FAT10 activating enzyme activity; IMP:UniProtKB.
DR GO; GO:0004839; F:ubiquitin activating enzyme activity; IMP:MGI.
DR GO; GO:0021764; P:amygdala development; IMP:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central.
DR GO; GO:0060996; P:dendritic spine development; IMP:MGI.
DR GO; GO:0021766; P:hippocampus development; IMP:MGI.
DR GO; GO:0007612; P:learning; IMP:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR Gene3D; 1.10.10.2660; -; 1.
DR Gene3D; 2.40.30.180; -; 1.
DR Gene3D; 3.10.290.60; -; 1.
DR Gene3D; 3.50.50.80; -; 1.
DR InterPro; IPR032420; E1_4HB.
DR InterPro; IPR032418; E1_FCCH.
DR InterPro; IPR042302; E1_FCCH_sf.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR018965; Ub-activating_enz_E1_C.
DR InterPro; IPR042449; Ub-E1_IAD_1.
DR InterPro; IPR038252; UBA_E1_C_sf.
DR InterPro; IPR019572; UBA_E1_SCCH.
DR InterPro; IPR042063; Ubi_acti_E1_SCCH.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR InterPro; IPR018075; UBQ-activ_enz_E1.
DR InterPro; IPR000011; UBQ/SUMO-activ_enz_E1-like.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF16191; E1_4HB; 1.
DR Pfam; PF16190; E1_FCCH; 1.
DR Pfam; PF09358; E1_UFD; 1.
DR Pfam; PF00899; ThiF; 2.
DR Pfam; PF10585; UBA_e1_thiolCys; 1.
DR PRINTS; PR01849; UBIQUITINACT.
DR SMART; SM00985; UBA_e1_C; 1.
DR SUPFAM; SSF69572; SSF69572; 2.
DR TIGRFAMs; TIGR01408; Ube1; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Ligase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..1053
FT /note="Ubiquitin-like modifier-activating enzyme 6"
FT /id="PRO_0000277798"
FT ACT_SITE 625
FT /note="Glycyl thioester intermediate"
FT BINDING 470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT BINDING 497
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT BINDING 508
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT BINDING 521
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT BINDING 569..570
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:A0AVT1"
FT MOD_RES 54
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A0AVT1"
FT MOD_RES 544
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:A0AVT1"
FT MOD_RES 729
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 737
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0AVT1"
SQ SEQUENCE 1053 AA; 117966 MW; 90529575F77DE09B CRC64;
MERSEPLAVL SCEEASCSSW GACGASKNLP TMTTESLEID DGLYSRQRYV LGDTAMQKMA
KSCVFLSGMG GLGVEIAKNL VLAGIKALTI HDTKKCQAWD LGTNFFLCED DVVNERNRAE
AVLHRIAELN PYVQVSSSSA PLDETTDLSF LEKYQCVVLT EIKLTLQKKI NNFCHSHCPP
IKFISADVHG IWSRLFCDFG DEFEVSDTTG EEPKEIFISN ITQANPGIVT CLESHPHKLE
TGQFLTFREI HGMTGLNGSV QQITVISPFS FSIGDTTKLD PYLHGGIAVQ VKTPKTFCFE
PLESQIKHPR CLIADFSKPE APLEIHLAML ALDQFQENYN RKPNIRCQQD SDELLKLTVS
INETLEEKPE VNADIVHWLS WTAQGFLPPL AAAVGGVASQ EVLKAVTGKF SPLCQWLYLE
AADTVESLGN PGHEEFLPRG DRYDAIRACI GNTLCQKLQN LNIFLVGCGA IGCEMLKNFA
LLGVGTGREK GMVTVTDPDL IEKSNLNRQF LFRPHHIQKP KSYTAAEATL KINPQLKIDA
HLNKVCPATE SIYSDEFYTK QDIIITALDN VEARRYVDSR CLANLRPLLD SGTMGTKGHT
EIIVPQLTES YNSHRDPPEE EIPFCTLKSF PAAIEHTIQW ARDKFESSFS HKPSLFNKFW
QAYPSAEDVL QKIQNGQSLE GCFQVIKLLS RRPRIWSQCV ELARLKFEKY FNHKALQLLH
CFPLETRLKD GSLFWQSPKR PPSPIKFDLN EPLHLSFLQS AAKLYATVYC IPFSEKDLSV
NSLMDILSEV KIEEFKPSNK VVQTDETARK PDHVPVSSED ERNAVFQLEE ALSSNKATKS
DLQMTVLSFE KDDDRNGHID FITAASNLRA KMYSIEPADR FKTKRIAGKI IPAIATSTAA
VSGLVALEMI KVAGGYPFDA YKNCFLNLAI PIIVFTETSE VRKTEIRNGI SFTIWDRWTV
HGKEDFTLSD FINAVKENYG IEPTMVVQGV KMLYVPVMPG HAKRLKLTMH KLVKPSTEKK
YVDLTVSFAP DADGDEDLPG PPVRYYFSHD TNE
