ID UBA6_HUMAN Reviewed; 1052 AA. AC A0AVT1; A6N8M7; B2RAV3; Q4W5K0; Q6UV21; Q86T78; Q86TC7; Q8N5T3; Q8N9E4; AC Q9H3T7; Q9NVC9; DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot. DT 28-NOV-2006, sequence version 1. DT 27-MAR-2024, entry version 153. 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=Monocyte protein 4; DE Short=MOP-4; DE AltName: Full=Ubiquitin-activating enzyme E1-like protein 2; DE Short=E1-L2; GN Name=UBA6; Synonyms=MOP4, UBE1L2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=15202508; DOI=10.1093/abbs/36.3.227; RA Zhu H., Zhou Z.-M., Huo R., Huang X.-Y., Lu L., Lin M., Wang L.-R., RA Zhou Y.-D., Li J.-M., Sha J.-H.; RT "Identification and characteristics of a novel E1 like gene nUBE1L in human RT testis."; RL Acta Biochim. Biophys. Sin. 36:227-234(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-224, FUNCTION, TISSUE RP SPECIFICITY, AND MUTAGENESIS OF CYS-625. RX PubMed=17597759; DOI=10.1038/nature05902; RA Jin J., Li X., Gygi S.P., Harper J.W.; RT "Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme RT charging."; RL Nature 447:1135-1138(2007). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Blood; RA Takayama K., Fujii Y., Ukai Y., Yoshimoto M.; RT "Molecular and biological characterization of a new ubiquitin-activating RT enzyme E1 like protein, MOP-4 which is highly expressed in human RT monocytes."; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND VARIANT RP THR-224. RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-224. RC TISSUE=Skeletal muscle; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC 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 [8] RP FUNCTION, INTERACTION WITH UBD, THIOESTER FORMATION, AND MUTAGENESIS OF RP CYS-625. 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 [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-544, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54; SER-301 AND SER-737, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP INTERACTION WITH UBD. RX PubMed=25422469; DOI=10.1073/pnas.1403383111; RA Theng S.S., Wang W., Mah W.C., Chan C., Zhuo J., Gao Y., Qin H., Lim L., RA Chong S.S., Song J., Lee C.G.; RT "Disruption of FAT10-MAD2 binding inhibits tumor progression."; RL Proc. Natl. Acad. Sci. U.S.A. 111:E5282-E5291(2014). 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 Essential for embryonic development. Required for UBD/FAT10 CC conjugation. Isoform 2 may play a key role in ubiquitin system and may CC influence spermatogenesis and male fertility. CC {ECO:0000269|PubMed:15202508, ECO:0000269|PubMed:17597759, CC 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, PubMed:25422469). {ECO:0000269|PubMed:17889673, CC ECO:0000269|PubMed:25422469}. CC -!- INTERACTION: CC A0AVT1; Q6NT76: HMBOX1; NbExp=3; IntAct=EBI-5282516, EBI-2549423; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=A0AVT1-1; Sequence=Displayed; CC Name=2; Synonyms=nUBE1L; CC IsoId=A0AVT1-2; Sequence=VSP_023083; CC Name=3; CC IsoId=A0AVT1-3; Sequence=VSP_023086, VSP_023087; CC Name=4; CC IsoId=A0AVT1-4; Sequence=VSP_023084, VSP_023085; CC -!- TISSUE SPECIFICITY: Widely expressed. Isoform 2 is predominantly CC expressed in testis with higher expression in adult testis than in CC fetal testis. {ECO:0000269|PubMed:15202508, CC ECO:0000269|PubMed:17597759}. CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA91824.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY359880; AAQ63403.1; -; mRNA. DR EMBL; EF623993; ABR25253.1; -; mRNA. DR EMBL; AB014773; BAB19785.1; -; mRNA. DR EMBL; AK001670; BAA91824.1; ALT_INIT; mRNA. DR EMBL; AK094969; BAC04463.1; -; mRNA. DR EMBL; AK314371; BAG37000.1; -; mRNA. DR EMBL; AL832015; CAD89908.1; -; mRNA. DR EMBL; AL832458; CAD89959.1; -; mRNA. DR EMBL; AC079880; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC096720; AAY40999.1; -; Genomic_DNA. DR EMBL; BC031637; AAH31637.1; -; mRNA. DR EMBL; BC126484; AAI26485.1; -; mRNA. DR EMBL; BC126486; AAI26487.1; -; mRNA. DR CCDS; CCDS3516.1; -. [A0AVT1-1] DR RefSeq; NP_060697.4; NM_018227.5. [A0AVT1-1] DR PDB; 7PVN; X-ray; 2.71 A; A/B=1-1052. DR PDB; 7PYV; X-ray; 3.27 A; A/B=1-623, A/B=900-1052. DR PDB; 7SOL; X-ray; 2.25 A; A/C=37-1052. DR PDBsum; 7PVN; -. DR PDBsum; 7PYV; -. DR PDBsum; 7SOL; -. DR AlphaFoldDB; A0AVT1; -. DR SMR; A0AVT1; -. DR BioGRID; 120529; 193. DR DIP; DIP-57633N; -. DR IntAct; A0AVT1; 17. DR MINT; A0AVT1; -. DR STRING; 9606.ENSP00000313454; -. DR BindingDB; A0AVT1; -. DR ChEMBL; CHEMBL2321622; -. DR GlyCosmos; A0AVT1; 1 site, 1 glycan. DR GlyGen; A0AVT1; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; A0AVT1; -. DR MetOSite; A0AVT1; -. DR PhosphoSitePlus; A0AVT1; -. DR SwissPalm; A0AVT1; -. DR BioMuta; UBA6; -. DR EPD; A0AVT1; -. DR jPOST; A0AVT1; -. DR MassIVE; A0AVT1; -. DR MaxQB; A0AVT1; -. DR PaxDb; 9606-ENSP00000313454; -. DR PeptideAtlas; A0AVT1; -. DR ProteomicsDB; 26; -. [A0AVT1-1] DR ProteomicsDB; 27; -. [A0AVT1-2] DR ProteomicsDB; 28; -. [A0AVT1-3] DR ProteomicsDB; 29; -. [A0AVT1-4] DR Pumba; A0AVT1; -. DR Antibodypedia; 24140; 328 antibodies from 32 providers. DR DNASU; 55236; -. DR Ensembl; ENST00000322244.10; ENSP00000313454.4; ENSG00000033178.13. [A0AVT1-1] DR Ensembl; ENST00000420827.2; ENSP00000399234.2; ENSG00000033178.13. [A0AVT1-3] DR GeneID; 55236; -. DR KEGG; hsa:55236; -. DR MANE-Select; ENST00000322244.10; ENSP00000313454.4; NM_018227.6; NP_060697.4. DR UCSC; uc003hdg.5; human. [A0AVT1-1] DR AGR; HGNC:25581; -. DR CTD; 55236; -. DR DisGeNET; 55236; -. DR GeneCards; UBA6; -. DR HGNC; HGNC:25581; UBA6. DR HPA; ENSG00000033178; Low tissue specificity. DR MIM; 611361; gene. DR neXtProt; NX_A0AVT1; -. DR OpenTargets; ENSG00000033178; -. DR PharmGKB; PA162407690; -. DR VEuPathDB; HostDB:ENSG00000033178; -. DR eggNOG; KOG2012; Eukaryota. DR GeneTree; ENSGT00940000158826; -. DR HOGENOM; CLU_002556_0_0_1; -. DR InParanoid; A0AVT1; -. DR OMA; WSHCVEL; -. DR OrthoDB; 20494at2759; -. DR PhylomeDB; A0AVT1; -. DR TreeFam; TF300586; -. DR BRENDA; 6.2.1.45; 2681. DR PathwayCommons; A0AVT1; -. DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; A0AVT1; -. DR SIGNOR; A0AVT1; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 55236; 253 hits in 1157 CRISPR screens. DR ChiTaRS; UBA6; human. DR GeneWiki; UBE1L2; -. DR GenomeRNAi; 55236; -. DR Pharos; A0AVT1; Tchem. DR PRO; PR:A0AVT1; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; A0AVT1; Protein. DR Bgee; ENSG00000033178; Expressed in adrenal tissue and 193 other cell types or tissues. DR ExpressionAtlas; A0AVT1; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019780; F:FAT10 activating enzyme activity; IMP:UniProtKB. DR GO; GO:0016779; F:nucleotidyltransferase activity; IBA:GO_Central. DR GO; GO:0004792; F:thiosulfate sulfurtransferase activity; IBA:GO_Central. DR GO; GO:0004839; F:ubiquitin activating enzyme activity; IEA:UniProtKB-EC. DR GO; GO:0021764; P:amygdala development; IEA:Ensembl. DR GO; GO:0060996; P:dendritic spine development; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0007612; P:learning; IEA:Ensembl. DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl. 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 CDD; cd01491; Ube1_repeat1; 1. DR CDD; cd01490; Ube1_repeat2; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 2.40.30.180; Ubiquitin-activating enzyme E1, FCCH domain; 1. DR Gene3D; 3.50.50.80; Ubiquitin-activating enzyme E1, inactive adenylation domain, subdomain 1; 1. DR Gene3D; 3.40.50.12550; Ubiquitin-activating enzyme E1, inactive adenylation domain, subdomain 2; 1. DR Gene3D; 1.10.10.2660; Ubiquitin-activating enzyme E1, SCCH domain; 1. DR Gene3D; 3.10.290.60; Ubiquitin-activating enzyme E1, UFD domain; 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 NCBIfam; TIGR01408; Ube1; 1. DR PANTHER; PTHR10953; UBIQUITIN-ACTIVATING ENZYME E1; 1. DR PANTHER; PTHR10953:SF186; UBIQUITIN-LIKE MODIFIER-ACTIVATING ENZYME 6; 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_SCCH; 1. DR PRINTS; PR01849; UBIQUITINACT. DR SMART; SM00985; UBA_e1_C; 1. DR SUPFAM; SSF69572; Activating enzymes of the ubiquitin-like proteins; 2. DR Genevisible; A0AVT1; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Ligase; KW Nucleotide-binding; Phosphoprotein; Reference proteome; KW Ubl conjugation pathway. FT CHAIN 1..1052 FT /note="Ubiquitin-like modifier-activating enzyme 6" FT /id="PRO_0000277797" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 625 FT /note="Glycyl thioester intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10132" 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:0007744|PubMed:19413330" FT MOD_RES 54 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 301 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 544 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 729 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8C7R4" FT MOD_RES 737 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..474 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15202508" FT /id="VSP_023083" FT VAR_SEQ 321..340 FT /note="APLEIHTAMLALDQFQEKYS -> VNKHFAGLREAAESEMRISE (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_023084" FT VAR_SEQ 341..1052 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_023085" FT VAR_SEQ 369..389 FT /note="PDVNADIVHWLSWTAQGFLSP -> VTIEIYGCPNICLLIHKCSVY (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023086" FT VAR_SEQ 390..1052 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023087" FT VARIANT 224 FT /note="A -> T (in dbSNP:rs10010188)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:17597759, ECO:0000269|PubMed:17974005" FT /id="VAR_030594" FT MUTAGEN 625 FT /note="C->A,S: Impairs ubiquitin activation." FT /evidence="ECO:0000269|PubMed:17597759, FT ECO:0000269|PubMed:17889673" FT CONFLICT 14 FT /note="E -> K (in Ref. 5; CAD89908)" FT /evidence="ECO:0000305" FT CONFLICT 140 FT /note="V -> A (in Ref. 5; CAD89908)" FT /evidence="ECO:0000305" FT CONFLICT 197 FT /note="C -> Y (in Ref. 4; BAC04463)" FT /evidence="ECO:0000305" FT CONFLICT 234 FT /note="N -> D (in Ref. 5; CAD89959)" FT /evidence="ECO:0000305" FT CONFLICT 297 FT /note="V -> A (in Ref. 4; BAC04463)" FT /evidence="ECO:0000305" FT CONFLICT 645 FT /note="F -> V (in Ref. 1; AAQ63403)" FT /evidence="ECO:0000305" FT CONFLICT 803 FT /note="Q -> H (in Ref. 4; BAA91824)" FT /evidence="ECO:0000305" FT CONFLICT 821 FT /note="E -> G (in Ref. 5; CAD89959)" FT /evidence="ECO:0000305" FT CONFLICT 868 FT /note="L -> P (in Ref. 5; CAD89908)" FT /evidence="ECO:0000305" FT CONFLICT 905 FT /note="V -> G (in Ref. 1; AAQ63403)" FT /evidence="ECO:0000305" FT CONFLICT 909 FT /note="M -> K (in Ref. 5; CAD89959)" FT /evidence="ECO:0000305" FT CONFLICT 920 FT /note="A -> V (in Ref. 3; BAB19785)" FT /evidence="ECO:0000305" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 45..51 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 53..59 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 63..67 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 71..83 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 86..91 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 98..102 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 109..113 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 118..127 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 133..138 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 144..146 FT /evidence="ECO:0007829|PDB:7PVN" FT HELIX 148..153 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 155..159 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 164..175 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 177..179 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 182..190 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 192..198 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 201..209 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 215..221 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 224..226 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 228..231 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 233..235 FT /evidence="ECO:0007829|PDB:7PYV" FT STRAND 244..248 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:7PVN" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 264..267 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:7PVN" FT STRAND 287..291 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 295..298 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 302..307 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 316..320 FT /evidence="ECO:0007829|PDB:7PVN" FT HELIX 321..339 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 348..364 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 365..367 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 373..382 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 388..407 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 415..417 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 422..424 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 426..428 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 433..436 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 444..450 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 452..459 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 462..466 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 470..482 FT /evidence="ECO:0007829|PDB:7SOL" FT TURN 483..485 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 488..490 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 492..496 FT /evidence="ECO:0007829|PDB:7SOL" FT TURN 506..508 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 514..516 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 521..532 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 538..541 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 547..549 FT /evidence="ECO:0007829|PDB:7SOL" FT TURN 550..552 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 555..560 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 562..566 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 571..583 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 588..594 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 597..603 FT /evidence="ECO:0007829|PDB:7SOL" FT TURN 605..607 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 611..613 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 624..628 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 634..649 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 651..663 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 666..674 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 682..690 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 696..711 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 713..721 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 733..735 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 752..768 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 775..778 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 780..788 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 818..833 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 840..842 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 858..872 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 880..887 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 895..913 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 918..920 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 923..927 FT /evidence="ECO:0007829|PDB:7SOL" FT TURN 928..931 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 932..936 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 944..947 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 950..952 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 958..961 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 968..979 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 984..988 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 991..994 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 996..998 FT /evidence="ECO:0007829|PDB:7PVN" FT HELIX 1001..1006 FT /evidence="ECO:0007829|PDB:7SOL" FT HELIX 1009..1013 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 1017..1028 FT /evidence="ECO:0007829|PDB:7SOL" FT STRAND 1032..1034 FT /evidence="ECO:0007829|PDB:7PVN" FT STRAND 1038..1048 FT /evidence="ECO:0007829|PDB:7SOL" SQ SEQUENCE 1052 AA; 117970 MW; 9F9C70EABA750A71 CRC64; MEGSEPVAAH QGEEASCSSW GTGSTNKNLP IMSTASVEID DALYSRQRYV LGDTAMQKMA KSHVFLSGMG GLGLEIAKNL VLAGIKAVTI HDTEKCQAWD LGTNFFLSED DVVNKRNRAE AVLKHIAELN PYVHVTSSSV PFNETTDLSF LDKYQCVVLT EMKLPLQKKI NDFCRSQCPP IKFISADVHG IWSRLFCDFG DEFEVLDTTG EEPKEIFISN ITQANPGIVT CLENHPHKLE TGQFLTFREI NGMTGLNGSI QQITVISPFS FSIGDTTELE PYLHGGIAVQ VKTPKTVFFE SLERQLKHPK CLIVDFSNPE APLEIHTAML ALDQFQEKYS RKPNVGCQQD SEELLKLATS ISETLEEKPD VNADIVHWLS WTAQGFLSPL AAAVGGVASQ EVLKAVTGKF SPLCQWLYLE AADIVESLGK PECEEFLPRG DRYDALRACI GDTLCQKLQN LNIFLVGCGA IGCEMLKNFA LLGVGTSKEK GMITVTDPDL IEKSNLNRQF LFRPHHIQKP KSYTAADATL KINSQIKIDA HLNKVCPTTE TIYNDEFYTK QDVIITALDN VEARRYVDSR CLANLRPLLD SGTMGTKGHT EVIVPHLTES YNSHRDPPEE EIPFCTLKSF PAAIEHTIQW ARDKFESSFS HKPSLFNKFW QTYSSAEEVL QKIQSGHSLE GCFQVIKLLS RRPRNWSQCV ELARLKFEKY FNHKALQLLH CFPLDIRLKD GSLFWQSPKR PPSPIKFDLN EPLHLSFLQN AAKLYATVYC IPFAEEDLSA DALLNILSEV KIQEFKPSNK VVQTDETARK PDHVPISSED ERNAIFQLEK AILSNEATKS DLQMAVLSFE KDDDHNGHID FITAASNLRA KMYSIEPADR FKTKRIAGKI IPAIATTTAT VSGLVALEMI KVTGGYPFEA YKNCFLNLAI PIVVFTETTE VRKTKIRNGI SFTIWDRWTV HGKEDFTLLD FINAVKEKYG IEPTMVVQGV KMLYVPVMPG HAKRLKLTMH KLVKPTTEKK YVDLTVSFAP DIDGDEDLPG PPVRYYFSHD TD //