UBA1_HUMAN
ID UBA1_HUMAN Reviewed; 1058 AA.
AC P22314; Q5JRR8; Q96E13;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2002, sequence version 3.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme 1;
DE EC=6.2.1.45 {ECO:0000305|PubMed:1447181};
DE AltName: Full=Protein A1S9;
DE AltName: Full=Ubiquitin-activating enzyme E1;
GN Name=UBA1; Synonyms=A1S9T, UBE1;
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 1), FUNCTION, AND PATHWAY.
RX PubMed=1606621; DOI=10.1247/csf.17.113;
RA Ayusawa D., Kaneda S., Itoh Y., Yasuda H., Murakami Y., Sugasawa K.,
RA Hanaoka F., Seno T.;
RT "Complementation by a cloned human ubiquitin-activating enzyme E1 of the S-
RT phase-arrested mouse FM3A cell mutant with thermolabile E1.";
RL Cell Struct. Funct. 17:113-122(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 136-158;
RP 369-383; 417-430 AND 559-580, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=1986373; DOI=10.1073/pnas.88.1.258;
RA Handley P.M., Mueckler M., Siegel N.R., Ciechanover A., Schwartz A.L.;
RT "Molecular cloning, sequence, and tissue distribution of the human
RT ubiquitin-activating enzyme E1.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:258-262(1991).
RN [3]
RP ERRATUM OF PUBMED:1986373.
RX PubMed=1871145; DOI=10.1073/pnas.88.16.7456c;
RA Handley P.M., Mueckler M., Siegel N.R., Ciechanover A., Schwartz A.L.;
RL Proc. Natl. Acad. Sci. U.S.A. 88:7456-7456(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 257-989.
RX PubMed=2390975; DOI=10.1002/j.1460-2075.1990.tb07483.x;
RA Zacksenhaus E., Sheinin R.;
RT "Molecular cloning, primary structure and expression of the human X linked
RT A1S9 gene cDNA which complements the ts A1S9 mouse L cell defect in DNA
RT replication.";
RL EMBO J. 9:2923-2929(1990).
RN [8]
RP PROTEIN SEQUENCE OF 559-581 AND 924-944, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, AND PATHWAY.
RX PubMed=1447181; DOI=10.1016/s0021-9258(18)35767-3;
RA Cook J.C., Chock P.B.;
RT "Isoforms of mammalian ubiquitin-activating enzyme.";
RL J. Biol. Chem. 267:24315-24321(1992).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=1376922; DOI=10.1073/pnas.89.12.5542;
RA Schwartz A.L., Trausch J.S., Ciechanover A., Slot J.W., Geuze H.;
RT "Immunoelectron microscopic localization of the ubiquitin-activating enzyme
RT E1 in HepG2 cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5542-5546(1992).
RN [11]
RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF ISOFORM 1 AND ISOFORM 2.
RX PubMed=7528747; DOI=10.1016/s0021-9258(20)30113-7;
RA Handley-Gearhart P.M., Stephen A.G., Trausch-Azar J.S., Ciechanover A.,
RA Schwartz A.L.;
RT "Human ubiquitin-activating enzyme, E1. Indication of potential nuclear and
RT cytoplasmic subpopulations using epitope-tagged cDNA constructs.";
RL J. Biol. Chem. 269:33171-33178(1994).
RN [12]
RP PHOSPHORYLATION AT SER-4, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-4
RP AND 8-LYS--ARG-11.
RX PubMed=9099746; DOI=10.1074/jbc.272.16.10895;
RA Stephen A.G., Trausch-Azar J.S., Handley-Gearhart P.M., Ciechanover A.,
RA Schwartz A.L.;
RT "Identification of a region within the ubiquitin-activating enzyme required
RT for nuclear targeting and phosphorylation.";
RL J. Biol. Chem. 272:10895-10903(1997).
RN [13]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [15]
RP INTERACTION WITH GAN.
RX PubMed=16227972; DOI=10.1038/nature04256;
RA Allen E., Ding J., Wang W., Pramanik S., Chou J., Yau V., Yang Y.;
RT "Gigaxonin-controlled degradation of MAP1B light chain is critical to
RT neuronal survival.";
RL Nature 438:224-228(2005).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-46; THR-800 AND
RP SER-835, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP IDENTIFICATION BY MASS 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-810, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-671 AND LYS-980, AND
RP IDENTIFICATION BY MASS 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-810, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=22456334; DOI=10.4161/cc.19978;
RA Moudry P., Lukas C., Macurek L., Hanzlikova H., Hodny Z., Lukas J.,
RA Bartek J.;
RT "Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA
RT damage.";
RL Cell Cycle 11:1573-1582(2012).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, ACETYLATION [LARGE SCALE
RP ANALYSIS] AT ALA-2 (ISOFORM 2), CLEAVAGE OF INITIATOR METHIONINE [LARGE
RP SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]
RP (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-835, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-820, AND IDENTIFICATION BY
RP 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 [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [28]
RP INVOLVEMENT IN VEXAS, VARIANTS VEXAS LEU-41; THR-41 AND VAL-41,
RP CHARACTERIZATION OF VARIANT VEXAS VAL-41, FUNCTION, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF 1-MET--ALA-66; 1-MET--GLY-40; MET-41 AND MET-67.
RX PubMed=33108101; DOI=10.1056/nejmoa2026834;
RA Beck D.B., Ferrada M.A., Sikora K.A., Ombrello A.K., Collins J.C., Pei W.,
RA Balanda N., Ross D.L., Ospina Cardona D., Wu Z., Patel B., Manthiram K.,
RA Groarke E.M., Gutierrez-Rodrigues F., Hoffmann P., Rosenzweig S.,
RA Nakabo S., Dillon L.W., Hourigan C.S., Tsai W.L., Gupta S.,
RA Carmona-Rivera C., Asmar A.J., Xu L., Oda H., Goodspeed W., Barron K.S.,
RA Nehrebecky M., Jones A., Laird R.S., Deuitch N., Rowczenio D., Rominger E.,
RA Wells K.V., Lee C.R., Wang W., Trick M., Mullikin J., Wigerblad G.,
RA Brooks S., Dell'Orso S., Deng Z., Chae J.J., Dulau-Florea A.,
RA Malicdan M.C.V., Novacic D., Colbert R.A., Kaplan M.J., Gadina M.,
RA Savic S., Lachmann H.J., Abu-Asab M., Solomon B.D., Retterer K., Gahl W.A.,
RA Burgess S.M., Aksentijevich I., Young N.S., Calvo K.R., Werner A.,
RA Kastner D.L., Grayson P.C.;
RT "Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory
RT Disease.";
RL N. Engl. J. Med. 383:2628-2638(2020).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 1-439.
RX PubMed=25209502; DOI=10.1080/09168451.2014.923301;
RA Xie S.T.;
RT "Expression, purification, and crystal structure of N-terminal domains of
RT human ubiquitin-activating enzyme (E1).";
RL Biosci. Biotechnol. Biochem. 78:1542-1549(2014).
RN [30]
RP VARIANTS SMAX2 ILE-539 AND GLY-547.
RX PubMed=18179898; DOI=10.1016/j.ajhg.2007.09.009;
RA Ramser J., Ahearn M.E., Lenski C., Yariz K.O., Hellebrand H., von Rhein M.,
RA Clark R.D., Schmutzler R.K., Lichtner P., Hoffman E.P., Meindl A.,
RA Baumbach-Reardon L.;
RT "Rare missense and synonymous variants in UBE1 are associated with X-linked
RT infantile spinal muscular atrophy.";
RL Am. J. Hum. Genet. 82:188-193(2008).
RN [31]
RP VARIANT SMAX2 VAL-557.
RX PubMed=23518311; DOI=10.1016/j.nmd.2013.02.001;
RA Dlamini N., Josifova D.J., Paine S.M., Wraige E., Pitt M., Murphy A.J.,
RA King A., Buk S., Smith F., Abbs S., Sewry C., Jacques T.S., Jungbluth H.;
RT "Clinical and neuropathological features of X-linked spinal muscular
RT atrophy (SMAX2) associated with a novel mutation in the UBA1 gene.";
RL Neuromuscul. Disord. 23:391-398(2013).
CC -!- FUNCTION: Catalyzes the first step in ubiquitin conjugation to mark
CC cellular proteins for degradation through the ubiquitin-proteasome
CC system (PubMed:1606621, PubMed:1447181, PubMed:33108101). Activates
CC ubiquitin by first adenylating its C-terminal glycine residue with ATP,
CC and thereafter linking this residue to the side chain of a cysteine
CC residue in E1, yielding a ubiquitin-E1 thioester and free AMP
CC (PubMed:1447181). Essential for the formation of radiation-induced
CC foci, timely DNA repair and for response to replication stress.
CC Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites
CC (PubMed:22456334). {ECO:0000269|PubMed:1447181,
CC ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334,
CC ECO:0000269|PubMed:33108101}.
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:0000305|PubMed:1447181};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with GAN (via BTB domain).
CC {ECO:0000250, ECO:0000269|PubMed:16227972}.
CC -!- INTERACTION:
CC P22314; Q9H2C0: GAN; NbExp=5; IntAct=EBI-709688, EBI-764342;
CC P22314; P42858: HTT; NbExp=3; IntAct=EBI-709688, EBI-466029;
CC P22314; Q96FW1: OTUB1; NbExp=4; IntAct=EBI-709688, EBI-1058491;
CC P22314; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-709688, EBI-3650647;
CC P22314; P63279: UBE2I; NbExp=2; IntAct=EBI-709688, EBI-80168;
CC P22314; O00308: WWP2; NbExp=3; IntAct=EBI-709688, EBI-743923;
CC P22314; Q76353; Xeno; NbExp=2; IntAct=EBI-709688, EBI-6248077;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1376922}.
CC Mitochondrion {ECO:0000269|PubMed:1376922}. Nucleus
CC {ECO:0000269|PubMed:1376922, ECO:0000269|PubMed:22456334}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:33108101, ECO:0000269|PubMed:7528747,
CC ECO:0000269|PubMed:9099746}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:33108101, ECO:0000269|PubMed:7528747}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=E1a;
CC IsoId=P22314-1; Sequence=Displayed;
CC Name=2; Synonyms=E1b;
CC IsoId=P22314-2; Sequence=VSP_055913;
CC -!- TISSUE SPECIFICITY: Detected in erythrocytes (at protein level).
CC Ubiquitous. {ECO:0000269|PubMed:1986373}.
CC -!- DOMAIN: The first 11 amino acids are essential for phosphorylation and
CC exclusive nuclear localization.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
CC -!- DISEASE: Spinal muscular atrophy X-linked 2 (SMAX2) [MIM:301830]: A
CC lethal infantile form of spinal muscular atrophy, a neuromuscular
CC disorder characterized by degeneration of the anterior horn cells of
CC the spinal cord, leading to symmetrical muscle weakness and atrophy.
CC Clinical features include hypotonia, areflexia, and multiple congenital
CC contractures. {ECO:0000269|PubMed:18179898,
CC ECO:0000269|PubMed:23518311}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: VEXAS syndrome (VEXAS) [MIM:301054]: A sporadic, often fatal,
CC treatment-refractory inflammatory syndrome that develops in late
CC adulthood. Clinical features include fevers, cytopenias, characteristic
CC vacuoles in myeloid and erythroid precursor cells, dysplastic bone
CC marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis,
CC and vasculitis. The disease affects only males and is associated with
CC de novo somatic mutations. {ECO:0000269|PubMed:33108101}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. Somatic variants affecting the initiator methionine of isoform 2
CC are recurrently found in VEXAS patients. These variants cause loss of
CC isoform 2 and production of a shorter isoform with strongly reduced
CC enzymatic activity from a downstream methionine (Met-67).
CC {ECO:0000269|PubMed:33108101}.
CC -!- MISCELLANEOUS: There are two active sites within the E1 molecule,
CC allowing it to accommodate two ubiquitin moieties at a time, with a new
CC ubiquitin forming an adenylate intermediate as the previous one is
CC transferred to the thiol site. {ECO:0000250|UniProtKB:P22515}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family.
CC {ECO:0000305}.
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DR EMBL; X56976; CAA40296.1; -; mRNA.
DR EMBL; M58028; AAA61246.1; -; mRNA.
DR EMBL; AL513366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471164; EAW59290.1; -; Genomic_DNA.
DR EMBL; BC013041; AAH13041.1; -; mRNA.
DR EMBL; X52897; CAA37078.1; -; mRNA.
DR CCDS; CCDS14275.1; -. [P22314-1]
DR PIR; A38564; A38564.
DR RefSeq; NP_003325.2; NM_003334.3. [P22314-1]
DR RefSeq; NP_695012.1; NM_153280.2. [P22314-1]
DR RefSeq; XP_016885269.1; XM_017029780.1. [P22314-1]
DR RefSeq; XP_016885270.1; XM_017029781.1. [P22314-1]
DR PDB; 4P22; X-ray; 2.75 A; A/B=1-439.
DR PDB; 6DC6; X-ray; 3.14 A; A/C=49-1058.
DR PDBsum; 4P22; -.
DR PDBsum; 6DC6; -.
DR AlphaFoldDB; P22314; -.
DR SMR; P22314; -.
DR BioGRID; 113165; 258.
DR DIP; DIP-33686N; -.
DR IntAct; P22314; 171.
DR MINT; P22314; -.
DR STRING; 9606.ENSP00000338413; -.
DR BindingDB; P22314; -.
DR ChEMBL; CHEMBL5924; -.
DR DrugBank; DB04119; Hexatantalum Dodecabromide.
DR DrugBank; DB04216; Quercetin.
DR GlyGen; P22314; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P22314; -.
DR MetOSite; P22314; -.
DR PhosphoSitePlus; P22314; -.
DR SwissPalm; P22314; -.
DR BioMuta; UBA1; -.
DR DMDM; 24418865; -.
DR REPRODUCTION-2DPAGE; IPI00645078; -.
DR CPTAC; CPTAC-136; -.
DR CPTAC; CPTAC-137; -.
DR EPD; P22314; -.
DR jPOST; P22314; -.
DR MassIVE; P22314; -.
DR MaxQB; P22314; -.
DR PaxDb; P22314; -.
DR PeptideAtlas; P22314; -.
DR PRIDE; P22314; -.
DR ProteomicsDB; 53983; -. [P22314-1]
DR Antibodypedia; 345; 428 antibodies from 40 providers.
DR CPTC; P22314; 3 antibodies.
DR DNASU; 7317; -.
DR Ensembl; ENST00000335972.11; ENSP00000338413.6; ENSG00000130985.17. [P22314-1]
DR Ensembl; ENST00000377351.8; ENSP00000366568.4; ENSG00000130985.17. [P22314-1]
DR GeneID; 7317; -.
DR KEGG; hsa:7317; -.
DR MANE-Select; ENST00000335972.11; ENSP00000338413.6; NM_003334.4; NP_003325.2.
DR UCSC; uc004dhj.5; human. [P22314-1]
DR CTD; 7317; -.
DR DisGeNET; 7317; -.
DR GeneCards; UBA1; -.
DR GeneReviews; UBA1; -.
DR HGNC; HGNC:12469; UBA1.
DR HPA; ENSG00000130985; Low tissue specificity.
DR MalaCards; UBA1; -.
DR MIM; 301054; phenotype.
DR MIM; 301830; phenotype.
DR MIM; 314370; gene.
DR neXtProt; NX_P22314; -.
DR OpenTargets; ENSG00000130985; -.
DR Orphanet; 1145; Infantile-onset X-linked spinal muscular atrophy.
DR Orphanet; 596753; VEXAS syndrome.
DR PharmGKB; PA37119; -.
DR VEuPathDB; HostDB:ENSG00000130985; -.
DR eggNOG; KOG2012; Eukaryota.
DR GeneTree; ENSGT00940000158975; -.
DR HOGENOM; CLU_002556_0_0_1; -.
DR InParanoid; P22314; -.
DR OMA; GANLHAF; -.
DR OrthoDB; 91748at2759; -.
DR PhylomeDB; P22314; -.
DR TreeFam; TF300586; -.
DR BioCyc; MetaCyc:HS05465-MON; -.
DR BRENDA; 2.3.2.23; 2681.
DR BRENDA; 6.2.1.45; 2681.
DR BRENDA; 6.2.1.64; 2681.
DR PathwayCommons; P22314; -.
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; P22314; -.
DR SIGNOR; P22314; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7317; 422 hits in 716 CRISPR screens.
DR ChiTaRS; UBA1; human.
DR GeneWiki; UBA1; -.
DR GenomeRNAi; 7317; -.
DR Pharos; P22314; Tbio.
DR PRO; PR:P22314; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P22314; protein.
DR Bgee; ENSG00000130985; Expressed in endometrium epithelium and 210 other tissues.
DR ExpressionAtlas; P22314; baseline and differential.
DR Genevisible; P22314; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0004839; F:ubiquitin activating enzyme activity; IDA:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
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; IPR018074; UBQ-activ_enz_E1_CS.
DR InterPro; IPR033127; UBQ-activ_enz_E1_Cys_AS.
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.
DR PROSITE; PS00536; UBIQUITIN_ACTIVAT_1; 1.
DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Disease variant; Ligase; Mitochondrion;
KW Neurodegeneration; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..1058
FT /note="Ubiquitin-like modifier-activating enzyme 1"
FT /id="PRO_0000194934"
FT REPEAT 63..199
FT /note="1-1"
FT REPEAT 459..611
FT /note="1-2"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 63..611
FT /note="2 approximate repeats"
FT MOTIF 5..11
FT /note="Nuclear localization signal"
FT COMPBIAS 20..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 632
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10132"
FT BINDING 478
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT BINDING 504
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT BINDING 515
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT BINDING 528
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT BINDING 576..577
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P22515"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9099746"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02053"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02053"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 55
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q02053"
FT MOD_RES 528
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q02053"
FT MOD_RES 671
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 800
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 816
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02053"
FT MOD_RES 820
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 835
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 980
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..40
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_055913"
FT VARIANT 41
FT /note="M -> L (in VEXAS; somatic mutation; the underlying
FT nucleotide substitution affects normal alternative
FT translation initiation and leads to aberrant initiation
FT from M-67 to produce a shorter protein with strongly
FT reduced enzymatic activity)"
FT /evidence="ECO:0000269|PubMed:33108101"
FT /id="VAR_085160"
FT VARIANT 41
FT /note="M -> T (in VEXAS; somatic mutation; the underlying
FT nucleotide substitution affects normal alternative
FT translation initiation and leads to aberrant initiation
FT from M-67 to produce a shorter protein with strongly
FT reduced enzymatic activity)"
FT /evidence="ECO:0000269|PubMed:33108101"
FT /id="VAR_085161"
FT VARIANT 41
FT /note="M -> V (in VEXAS; somatic mutation; does not affect
FT ubiquitin activating enzyme activity; does not affect
FT subcellular localization; the underlying nucleotide
FT substitution affects normal alternative translation
FT initiation and leads to aberrant initiation from M-67 to
FT produce a shorter protein with strongly reduced enzymatic
FT activity)"
FT /evidence="ECO:0000269|PubMed:33108101"
FT /id="VAR_085162"
FT VARIANT 447
FT /note="R -> H (in dbSNP:rs2070169)"
FT /id="VAR_043500"
FT VARIANT 539
FT /note="M -> I (in SMAX2; dbSNP:rs80356545)"
FT /evidence="ECO:0000269|PubMed:18179898"
FT /id="VAR_043501"
FT VARIANT 547
FT /note="S -> G (in SMAX2; dbSNP:rs80356546)"
FT /evidence="ECO:0000269|PubMed:18179898"
FT /id="VAR_043502"
FT VARIANT 557
FT /note="E -> V (in SMAX2)"
FT /evidence="ECO:0000269|PubMed:23518311"
FT /id="VAR_071121"
FT MUTAGEN 1..66
FT /note="Missing: Localizes to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:33108101"
FT MUTAGEN 1..40
FT /note="Missing: Localizes to the cytoplasm; when associated
FT with A-67."
FT /evidence="ECO:0000305|PubMed:33108101"
FT MUTAGEN 4
FT /note="S->A: Reduces phosphorylation."
FT /evidence="ECO:0000269|PubMed:9099746"
FT MUTAGEN 8..11
FT /note="KKRR->AAAA: Loss of nuclear localization and a 90-
FT 95% decrease in the phosphorylation."
FT /evidence="ECO:0000269|PubMed:9099746"
FT MUTAGEN 41
FT /note="M->A: Localizes to the nucleus; when associated with
FT A-67."
FT /evidence="ECO:0000269|PubMed:33108101"
FT MUTAGEN 67
FT /note="M->A: Localizes to the nucleus; when associated with
FT A-41. Localizes to the cytoplasm; when associated with 1-
FT M--G-40 del."
FT /evidence="ECO:0000269|PubMed:33108101"
FT CONFLICT 190
FT /note="D -> G (in Ref. 1; CAA40296)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="E -> Q (in Ref. 1; CAA40296)"
FT /evidence="ECO:0000305"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 55..62
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 82..93
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 127..136
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 169..181
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 185..192
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 195..201
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 219..224
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 244..252
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 265..269
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 291..301
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 306..311
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 326..343
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 352..368
FT /evidence="ECO:0007829|PDB:4P22"
FT TURN 371..373
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 380..388
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 395..413
FT /evidence="ECO:0007829|PDB:4P22"
FT STRAND 422..428
FT /evidence="ECO:0007829|PDB:4P22"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:6DC6"
FT TURN 440..444
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 452..455
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 460..467
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 478..490
FT /evidence="ECO:0007829|PDB:6DC6"
FT TURN 491..493
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 499..503
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 510..514
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 528..539
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 545..548
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 555..557
FT /evidence="ECO:0007829|PDB:6DC6"
FT TURN 558..560
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 562..566
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 570..573
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 578..590
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 595..601
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 604..610
FT /evidence="ECO:0007829|PDB:6DC6"
FT TURN 612..614
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 618..620
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 632..635
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 641..655
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 657..668
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 672..678
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 681..683
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 684..695
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 703..718
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 720..728
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 740..745
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 759..776
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 784..791
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 817..820
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 822..832
FT /evidence="ECO:0007829|PDB:6DC6"
FT TURN 836..838
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 858..872
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 880..887
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 895..912
FT /evidence="ECO:0007829|PDB:6DC6"
FT TURN 913..915
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 924..928
FT /evidence="ECO:0007829|PDB:6DC6"
FT TURN 929..932
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 933..937
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 944..947
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 950..953
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 957..963
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 965..969
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 972..981
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 986..992
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 995..999
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 1004..1011
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 1012..1014
FT /evidence="ECO:0007829|PDB:6DC6"
FT HELIX 1015..1022
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 1023..1025
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 1035..1041
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 1045..1049
FT /evidence="ECO:0007829|PDB:6DC6"
FT STRAND 1052..1056
FT /evidence="ECO:0007829|PDB:6DC6"
FT INIT_MET P22314-2:1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES P22314-2:2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
SQ SEQUENCE 1058 AA; 117849 MW; 4B413AAA75FAA562 CRC64;
MSSSPLSKKR RVSGPDPKPG SNCSPAQSVL SEVPSVPTNG MAKNGSEADI DEGLYSRQLY
VLGHEAMKRL QTSSVLVSGL RGLGVEIAKN IILGGVKAVT LHDQGTAQWA DLSSQFYLRE
EDIGKNRAEV SQPRLAELNS YVPVTAYTGP LVEDFLSGFQ VVVLTNTPLE DQLRVGEFCH
NRGIKLVVAD TRGLFGQLFC DFGEEMILTD SNGEQPLSAM VSMVTKDNPG VVTCLDEARH
GFESGDFVSF SEVQGMVELN GNQPMEIKVL GPYTFSICDT SNFSDYIRGG IVSQVKVPKK
ISFKSLVASL AEPDFVVTDF AKFSRPAQLH IGFQALHQFC AQHGRPPRPR NEEDAAELVA
LAQAVNARAL PAVQQNNLDE DLIRKLAYVA AGDLAPINAF IGGLAAQEVM KACSGKFMPI
MQWLYFDALE CLPEDKEVLT EDKCLQRQNR YDGQVAVFGS DLQEKLGKQK YFLVGAGAIG
CELLKNFAMI GLGCGEGGEI IVTDMDTIEK SNLNRQFLFR PWDVTKLKSD TAAAAVRQMN
PHIRVTSHQN RVGPDTERIY DDDFFQNLDG VANALDNVDA RMYMDRRCVY YRKPLLESGT
LGTKGNVQVV IPFLTESYSS SQDPPEKSIP ICTLKNFPNA IEHTLQWARD EFEGLFKQPA
ENVNQYLTDP KFVERTLRLA GTQPLEVLEA VQRSLVLQRP QTWADCVTWA CHHWHTQYSN
NIRQLLHNFP PDQLTSSGAP FWSGPKRCPH PLTFDVNNPL HLDYVMAAAN LFAQTYGLTG
SQDRAAVATF LQSVQVPEFT PKSGVKIHVS DQELQSANAS VDDSRLEELK ATLPSPDKLP
GFKMYPIDFE KDDDSNFHMD FIVAASNLRA ENYDIPSADR HKSKLIAGKI IPAIATTTAA
VVGLVCLELY KVVQGHRQLD SYKNGFLNLA LPFFGFSEPL AAPRHQYYNQ EWTLWDRFEV
QGLQPNGEEM TLKQFLDYFK TEHKLEITML SQGVSMLYSF FMPAAKLKER LDQPMTEIVS
RVSKRKLGRH VRALVLELCC NDESGEDVEV PYVRYTIR
