ID   SPEG_MOUSE              Reviewed;        3262 AA.
AC   Q62407; Q3TPH8; Q6P5V1; Q80TF7; Q80ZN0; Q8BZF4; Q9EQJ5;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   16-MAY-2006, sequence version 2.
DT   27-MAR-2024, entry version 187.
DE   RecName: Full=Striated muscle-specific serine/threonine-protein kinase;
DE            EC=2.7.11.1;
DE   AltName: Full=Aortic preferentially expressed protein 1;
DE            Short=APEG-1;
GN   Name=Speg; Synonyms=Apeg1, Kiaa1297;
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] (ISOFORM 3), TISSUE SPECIFICITY, SUBCELLULAR
RP   LOCATION, AND INDUCTION.
RC   STRAIN=C57BL/6J;
RX   PubMed=8663449; DOI=10.1074/jbc.271.29.17354;
RA   Hsieh C.-M., Yoshizumi M., Endege W.O., Kho C.-J., Jain M.K., Kashiki S.,
RA   de Los Santos R., Lee W.-S., Perrella M.A., Lee M.-E.;
RT   "APEG-1, a novel gene preferentially expressed in aortic smooth muscle
RT   cells, is down-regulated by vascular injury.";
RL   J. Biol. Chem. 271:17354-17359(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), TISSUE SPECIFICITY,
RP   AND PHOSPHORYLATION.
RC   STRAIN=BALB/cJ;
RX   PubMed=10973969; DOI=10.1074/jbc.m006028200;
RA   Hsieh C.-M., Fukumoto S., Layne M.D., Maemura K., Charles H., Patel A.,
RA   Perrella M.A., Lee M.-E.;
RT   "Striated muscle preferentially expressed genes alpha and beta are two
RT   serine/threonine protein kinases derived from the same gene as the aortic
RT   preferentially expressed gene-1.";
RL   J. Biol. Chem. 275:36966-36973(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J; TISSUE=Spinal ganglion, and Urinary bladder;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 723-3262 (ISOFORM 2).
RC   STRAIN=C57BL/6J; TISSUE=Embryonic brain, and Limb;
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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 2092-3262.
RC   TISSUE=Brain;
RX   PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA   Nakajima D., Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT   The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT   identified by screening of terminal sequences of cDNA clones randomly
RT   sampled from size-fractionated libraries.";
RL   DNA Res. 10:35-48(2003).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1177, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA   Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT   "Comprehensive identification of phosphorylation sites in postsynaptic
RT   density preparations.";
RL   Mol. Cell. Proteomics 5:914-922(2006).
RN   [7]
RP   TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=19118250; DOI=10.1161/circulationaha.108.799536;
RA   Liu X., Ramjiganesh T., Chen Y.H., Chung S.W., Hall S.R., Schissel S.L.,
RA   Padera R.F. Jr., Liao R., Ackerman K.G., Kajstura J., Leri A., Anversa P.,
RA   Yet S.F., Layne M.D., Perrella M.A.;
RT   "Disruption of striated preferentially expressed gene locus leads to
RT   dilated cardiomyopathy in mice.";
RL   Circulation 119:261-268(2009).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375; THR-379; SER-382;
RP   THR-453; SER-457; SER-531; SER-1133; SER-1177; SER-1993; SER-2004;
RP   SER-2019; SER-2020; SER-2379; THR-2383; SER-2442; SER-2447; SER-2451;
RP   SER-2524; SER-2527; THR-2774 AND SER-2944, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, and Lung;
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   [9]
RP   METHYLATION [LARGE SCALE ANALYSIS] AT ARG-33; ARG-2060 AND ARG-2144, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, and Embryo;
RX   PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA   Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA   Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA   Bedford M.T., Comb M.J.;
RT   "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT   methylation.";
RL   Mol. Cell. Proteomics 13:372-387(2014).
CC   -!- FUNCTION: Isoform 3 may have a role in regulating the growth and
CC       differentiation of arterial smooth muscle cells.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1;
CC   -!- SUBUNIT: Interacts with MTM1 (By similarity). Isoform 3 is found as a
CC       monomer or homodimer. {ECO:0000250|UniProtKB:Q15772}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage, Alternative splicing; Named isoforms=4;
CC       Name=1; Synonyms=SPEG-beta;
CC         IsoId=Q62407-1; Sequence=Displayed;
CC       Name=2; Synonyms=BPEG;
CC         IsoId=Q62407-2; Sequence=VSP_018265, VSP_018266, VSP_018267,
CC                                  VSP_018268;
CC       Name=3; Synonyms=APEG1;
CC         IsoId=Q62407-3; Sequence=VSP_018264, VSP_018267;
CC       Name=4; Synonyms=SPEG-alpha;
CC         IsoId=Q62407-4; Sequence=VSP_018264;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is preferentially expressed in striated
CC       muscle. Non-kinase form such as isoform 3 is predominantly expressed in
CC       the aorta. Isoform 3 appears to be expressed only in highly
CC       differentiated ASMC in normal vessel walls and down-regulated in
CC       dedifferentiated ASMC in vivo. In response to vascular injuries ASMC
CC       dedifferentiate and change from a quiescent and contractile phenotype
CC       to a proliferative and synthetic phenotype. This proliferation of
CC       vascular smooth muscle cells is one of the most prominent features of
CC       atherosclerosis. Isoform 1 and isoform 4 are expressed in
CC       cardiomyocytes of the developing heart. {ECO:0000269|PubMed:10973969,
CC       ECO:0000269|PubMed:19118250, ECO:0000269|PubMed:8663449}.
CC   -!- INDUCTION: Isoform 3 is quickly down-regulated in response to vascular
CC       injury, when ASMC cells change from a quiescent to a proliferative
CC       phenotype. {ECO:0000269|PubMed:8663449}.
CC   -!- PTM: May be autophosphorylated. {ECO:0000269|PubMed:10973969}.
CC   -!- DISRUPTION PHENOTYPE: Mice lacking SPEG demonstrate dilation of right
CC       and left atria and ventricles, cardiac hypertrophy, myofibril
CC       degeneration, and a marked decrease in cardiac function. Moreover,
CC       mutant mice exhibit significant neonatal mortality.
CC       {ECO:0000269|PubMed:19118250}.
CC   -!- MISCELLANEOUS: Expression is under the tight control of the locus
CC       control region (LCRs).
CC   -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative promoter usage.
CC       {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative promoter usage.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC       protein kinase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAG34791.1; Type=Frameshift; 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; U57098; AAC52666.1; -; mRNA.
DR   EMBL; AF215896; AAG34791.1; ALT_FRAME; mRNA.
DR   EMBL; AK035543; BAC29098.1; -; mRNA.
DR   EMBL; AK164360; BAE37758.1; -; mRNA.
DR   EMBL; BC048698; AAH48698.3; -; mRNA.
DR   EMBL; BC062643; AAH62643.1; -; mRNA.
DR   EMBL; AK122488; BAC65770.1; -; mRNA.
DR   CCDS; CCDS35626.1; -. [Q62407-1]
DR   CCDS; CCDS48292.1; -. [Q62407-2]
DR   RefSeq; NP_001078839.1; NM_001085370.1.
DR   RefSeq; NP_001078840.1; NM_001085371.1. [Q62407-2]
DR   RefSeq; NP_001166948.1; NM_001173477.1.
DR   BioGRID; 198144; 10.
DR   IntAct; Q62407; 2.
DR   STRING; 10090.ENSMUSP00000084361; -.
DR   GlyGen; Q62407; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q62407; -.
DR   PhosphoSitePlus; Q62407; -.
DR   MaxQB; Q62407; -.
DR   PaxDb; 10090-ENSMUSP00000084361; -.
DR   PeptideAtlas; Q62407; -.
DR   ProteomicsDB; 261129; -. [Q62407-1]
DR   ProteomicsDB; 261130; -. [Q62407-2]
DR   ProteomicsDB; 261131; -. [Q62407-3]
DR   ProteomicsDB; 261132; -. [Q62407-4]
DR   Antibodypedia; 11575; 83 antibodies from 23 providers.
DR   DNASU; 11790; -.
DR   Ensembl; ENSMUST00000113590.8; ENSMUSP00000109220.2; ENSMUSG00000026207.17. [Q62407-2]
DR   GeneID; 11790; -.
DR   KEGG; mmu:11790; -.
DR   UCSC; uc007bpa.1; mouse. [Q62407-2]
DR   AGR; MGI:109282; -.
DR   CTD; 10290; -.
DR   MGI; MGI:109282; Speg.
DR   VEuPathDB; HostDB:ENSMUSG00000026207; -.
DR   eggNOG; KOG0032; Eukaryota.
DR   eggNOG; KOG0613; Eukaryota.
DR   GeneTree; ENSGT00940000161126; -.
DR   HOGENOM; CLU_332308_0_0_1; -.
DR   InParanoid; Q62407; -.
DR   OMA; TWPWPLP; -.
DR   OrthoDB; 4215065at2759; -.
DR   PhylomeDB; Q62407; -.
DR   BioGRID-ORCS; 11790; 4 hits in 77 CRISPR screens.
DR   ChiTaRS; Speg; mouse.
DR   PRO; PR:Q62407; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q62407; Protein.
DR   Bgee; ENSMUSG00000026207; Expressed in ascending aorta and 246 other cell types or tissues.
DR   ExpressionAtlas; Q62407; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0055013; P:cardiac muscle cell development; IMP:MGI.
DR   GO; GO:0072359; P:circulatory system development; IMP:MGI.
DR   GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR   GO; GO:0042692; P:muscle cell differentiation; IBA:GO_Central.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0060541; P:respiratory system development; IMP:MGI.
DR   CDD; cd00063; FN3; 2.
DR   CDD; cd20975; IgI_APEG-1_like; 1.
DR   CDD; cd14108; STKc_SPEG_rpt1; 1.
DR   CDD; cd14111; STKc_SPEG_rpt2; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 11.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR013098; Ig_I-set.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR47633:SF7; IG-LIKE DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR47633; IMMUNOGLOBULIN; 1.
DR   Pfam; PF07679; I-set; 8.
DR   Pfam; PF00069; Pkinase; 2.
DR   Pfam; PF16650; SPEG_u2; 1.
DR   SMART; SM00060; FN3; 2.
DR   SMART; SM00409; IG; 9.
DR   SMART; SM00408; IGc2; 8.
DR   SMART; SM00220; S_TKc; 2.
DR   SUPFAM; SSF49265; Fibronectin type III; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 9.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 2.
DR   PROSITE; PS50853; FN3; 3.
DR   PROSITE; PS50835; IG_LIKE; 8.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 2.
DR   Genevisible; Q62407; MM.
PE   1: Evidence at protein level;
KW   Alternative promoter usage; Alternative splicing; ATP-binding;
KW   Differentiation; Disulfide bond; Immunoglobulin domain; Kinase;
KW   Methylation; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..3262
FT                   /note="Striated muscle-specific serine/threonine-protein
FT                   kinase"
FT                   /id="PRO_0000072667"
FT   DOMAIN          45..126
FT                   /note="Ig-like 1"
FT   DOMAIN          727..815
FT                   /note="Ig-like 2"
FT   DOMAIN          874..963
FT                   /note="Ig-like 3"
FT   DOMAIN          968..1062
FT                   /note="Ig-like 4"
FT   DOMAIN          1069..1157
FT                   /note="Ig-like 5"
FT   DOMAIN          1193..1283
FT                   /note="Ig-like 6"
FT   DOMAIN          1290..1387
FT                   /note="Fibronectin type-III 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          1389..1485
FT                   /note="Ig-like 7"
FT   DOMAIN          1490..1578
FT                   /note="Ig-like 8"
FT   DOMAIN          1606..1859
FT                   /note="Protein kinase 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          2586..2676
FT                   /note="Ig-like 9"
FT   DOMAIN          2683..2777
FT                   /note="Fibronectin type-III 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          2865..2968
FT                   /note="Fibronectin type-III 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          2946..3213
FT                   /note="Protein kinase 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..33
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          155..185
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          198..226
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          280..720
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          814..875
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1162..1185
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1913..2571
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2756..2832
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2857..2899
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2912..2960
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        159..185
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        297..321
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        343..363
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        368..385
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        406..422
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        464..492
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        500..521
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        590..604
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        666..688
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        814..833
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        853..875
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2204..2232
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2245..2265
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2335..2349
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2356..2371
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2465..2484
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2510..2543
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2792..2810
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2814..2832
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2877..2899
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2914..2930
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2937..2957
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1724
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        3080
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         1612..1620
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         1635
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         33
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   MOD_RES         141
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         368
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         375
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         379
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         382
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         385
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         423
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         453
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         457
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         463
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         493
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q15772"
FT   MOD_RES         511
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         531
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         554
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         1133
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         1177
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:16452087,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         1993
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2004
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2019
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2020
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2042
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2060
FT                   /note="Asymmetric dimethylarginine; alternate"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   MOD_RES         2060
FT                   /note="Omega-N-methylarginine; alternate"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   MOD_RES         2114
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2135
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2144
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   MOD_RES         2182
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2207
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2379
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2383
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2413
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2417
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2441
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2442
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2447
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2451
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2524
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2527
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2562
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2774
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2777
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63638"
FT   MOD_RES         2944
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   DISULFID        994..1046
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        1413..1469
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        2608..2660
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VAR_SEQ         1..854
FT                   /note="Missing (in isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:10973969,
FT                   ECO:0000303|PubMed:8663449"
FT                   /id="VSP_018264"
FT   VAR_SEQ         1..106
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10973969,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072"
FT                   /id="VSP_018265"
FT   VAR_SEQ         107..131
FT                   /note="VYSCSAQNERGQASCEAVLTVLEVR -> MKKLWVKKRFQKTGHSRRAFGRL
FT                   TH (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10973969,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072"
FT                   /id="VSP_018266"
FT   VAR_SEQ         966..967
FT                   /note="AH -> GE (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10973969,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072,
FT                   ECO:0000303|PubMed:8663449"
FT                   /id="VSP_018267"
FT   VAR_SEQ         968..3262
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10973969,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072"
FT                   /id="VSP_018268"
FT   CONFLICT        3237
FT                   /note="L -> R (in Ref. 3; BAC65770)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   3262 AA;  354343 MW;  0387BDD6518B7BB7 CRC64;
     MQKARGTRGE DAGTRAPPSP GVPPKRAKVG AGRGVLVTGD GAGAPVFLRP LKNAAVCAGS
     DVRLRVVVSG TPQPSLSWFR DGQLLPPPAP EPSCLWLRSC GAQDAGVYSC SAQNERGQAS
     CEAVLTVLEV RDSETAEDDI SDVPGTQRLE LRDDRAFSTP TGGSDTLVGT SLDTPPTSVT
     GTSEEQVSWW GSGQTVLEQE AGSGGGTRPL PGSPRQAQTT GAGPRHLGVE PLVRASRANL
     VGASWGSEDS LSVASDLYGS AFSLYRGRAL SIHVSIPPSG LHREEPDLQP QPASDALRPR
     PALPPPSKSA LLPPPSPRVG KRALPGPSTQ PPATPTSPHR RAQEPSLPED ITTTEEKRGK
     KPKSSGPSLA GTVESRPQTP LSEASGRLSA LGRSPRLVRA GSRILDKLQF FEERRRSLER
     SDSPPAPLRP WVPLRKARSL EQPKSEGGAA WGTPEASQEE LRSPRGSVAE RRRLFQQKAA
     SLDERTRQRS ATSDLELRFA QELGRIRRST SREELVRSHE SLRATLQRAP SPREPGEPPL
     FSRPSTPKTS RAVSPAATQP PPPSGAGKSG DEPGRPRSRG PVGRTEPGEG PQQEIKRRDQ
     FPLTRSRAIQ ECRSPVPPYT ADPPESRTKA PSGRKREPPA QAVRFLPWAT PGVEDSVLPQ
     TLEKNRAGPE AEKRLRRGPE EDGPWGPWDR RGTRSQGKGR RARPTSPELE SSDDSYVSAG
     EEPLEAPVFE IPLQNMVVAP GADVLLKCII TANPPPQVSW KKDGSMLHSE GRLLIRAEGE
     RHTLLLREAQ AADAGSYTAT ATNELGQATC ASSLAVRPGG STSPFSSPIT SDEEYLSPPE
     EFPEPGETWP RTPTMKLSPS QDHDSSDSSS KAPPTFKVSL MDQSVREGQD VIMSIRVQGE
     PKPVVSWLRN RQPVRPDQRR FAEEAEGGLC RLRILAAERG DAGFYTCKAV NEYGARQCEA
     RLEVRAHPES RSLAVLAPLQ DVDVGAGEMA LFECLVAGPA DVEVDWLCRG RLLQPALLKC
     KMHFDGRKCK LLLTSVHEDD SGVYTCKLST AKDELTCSAR LTVRPSLAPL FTRLLEDVEV
     LEGRAARLDC KISGTPPPSV TWTHFGHPVN EGDNLRLRQD GGLHSLHIAR VGSEDEGLYE
     VSATNTHGQA HCSAQLYVEE PRTAASGPSS KLEKMPSIPE EPEHGDLERL SIPDFLRPLQ
     DLEVGLAKEA MLECQVTGLP YPTISWFHNG HRIQSSDDRR MTQYRDIHRL VFPAVGPQHA
     GVYKSVIANK LGKAACYAHL YVTDVVPGPP DGAPEVVAVT GRMVTLSWNP PRSLDMAIDP
     DSLTYTVQHQ VLGSDQWTAL VTGLREPAWA ATGLKKGIQH IFRVLSSSGK SSSKPSAPSE
     PVQLLEHGPP LEEAPAVLDK QDIVYVVEGQ PACVTVTFNH VEAQVVWRSC RGALLEARTG
     VYELSQPDDD QYCLRICRVS RRDLGPLTCS ARNRHGTKAC SVTLELAEAP RFESIMEDVE
     VGPGETARFA VVVEGKPLPD IMWYKDEVLL AESNHVSFVY EENECSLVLL SAGSQDGGVY
     TCTARNLAGE VSCKAELSVL SAQTAMEVEG VGEDEEHRGR RLSDYYDIHQ EIGRGAFSYL
     RRVVERSSGL EFAAKFIPSQ AKPKASARRE ARLLARLQHG CVLYFHEAFE RRRGLVIVTE
     LCTEELLERM ARKPTVCESE TRTYMRQVLE GICYLHQSHV LHLDVKPENL LVWDGAGGEE
     QVRICDFGNA QELTPGEPQY CQYGTPEFVA PEIVNQSPVS GVTDIWPVGV VAFLCLTGIS
     PFVGENDRTT LMNIRNYNVA FEETTFLSLS REARGFLIKV LVQDRLRPTA EETLEHPWFK
     TEAKGAEVST DHLKLFLSRR RWQRSQISYK CHLVLRPIPE LLRAPPERVW VAMPRRQPPS
     GGLSSSSDSE EEELEELPSV PRPLQPEFSG SRVSLTDIPT EDEALGTPEA GAATPMDWQE
     QERTPSKDQE APSPEALPSP GQESPDGPSP RRPELRRGSS AESALPRVGS REPGRSLHKA
     ASVELPQRRS PSPGATRLTR GGLGEGEYAQ RLQALRQRLL RGGPEDGKVS GLRGPLLESL
     GGRARDPRMA RAASSEAAPH HQPPPESRGL QKSSSFSQGE AEPRGRHRRA GAPLEIPVAR
     LGARRLQESP SLSALSETQP PSPARPSVPK LSITKSPEPS AVTSRDSPQP PEPQPVPEKV
     PEPKPEPVRA AKPAQPPLAL QMPTQPLTPY AQIMQSLQLS SPTLSPQDPA VPPSEPKPHA
     AVFARVASPP PGVSEKRVPS ARTPPVLAEK ARVPTVPPRP GSSLSGSIEN LESEAVFEAK
     FKRSRESPLS RGLRLLSRSR SEERGPFRGA EDDGIYRPSP AGTPLELVRR PERSRSVQDL
     RVAGEPGLVR RLSLSLSQKL RRTPPGQRHP AWESRSGDGE SSEGGSSARA SPVLAVRRRL
     SSTLERLSSR LQRSGSSEDS GGASGRSTPL FGRLRRATSE GESLRRLGVP HNQLGSQTGA
     TTPSAESLGS EASGTSGSSA PGESRSRHRW GLSRLRKDKG LSQPNLSSSV QEDLGHQYVP
     SESDFPPVFH IKLKDQVLLE GEAATLLCLP AACPAPRISW MKDKQSLRSE PSVVIVSCKD
     GRQLLSIPRA GKRHAGLYEC SATNVLGSIT SSCTVAVARI PGKLAPPEVP QTYHDTALVV
     WKPGDGRAPC TYTLERRVDG ESVWHPVSSG IPDCYYNVTQ LPVGVTVRFR VACSNRAGQG
     PFSNPSEKVF IRGTPDSPAQ PAAAPRDAPV TSGPTRAPPP DSPTSLAPTP ALAPPASQAS
     TLSPSTSSMS ANQALSSLKA VGPPPATPPR KHRGLLATQQ AEPSPPSIVV TPSEPRSFVP
     DTGTLTPTSS PQGVKPAPSS TSLYMVTSFV SAPPAPQAPA PEPPPEPTKV TVRSLSPAKE
     VVSSPTPEST TLRQGPPQKP YTFLEEKARG RFGVVRSCRE NATGRTFVAK IVPYAAEGKR
     RVLQEYEVLR TLHHERLMSL HEAYITPRYL VLIAESCGNR ELLCGLSDRF RYSEDDVATY
     VVQLLQGLDY LHGHHVLHLD IKPDNLLLAA DNALKIVDFG SAQPYNPQAL KPLGHRTGTL
     EFMAPEMVKG DPIGSATDIW GAGVLTYIML SGYSPFYEPD PQETEARIVG GRFDAFQLYP
     NTSQSATLFL RKVLSVHPWS RPSLQDCLAH PWLQDAYLMK LRRQTLTFTT NRLKEFLGEQ
     RRRRAEAATR HKVLLRSYPG SP
//