SPEG_MOUSE
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 03-AUG-2022, entry version 178.
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};
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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 iPTMnet; Q62407; -.
DR PhosphoSitePlus; Q62407; -.
DR MaxQB; Q62407; -.
DR PaxDb; Q62407; -.
DR PeptideAtlas; Q62407; -.
DR PRIDE; Q62407; -.
DR ProteomicsDB; 261129; -. [Q62407-1]
DR ProteomicsDB; 261130; -. [Q62407-2]
DR ProteomicsDB; 261131; -. [Q62407-3]
DR ProteomicsDB; 261132; -. [Q62407-4]
DR Antibodypedia; 11575; 80 antibodies from 23 providers.
DR DNASU; 11790; -.
DR Ensembl; ENSMUST00000113590; ENSMUSP00000109220; ENSMUSG00000026207. [Q62407-2]
DR GeneID; 11790; -.
DR KEGG; mmu:11790; -.
DR UCSC; uc007bpa.1; mouse. [Q62407-2]
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; VKKKEQW; -.
DR OrthoDB; 7796at2759; -.
DR PhylomeDB; Q62407; -.
DR BioGRID-ORCS; 11790; 4 hits in 72 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 244 other tissues.
DR ExpressionAtlas; Q62407; baseline and differential.
DR Genevisible; Q62407; MM.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
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:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0060541; P:respiratory system development; IMP:MGI.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 2.60.40.10; -; 11.
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; IPR015726; Ser/Thr_kin_striated-sp.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR47633:SF3; PTHR47633:SF3; 3.
DR Pfam; PF07679; I-set; 8.
DR Pfam; PF00069; Pkinase; 2.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00409; IG; 9.
DR SMART; SM00408; IGc2; 8.
DR SMART; SM00220; S_TKc; 2.
DR SUPFAM; SSF48726; SSF48726; 9.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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
