SIK3_MOUSE
ID SIK3_MOUSE Reviewed; 1369 AA.
AC Q6P4S6; E9PU87; Q641L5; Q66JZ5; Q6ZQ09; Q8K075; Q9CYD5;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Serine/threonine-protein kinase SIK3;
DE EC=2.7.11.1;
DE AltName: Full=Salt-inducible kinase 3;
DE Short=SIK-3;
DE AltName: Full=Serine/threonine-protein kinase QSK;
GN Name=Sik3; Synonyms=Kiaa0999, Qsk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-1369 (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N;
RC TISSUE=Embryonic brain, Embryonic limb, Salivary gland, and Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 318-1369 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-551; SER-591 AND SER-592, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-221; SER-551; SER-591;
RP SER-592; SER-674 AND SER-695, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, INTERACTION WITH HDAC4, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=22318228; DOI=10.1242/dev.072652;
RA Sasagawa S., Takemori H., Uebi T., Ikegami D., Hiramatsu K., Ikegawa S.,
RA Yoshikawa H., Tsumaki N.;
RT "SIK3 is essential for chondrocyte hypertrophy during skeletal development
RT in mice.";
RL Development 139:1153-1163(2012).
RN [8]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1034, AND IDENTIFICATION BY MASS
RP 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).
RN [9]
RP DEVELOPMENTAL STAGE.
RX PubMed=30232230; DOI=10.1126/scitranslmed.aat9356;
RA Csukasi F., Duran I., Barad M., Barta T., Gudernova I., Trantirek L.,
RA Martin J.H., Kuo C.Y., Woods J., Lee H., Cohn D.H., Krejci P., Krakow D.;
RT "The PTH/PTHrP-SIK3 pathway affects skeletogenesis through altered mTOR
RT signaling.";
RL Sci. Transl. Med. 10:0-0(2018).
CC -!- FUNCTION: Positive regulator of mTOR signaling that functions by
CC triggering the degradation of DEPTOR, an mTOR inhibitor (By
CC similarity). Required for chondrocyte hypertrophy during skeletogenesis
CC (PubMed:22318228). Negatively regulates cAMP signaling pathway possibly
CC by acting on CRTC2/TORC2 and CRTC3/TORC3 (By similarity). Prevents
CC HDAC4 translocation to the nucleus (PubMed:22318228).
CC {ECO:0000250|UniProtKB:Q9Y2K2, ECO:0000269|PubMed:22318228}.
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 Evidence={ECO:0000250|UniProtKB:Q9Y2K2};
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; Evidence={ECO:0000250|UniProtKB:Q9Y2K2};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-221.
CC {ECO:0000250|UniProtKB:Q9H0K1}.
CC -!- SUBUNIT: Binds to and is activated by YWHAZ when phosphorylated on Thr-
CC 221 (By similarity). Interacts with 14-3-3 proteins (By similarity).
CC Interacts with HDAC4; this interaction leads to HDAC4 retention in the
CC cytoplasm (PubMed:22318228). Interacts with DEPTOR, MLST8/GbetaL,
CC RICTOR and RPTOR (By similarity). {ECO:0000250|UniProtKB:Q9Y2K2,
CC ECO:0000269|PubMed:22318228}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22318228}.
CC Note=Locates to punctate structures within the cytoplasm on binding to
CC YWHAZ. {ECO:0000250|UniProtKB:Q9Y2K2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P4S6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P4S6-2; Sequence=VSP_020894, VSP_020895;
CC -!- TISSUE SPECIFICITY: Expressed in hypertrophic chondrocytes in the
CC growth plate. {ECO:0000269|PubMed:22318228}.
CC -!- DEVELOPMENTAL STAGE: In the embryo, detected at 15.5 dpc in both
CC prehypertrophic and hypertrophic chondrocytes in developing bones
CC (PubMed:22318228). At postnatal day 1 (P1), in cartilage growth plate,
CC expressed in early proliferating and prehypertrophic chondrocytes. This
CC expression pattern is maintained at least until P21 (at protein level)
CC (PubMed:30232230). {ECO:0000269|PubMed:22318228,
CC ECO:0000269|PubMed:30232230}.
CC -!- PTM: Phosphorylated at Thr-221 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate, but 90% die on the first day after birth. The surviving animals
CC show dwarfism throughout their postnatal life. They exhibit marked
CC expansion of the growth plate and articular cartilage regions in the
CC limbs, accumulation of chondrocytes in the sternum, ribs and spine, and
CC impaired skull bone formation. Although chondrocyte hypertrophy and
CC bone mineralization are markedly delayed, the body size is unaffected
CC during embryogenesis, dwarfism appears as animals age.
CC {ECO:0000269|PubMed:22318228}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION: [Isoform 1]:
CC Sequence=AAH63268.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH80688.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH82313.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK017789; BAB30934.1; -; mRNA.
DR EMBL; AC122273; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116503; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033915; AAH33915.1; -; mRNA.
DR EMBL; BC063268; AAH63268.2; ALT_INIT; mRNA.
DR EMBL; BC080688; AAH80688.1; ALT_INIT; mRNA.
DR EMBL; BC082313; AAH82313.1; ALT_FRAME; mRNA.
DR EMBL; AK129257; BAC98067.1; -; mRNA.
DR CCDS; CCDS23140.2; -. [Q6P4S6-1]
DR RefSeq; NP_081774.3; NM_027498.3.
DR AlphaFoldDB; Q6P4S6; -.
DR SMR; Q6P4S6; -.
DR BioGRID; 214193; 8.
DR IntAct; Q6P4S6; 5.
DR STRING; 10090.ENSMUSP00000121032; -.
DR iPTMnet; Q6P4S6; -.
DR PhosphoSitePlus; Q6P4S6; -.
DR EPD; Q6P4S6; -.
DR jPOST; Q6P4S6; -.
DR MaxQB; Q6P4S6; -.
DR PaxDb; Q6P4S6; -.
DR PeptideAtlas; Q6P4S6; -.
DR PRIDE; Q6P4S6; -.
DR ProteomicsDB; 257248; -. [Q6P4S6-1]
DR ProteomicsDB; 257249; -. [Q6P4S6-2]
DR ProteomicsDB; 344903; -.
DR Antibodypedia; 56803; 167 antibodies from 27 providers.
DR DNASU; 70661; -.
DR Ensembl; ENSMUST00000126865; ENSMUSP00000121032; ENSMUSG00000034135. [Q6P4S6-1]
DR GeneID; 70661; -.
DR KEGG; mmu:70661; -.
DR UCSC; uc009pha.1; mouse. [Q6P4S6-2]
DR CTD; 23387; -.
DR MGI; MGI:2446296; Sik3.
DR VEuPathDB; HostDB:ENSMUSG00000034135; -.
DR eggNOG; KOG0586; Eukaryota.
DR GeneTree; ENSGT00940000157259; -.
DR InParanoid; Q6P4S6; -.
DR OMA; CQQLKED; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q6P4S6; -.
DR TreeFam; TF315213; -.
DR BioGRID-ORCS; 70661; 6 hits in 77 CRISPR screens.
DR ChiTaRS; Sik3; mouse.
DR PRO; PR:Q6P4S6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q6P4S6; protein.
DR Bgee; ENSMUSG00000034135; Expressed in substantia nigra and 225 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0050321; F:tau-protein kinase activity; IBA:GO_Central.
DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IMP:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0035108; P:limb morphogenesis; IMP:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
DR CDD; cd14071; STKc_SIK; 1.
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 InterPro; IPR034672; SIK.
DR InterPro; IPR015940; UBA.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50030; UBA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Magnesium;
KW Metal-binding; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1369
FT /note="Serine/threonine-protein kinase SIK3"
FT /id="PRO_0000252258"
FT DOMAIN 66..317
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 344..384
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT REGION 26..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 775..821
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 942..993
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1314..1338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..49
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 788..821
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 945..962
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 188
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 72..80
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 95
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 71
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2K2"
FT MOD_RES 221
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 469
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2K2"
FT MOD_RES 551
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 591
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 592
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 674
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 914
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2K2"
FT MOD_RES 1026
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2K2"
FT MOD_RES 1034
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..116
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020894"
FT VAR_SEQ 604..1369
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020895"
FT CONFLICT 1090
FT /note="Q -> H (in Ref. 3; AAH63268/AAH80688)"
FT /evidence="ECO:0000305"
FT CONFLICT 1335
FT /note="S -> N (in Ref. 3; AAH63268/AAH80688)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1369 AA; 150659 MW; 6458B2665C4A7B5A CRC64;
MAAAAASGAG GVAVAGAGGA GPAGRLLPPP AAGPPAAPAA VPPAAVPARP TAPASRGSMA
ARIGYYEIDR TIGKGNFAVV KRATHLVTKA KVAIKIIDKS QLDEENLKKI FREVQIMKML
CHPHIIRLYQ VMETERMIYL VTEYASGGEI FDHLVAHGRM AEKEARRKFK QIVTAVYFCH
CRNIVHRDLK AENLLLDANL NIKIADFGFS NLFTPGQLLK TWCGSPPYAA PELFEGKEYD
GPKVDIWSLG VVLYVLVCGA LPFDGSTLQN LRARVLSGKF RIPFFMSTEC EHLIRHMLVL
DPNKRLSMEQ ICRHKWMKLG DADPNFDRLI AECQQLKEER QSDPLNDDVL LAMEDMGLDK
ERTLQSLRSD AYDHYSAIYS LLCDRHKKHK TLRPGALPSM PQAMTFQAPV NLQAEQTGTA
MNLSVPQVQL INPENQIIEP DGAVNLDSDE GEEPSPEALV RYLSMRRHTV GVADPRTEVM
EDLQKLLPGF PGVNPQGPFL QVAPNMNFTH NLLPMQSLQP TGQLEYKEQS LLQPPTLQLL
NGMGPLGRRA SDGGANIQLH AQQLLKRPRG PSPLVTMTPA VPAVTPVDEE SSDGEPDQEA
VQRYLANRSK RHTLAMTSPT AEIPPDLQRQ LGQQSFRSRV WPPHLVPDQH RSTYKDSNTL
HLPTERFSPV RRFSDGAASI QAFKAHLEKM GNSSSIKQLQ QECEQLQKMY GGQVDERTLE
KTQQQHMLYQ QEQHHQILQQ QIQDSICPPQ PSPPLQVACE NQPALLTHQL QRLRIQPSSP
PPNHPSNHLF RQPSNSPPPV SSAMITSHGA TSPSQFQGLP SHGAIFQQQP ENCSPPPSVA
LTCLGLQQAS QSQPVTIQLQ EPVDMLSNMA GTAAGSAGRS IPISPSASQI QIQHRASLMA
PFSYGHRPLS KQLSADSAEA HSLNMNRFSP ANYDQAHLHP HLFSDQSRGS PSSYSPSTGV
GFPPTQALKV PPLDQFPTFP PSAQQQPPHY TTSALQQALL SPTPPDYPRH QQVPHILQGL
LSPRHSLTGH SDIRLPPAEF AQLIKRQQQH RQQQQQQQQQ QEYHELFRHM NQGDAVSLAP
SLGGQNMTEQ QALSYQNADS YHRHHTSPQH ILQIRAQDCI SQGPSPTPTH GYAHQPPLMH
SESMEEDCLC EGLKEGFPDK SSSTLTKGCH NSPLLLCTSG PGDPEPLLGT VSQARELGIH
PYGHQPTATT FSRNKVPSRE SVLGNCLERS SPGQAMELPD HNGLGYPVRP LVSEHLRSRT
LQRHHTIQNS DDAYVQLDTL PGMSLVAGKA LSSARMSDAV LSQSSLMGSQ QFQDEEDEEC
GVSLGHEHPG LGDGSQHLNS SRYPATCVTD IMLSHKHPEV SFSMEQAGV
