FLT3_MOUSE
ID FLT3_MOUSE Reviewed; 1000 AA.
AC Q00342;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Receptor-type tyrosine-protein kinase FLT3;
DE EC=2.7.10.1;
DE AltName: Full=FL cytokine receptor;
DE AltName: Full=Fetal liver kinase 2;
DE Short=FLK-2;
DE AltName: Full=Fms-like tyrosine kinase 3;
DE Short=FLT-3;
DE AltName: Full=Tyrosine-protein kinase receptor flk-2;
DE AltName: CD_antigen=CD135;
DE Flags: Precursor;
GN Name=Flt3; Synonyms=Flk-2, Flt-3;
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].
RC TISSUE=Liver;
RX PubMed=1648448; DOI=10.1016/0092-8674(91)90010-v;
RA Matthews W., Jordan C.T., Wiegand G.W., Pardoll D., Lemischka I.R.;
RT "A receptor tyrosine kinase specific to hematopoietic stem and progenitor
RT cell-enriched populations.";
RL Cell 65:1143-1152(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1656368;
RA Rosnet O., Marchetto S., Delapeyriere O., Birnbaum D.;
RT "Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the
RT PDGFR/CSF1R family.";
RL Oncogene 6:1641-1650(1991).
RN [3]
RP CHARACTERIZATION.
RX PubMed=8384358;
RA Maroc N., Rottapel R., Rosnet O., Marchetto S., Lavezzi C., Mannoni P.,
RA Birnbaum D., Dubreuil P.;
RT "Biochemical characterization and analysis of the transforming potential of
RT the FLT3/FLK2 receptor tyrosine kinase.";
RL Oncogene 8:909-918(1993).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=7621074; DOI=10.1016/1074-7613(95)90167-1;
RA Mackarehtschian K., Hardin J.D., Moore K.A., Boast S., Goff S.P.,
RA Lemischka I.R.;
RT "Targeted disruption of the flk2/flt3 gene leads to deficiencies in
RT primitive hematopoietic progenitors.";
RL Immunity 3:147-161(1995).
RN [5]
RP FUNCTION IN REGULATION OF DENDRITIC CELL DEVELOPMENT.
RX PubMed=8920882; DOI=10.1084/jem.184.5.1953;
RA Maraskovsky E., Brasel K., Teepe M., Roux E.R., Lyman S.D., Shortman K.,
RA McKenna H.J.;
RT "Dramatic increase in the numbers of functionally mature dendritic cells in
RT Flt3 ligand-treated mice: multiple dendritic cell subpopulations
RT identified.";
RL J. Exp. Med. 184:1953-1962(1996).
RN [6]
RP INTERACTION WITH FIZ1, AND MUTAGENESIS OF LYS-645.
RX PubMed=10409713; DOI=10.1074/jbc.274.30.21478;
RA Wolf I., Rohrschneider L.R.;
RT "Fiz1, a novel zinc finger protein interacting with the receptor tyrosine
RT kinase Flt3.";
RL J. Biol. Chem. 274:21478-21484(1999).
RN [7]
RP FUNCTION.
RX PubMed=18469816; DOI=10.1038/ni.1615;
RA Waskow C., Liu K., Darrasse-Jeze G., Guermonprez P., Ginhoux F., Merad M.,
RA Shengelia T., Yao K., Nussenzweig M.;
RT "The receptor tyrosine kinase Flt3 is required for dendritic cell
RT development in peripheral lymphoid tissues.";
RL Nat. Immunol. 9:676-683(2008).
RN [8]
RP FUNCTION.
RX PubMed=19286519; DOI=10.1126/science.1170540;
RA Liu K., Victora G.D., Schwickert T.A., Guermonprez P., Meredith M.M.,
RA Yao K., Chu F.F., Randolph G.J., Rudensky A.Y., Nussenzweig M.;
RT "In vivo analysis of dendritic cell development and homeostasis.";
RL Science 324:392-397(2009).
RN [9]
RP FUNCTION IN REGULATION OF DENDRITIC CELL DEVELOPMENT.
RX PubMed=20457904; DOI=10.1073/pnas.1005186107;
RA Eidenschenk C., Crozat K., Krebs P., Arens R., Popkin D., Arnold C.N.,
RA Blasius A.L., Benedict C.A., Moresco E.M., Xia Y., Beutler B.;
RT "Flt3 permits survival during infection by rendering dendritic cells
RT competent to activate NK cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9759-9764(2010).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, DOMAIN, AND ACTIVITY
RP REGULATION.
RX PubMed=21516120; DOI=10.1038/onc.2011.110;
RA Zheng R., Bailey E., Nguyen B., Yang X., Piloto O., Levis M., Small D.;
RT "Further activation of FLT3 mutants by FLT3 ligand.";
RL Oncogene 30:4004-4014(2011).
RN [11]
RP INTERACTION WITH RNF115 AND RNF126.
RX PubMed=23418353; DOI=10.1242/jcs.116129;
RA Smith C.J., Berry D.M., McGlade C.J.;
RT "The E3 ubiquitin ligases RNF126 and Rabring7 regulate endosomal sorting of
RT the epidermal growth factor receptor.";
RL J. Cell Sci. 126:1366-1380(2013).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for the cytokine FLT3LG and regulates differentiation, proliferation
CC and survival of hematopoietic progenitor cells and of dendritic cells.
CC Promotes phosphorylation of SHC1 and AKT1, and activation of the
CC downstream effector MTOR. Promotes activation of RAS signaling and
CC phosphorylation of downstream kinases, including MAPK1/ERK2 and/or
CC MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP,
CC PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type
CC FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations
CC that cause constitutive kinase activity promote cell proliferation and
CC resistance to apoptosis via the activation of multiple signaling
CC pathways. {ECO:0000269|PubMed:18469816, ECO:0000269|PubMed:19286519,
CC ECO:0000269|PubMed:20457904, ECO:0000269|PubMed:21516120,
CC ECO:0000269|PubMed:8920882}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:21516120};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. FLT3LG binding leads to dimerization and activation by
CC autophosphorylation. {ECO:0000269|PubMed:21516120}.
CC -!- SUBUNIT: Monomer in the absence of bound FLT3LG. Homodimer in the
CC presence of bound FLT3LG. Interacts with FIZ1 following ligand
CC activation. Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2.
CC Interacts with PTPRJ/DEP-1 and PTPN11/SHP2 (By similarity). Interacts
CC with RNF115 and RNF126. {ECO:0000250|UniProtKB:P36888,
CC ECO:0000269|PubMed:23418353}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC Endoplasmic reticulum lumen {ECO:0000250}. Note=Constitutively
CC activated mutant forms with internal tandem duplications are less
CC efficiently transported to the cell surface and a significant
CC proportion is retained in an immature form in the endoplasmic reticulum
CC lumen. The activated kinase is rapidly targeted for degradation (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Hematopoietic stem and progenitor cell-enriched
CC populations. Found in brain, placenta and testis.
CC -!- DOMAIN: The juxtamembrane autoregulatory region is important for normal
CC regulation of the kinase activity and for maintaining the kinase in an
CC inactive state in the absence of bound ligand. Upon tyrosine
CC phosphorylation, it mediates interaction with the SH2 domains of
CC numerous signaling partners. In-frame internal tandem duplications
CC (ITDs) result in constitutive activation of the kinase. The activity of
CC the mutant kinase can be stimulated further by FLT3LG binding (By
CC similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated, contains complex N-glycans with sialic acid.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylated on several tyrosine residues in response to
CC FLT3LG binding. FLT3LG binding also increases phosphorylation of mutant
CC kinases that are constitutively activated. Dephosphorylated by
CC PTPRJ/DEP-1, PTPN1, PTPN6/SHP-1, and to a lesser degree by PTPN12.
CC Dephosphorylation is important for export from the endoplasmic
CC reticulum and location at the cell membrane (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein
CC ligase SIAH1 after autophosphorylation, leading to its proteasomal
CC degradation. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are born at the
CC expected Mendelian rate, develop normally and are fertile. They show
CC normal blood cell counts, excepting reduced levels of primitive B-cell
CC progenitors. Mice lacking both Flt3 and Kit show a reduction in both
CC lymphoid and myeloid cell lineages. They appear normal, but are born at
CC a lower frequency than expected and exhibit severely reduced viability
CC after 3 weeks, none surviving more than six weeks.
CC {ECO:0000269|PubMed:7621074}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; M64689; AAA37634.1; -; mRNA.
DR EMBL; X59398; CAA42041.1; -; mRNA.
DR CCDS; CCDS39400.1; -.
DR PIR; A39931; A39931.
DR PIR; S18827; S18827.
DR RefSeq; NP_034359.2; NM_010229.2.
DR AlphaFoldDB; Q00342; -.
DR SMR; Q00342; -.
DR BioGRID; 199707; 3.
DR STRING; 10090.ENSMUSP00000039041; -.
DR BindingDB; Q00342; -.
DR ChEMBL; CHEMBL2034796; -.
DR GlyGen; Q00342; 10 sites.
DR iPTMnet; Q00342; -.
DR PhosphoSitePlus; Q00342; -.
DR PaxDb; Q00342; -.
DR PRIDE; Q00342; -.
DR ProteomicsDB; 266854; -.
DR DNASU; 14255; -.
DR GeneID; 14255; -.
DR KEGG; mmu:14255; -.
DR CTD; 2322; -.
DR MGI; MGI:95559; Flt3.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q00342; -.
DR OrthoDB; 236292at2759; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR Reactome; R-MMU-9706369; Negative regulation of FLT3.
DR Reactome; R-MMU-9706374; FLT3 signaling through SRC family kinases.
DR BioGRID-ORCS; 14255; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Flt3; mouse.
DR PRO; PR:Q00342; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q00342; protein.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004896; F:cytokine receptor activity; IMP:UniProtKB.
DR GO; GO:0019838; F:growth factor binding; IBA:GO_Central.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IDA:MGI.
DR GO; GO:0043621; F:protein self-association; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0019882; P:antigen processing and presentation; IMP:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; IMP:MGI.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; IMP:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0097028; P:dendritic cell differentiation; IMP:UniProtKB.
DR GO; GO:0036145; P:dendritic cell homeostasis; IMP:MGI.
DR GO; GO:0030097; P:hemopoiesis; ISO:MGI.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IMP:MGI.
DR GO; GO:0001776; P:leukocyte homeostasis; IMP:UniProtKB.
DR GO; GO:0048535; P:lymph node development; IMP:MGI.
DR GO; GO:0030098; P:lymphocyte differentiation; IDA:MGI.
DR GO; GO:0046651; P:lymphocyte proliferation; IMP:UniProtKB.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IGI:MGI.
DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IMP:UniProtKB.
DR GO; GO:0045578; P:negative regulation of B cell differentiation; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IMP:MGI.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IMP:MGI.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IMP:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:0009791; P:post-embryonic development; IGI:MGI.
DR GO; GO:0002328; P:pro-B cell differentiation; IMP:UniProtKB.
DR GO; GO:0002572; P:pro-T cell differentiation; IMP:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IGI:MGI.
DR GO; GO:0048536; P:spleen development; IGI:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR030118; FLT3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR PANTHER; PTHR24416:SF356; PTHR24416:SF356; 1.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..1000
FT /note="Receptor-type tyrosine-protein kinase FLT3"
FT /id="PRO_0000016779"
FT TOPO_DOM 28..544
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 545..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565..992
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 254..344
FT /note="Ig-like C2-type"
FT DOMAIN 611..946
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 45..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 592..598
FT /note="Important for normal regulation of the kinase
FT activity and for maintaining the kinase in an inactive
FT state in the absence of ligand binding"
FT /evidence="ECO:0000250"
FT REGION 968..1000
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 814
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 617..625
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 645
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 573
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 575
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 590
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 592
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 600
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 727
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 760
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 769
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 796
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 845
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 958
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 972
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT MOD_RES 1000
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36888"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 474
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 503
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 542
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..66
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 104..115
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 200..207
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 273..331
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 369..408
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 382..393
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT MUTAGEN 645
FT /note="K->A: Loss of kinase activity; no effect on FIZ1-
FT binding."
FT /evidence="ECO:0000269|PubMed:10409713"
FT CONFLICT 150
FT /note="A -> R (in Ref. 1; AAA37634)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="S -> C (in Ref. 1; AAA37634)"
FT /evidence="ECO:0000305"
FT CONFLICT 726
FT /note="F -> S (in Ref. 1; AAA37634)"
FT /evidence="ECO:0000305"
FT CONFLICT 957..991
FT /note="MYQNMGGNVPEHPSIYQNRRPLSREAGSEPPSPQA -> CIRTSIHLPKQAA
FT PQQRGGLRAQSPQR (in Ref. 1; AAA37634)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1000 AA; 113496 MW; E67CA9526D7DEE2F CRC64;
MRALAQRSDR RLLLLVVLSV MILETVTNQD LPVIKCVLIS HENNGSSAGK PSSYRMVRGS
PEDLQCTPRR QSEGTVYEAA TVEVAESGSI TLQVQLATPG DLSCLWVFKH SSLGCQPHFD
LQNRGIVSMA ILNVTETQAG EYLLHIQSEA ANYTVLFTVN VRDTQLYVLR RPYFRKMENQ
DALLCISEGV PEPTVEWVLC SSHRESCKEE GPAVVRKEEK VLHELFGTDI RCCARNALGR
ESTKLFTIDL NQAPQSTLPQ LFLKVGEPLW IRCKAIHVNH GFGLTWELED KALEEGSYFE
MSTYSTNRTM IRILLAFVSS VGRNDTGYYT CSSSKHPSQS ALVTILEKGF INATSSQEEY
EIDPYEKFCF SVRFKAYPRI RCTWIFSQAS FPCEQRGLED GYSISKFCDH KNKPGEYIFY
AENDDAQFTK MFTLNIRKKP QVLANASASQ ASCSSDGYPL PSWTWKKCSD KSPNCTEEIP
EGVWNKKANR KVFGQWVSSS TLNMSEAGKG LLVKCCAYNS MGTSCETIFL NSPGPFPFIQ
DNISFYATIG LCLPFIVVLI VLICHKYKKQ FRYESQLQMI QVTGPLDNEY FYVDFRDYEY
DLKWEFPREN LEFGKVLGSG AFGRVMNATA YGISKTGVSI QVAVKMLKEK ADSCEKEALM
SELKMMTHLG HHDNIVNLLG ACTLSGPVYL IFEYCCYGDL LNYLRSKREK FHRTWTEIFK
EHNFSFYPTF QAHSNSSMPG SREVQLHPPL DQLSGFNGNS IHSEDEIEYE NQKRLAEEEE
EDLNVLTFED LLCFAYQVAK GMEFLEFKSC VHRDLAARNV LVTHGKVVKI CDFGLARDIL
SDSSYVVRGN ARLPVKWMAP ESLFEGIYTI KSDVWSYGIL LWEIFSLGVN PYPGIPVDAN
FYKLIQSGFK MEQPFYATEG IYFVMQSCWA FDSRKRPSFP NLTSFLGCQL AEAEEAMYQN
MGGNVPEHPS IYQNRRPLSR EAGSEPPSPQ AQVKIHRERS
