KALRN_RAT
ID KALRN_RAT Reviewed; 2959 AA.
AC P97924; O70135; Q6IV51; Q9JIF1; Q9JIF2; Q9JIG0; Q9JIH3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 3.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Kalirin {ECO:0000303|PubMed:9139723};
DE EC=2.7.11.1;
DE AltName: Full=Huntingtin-associated protein-interacting protein;
DE AltName: Full=PAM COOH-terminal interactor protein 10;
DE Short=P-CIP10;
DE AltName: Full=Protein Duo;
DE AltName: Full=Serine/threonine-protein kinase with Dbl- and pleckstrin homology domain;
GN Name=Kalrn {ECO:0000312|RGD:621865}; Synonyms=Duo, Hapip;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Hippocampus;
RX PubMed=8910496; DOI=10.1074/jbc.271.45.28636;
RA Alam M.R., Caldwell B.D., Johnson R.C., Darlington D.N., Mains R.E.,
RA Eipper B.A.;
RT "Novel proteins that interact with the COOH-terminal cytosolic routing
RT determinants of an integral membrane peptide-processing enzyme.";
RL J. Biol. Chem. 271:28636-28640(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND INTERACTION WITH PAM.
RC TISSUE=Hippocampus;
RX PubMed=9139723; DOI=10.1074/jbc.272.19.12667;
RA Alam M.R., Johnson R.C., Darlington D.N., Hand T.A., Mains R.E.,
RA Eipper B.A.;
RT "Kalirin, a cytosolic protein with spectrin-like and GDP/GTP exchange
RT factor-like domains that interacts with peptidylglycine alpha-amidating
RT monooxygenase, an integral membrane peptide-processing enzyme.";
RL J. Biol. Chem. 272:12667-12675(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=10692441; DOI=10.1074/jbc.275.9.6395;
RA Penzes P., Johnson R.C., Alam M.R., Kambampati V., Mains R.E., Eipper B.A.;
RT "An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is
RT enriched in the postsynaptic density fraction.";
RL J. Biol. Chem. 275:6395-6403(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 5 AND 7), ALTERNATIVE INITIATION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10777487; DOI=10.1074/jbc.m000676200;
RA Johnson R.C., Penzes P., Eipper B.A., Mains R.E.;
RT "Isoforms of kalirin, a neuronal Dbl family member, generated through use
RT of different 5'- and 3'-ends along with an internal translational
RT initiation site.";
RL J. Biol. Chem. 275:19324-19333(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), AND FUNCTION.
RX PubMed=15950621; DOI=10.1016/j.yexcr.2005.03.024;
RA Schiller M.R., Blangy A., Huang J., Mains R.E., Eipper B.A.;
RT "Induction of lamellipodia by Kalirin does not require its guanine
RT nucleotide exchange factor activity.";
RL Exp. Cell Res. 307:402-417(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 638-1216 (ISOFORM 4).
RC TISSUE=Brain cortex, and Hippocampus;
RX PubMed=9285789; DOI=10.1093/hmg/6.9.1519;
RA Colomer V., Engelender S., Sharp A.H., Duan K., Cooper J.K., Lanahan A.,
RA Lyford G., Worley P., Ross C.A.;
RT "Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide,
RT with a rac1 guanine nucleotide exchange factor domain.";
RL Hum. Mol. Genet. 6:1519-1525(1997).
RN [7]
RP FUNCTION, DOMAIN, AND DEVELOPMENTAL STAGE.
RX PubMed=11606631; DOI=10.1523/jneurosci.21-21-08426.2001;
RA Penzes P., Johnson R.C., Kambampati V., Mains R.E., Eipper B.A.;
RT "Distinct roles for the two Rho GDP/GTP exchange factor domains of kalirin
RT in regulation of neurite growth and neuronal morphology.";
RL J. Neurosci. 21:8426-8434(2001).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1772; THR-1785 AND SER-1790,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [9]
RP STRUCTURE BY NMR OF 1617-1707, DOMAIN, AND INTERACTION WITH CRK1.
RX PubMed=16644733; DOI=10.1074/jbc.m512482200;
RA Schiller M.R., Chakrabarti K., King G.F., Schiller N.I., Eipper B.A.,
RA Maciejewski M.W.;
RT "Regulation of RhoGEF activity by intramolecular and intermolecular SH3
RT domain interactions.";
RL J. Biol. Chem. 281:18774-18786(2006).
CC -!- FUNCTION: Promotes the exchange of GDP by GTP. Activates specific Rho
CC GTPase family members, thereby inducing various signaling mechanisms
CC that regulate neuronal shape, growth, and plasticity, through their
CC effects on the actin cytoskeleton. Induces lamellipodia independent of
CC its GEF activity. Isoforms 1 and 7 are necessary for neuronal
CC development and axonal outgrowth. Isoform 6 is required for dendritic
CC spine formation. {ECO:0000269|PubMed:10692441,
CC ECO:0000269|PubMed:11606631, ECO:0000269|PubMed:15950621}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- SUBUNIT: Interacts with the C-terminal of peptidylglycine alpha-
CC amidating monooxygenase (PAM) and with the huntingtin-associated
CC protein 1 (HAP1). Interacts with FASLG (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P97924; P54256: Hap1; NbExp=3; IntAct=EBI-1397166, EBI-994539;
CC P97924-5; Q62765: Nlgn1; NbExp=5; IntAct=EBI-26961214, EBI-7281118;
CC P97924-5; Q99K10: Nlgn1; Xeno; NbExp=2; IntAct=EBI-26961214, EBI-775037;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. Note=Isoform
CC 6 is largely associated with synaptosomal membranes and to punctate
CC structures in cortical neurons. Isoforms 1 and 7 are expressed in
CC neuronal cell bodies, isoform 7 is also found in neuronal processes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=8;
CC Name=1; Synonyms=Kalirin-12A;
CC IsoId=P97924-1; Sequence=Displayed;
CC Name=2; Synonyms=Kalirin-8B, P-CIP10B;
CC IsoId=P97924-2; Sequence=VSP_028891, VSP_028899, VSP_028900;
CC Name=3; Synonyms=Kalirin-8A, P-CIP10A;
CC IsoId=P97924-3; Sequence=VSP_028899, VSP_028900;
CC Name=4;
CC IsoId=P97924-4; Sequence=VSP_028896;
CC Name=5; Synonyms=Delta Kalirin-7;
CC IsoId=P97924-5; Sequence=VSP_028893, VSP_028897, VSP_028898;
CC Name=6; Synonyms=Kalirin-7, Kalirin-7c, HAPIP;
CC IsoId=P97924-6; Sequence=VSP_028892, VSP_028897, VSP_028898;
CC Name=7; Synonyms=Kalirin-9A;
CC IsoId=P97924-7; Sequence=VSP_028901, VSP_028902;
CC Name=8; Synonyms=Kalirin-4a;
CC IsoId=P97924-8; Sequence=VSP_028894, VSP_028895;
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain and nervous system.
CC Isoform 6 is highly enriched in the postsynaptic density fraction of
CC the cerebral cortex. {ECO:0000269|PubMed:10692441,
CC ECO:0000269|PubMed:10777487}.
CC -!- DEVELOPMENTAL STAGE: Isoforms 1 and 7 are prevelant 2 dpp, isoform 6 is
CC not detectable until 2 weeks after birth.
CC {ECO:0000269|PubMed:11606631}.
CC -!- DOMAIN: The two GEF domains catalyze nucleotide exchange for RAC1 and
CC RhoA which are bound by DH1 and DH2 respectively. The two GEF domains
CC appear to play differing roles in neuronal development and axonal
CC outgrowth. SH3 1 binds to the first GEF domain inhibiting GEF activity
CC only when in the presence of a PXXP peptide, suggesting that the SH3
CC domain/peptide interaction mediates binding to GEF1. CRK1 SH3 domain
CC binds to and inhibits GEF1 activity. {ECO:0000269|PubMed:11606631,
CC ECO:0000269|PubMed:16644733}.
CC -!- PTM: Autophosphorylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: Called DUO because the encoded protein is closely
CC related to but shorter than TRIO.
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative splicing.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative initiation at Met-
CC 624 of isoform 6. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 7]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 8]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; U88156; AAB66366.1; -; mRNA.
DR EMBL; U88157; AAB66367.1; -; mRNA.
DR EMBL; AF230644; AAF69144.1; -; mRNA.
DR EMBL; AF229255; AAF66014.1; -; mRNA.
DR EMBL; AF232668; AAF66018.1; -; mRNA.
DR EMBL; AF232669; AAF66019.1; -; mRNA.
DR EMBL; AY621095; AAT39517.1; -; mRNA.
DR EMBL; U94189; AAC15790.1; -; mRNA.
DR PIR; T32732; T32732.
DR PIR; T42098; T42098.
DR RefSeq; NP_114451.2; NM_032062.2.
DR PDB; 1U3O; NMR; -; A=1617-1686.
DR PDB; 2KR9; NMR; -; A=1253-1432.
DR PDB; 5O33; X-ray; 1.64 A; B=1253-1432.
DR PDBsum; 1U3O; -.
DR PDBsum; 2KR9; -.
DR PDBsum; 5O33; -.
DR SMR; P97924; -.
DR BioGRID; 249875; 7.
DR CORUM; P97924; -.
DR IntAct; P97924; 17.
DR MINT; P97924; -.
DR STRING; 10116.ENSRNOP00000039072; -.
DR ChEMBL; CHEMBL2176786; -.
DR iPTMnet; P97924; -.
DR PhosphoSitePlus; P97924; -.
DR PaxDb; P97924; -.
DR PRIDE; P97924; -.
DR DNASU; 84009; -.
DR GeneID; 84009; -.
DR KEGG; rno:84009; -.
DR UCSC; RGD:621865; rat. [P97924-1]
DR CTD; 8997; -.
DR RGD; 621865; Kalrn.
DR VEuPathDB; HostDB:ENSRNOG00000001706; -.
DR eggNOG; KOG0032; Eukaryota.
DR eggNOG; KOG0613; Eukaryota.
DR eggNOG; KOG4240; Eukaryota.
DR InParanoid; P97924; -.
DR OrthoDB; 5761at2759; -.
DR PhylomeDB; P97924; -.
DR Reactome; R-RNO-193648; NRAGE signals death through JNK.
DR Reactome; R-RNO-3928662; EPHB-mediated forward signaling.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR Reactome; R-RNO-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR EvolutionaryTrace; P97924; -.
DR PRO; PR:P97924; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000001706; Expressed in frontal cortex and 20 other tissues.
DR ExpressionAtlas; P97924; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic component of membrane; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007409; P:axonogenesis; IDA:RGD.
DR GO; GO:0007417; P:central nervous system development; IEA:InterPro.
DR GO; GO:0046959; P:habituation; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:HGNC-UCL.
DR GO; GO:0007595; P:lactation; ISO:RGD.
DR GO; GO:0042711; P:maternal behavior; ISO:RGD.
DR GO; GO:0060137; P:maternal process involved in parturition; ISO:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:0098885; P:modification of postsynaptic actin cytoskeleton; IMP:SynGO.
DR GO; GO:0060125; P:negative regulation of growth hormone secretion; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IDA:HGNC-UCL.
DR GO; GO:0007528; P:neuromuscular junction development; ISO:RGD.
DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; IMP:SynGO.
DR GO; GO:0098989; P:NMDA selective glutamate receptor signaling pathway; IMP:SynGO.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISO:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0050773; P:regulation of dendrite development; IDA:RGD.
DR GO; GO:1905274; P:regulation of modification of postsynaptic actin cytoskeleton; IDA:SynGO.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0035176; P:social behavior; ISO:RGD.
DR CDD; cd00063; FN3; 1.
DR CDD; cd00160; RhoGEF; 2.
DR CDD; cd00170; SEC14; 1.
DR CDD; cd00176; SPEC; 5.
DR Gene3D; 1.20.900.10; -; 2.
DR Gene3D; 2.30.29.30; -; 2.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.40.525.10; -; 1.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
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; IPR028570; Kalirin/TRIO.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR PANTHER; PTHR22826:SF104; PTHR22826:SF104; 2.
DR Pfam; PF13716; CRAL_TRIO_2; 1.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00621; RhoGEF; 2.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF00435; Spectrin; 4.
DR SMART; SM00060; FN3; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00325; RhoGEF; 2.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00516; SEC14; 1.
DR SMART; SM00326; SH3; 2.
DR SMART; SM00150; SPEC; 7.
DR SUPFAM; SSF48065; SSF48065; 2.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF52087; SSF52087; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
DR PROSITE; PS50010; DH_2; 2.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS50003; PH_DOMAIN; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing; ATP-binding;
KW Cytoplasm; Cytoskeleton; Disulfide bond;
KW Guanine-nucleotide releasing factor; Immunoglobulin domain; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; SH3 domain;
KW Transferase.
FT CHAIN 1..2959
FT /note="Kalirin"
FT /id="PRO_0000080956"
FT DOMAIN 17..162
FT /note="CRAL-TRIO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT REPEAT 149..290
FT /note="Spectrin 1"
FT /evidence="ECO:0000255"
FT REPEAT 292..399
FT /note="Spectrin 2"
FT /evidence="ECO:0000255"
FT REPEAT 400..517
FT /note="Spectrin 3"
FT /evidence="ECO:0000255"
FT REPEAT 518..621
FT /note="Spectrin 4"
FT /evidence="ECO:0000255"
FT REPEAT 622..752
FT /note="Spectrin 5"
FT /evidence="ECO:0000255"
FT REPEAT 753..870
FT /note="Spectrin 6"
FT /evidence="ECO:0000255"
FT REPEAT 871..977
FT /note="Spectrin 7"
FT /evidence="ECO:0000255"
FT REPEAT 978..1101
FT /note="Spectrin 8"
FT /evidence="ECO:0000255"
FT REPEAT 1102..1207
FT /note="Spectrin 9"
FT /evidence="ECO:0000255"
FT DOMAIN 1254..1429
FT /note="DH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1441..1553
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1619..1684
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 1901..2076
FT /note="DH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 2088..2198
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 2293..2358
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 2444..2537
FT /note="Ig-like C2-type"
FT DOMAIN 2544..2638
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 2657..2911
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 692..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1568..1615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1703..1828
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2216..2280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2385..2427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..719
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1590..1615
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1703..1746
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1755..1777
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1786..1810
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2258..2272
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2385..2407
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2776
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 2663..2671
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 2686
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1723
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60229"
FT MOD_RES 1726
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60229"
FT MOD_RES 1772
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1785
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1790
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1885
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A2CG49"
FT MOD_RES 2234
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60229"
FT DISULFID 2465..2521
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..623
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10777487"
FT /id="VSP_028893"
FT VAR_SEQ 1..4
FT /note="MVLS -> MNPPEGASEEGGAADSDVDAFFRT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8910496,
FT ECO:0000303|PubMed:9139723"
FT /id="VSP_028891"
FT VAR_SEQ 1..4
FT /note="MVLS -> MTDRFWDQWYLWYLRLLRLLDR (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10692441"
FT /id="VSP_028892"
FT VAR_SEQ 705..718
FT /note="DSAVSNNKTPHSSS -> SAWAVIPVGNASG (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:15950621"
FT /id="VSP_028894"
FT VAR_SEQ 719..2959
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:15950621"
FT /id="VSP_028895"
FT VAR_SEQ 923
FT /note="E -> ESLFHATSLQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9285789"
FT /id="VSP_028896"
FT VAR_SEQ 1617..1636
FT /note="LSGGCELTVVLQDFSAAHSS -> DGNLVPRWHLGPGDPFSTYV (in
FT isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:10692441,
FT ECO:0000303|PubMed:10777487"
FT /id="VSP_028897"
FT VAR_SEQ 1637..2959
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:10692441,
FT ECO:0000303|PubMed:10777487"
FT /id="VSP_028898"
FT VAR_SEQ 1860..1899
FT /note="TLEGGSYRGSLKDPTVCLNEGMAPPTPPRNLEEEQKAKAL -> VSGHAGGS
FT RVLPLTSMWLPGPQLGPQISYLHPDFVYSNCI (in isoform 2 and isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:8910496,
FT ECO:0000303|PubMed:9139723"
FT /id="VSP_028899"
FT VAR_SEQ 1900..2959
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:8910496,
FT ECO:0000303|PubMed:9139723"
FT /id="VSP_028900"
FT VAR_SEQ 2372..2376
FT /note="KSCSW -> TLLKP (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:10777487"
FT /id="VSP_028901"
FT VAR_SEQ 2377..2959
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:10777487"
FT /id="VSP_028902"
FT CONFLICT 46
FT /note="T -> S (in Ref. 5; AAT39517)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="N -> Y (in Ref. 5; AAT39517)"
FT /evidence="ECO:0000305"
FT HELIX 1254..1278
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1280..1286
FT /evidence="ECO:0007829|PDB:5O33"
FT STRAND 1287..1289
FT /evidence="ECO:0007829|PDB:5O33"
FT TURN 1293..1297
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1299..1303
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1306..1315
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1317..1323
FT /evidence="ECO:0007829|PDB:5O33"
FT TURN 1324..1326
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1328..1331
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1332..1337
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1339..1343
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1344..1362
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1366..1374
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1380..1384
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1386..1391
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1394..1402
FT /evidence="ECO:0007829|PDB:5O33"
FT HELIX 1409..1428
FT /evidence="ECO:0007829|PDB:5O33"
FT STRAND 1622..1625
FT /evidence="ECO:0007829|PDB:1U3O"
FT STRAND 1645..1650
FT /evidence="ECO:0007829|PDB:1U3O"
FT STRAND 1658..1668
FT /evidence="ECO:0007829|PDB:1U3O"
FT STRAND 1670..1675
FT /evidence="ECO:0007829|PDB:1U3O"
FT HELIX 1676..1678
FT /evidence="ECO:0007829|PDB:1U3O"
SQ SEQUENCE 2959 AA; 336587 MW; 1A3C6770D1CBCC1F CRC64;
MVLSGSFRND GLKASDVLPI LKEKVAFVSG GRDKRGGPIL TFPARTNHDR IRQEDLRKLV
TNLASVPSED VCKRGFTVII DMRGSKWDLI KPLLKTLQEA FPAEIHVALI IKPDNFWQKQ
KTNFGSSKFI FETSMVSVEG LTKLVDPSQL TEEFDGSLDY NHEEWIELRL SLEEFFNSAV
HLLSRLEDLQ EMLARKEFPV DVEGSRRLID EHTQLKKKVL KAPVEELDRE GQRLLQCIRC
SDGFSGRNCI PGSADFQSLV PKITSLLDKL HSTRQHLHQM WHVRKLKLDQ CFQLRLFEQD
AEKMFDWISH NKELFLQSHT EIGVSYQHAL DLQTQHNHFA MNSMNAYVNI NRIMSVASRL
SEAGHYASQQ IKQISTQLDQ EWKSFAAALD ERSTILAMSA VFHQKAEQFL SGVDAWCKMC
SEGGLPSEMQ DLELAIHHHQ SLYEQVTQAY TEVSQDGKAL LDVLQRPLSP GNSESLTATA
NYSKAVHQVL DVVHEVLHHQ RRLESIWQHR KVRLHQRLQL CVFQQDVQQV LDWIENHGEA
FLSKHTGVGK SLHRARALQK RHDDFEEVAQ NTYTNADKLL EAAEQLAQTG ECDPEEIYKA
ARHLEVRIQD FVRRVEQRKL LLDMSVSFHT HTKELWTWME DLQKEVLEDV CADSVDAVQE
LIKQFQQQQT ATLDATLNVI KEGEDLIQQL RSAPPSLGEP TEARDSAVSN NKTPHSSSIS
HIESVLQQLD DAQVQMEELF HERKIKLDIF LQLRIFEQYT IEVTAELDAW NEDLLRQMND
FNTEDLTLAE QRLQRHTERK LAMNNMTFEV IQQGQDLHQY IMEVQASGIE LICEKDVDLA
AQVQELLEFL HEKQHELELN AEQTHKRLEQ CLQLRHLQAE VKQVLGWIRN GESMLNASLV
NASSLSEAEQ LQREHEQFQL AIEKTHQSAL QVQQKAEALL QAGHYDADAI RECAEKVALH
WQQLMLKMED RLKLVNASVA FYKTSEQVCS VLESLEQEYR RDEDWCGGRD KLGPAAEMDH
VIPLLSKHLE QKEAFLKACT LARRNAEVFL KYIHRNNVSM PSVASHTRGP EQQVKAILSE
LLQRENRVLH FWTLKKRRLD QCQQYVVFER SAKQALDWIQ ETGEYYLSTH TSTGETTEET
QELLKEYGEF RVPAKQTKEK VKLLIQLADS FVEKGHIHAT EIRKWVTTVD KHYRDFSLRM
GKYRYTLEKA LGVNTEDNKD LELDIIPASL SDREVKLRDA NHEVNEEKRK SARKKEFIMA
ELLQTEKAYV RDLHECLETY LWEMTSGVEE IPPGILNKEH IIFGNIQEIY DFHNNIFLKE
LEKYEQLPED VGHCFVTWAD KFQMYVTYCK NKPDSNQLIL EHAGTFFDEI QQRHGLANSI
SSYLIKPVQR VTKYQLLLKE LLTCCEEGKG ELKDGLEVML SVPKKANDAM HVSMLEGFDE
NLDVQGELIL QDAFQVWDPK SLIRKGRERH LFLFEISLVF SKEIKDSSGH TKYVYKNKLL
TSELGVTEHV EGDPCKFALW SGRTPSSDNK TVLKASNIET KQEWIKNIRE VIQERIIHLK
GALKEPIQLP KTPAKLRNNS KRDGVEDGDS QGDGSSQPDT ISIASRTSQN TVESDKLSGG
CELTVVLQDF SAAHSSELSI QVGQTVELLE RPSERPGWCL VRTTERSPPQ EGLVPSSTLC
ISHSRSSVEM DCFFPLVKDS YSHSSGENGG KSESVANLQS QPSLNSIHSS PGPKRSTNTL
KKWLTSPVRR LNSGKADGNI KKQKKVRDGR KSFDLGSPKP GDETTPQGDS ADEKSKKGWG
EDEPDEESHT PLPPPMKIFD NDPTQDEMSS LLAARQAPTD VPTAADLVSA IEKLVKSKLT
LEGGSYRGSL KDPTVCLNEG MAPPTPPRNL EEEQKAKALR GRMFVLNELV QTEKDYVKDL
GIVVEGFMKR IEEKGVPEDM RGKEKIVFGN IHQIYDWHKD FFLAELEKCI QEQDRLAQLF
IKHERKLHIY VWYCQNKPRS EYIVAEYDAY FEEVKQEINQ RLTLSDFLIK PIQRITKYQL
LLKDFLRYSE KAGLECSDIE KAVELMCLVP KRCNDMMNLG RLQGFEGTLT AQGKLLQQDT
FYVIELDAGM QSRTKERRVF LFEQIVIFSE LLRKGSLTPG YMFKRSIKMN YLVLEEDVDD
DPCKFALMNR ETSERVILQA ANSDIQQAWV QDINQVLETQ RDFLNALQSP IEYQRKERST
AVIRSQPPRV PQASPRPYSS VPVGSEKPPK GSSYNPPLPP LKISTSNGSP GFDYHQPGDK
FDASKQNDLG GCNGTSTMAV IKDYYALKEN EICVSQGEVV QVLAVNQQNM CLVYQPASDH
SPAAEGWVPG SILAPLTKAT APAESSDESI KKSCSWHTLR MRKRADVENT GKNEATGPRK
PKDILGNKAS VKETNSSEES ECDDLDPNTS MEILNPNFIQ EVAPEFLVPL VDVTCLLGDT
VLLQCKACGR PKPTITWKGP DQNILDTDNS SATYTISSCD SGESTLKICN LMPQDSGIYT
CIATNDHGTA STSATVKVQG VPAAPNRPIA QERSCTSVIL RWLPPASTGN CTISGYTVEY
REEGSQVWQQ SVASTLDTYL VIEDLSPGCP YQFRVSASNP WGISLPSEPS EFVHLPEYDA
AADGATISWK ENFDSAYTEL NEIGRGRFSI VKKCIHKATR KDVAVKFVSK KMKKKEQAAH
EAALLQHLQH PQYVTLHDTY ESPTSYILIL ELMDDGRLLD YLMNHDELME EKVAFYIRDI
MEALQYLHNC RVAHLDIKPE NLLIDLRIPV PRVKLIDLED AVQISGHFHI HHLLGNPEFA
APEVIQGIPV SLGTDIWSIG VLTYVMLSGV SPFLDESKEE TCINVCRVDF SFPHEYFCGV
SNAARDFINV ILQEDFRRRP TAATCLQHPW LQPHNGSYSK IPLDTSRLAC FIERRKHQND
VRPIPNVKSY IVNRVNQGT
