ID SHIP2_RAT Reviewed; 1257 AA.
AC Q9WVR3; Q9R1V2;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 24-JAN-2024, entry version 145.
DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 {ECO:0000305};
DE EC=3.1.3.86 {ECO:0000269|PubMed:11238900};
DE AltName: Full=Inositol polyphosphate phosphatase-like protein 1 {ECO:0000250|UniProtKB:O15357};
DE Short=INPPL-1 {ECO:0000250|UniProtKB:O15357};
DE AltName: Full=Protein 51C {ECO:0000250|UniProtKB:O15357};
DE AltName: Full=SH2 domain-containing inositol 5'-phosphatase 2 {ECO:0000250|UniProtKB:O15357};
DE Short=SH2 domain-containing inositol phosphatase 2 {ECO:0000250|UniProtKB:O15357};
DE Short=SHIP-2 {ECO:0000250|UniProtKB:O15357};
GN Name=Inppl1 {ECO:0000312|RGD:68396};
GN Synonyms=Ship2 {ECO:0000303|PubMed:10381377};
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), FUNCTION, AND PHOSPHORYLATION.
RC STRAIN=Sprague-Dawley;
RX PubMed=10381377; DOI=10.1006/bbrc.1999.0888;
RA Ishihara H., Sasaoka T., Hori H., Wada T., Hirai H., Haruta T.,
RA Kobayashi M.;
RT "Molecular cloning of rat SH2-containing inositol phosphatase 2 (SHIP2) and
RT its role in the regulation of insulin signaling.";
RL Biochem. Biophys. Res. Commun. 260:265-272(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10648902; DOI=10.1016/s0169-328x(99)00311-3;
RA Kudo M., Saito S., Owada Y., Suzaki H., Kondo H.;
RT "Localization of mRNA for SHIP2, SH2 domain-containing inositol
RT polyphosphate 5-phosphatase, in the brain of developing and mature rats.";
RL Brain Res. Mol. Brain Res. 75:172-177(2000).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11238900; DOI=10.1128/mcb.21.5.1633-1646.2001;
RA Wada T., Sasaoka T., Funaki M., Hori H., Murakami S., Ishiki M., Haruta T.,
RA Asano T., Ogawa W., Ishihara H., Kobayashi M.;
RT "Overexpression of SH2-containing inositol phosphatase 2 results in
RT negative regulation of insulin-induced metabolic actions in 3T3-L1
RT adipocytes via its 5'-phosphatase catalytic activity.";
RL Mol. Cell. Biol. 21:1633-1646(2001).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-987.
RX PubMed=12351701; DOI=10.1210/me.2002-0083;
RA Ishihara H., Sasaoka T., Ishiki M., Wada T., Hori H., Kagawa S.,
RA Kobayashi M.;
RT "Membrane localization of Src homology 2-containing inositol 5'-phosphatase
RT 2 via Shc association is required for the negative regulation of insulin
RT signaling in Rat1 fibroblasts overexpressing insulin receptors.";
RL Mol. Endocrinol. 16:2371-2381(2002).
RN [5]
RP FUNCTION.
RX PubMed=17535963; DOI=10.1083/jcb.200609017;
RA Aoki K., Nakamura T., Inoue T., Meyer T., Matsuda M.;
RT "An essential role for the SHIP2-dependent negative feedback loop in
RT neuritogenesis of nerve growth factor-stimulated PC12 cells.";
RL J. Cell Biol. 177:817-827(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132, AND IDENTIFICATION BY
RP 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 [7]
RP VARIANT CYS-1142, AND POLYMORPHISM.
RX PubMed=12086927; DOI=10.2337/diabetes.51.7.2012;
RA Marion E., Kaisaki P.J., Pouillon V., Gueydan C., Levy J.C., Bodson A.,
RA Krzentowski G., Daubresse J.-C., Mockel J., Behrends J., Servais G.,
RA Szpirer C., Kruys V., Gauguier D., Schurmans S.;
RT "The gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for
RT type 2 diabetes in rat and man.";
RL Diabetes 51:2012-2017(2002).
CC -!- FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically
CC hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate
CC (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively
CC regulating the PI3K (phosphoinositide 3-kinase) pathways
CC (PubMed:11238900, PubMed:17535963). Required for correct mitotic
CC spindle orientation and therefore progression of mitosis (By
CC similarity). Plays a central role in regulation of PI3K-dependent
CC insulin signaling, although the precise molecular mechanisms and
CC signaling pathways remain unclear (PubMed:11238900). While
CC overexpression reduces both insulin-stimulated MAP kinase and Akt
CC activation, its absence does not affect insulin signaling or GLUT4
CC trafficking (PubMed:12351701, PubMed:10381377). Confers resistance to
CC dietary obesity (By similarity). May act by regulating AKT2, but not
CC AKT1, phosphorylation at the plasma membrane (By similarity). Part of a
CC signaling pathway that regulates actin cytoskeleton remodeling (By
CC similarity). Required for the maintenance and dynamic remodeling of
CC actin structures as well as in endocytosis, having a major impact on
CC ligand-induced EGFR internalization and degradation (By similarity).
CC Participates in regulation of cortical and submembraneous actin by
CC hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (By
CC similarity). Regulates cell adhesion and cell spreading (By
CC similarity). Required for HGF-mediated lamellipodium formation, cell
CC scattering and spreading (By similarity). Acts as a negative regulator
CC of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1
CC activation (By similarity). Acts as a regulator of neuritogenesis by
CC regulating PtdIns(3,4,5)P3 level and is required to form an initial
CC protrusive pattern, and later, maintain proper neurite outgrowth
CC (PubMed:17535963). Acts as a negative regulator of the FC-gamma-RIIA
CC receptor (FCGR2A) (By similarity). Mediates signaling from the FC-
CC gamma-RIIB receptor (FCGR2B), playing a central role in terminating
CC signal transduction from activating immune/hematopoietic cell receptor
CC systems (By similarity). Involved in EGF signaling pathway (By
CC similarity). Upon stimulation by EGF, it is recruited by EGFR and
CC dephosphorylates PtdIns(3,4,5)P3 (By similarity). Plays a negative role
CC in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity
CC (By similarity). Down-regulates Fc-gamma-R-mediated phagocytosis in
CC macrophages independently of INPP5D/SHIP1 (By similarity). In
CC macrophages, down-regulates NF-kappa-B-dependent gene transcription by
CC regulating macrophage colony-stimulating factor (M-CSF)-induced
CC signaling (By similarity). Plays a role in the localization of AURKA
CC and NEDD9/HEF1 to the basolateral membrane at interphase in polarized
CC cysts, thereby mediates cell cycle homeostasis, cell polarization and
CC cilia assembly (By similarity). Additionally promotion of cilia growth
CC is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2
CC (By similarity). Promotes formation of apical membrane-initiation sites
CC during the initial stages of lumen formation via Rho family-induced
CC actin filament organization and CTNNB1 localization to cell-cell
CC contacts (By similarity). May also hydrolyze PtdIns(1,3,4,5)P4, and
CC could thus affect the levels of the higher inositol polyphosphates like
CC InsP6. Involved in endochondral ossification (By similarity).
CC {ECO:0000250|UniProtKB:F1PNY0, ECO:0000250|UniProtKB:O15357,
CC ECO:0000250|UniProtKB:Q6P549, ECO:0000269|PubMed:10381377,
CC ECO:0000269|PubMed:11238900, ECO:0000269|PubMed:12351701,
CC ECO:0000269|PubMed:17535963}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-
CC trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:25528,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57658,
CC ChEBI:CHEBI:57836; EC=3.1.3.86;
CC Evidence={ECO:0000269|PubMed:11238900};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529;
CC Evidence={ECO:0000305|PubMed:11238900};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-
CC trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43548,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83416,
CC ChEBI:CHEBI:83417; Evidence={ECO:0000250|UniProtKB:O15357};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43549;
CC Evidence={ECO:0000250|UniProtKB:O15357};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-
CC 3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-
CC (1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43556,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83420,
CC ChEBI:CHEBI:83422; Evidence={ECO:0000250|UniProtKB:O15357};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43557;
CC Evidence={ECO:0000250|UniProtKB:O15357};
CC -!- ACTIVITY REGULATION: Activated upon translocation to the sites of
CC synthesis of PtdIns(3,4,5)P3 in the membrane. Enzymatic activity is
CC enhanced in the presence of phosphatidylserine (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with tyrosine phosphorylated form of SHC1 (By
CC similarity). Interacts with EGFR (By similarity). Upon stimulation by
CC the EGF signaling pathway, it forms a complex with SHC1 and EGFR (By
CC similarity). Interacts with cytoskeletal protein SORBS3/vinexin,
CC promoting its localization to the periphery of cells (By similarity).
CC Forms a complex with filamin (FLNA or FLNB), actin, GPIb (GP1BA or
CC GP1BB) that regulates cortical and submembraneous actin (By
CC similarity). Interacts with c-Met/MET, when c-Met/MET is phosphorylated
CC on 'Tyr-1356' (By similarity). Interacts with p130Cas/BCAR1 (By
CC similarity). Interacts with CENTD3/ARAP3 via its SAM domain (By
CC similarity). Interacts with c-Cbl/CBL and CAP/SORBS1 (By similarity).
CC Interacts with activated EPHA2 receptor (By similarity). Interacts with
CC receptors FCGR2A (By similarity). Interacts with FCGR2B (By
CC similarity). Interacts with tyrosine kinase ABL1 (By similarity).
CC Interacts with tyrosine kinase TEC (By similarity). Interacts with
CC CSF1R (By similarity). Interacts (via N-terminus) with SH3YL1 (via SH3
CC domain) (By similarity). Interacts (via SH2 domain) with tyrosine
CC phosphorylated KLRC1 (via ITIM) (By similarity). Interacts with
CC NEDD9/HEF1 (By similarity). {ECO:0000250|UniProtKB:F1PNY0,
CC ECO:0000250|UniProtKB:O15357, ECO:0000250|UniProtKB:Q6P549}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12351701}.
CC Cytoplasm, cytoskeleton {ECO:0000250}. Membrane
CC {ECO:0000269|PubMed:12351701}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12351701}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:O15357}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:O15357}. Basal cell membrane
CC {ECO:0000250|UniProtKB:F1PNY0}. Nucleus {ECO:0000250|UniProtKB:D7PF45}.
CC Nucleus speckle {ECO:0000250|UniProtKB:D7PF45}. Cytoplasm,
CC cytoskeleton, spindle pole {ECO:0000250|UniProtKB:F1PNY0}.
CC Note=Translocates to membrane ruffles when activated, translocation is
CC probably due to different mechanisms depending on the stimulus and cell
CC type. Partly translocated via its SH2 domain which mediates interaction
CC with tyrosine phosphorylated receptors such as the FC-gamma-RIIB
CC receptor (FCGR2B). Tyrosine phosphorylation may also participate in
CC membrane localization. Insulin specifically stimulates its
CC redistribution from the cytosol to the plasma membrane. Recruited to
CC the membrane following M-CSF stimulation. In activated spreading
CC platelets, localizes with actin at filopodia, lamellipodia and the
CC central actin ring.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9WVR3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9WVR3-2; Sequence=VSP_027986;
CC -!- DOMAIN: The SH2 domain interacts with tyrosine phosphorylated forms of
CC proteins such as SHC1 or FCGR2A (By similarity). It also mediates the
CC interaction with p130Cas/BCAR1 (By similarity).
CC {ECO:0000250|UniProtKB:O15357}.
CC -!- DOMAIN: The NPXY sequence motif found in many tyrosine-phosphorylated
CC proteins is required for the specific binding of the PID domain.
CC {ECO:0000250|UniProtKB:Q9ES52}.
CC -!- PTM: Tyrosine phosphorylated by the members of the SRC family after
CC exposure to a diverse array of extracellular stimuli such as insulin,
CC growth factors such as EGF or PDGF, chemokines, integrin ligands and
CC hypertonic and oxidative stress. May be phosphorylated upon IgG
CC receptor FCGR2B-binding. Phosphorylated at Tyr-987 following cell
CC attachment and spreading. Phosphorylated at Tyr-1161 following EGF
CC signaling pathway stimulation (By similarity). {ECO:0000250}.
CC -!- POLYMORPHISM: Variant Cys-1142 found in diabetic GK strain may be a
CC cause of diabete in this strain. Genetic variations in Inppl1 may also
CC be a cause of susceptibility to hypertension.
CC {ECO:0000269|PubMed:12086927}.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC family. {ECO:0000305}.
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DR EMBL; AB011439; BAA81818.1; -; mRNA.
DR EMBL; AB025794; BAA82308.1; -; mRNA.
DR RefSeq; NP_001257772.1; NM_001270843.1. [Q9WVR3-2]
DR RefSeq; NP_075233.1; NM_022944.2. [Q9WVR3-1]
DR AlphaFoldDB; Q9WVR3; -.
DR BMRB; Q9WVR3; -.
DR SMR; Q9WVR3; -.
DR IntAct; Q9WVR3; 2.
DR STRING; 10116.ENSRNOP00000061371; -.
DR BindingDB; Q9WVR3; -.
DR ChEMBL; CHEMBL2331062; -.
DR iPTMnet; Q9WVR3; -.
DR PhosphoSitePlus; Q9WVR3; -.
DR jPOST; Q9WVR3; -.
DR PaxDb; 10116-ENSRNOP00000061371; -.
DR Ensembl; ENSRNOT00000066915.4; ENSRNOP00000061371.4; ENSRNOG00000019730.8. [Q9WVR3-2]
DR GeneID; 65038; -.
DR KEGG; rno:65038; -.
DR UCSC; RGD:68396; rat. [Q9WVR3-1]
DR AGR; RGD:68396; -.
DR CTD; 3636; -.
DR RGD; 68396; Inppl1.
DR eggNOG; KOG0565; Eukaryota.
DR eggNOG; KOG4384; Eukaryota.
DR InParanoid; Q9WVR3; -.
DR OrthoDB; 21647at2759; -.
DR PhylomeDB; Q9WVR3; -.
DR TreeFam; TF323475; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling.
DR PRO; PR:Q9WVR3; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0009925; C:basal plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IDA:RGD.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0000922; C:spindle pole; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IDA:RGD.
DR GO; GO:0034485; F:phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0007015; P:actin filament organization; ISO:RGD.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0044255; P:cellular lipid metabolic process; ISO:RGD.
DR GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; ISO:RGD.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; ISO:RGD.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0032957; P:inositol trisphosphate metabolic process; IDA:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0008156; P:negative regulation of DNA replication; IMP:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:RGD.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IMP:RGD.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:RGD.
DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; IMP:RGD.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; ISO:RGD.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0110053; P:regulation of actin filament organization; ISS:UniProtKB.
DR GO; GO:0050776; P:regulation of immune response; IBA:GO_Central.
DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0097178; P:ruffle assembly; ISO:RGD.
DR CDD; cd09101; INPP5c_SHIP2-INPPL1; 1.
DR CDD; cd09491; SAM_Ship2; 1.
DR CDD; cd10343; SH2_SHIP; 1.
DR Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR000300; IPPc.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR PANTHER; PTHR46051:SF2; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE 5-PHOSPHATASE 2; 1.
DR PANTHER; PTHR46051; SH2 DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00128; IPPc; 1.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF56219; DNase I-like; 1.
DR SUPFAM; SSF47769; SAM/Pointed domain; 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Cell adhesion; Cell membrane;
KW Cell projection; Cytoplasm; Cytoskeleton; Hydrolase; Immunity;
KW Lipid metabolism; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW SH2 domain; SH3-binding.
FT CHAIN 1..1257
FT /note="Phosphatidylinositol 3,4,5-trisphosphate 5-
FT phosphatase 2"
FT /id="PRO_0000302872"
FT DOMAIN 21..117
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 1195..1257
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 119..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 897..986
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1004..1115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 945..950
FT /note="SH3-binding"
FT MOTIF 984..987
FT /note="NPXY motif"
FT COMPBIAS 120..140
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 939..953
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1049..1065
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1089..1105
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 165
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 887
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 891
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 987
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 1132
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 1136
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 1161
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT MOD_RES 1256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15357"
FT VAR_SEQ 1184..1257
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10381377"
FT /id="VSP_027986"
FT VARIANT 1142
FT /note="R -> C (in strain: GK)"
FT /evidence="ECO:0000269|PubMed:12086927"
FT MUTAGEN 987
FT /note="Y->F: Loss of phosphorylation following insulin
FT stimulation."
FT /evidence="ECO:0000269|PubMed:12351701"
FT CONFLICT 910
FT /note="S -> N (in Ref. 1; BAA81818)"
FT /evidence="ECO:0000305"
FT CONFLICT 1009
FT /note="P -> L (in Ref. 1; BAA81818)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1257 AA; 139143 MW; 3A994C8E52940083 CRC64;
MASVCGAPSP GGALGSQAPA WYHRDLSRAA AEELLARAGR DGSFLVRDSE SVAGAFALCV
LYQKHVHTYR ILPDGEDFLA VQTSQGVPVR RFQTLGELIG LYAQPNQGLV CALLLPVEGE
REPDPPDDRD ASDVEDEKPP LPPRSGSTSI SVPAGPSSPL PAPETPTTPA AESTPNGLST
VSHEYLKGSY GLDLEAVRGG ASNLPHLTRT LVTSCRRLHS EVDKVLSGLE ILSKVFDQQS
SPMVTRLLQQ QSLPQTGEQE LESLVLKLSV LKDFLSGIQK KALKALQDMS STAPPAPLQP
SIRKAKTIPV QAFEVKLDVT LGDLTKIGKS QKFTLSVDVE GGRLVLLRRQ RDSQEDWTTF
THDRIRQLIK SQRVQNKLGV VFEKEKDRTQ RKDFIFVSAR KREAFCQLLQ LMKNKHSKQD
EPDMISVFIG TWNMGSVPPP KNVTSWFTSK GLGKALDEVT VTIPHDIYVF GTQENSVGDR
EWLDLLRGGL KELTDLDYRP IAMQSLWNIK VAVLVKPEHE NRISHVSTSS VKTGIANTLG
NKGAVGVSFM FNGTSFGFVN CHLTSGNEKT TRRNQNYLDI LRLLSLGDRQ LSAFDISLRF
THLFWFGDLN YRLDMDIQEI LNYISRREFE PLLRVDQLNL EREKHKVFLR FSEEEISFPP
TYRYERGSRD TYAWHKQKPT GVRTNVPSWC DRILWKSYPE THIICNSYGC TDDIVTSDHS
PVFGTFEVGV TSQFISKKGL SKTSDQAYIE FESIEAIVKT ASRTKFFIEF YSTCLEEYKK
SFENDAQSSD NINFLKVQWS SRQLPTLKPI LADIEYLQDQ HLLLTVKSMD GYESYGECVV
ALKSMIGSTA QQFLTFLSHR GEETGNIRGS MKVRVPTERL GTRERLYEWI SIDKDDTGAK
SKAPSVLRGS QEHRSGSRKP TSTEASCPLS KLFEEPEKPP PTGRPPAPPR AVPREESLNP
RLKSEGTPEQ EGVAAPPPKN SFNNPAYYVL EGVPHQLLPL EPTSFARAPI PPTTKNKVAI
TVPAPQLGRH RTPRVGEGSS SDEDSGGTLP PPDFPPPPLP DSAIFLPPNL DPLSMPVVRG
RSVGEARGPP PPKAHPRPPL PPGTSPASTF LEEVASADDR SCSVLQMAKT LSEVDYSPGP
GRSALLPNPL ELQLPRGPSD YGRPLSFPPP RIRESIQEDL AEEAPCPQGG RASGLGEAGM
GAWLRAIGLE RYEEGLVHNG WDDLEFLSDI TEEDLEEAGV QDPAHKRLLL DTLQLSK
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