SHP2A_DANRE
ID SHP2A_DANRE Reviewed; 1266 AA.
AC Q2I6J1; B7ZVH1;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2A;
DE EC=3.1.3.86 {ECO:0000250|UniProtKB:O15357};
DE AltName: Full=Inositol polyphosphate phosphatase-like protein 1A;
DE Short=INPPL1-A;
DE AltName: Full=SH2 domain-containing inositol 5'-phosphatase 2A;
DE Short=SH2 domain-containing inositol phosphatase 2A;
DE Short=SHIP-2A;
GN Name=inppl1a; Synonyms=ship2a; ORFNames=wu:fc58a04, zgc:198309;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=AB; TISSUE=Embryo;
RA Jurynec M.J., Grunwald D.J.;
RT "Cloning of 2 ship2 cDNAs in zebrafish.";
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
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. Plays a
CC central role in regulation of PI3K-dependent insulin signaling,
CC although the precise molecular mechanisms and signaling pathways remain
CC unclear. Part of a signaling pathway that regulates actin cytoskeleton
CC remodeling. 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. Participates in
CC regulation of cortical and submembraneous actin. Regulates cell
CC adhesion and cell spreading. Acts as a negative regulator of the FC-
CC gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB
CC receptor (FCGR2B), playing a central role in terminating signal
CC transduction from activating immune/hematopoietic cell receptor
CC systems. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect
CC the levels of the higher inositol polyphosphates like InsP6 (By
CC similarity). {ECO:0000250|UniProtKB:O15357}.
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:0000250|UniProtKB:O15357};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529;
CC Evidence={ECO:0000250|UniProtKB:O15357};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9WVR3}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:O15357}. Membrane
CC {ECO:0000250|UniProtKB:Q9WVR3}; Peripheral membrane protein
CC {ECO:0000250}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:O15357}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:O15357}. Nucleus {ECO:0000250|UniProtKB:D7PF45}.
CC Nucleus speckle {ECO:0000250|UniProtKB:D7PF45}. Note=Translocates to
CC membrane ruffles when activated, translocation is probably due to
CC different mechanisms depending on the stimulus and cell type.
CC {ECO:0000250}.
CC -!- DOMAIN: The SH2 domain interacts with tyrosine phosphorylated forms of
CC proteins. {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:O15357}.
CC -!- PTM: Tyrosine phosphorylated by the members of the SRC family after
CC exposure to a diverse array of extracellular stimuli.
CC {ECO:0000250|UniProtKB:O15357}.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC family. {ECO:0000305}.
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DR EMBL; DQ272661; ABB84851.1; -; mRNA.
DR EMBL; BC171582; AAI71582.1; -; mRNA.
DR RefSeq; NP_001034893.1; NM_001039804.2.
DR AlphaFoldDB; Q2I6J1; -.
DR SMR; Q2I6J1; -.
DR PRIDE; Q2I6J1; -.
DR GeneID; 325179; -.
DR KEGG; dre:325179; -.
DR CTD; 325179; -.
DR ZFIN; ZDB-GENE-030131-3904; inppl1a.
DR eggNOG; KOG0565; Eukaryota.
DR eggNOG; KOG4384; Eukaryota.
DR InParanoid; Q2I6J1; -.
DR OrthoDB; 311217at2759; -.
DR PhylomeDB; Q2I6J1; -.
DR Reactome; R-DRE-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-DRE-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR PRO; PR:Q2I6J1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IBA:GO_Central.
DR GO; GO:0034485; F:phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity; IEA:RHEA.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:ZFIN.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IMP:ZFIN.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0090024; P:negative regulation of neutrophil chemotaxis; IGI:ZFIN.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
DR GO; GO:0050776; P:regulation of immune response; IBA:GO_Central.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
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 Pfam; PF03372; Exo_endo_phos; 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; SSF47769; SSF47769; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS50001; SH2; 1.
PE 2: Evidence at transcript level;
KW Actin-binding; Cell adhesion; Cell projection; Cytoplasm; Cytoskeleton;
KW Hydrolase; Immunity; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW SH2 domain.
FT CHAIN 1..1266
FT /note="Phosphatidylinositol 3,4,5-trisphosphate 5-
FT phosphatase 2A"
FT /id="PRO_0000302873"
FT DOMAIN 15..111
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 1203..1266
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 114..159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 879..951
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 986..1132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1147..1174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 958..961
FT /note="NPXY motif"
FT COMPBIAS 114..131
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..159
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 894..910
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 911..946
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1002..1024
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1044..1058
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1084..1098
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 961
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT CONFLICT 23
FT /note="A -> T (in Ref. 1; ABB84851)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="L -> P (in Ref. 1; ABB84851)"
FT /evidence="ECO:0000305"
FT CONFLICT 929
FT /note="T -> P (in Ref. 1; ABB84851)"
FT /evidence="ECO:0000305"
FT CONFLICT 1037
FT /note="G -> V (in Ref. 1; ABB84851)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1266 AA; 140371 MW; 46AC69D19E22225B CRC64;
MAAVGPASPP PPPLWMHRDL SRAAAEELLA RAGRDGSFLV RDSESVSGAY ALCVLFQKHV
HTYRILPDEE NFLAVQTSQG VQPKRFKTLP ELIQLYLQPS QGLVTTLLYP VEREETTEDR
DYSDGEDEKP PLPPRTASTS SMTGSALVST DTPPENVTAA NGLSTISHEY LKGNYALDLE
AVKQGANSLP HLNKTLLSSC KRLHGEVDKV LCGLEILSKV FDQQSASMVS RMIQQSMSQG
GDQELEHLVT KLAILKDLLS SIEKKALKAL QDMSSSTPAI SPLLSIRNKV IPVQTFEVKL
DVYLADLTKI GKSQKYSLSV DVEGGKLVVM KKMKDAQEDW NTFTHDKIRQ LIKSQRVQNK
LGIVFEKEKD KSQRKDFIFA SAKKREAFCQ LLQLMKNKHS NQDEPDMISI FIGTWNMGSV
PAPKPLGSWI LSRGLGKTLD EMAVTIPHDI YVFGTQENSV CDKEWVETLR CSLKEYTDME
YKPIAVQTLW NIKIVVLVKA EHENRISHVG MSSVKTGIAN TLGNKGAVGV SFMFNGTSFG
FVNCHLTSGN EKIHRRNQNY LDILRQLSLG DKQLNSFDIS LRFTHLFWFG DLNYRLDMDI
QEILNYINRK EFDPLLKVDQ LNLEREKNKI FLRFAEEEIS YPPTYRYERG SRDTYVWQKQ
KATGMRTNVP SWCDRILWKS YPETHIVCNS YGCTDDIVTS DHSPVFGTFE VGVTSQFVSK
KGLPKSSEQA YIEFENIEAI VKTASRTKFF IEFYSTCLEE FKKSYENDTQ SSDNVNFLRV
GWSSKQLTTL KPILSDIEYL QDQHLLLTVK SLDGYESYGE CVLALKSMIG STAQQFHTYL
SHRGEETGNI RGSMRVRVPS ERMGTRERLY EWISVDKDDM GGPKGRTLPP RTSHDYVKPT
SSSSSRKHGS AELSRVSEEG EKSSTSRHTH TKEENTHNRG KQDPFESDAT TCKNSFNNPA
YYILEGVPNQ SAALASDILP GSALPPLANK TTAPPAGSVG KSKPPSGSSA QGRWQTSGRS
VRPISEEGSS EDDGNIGPHT GSLNRPPPDF PPPPLPKAAL EMSENSFGKP RVFSDLADGK
IPPPSKPLVS PGLTPPPGGA PGGGVAFCIE SPPVLSPNSA PFRRGGGASA LDDQSCSVLQ
MAKTLSEVEY PSGRERGASQ GPTGPQLRGL SFPSHPIQEE SIAEDLPEEG GLWGAESSSS
SLSVDCSVGE WLQKLGLQHY EEGLLHNGWD DLEFLSDITE EDLEEAGVRD PAHKKILLAS
LKQQQK
