SHP2B_DANRE
ID SHP2B_DANRE Reviewed; 1226 AA.
AC Q2I6J0;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2B;
DE EC=3.1.3.86 {ECO:0000250|UniProtKB:O15357};
DE AltName: Full=Inositol polyphosphate phosphatase-like protein 1B;
DE Short=INPPL-1B;
DE AltName: Full=SH2 domain-containing inositol 5'-phosphatase 2B;
DE Short=SH2 domain-containing inositol phosphatase 2B;
DE Short=SHIP-2B;
GN Name=inppl1b; Synonyms=inppl1, ship2b;
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;
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.
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 -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9WVR3}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Membrane {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 -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC family. {ECO:0000305}.
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DR EMBL; DQ272662; ABB84852.1; -; mRNA.
DR AlphaFoldDB; Q2I6J0; -.
DR SMR; Q2I6J0; -.
DR STRING; 7955.ENSDARP00000096523; -.
DR PaxDb; Q2I6J0; -.
DR ZFIN; ZDB-GENE-030616-75; inppl1b.
DR eggNOG; KOG0565; Eukaryota.
DR InParanoid; Q2I6J0; -.
DR PhylomeDB; Q2I6J0; -.
DR PRO; PR:Q2I6J0; -.
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:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IBA:GO_Central.
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; IPR000300; IPPc.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00128; IPPc; 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; Lipid metabolism; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; SH2 domain; SH3-binding.
FT CHAIN 1..1226
FT /note="Phosphatidylinositol 3,4,5-trisphosphate 5-
FT phosphatase 2B"
FT /id="PRO_0000302874"
FT DOMAIN 6..102
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 1163..1226
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 106..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 945..964
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 985..1035
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 906..909
FT /note="NPXY motif"
FT COMPBIAS 126..144
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 909
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1226 AA; 137320 MW; 32C8C68DF2B80844 CRC64;
MTGAPWYHRD ISRVRAEELL AHAGIDGSFL VRDSESVPGA YALCLLFQRH VHTYRILPDA
DGLLAVQATQ GVQVNCFRTL GDLVLGYQNP NKGLVAPLLY PVMRESEAND ESSDGDDEKP
GSTFANSPPR AISPTATSPP SSSAAPHLLL QRLQELSPNS VGCEIVSLLD EYLHGNVCKD
LENLKGGASG LQHFQGILSH ICDSLHSEID QTLSSLETLA KVFDHPSGHL TFSTMQNIGK
SPEENMDNLL QKLTTLCNLL SSLEKRVLKA LQEAVANHNL SLQPATPPES SRAPKKLARP
NPVHSFQVKV VRYGRQTVSV DINEGVLLFD KKSGSFGVET VTLDRIVQLV KFQRGPAKLK
MVVDSHHNPP RELVFESTKK REAFCRLLQL MKTTHSQKSE LDVISVFVGT WNMGGTPPPG
SLQSWVTCSG LGLTPDESIS SLPHDIYAVG TQDNPQGERE WAEHIRATLR TSTNIDYKQV
AVQSLWNIRL AVFVKPEHEA RISQVNTASV KTGLGNTLGN KGAVGVSLLF NGTSMGFVNC
HLTSGSDKAL RRNHNFQDIL RLLSLGEKQL STFDISLRFN HLFWCGDLNY RLDLDALDIL
KHVSKREFEE LMCADQLTRE RHKRKAFFNF KEEKIMFPPT YRYERGSRDC YLWQKYKSSG
VQVNGPSWCD RVLWKSYPES HVICTSYGCT DDIFTSEHSP VFATFEVGVI SLFPRTESCS
ERASIELEAI EAIVKTSSKA KFFIEFHSRC LEEPRRSAEN DSQYCEVPGF LKLGWSSKQL
PKLHPVFSDL EHLRDQHLLL SVKSCDGFES YGECCVALRP TAGKLLDTFE TCLTHRGEEM
GSIRGRFRVY VPPDRRRIRE RVYEWLSIEK DEREMMKDQL SPPSSSAFSI KAPSASYVAS
PNSYTNPAYF IFEEMPVFRK AEEIPSTIKE SQVVCANNTV IQLPRVTGSH GHGKRSARRS
DFTEIEIPGS LAPYKPSCET QSELSSAASS YQLFPGPHVP STSPNQRHTT HSSNSSLQLQ
SHKNNMAPDS ELSGKKLTNS YMNHSVFSRD MHKEKVRQDY QGVHQGRPVP IRNGPKLYPY
VSTRVPAQCS ASWIVEQPTP ASGDNSLTAL QIAKSLSEVD FQPADKKYPF HQMPSQQRQH
GYDYGLASER NYSWEKEVSV LHGAPETVRE LLSTLGLQRY TLDLSRSGWD DLDYFSGITE
EELCAAGVSN PSHRRRILEN LPKIWD
