SHIP1_RAT
ID SHIP1_RAT Reviewed; 1190 AA.
AC P97573;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1;
DE EC=3.1.3.86 {ECO:0000269|PubMed:8910587};
DE AltName: Full=Inositol polyphosphate-5-phosphatase D;
DE EC=3.1.3.56 {ECO:0000250|UniProtKB:Q92835};
DE AltName: Full=Phosphatidylinositol-4,5-bisphosphate 5-phosphatase;
DE EC=3.1.3.36 {ECO:0000250|UniProtKB:Q92835};
DE AltName: Full=SH2 domain-containing inositol 5'-phosphatase 1;
DE Short=SH2 domain-containing inositol phosphatase 1;
DE Short=SHIP-1;
GN Name=Inpp5d; Synonyms=Ship, Ship1;
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], CATALYTIC ACTIVITY, PHOSPHORYLATION, AND
RP INTERACTION WITH MS4A2; SHC1; GRB2 AND FCER1G.
RX PubMed=8910587; DOI=10.1074/jbc.271.46.29271;
RA Osborne M.A., Zenner G., Lubinus M., Zhang X., Songyang Z., Cantley L.C.,
RA Majerus P., Burn P., Kochan J.P.;
RT "The inositol 5'-phosphatase SHIP binds to immunoreceptor signaling motifs
RT and responds to high affinity IgE receptor aggregation.";
RL J. Biol. Chem. 271:29271-29278(1996).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245; THR-963 AND SER-971, AND
RP 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).
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:8910587). Also able to hydrolyze the 5-phosphate of
CC phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol
CC 1,3,4,5-tetrakisphosphate (By similarity). Acts as a negative regulator
CC of B-cell antigen receptor signaling. 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. Acts as a negative regulator of myeloid cell
CC proliferation/survival and chemotaxis, mast cell degranulation, immune
CC cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and
CC JNK signaling in B-cells. Regulates proliferation of osteoclast
CC precursors, macrophage programming, phagocytosis and activation and is
CC required for endotoxin tolerance. Involved in the control of cell-cell
CC junctions, CD32a signaling in neutrophils and modulation of EGF-induced
CC phospholipase C activity. Key regulator of neutrophil migration, by
CC governing the formation of the leading edge and polarization required
CC for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells.
CC Mediates the activin/TGF-beta-induced apoptosis through its Smad-
CC dependent expression (By similarity). {ECO:0000250|UniProtKB:Q92835,
CC ECO:0000269|PubMed:8910587}.
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:8910587};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-
CC inositol 1,3,4-trisphosphate + phosphate; Xref=Rhea:RHEA:11392,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57895,
CC ChEBI:CHEBI:58414; EC=3.1.3.56;
CC Evidence={ECO:0000250|UniProtKB:Q92835};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178,
CC ChEBI:CHEBI:58456; EC=3.1.3.36;
CC Evidence={ECO:0000250|UniProtKB:Q92835};
CC -!- ACTIVITY REGULATION: Activated upon translocation to the sites of
CC synthesis of PtdIns(3,4,5)P3 in the membrane. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with tyrosine phosphorylated forms of SHC1
CC (PubMed:8910587). Interacts with tyrosine phosphorylated form of DOK1
CC (By similarity). Interacts with tyrosine phosphorylated form of DOK3
CC (By similarity). Interacts with tyrosine phosphorylated form of
CC SLAMF1/CD150 (By similarity). Interacts with PTPN11/SHP-2 in response
CC to IL-3 (By similarity). Interacts with receptor EPOR (By similarity).
CC Interacts with receptors MS4A2/FCER1B and FCER1G (PubMed:8910587).
CC Interacts with receptors FCGR2B and FCGR3 (By similarity). Interacts
CC with receptor FCGR2A, leading to regulate gene expression during the
CC phagocytic process (By similarity). Interacts with GRB2
CC (PubMed:8910587). Interacts with PLCG1 (By similarity). Interacts with
CC tyrosine kinases SRC and TEC (By similarity). Interacts with c-Met/MET
CC (By similarity). Interacts with MILR1 (tyrosine-phosphorylated) (By
CC similarity). Can weakly interact (via NPXY motif 2) with DAB2 (via PID
CC domain); the interaction is impaired by tyrosine phosphorylation of the
CC NPXY motif (By similarity). Interacts (via SH2 domain) with tyrosine
CC phosphorylated KLRC1 (via ITIM). {ECO:0000250|UniProtKB:Q92835,
CC ECO:0000250|UniProtKB:Q9ES52, ECO:0000269|PubMed:8910587}.
CC -!- INTERACTION:
CC P97573; Q96RU3: FNBP1; Xeno; NbExp=2; IntAct=EBI-8008869, EBI-1111248;
CC P97573; Q15642-1: TRIP10; Xeno; NbExp=2; IntAct=EBI-8008869, EBI-16191375;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9ES52}. Cell
CC membrane {ECO:0000250|UniProtKB:Q9ES52}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9ES52}. Membrane raft
CC {ECO:0000250|UniProtKB:Q9ES52}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q9ES52}. Note=Translocates to the plasma
CC membrane when activated, translocation is probably due to different
CC mechanisms depending on the stimulus and cell type. Translocates from
CC the cytoplasm to membrane ruffles in a FCGR3/CD16-dependent manner.
CC Colocalizes with FC-gamma-RIIB receptor (FCGR2B) or FCGR3/CD16 at
CC membrane ruffles. Tyrosine phosphorylation may also participate in
CC membrane localization. {ECO:0000250|UniProtKB:Q9ES52}.
CC -!- DOMAIN: The SH2 domain interacts with tyrosine phosphorylated forms of
CC proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2
CC for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is
CC also required for tyrosine phosphorylation (By similarity).
CC {ECO:0000250|UniProtKB:Q9ES52}.
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 cytokines,
CC growth factors, antibodies, chemokines, integrin ligands and hypertonic
CC and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.
CC {ECO:0000269|PubMed:8910587}.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC family. {ECO:0000305}.
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DR EMBL; U55192; AAB40610.1; -; mRNA.
DR RefSeq; NP_062184.1; NM_019311.1.
DR AlphaFoldDB; P97573; -.
DR SMR; P97573; -.
DR BioGRID; 248482; 6.
DR DIP; DIP-42709N; -.
DR IntAct; P97573; 15.
DR MINT; P97573; -.
DR STRING; 10116.ENSRNOP00000040111; -.
DR iPTMnet; P97573; -.
DR PhosphoSitePlus; P97573; -.
DR PaxDb; P97573; -.
DR PRIDE; P97573; -.
DR GeneID; 54259; -.
DR KEGG; rno:54259; -.
DR UCSC; RGD:2914; rat.
DR CTD; 3635; -.
DR RGD; 2914; Inpp5d.
DR eggNOG; KOG0565; Eukaryota.
DR InParanoid; P97573; -.
DR OrthoDB; 311217at2759; -.
DR PhylomeDB; P97573; -.
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-202424; Downstream TCR signaling.
DR Reactome; R-RNO-210990; PECAM1 interactions.
DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling.
DR PRO; PR:P97573; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005884; C:actin filament; IDA:RGD.
DR GO; GO:0030863; C:cortical cytoskeleton; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0052659; F:inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052658; F:inositol-1,4,5-trisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0030487; F:inositol-4,5-bisphosphate 5-phosphatase activity; IDA:RGD.
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:0004439; F:phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008340; P:determination of adult lifespan; ISO:RGD.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0050869; P:negative regulation of B cell activation; ISO:RGD.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:RGD.
DR GO; GO:0045779; P:negative regulation of bone resorption; ISO:RGD.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; ISO:RGD.
DR GO; GO:0050777; P:negative regulation of immune response; ISO:RGD.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0045656; P:negative regulation of monocyte differentiation; ISO:RGD.
DR GO; GO:0045659; P:negative regulation of neutrophil differentiation; ISO:RGD.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:0009968; P:negative regulation of signal transduction; ISO:RGD.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISO:RGD.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISO:RGD.
DR GO; GO:0045621; P:positive regulation of lymphocyte differentiation; ISO:RGD.
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; 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; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00128; IPPc; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell membrane; Cytoplasm; Cytoskeleton; Hydrolase; Immunity;
KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW SH2 domain; SH3-binding.
FT CHAIN 1..1190
FT /note="Phosphatidylinositol 3,4,5-trisphosphate 5-
FT phosphatase 1"
FT /id="PRO_0000302868"
FT DOMAIN 8..104
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 110..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 946..1190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1014..1028
FT /note="Interaction with DAB2"
FT /evidence="ECO:0000250"
FT MOTIF 126..131
FT /note="SH3-binding 1"
FT MOTIF 914..917
FT /note="NPXY motif 1"
FT MOTIF 969..974
FT /note="SH3-binding 2"
FT MOTIF 1017..1020
FT /note="NPXY motif 2"
FT MOTIF 1038..1049
FT /note="SH3-binding 3"
FT COMPBIAS 972..986
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1087..1101
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1160..1183
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 917
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q92835"
FT MOD_RES 934
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ES52"
FT MOD_RES 944
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9ES52"
FT MOD_RES 963
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 966
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ES52"
FT MOD_RES 971
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1020
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9ES52"
SQ SEQUENCE 1190 AA; 133593 MW; 85DD4F2190F98700 CRC64;
MPAMVPGWNH GNITRSKAEE LLSRAGKDGS FLVRASESIP RAYALCVLFR NCVYTYRILP
NEDDKFTVQA SEGVPMRFFT KLDQLIEFYK KENMGLVTHL QFPVPLEEED AIDEPEEDTE
SVMSPPELPP RNIPVSGGPC EAKDLPLPTE NPRAPEVTRL SLSETLFQRL QSMDTSGLPE
EHLKAIQDYL STQLMLDSDF LKTGSSNLPH LKKLTSLLCK ELHGEVIRTL PSLESLQRLF
DQQLSPGLRP RPQVPGEANP ITMVAKLSQL TSLLSSIEDK VKALLHEGSE STNRRSLIPP
VTFEVKSESL GIPQKMHLKV DVESGKLIIK KSRDGSEDKF YSHKKILQLI KSQKFLNKLV
ILVETEKEKI LRKEYVFSDS KKREGFCQLL QQMKNKHSEQ SEPDMITIFI GTWNMGNAPP
PKKITSWFLS KGQGKTRDDS ADYIPHDIYV IGTQEDPLGE KEWLEILRHS LQEVTSMTFK
TVAIHTLWNI RIVVLAKPEH ENRISHICTD NVKTGIANTL GNKGAVGVSF MFNGTSLGFV
NSHLTSGSEK KLRRNQNYMN ILRFLALGDK KLSPFNITHR FTHLFWLGDL NYRVELPTWE
AEAIIQKIKQ QQYSDLLAHD QLLLERKEQE VFLHFEEEEI TFAPTYRFER LTRDKYAYTK
QKATGMKYNL PSWCDRVLWK SYPLVHVVCQ SYGSTSDIMT SDHSPVFATF EAGVTSQFVS
KNGPGAVDSQ GQIEFLACYA TLKTKSQTKF YLELHSSCLE SFVKSQEGEN EEGDEGELVV
RFGETLPKLK PIISDPEYLL DQHILISIKS SDSDESYGEG CIALRLETTE SQLPIYTPLT
HHGEMTGHFR GEIKLQTSEG KMREKLYDFV KTERDESSGM KCLKNLTSHD PMRQWEPAGR
VPACGISSLN EIINPNYIGM GPFGQPLHGK STLSPDQQLT AWSYDQLPKD SSLGPGRGEG
PPTPPSQPPL SPKKFSSSTA NRGSCPRVQE TRPGDLGKVE ALPQEDLPLT KPEMFENPLY
GSVSPFPKLV PRKEQESPKM MRKEPPPCPD PGVSSPSIML PKAQEVENVK GTSKQAPVPV
FGPTPRIRSF TCSSSAEGRM PSGDKSQGKP KAPASSQAPV PVKRPVKPSR SEMSQQTTPI
PAPRPPLPVK SPAVLQLQHS KGRDYRDNTE LPHHGKHRQE ESLLGRTAMQ
