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Protein

Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1

Gene

Inpp5d

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6 (By similarity).By similarity

Catalytic activityi

1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate.1 Publication

Activity regulationi

Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane.By similarity

GO - Molecular functioni

  • inositol-4,5-bisphosphate 5-phosphatase activity Source: RGD
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, Immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (EC:3.1.3.86)
Alternative name(s):
SH2 domain-containing inositol 5'-phosphatase 1
Short name:
SH2 domain-containing inositol phosphatase 1
Short name:
SHIP-1
Gene namesi
Name:Inpp5d
Synonyms:Ship, Ship1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2914 Inpp5d

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003028681 – 1190Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1Add BLAST1190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei245PhosphoserineCombined sources1
Modified residuei917PhosphotyrosineBy similarity1
Modified residuei934PhosphoserineBy similarity1
Modified residuei944PhosphotyrosineBy similarity1
Modified residuei963PhosphothreonineCombined sources1
Modified residuei966PhosphoserineBy similarity1
Modified residuei971PhosphoserineCombined sources1
Modified residuei1020PhosphotyrosineBy similarity1

Post-translational modificationi

Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as cytokines, growth factors, antibodies, chemokines, integrin ligands and hypertonic and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP97573
PRIDEiP97573

PTM databases

iPTMnetiP97573
PhosphoSitePlusiP97573

Interactioni

Subunit structurei

Interacts with tyrosine phosphorylated forms of SHC1 (PubMed:8910587). Interacts with tyrosine phosphorylated form of DOK1 (By similarity). Interacts with tyrosine phosphorylated form of DOK3 (By similarity). Interacts with tyrosine phosphorylated form of SLAMF1/CD150 (By similarity). Interacts with PTPN11/SHP-2 in response to IL-3 (By similarity). Interacts with receptor EPOR (By similarity). Interacts with receptors MS4A2/FCER1B and FCER1G (PubMed:8910587). Interacts with receptors FCGR2B and FCGR3 (By similarity). Interacts with receptor FCGR2A, leading to regulate gene expression during the phagocytic process (By similarity). Interacts with GRB2 (PubMed:8910587). Interacts with PLCG1 (By similarity). Interacts with tyrosine kinases SRC and TEC (By similarity). Interacts with c-Met/MET (By similarity). Interacts with MILR1 (tyrosine-phosphorylated) (By similarity). Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (By similarity).By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi248482, 6 interactors
DIPiDIP-42709N
IntActiP97573, 4 interactors
MINTiP97573
STRINGi10116.ENSRNOP00000040111

Structurei

3D structure databases

ProteinModelPortaliP97573
SMRiP97573
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 104SH2PROSITE-ProRule annotationAdd BLAST97

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1014 – 1028Interaction with DAB2By similarityAdd BLAST15

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi126 – 131SH3-binding 16
Motifi914 – 917NPXY motif 14
Motifi969 – 974SH3-binding 26
Motifi1017 – 1020NPXY motif 24
Motifi1038 – 1049SH3-binding 3Add BLAST12

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi961 – 1152Pro-richAdd BLAST192

Domaini

The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2 for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is also required for tyrosine phosphorylation (By similarity).By similarity
The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.By similarity

Sequence similaritiesi

Keywords - Domaini

Repeat, SH2 domain, SH3-binding

Phylogenomic databases

eggNOGiKOG0565 Eukaryota
COG5411 LUCA
HOGENOMiHOG000004836
HOVERGENiHBG106726
InParanoidiP97573
KOiK03084
PhylomeDBiP97573

Family and domain databases

Gene3Di3.30.505.10, 1 hit
3.60.10.10, 1 hit
InterProiView protein in InterPro
IPR036691 Endo/exonu/phosph_ase_sf
IPR005135 Endo/exonuclease/phosphatase
IPR000300 IPPc
IPR000980 SH2
IPR036860 SH2_dom_sf
PfamiView protein in Pfam
PF03372 Exo_endo_phos, 1 hit
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00128 IPPc, 1 hit
SM00252 SH2, 1 hit
SUPFAMiSSF55550 SSF55550, 1 hit
SSF56219 SSF56219, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P97573-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPAMVPGWNH GNITRSKAEE LLSRAGKDGS FLVRASESIP RAYALCVLFR
60 70 80 90 100
NCVYTYRILP NEDDKFTVQA SEGVPMRFFT KLDQLIEFYK KENMGLVTHL
110 120 130 140 150
QFPVPLEEED AIDEPEEDTE SVMSPPELPP RNIPVSGGPC EAKDLPLPTE
160 170 180 190 200
NPRAPEVTRL SLSETLFQRL QSMDTSGLPE EHLKAIQDYL STQLMLDSDF
210 220 230 240 250
LKTGSSNLPH LKKLTSLLCK ELHGEVIRTL PSLESLQRLF DQQLSPGLRP
260 270 280 290 300
RPQVPGEANP ITMVAKLSQL TSLLSSIEDK VKALLHEGSE STNRRSLIPP
310 320 330 340 350
VTFEVKSESL GIPQKMHLKV DVESGKLIIK KSRDGSEDKF YSHKKILQLI
360 370 380 390 400
KSQKFLNKLV ILVETEKEKI LRKEYVFSDS KKREGFCQLL QQMKNKHSEQ
410 420 430 440 450
SEPDMITIFI GTWNMGNAPP PKKITSWFLS KGQGKTRDDS ADYIPHDIYV
460 470 480 490 500
IGTQEDPLGE KEWLEILRHS LQEVTSMTFK TVAIHTLWNI RIVVLAKPEH
510 520 530 540 550
ENRISHICTD NVKTGIANTL GNKGAVGVSF MFNGTSLGFV NSHLTSGSEK
560 570 580 590 600
KLRRNQNYMN ILRFLALGDK KLSPFNITHR FTHLFWLGDL NYRVELPTWE
610 620 630 640 650
AEAIIQKIKQ QQYSDLLAHD QLLLERKEQE VFLHFEEEEI TFAPTYRFER
660 670 680 690 700
LTRDKYAYTK QKATGMKYNL PSWCDRVLWK SYPLVHVVCQ SYGSTSDIMT
710 720 730 740 750
SDHSPVFATF EAGVTSQFVS KNGPGAVDSQ GQIEFLACYA TLKTKSQTKF
760 770 780 790 800
YLELHSSCLE SFVKSQEGEN EEGDEGELVV RFGETLPKLK PIISDPEYLL
810 820 830 840 850
DQHILISIKS SDSDESYGEG CIALRLETTE SQLPIYTPLT HHGEMTGHFR
860 870 880 890 900
GEIKLQTSEG KMREKLYDFV KTERDESSGM KCLKNLTSHD PMRQWEPAGR
910 920 930 940 950
VPACGISSLN EIINPNYIGM GPFGQPLHGK STLSPDQQLT AWSYDQLPKD
960 970 980 990 1000
SSLGPGRGEG PPTPPSQPPL SPKKFSSSTA NRGSCPRVQE TRPGDLGKVE
1010 1020 1030 1040 1050
ALPQEDLPLT KPEMFENPLY GSVSPFPKLV PRKEQESPKM MRKEPPPCPD
1060 1070 1080 1090 1100
PGVSSPSIML PKAQEVENVK GTSKQAPVPV FGPTPRIRSF TCSSSAEGRM
1110 1120 1130 1140 1150
PSGDKSQGKP KAPASSQAPV PVKRPVKPSR SEMSQQTTPI PAPRPPLPVK
1160 1170 1180 1190
SPAVLQLQHS KGRDYRDNTE LPHHGKHRQE ESLLGRTAMQ
Length:1,190
Mass (Da):133,593
Last modified:May 1, 1997 - v1
Checksum:i85DD4F2190F98700
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F1M981F1M981_RAT
Phosphatidylinositol 3,4,5-trisphos...
Inpp5d
1,190Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U55192 mRNA Translation: AAB40610.1
RefSeqiNP_062184.1, NM_019311.1
UniGeneiRn.10659

Genome annotation databases

GeneIDi54259
KEGGirno:54259
UCSCiRGD:2914 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U55192 mRNA Translation: AAB40610.1
RefSeqiNP_062184.1, NM_019311.1
UniGeneiRn.10659

3D structure databases

ProteinModelPortaliP97573
SMRiP97573
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248482, 6 interactors
DIPiDIP-42709N
IntActiP97573, 4 interactors
MINTiP97573
STRINGi10116.ENSRNOP00000040111

PTM databases

iPTMnetiP97573
PhosphoSitePlusiP97573

Proteomic databases

PaxDbiP97573
PRIDEiP97573

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi54259
KEGGirno:54259
UCSCiRGD:2914 rat

Organism-specific databases

CTDi3635
RGDi2914 Inpp5d

Phylogenomic databases

eggNOGiKOG0565 Eukaryota
COG5411 LUCA
HOGENOMiHOG000004836
HOVERGENiHBG106726
InParanoidiP97573
KOiK03084
PhylomeDBiP97573

Miscellaneous databases

PROiPR:P97573

Family and domain databases

Gene3Di3.30.505.10, 1 hit
3.60.10.10, 1 hit
InterProiView protein in InterPro
IPR036691 Endo/exonu/phosph_ase_sf
IPR005135 Endo/exonuclease/phosphatase
IPR000300 IPPc
IPR000980 SH2
IPR036860 SH2_dom_sf
PfamiView protein in Pfam
PF03372 Exo_endo_phos, 1 hit
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00128 IPPc, 1 hit
SM00252 SH2, 1 hit
SUPFAMiSSF55550 SSF55550, 1 hit
SSF56219 SSF56219, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSHIP1_RAT
AccessioniPrimary (citable) accession number: P97573
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: May 1, 1997
Last modified: September 12, 2018
This is version 111 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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