P97573 (SHIP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Inpp5d
Synonyms:	Ship, Ship1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1190 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Catalytic activity	1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate. Ref.1
Enzyme regulation	Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane By similarity.
Subunit structure	Interacts with tyrosine phosphorylated forms of SHC1, DOK1, DOK3, PTPN11/SHP-2, SLAMF1/CD150. Interacts with PTPN11 in response to IL-3. Interacts with receptors EPOR, MS4A2/FCER1B and FCER1G, FCGR2A, FCGR2B and FCGR3. Interacts with GRB2 and PLCG1. Interacts with tyrosine kinases SRC and TEC. Interacts with FCGR2A, leading to regulate gene expression during the phagocytic process. Interacts with c-Met/MET By similarity. Interacts with MILR1 (tyrosine-phosphorylated). Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Ref.1
Subcellular location	Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity. Note: Translocates to the plasma membrane when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Partly translocated via its SH2 domain which mediates interaction with tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor (FCGR2B) or CD16/FCGR3. Tyrosine phosphorylation may also participate in membrane localization By similarity.
Domain	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. The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain By similarity.
Post-translational modification	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. Ref.1
Sequence similarities	Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Apoptosis Immunity
Cellular component	Cytoplasm Membrane
Domain	Repeat SH2 domain SH3-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular_component	actin filament Inferred from direct assay PubMed 15661894. Source: RGD cortical cytoskeleton Inferred from direct assay PubMed 15661894. Source: RGD cytosol Inferred from direct assay PubMed 15661894. Source: RGD membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	inositol-4,5-bisphosphate 5-phosphatase activity Inferred from direct assay PubMed 11714805. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1190	1190	Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1		PRO_0000302868
Regions
	Domain	8 – 104	97	SH2
	Region	1014 – 1028	15	Interaction with DAB2 By similarity
	Motif	126 – 131	6	SH3-binding 1
	Motif	914 – 917	4	NPXY motif 1
	Motif	969 – 974	6	SH3-binding 2
	Motif	1017 – 1020	4	NPXY motif 2
	Motif	1038 – 1049	12	SH3-binding 3
	Compositional bias	961 – 1152	192	Pro-rich
Amino acid modifications
	Modified residue	867	1	Phosphotyrosine By similarity
	Modified residue	917	1	Phosphotyrosine By similarity
	Modified residue	934	1	Phosphoserine By similarity
	Modified residue	944	1	Phosphotyrosine By similarity
	Modified residue	971	1	Phosphoserine By similarity
	Modified residue	1020	1	Phosphotyrosine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P97573 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 85DD4F2190F98700	FASTA	1,190	133,593
	10 20 30 40 50 60 MPAMVPGWNH GNITRSKAEE LLSRAGKDGS FLVRASESIP RAYALCVLFR NCVYTYRILP 70 80 90 100 110 120 NEDDKFTVQA SEGVPMRFFT KLDQLIEFYK KENMGLVTHL QFPVPLEEED AIDEPEEDTE 130 140 150 160 170 180 SVMSPPELPP RNIPVSGGPC EAKDLPLPTE NPRAPEVTRL SLSETLFQRL QSMDTSGLPE 190 200 210 220 230 240 EHLKAIQDYL STQLMLDSDF LKTGSSNLPH LKKLTSLLCK ELHGEVIRTL PSLESLQRLF 250 260 270 280 290 300 DQQLSPGLRP RPQVPGEANP ITMVAKLSQL TSLLSSIEDK VKALLHEGSE STNRRSLIPP 310 320 330 340 350 360 VTFEVKSESL GIPQKMHLKV DVESGKLIIK KSRDGSEDKF YSHKKILQLI KSQKFLNKLV 370 380 390 400 410 420 ILVETEKEKI LRKEYVFSDS KKREGFCQLL QQMKNKHSEQ SEPDMITIFI GTWNMGNAPP 430 440 450 460 470 480 PKKITSWFLS KGQGKTRDDS ADYIPHDIYV IGTQEDPLGE KEWLEILRHS LQEVTSMTFK 490 500 510 520 530 540 TVAIHTLWNI RIVVLAKPEH ENRISHICTD NVKTGIANTL GNKGAVGVSF MFNGTSLGFV 550 560 570 580 590 600 NSHLTSGSEK KLRRNQNYMN ILRFLALGDK KLSPFNITHR FTHLFWLGDL NYRVELPTWE 610 620 630 640 650 660 AEAIIQKIKQ QQYSDLLAHD QLLLERKEQE VFLHFEEEEI TFAPTYRFER LTRDKYAYTK 670 680 690 700 710 720 QKATGMKYNL PSWCDRVLWK SYPLVHVVCQ SYGSTSDIMT SDHSPVFATF EAGVTSQFVS 730 740 750 760 770 780 KNGPGAVDSQ GQIEFLACYA TLKTKSQTKF YLELHSSCLE SFVKSQEGEN EEGDEGELVV 790 800 810 820 830 840 RFGETLPKLK PIISDPEYLL DQHILISIKS SDSDESYGEG CIALRLETTE SQLPIYTPLT 850 860 870 880 890 900 HHGEMTGHFR GEIKLQTSEG KMREKLYDFV KTERDESSGM KCLKNLTSHD PMRQWEPAGR 910 920 930 940 950 960 VPACGISSLN EIINPNYIGM GPFGQPLHGK STLSPDQQLT AWSYDQLPKD SSLGPGRGEG 970 980 990 1000 1010 1020 PPTPPSQPPL SPKKFSSSTA NRGSCPRVQE TRPGDLGKVE ALPQEDLPLT KPEMFENPLY 1030 1040 1050 1060 1070 1080 GSVSPFPKLV PRKEQESPKM MRKEPPPCPD PGVSSPSIML PKAQEVENVK GTSKQAPVPV 1090 1100 1110 1120 1130 1140 FGPTPRIRSF TCSSSAEGRM PSGDKSQGKP KAPASSQAPV PVKRPVKPSR SEMSQQTTPI 1150 1160 1170 1180 1190 PAPRPPLPVK SPAVLQLQHS KGRDYRDNTE LPHHGKHRQE ESLLGRTAMQ

References

[1]

"The inositol 5'-phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation." Osborne M.A., Zenner G., Lubinus M., Zhang X., Songyang Z., Cantley L.C., Majerus P., Burn P., Kochan J.P. J. Biol. Chem. 271:29271-29278(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, PHOSPHORYLATION, INTERACTION WITH MS4A2; SHC1; GRB2 AND FCER1G.

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Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U55192 mRNA. Translation: AAB40610.1.
IPI	IPI00187836.
RefSeq	NP_062184.1. NM_019311.1.
UniGene	Rn.10659.
3D structure databases
HSSP	HSSP built from PDB template 1QAD based on UniProtKB P23727.
ProteinModelPortal	P97573.
SMR	P97573. Positions 3-115.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2517198.
STRING	10116.ENSRNOP00000040111.
PTM databases
PhosphoSite	P97573.
Proteomic databases
PaxDb	P97573.
PRIDE	P97573.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	54259.
KEGG	rno:54259.
UCSC	RGD:2914. rat.
Organism-specific databases
CTD	3635.
RGD	2914. Inpp5d.
Phylogenomic databases
eggNOG	COG5411.
HOGENOM	HOG000004836.
HOVERGEN	HBG106726.
InParanoid	P97573.
KO	K03084.
OrthoDB	EOG4M397X.
Gene expression databases
ArrayExpress	P97573.
Genevestigator	P97573.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR005135. Endo/exonuclease/phosphatase. IPR000300. IPPc. IPR000980. SH2. [Graphical view]
Pfam	PF03372. Exo_endo_phos. 1 hit. PF00017. SH2. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN.
SMART	SM00128. IPPc. 1 hit. SM00252. SH2. 1 hit. [Graphical view]
SUPFAM	SSF56219. Exo_endo_phos. 1 hit.
PROSITE	PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	610778.

Entry information

Entry name

SHIP1_RAT

Accession

Primary (citable) accession number: P97573

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 11, 2007
Last sequence update:	May 1, 1997
Last modified:	April 3, 2013
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program