Gene/Proteome Database (LMPD)

LMPD ID
LMP006659
Gene ID
3635
Species
Homo sapiens (Human)
Gene Name
inositol polyphosphate-5-phosphatase, 145kDa
Gene Symbol
INPP5D
Synonyms
SHIP; SHIP-1; SHIP1; SIP-145; hp51CN; p150Ship
Alternate Names
phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1; inositol polyphosphate-5-phosphatase, 145kD', "SH2 domain-containing inositol 5'-phosphatase 1;,signaling inositol polyphosphate phosphatase SHIP II; signaling inositol polyphosphate 5 phosphatase SIP-145
Chromosome
2
Map Location
2q37.1
EC Number
3.1.3.86
Summary
This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]
Orthologs
View orthologs and multiple alignments for INPP5D

Proteins

phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform a
Refseq ID NP_001017915
Protein GI 64085167
UniProt ID Q92835
mRNA ID NM_001017915
Length 1189
RefSeq Status REVIEWED
MVPCWNHGNITRSKAEELLSRTGKDGSFLVRASESISRAYALCVLYRNCVYTYRILPNEDDKFTVQASEGVSMRFFTKLDQLIEFYKKENMGLVTHLQYPVPLEEEDTGDDPEEDTVESVVSPPELPPRNIPLTASSCEAKEVPFSNENPRATETSRPSLSETLFQRLQSMDTSGLPEEHLKAIQDYLSTQLAQDSEFVKTGSSSLPHLKKLTTLLCKELYGEVIRTLPSLESLQRLFDQQLSPGLRPRPQVPGEANPINMVSKLSQLTSLLSSIEDKVKALLHEGPESPHRPSLIPPVTFEVKAESLGIPQKMQLKVDVESGKLIIKKSKDGSEDKFYSHKKILQLIKSQKFLNKLVILVETEKEKILRKEYVFADSKKREGFCQLLQQMKNKHSEQPEPDMITIFIGTWNMGNAPPPKKITSWFLSKGQGKTRDDSADYIPHDIYVIGTQEDPLSEKEWLEILKHSLQEITSVTFKTVAIHTLWNIRIVVLAKPEHENRISHICTDNVKTGIANTLGNKGAVGVSFMFNGTSLGFVNSHLTSGSEKKLRRNQNYMNILRFLALGDKKLSPFNITHRFTHLFWFGDLNYRVDLPTWEAETIIQKIKQQQYADLLSHDQLLTERREQKVFLHFEEEEITFAPTYRFERLTRDKYAYTKQKATGMKYNLPSWCDRVLWKSYPLVHVVCQSYGSTSDIMTSDHSPVFATFEAGVTSQFVSKNGPGTVDSQGQIEFLRCYATLKTKSQTKFYLEFHSSCLESFVKSQEGENEEGSEGELVVKFGETLPKLKPIISDPEYLLDQHILISIKSSDSDESYGEGCIALRLEATETQLPIYTPLTHHGELTGHFQGEIKLQTSQGKTREKLYDFVKTERDESSGPKTLKSLTSHDPMKQWEVTSRAPPCSGSSITEIINPNYMGVGPFGPPMPLHVKQTLSPDQQPTAWSYDQPPKDSPLGPCRGESPPTPPGQPPISPKKFLPSTANRGLPPRTQESRPSDLGKNAGDTLPQEDLPLTKPEMFENPLYGSLSSFPKPAPRKDQESPKMPRKEPPPCPEPGILSPSIVLTKAQEADRGEGPGKQVPAPRLRSFTCSSSAEGRAAGGDKSQGKPKTPVSSQAPVPAKRPIKPSRSEINQQTPPTPTPRPPLPVKSPAVLHLQHSKGRDYRDNTELPHHGKHRPEEGPPGPLGRTAMQ
phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform b
Refseq ID NP_005532
Protein GI 40254823
UniProt ID Q92835
mRNA ID NM_005541
Length 1188
RefSeq Status REVIEWED
MVPCWNHGNITRSKAEELLSRTGKDGSFLVRASESISRAYALCVLYRNCVYTYRILPNEDDKFTVQASEGVSMRFFTKLDQLIEFYKKENMGLVTHLQYPVPLEEEDTGDDPEEDTESVVSPPELPPRNIPLTASSCEAKEVPFSNENPRATETSRPSLSETLFQRLQSMDTSGLPEEHLKAIQDYLSTQLAQDSEFVKTGSSSLPHLKKLTTLLCKELYGEVIRTLPSLESLQRLFDQQLSPGLRPRPQVPGEANPINMVSKLSQLTSLLSSIEDKVKALLHEGPESPHRPSLIPPVTFEVKAESLGIPQKMQLKVDVESGKLIIKKSKDGSEDKFYSHKKILQLIKSQKFLNKLVILVETEKEKILRKEYVFADSKKREGFCQLLQQMKNKHSEQPEPDMITIFIGTWNMGNAPPPKKITSWFLSKGQGKTRDDSADYIPHDIYVIGTQEDPLSEKEWLEILKHSLQEITSVTFKTVAIHTLWNIRIVVLAKPEHENRISHICTDNVKTGIANTLGNKGAVGVSFMFNGTSLGFVNSHLTSGSEKKLRRNQNYMNILRFLALGDKKLSPFNITHRFTHLFWFGDLNYRVDLPTWEAETIIQKIKQQQYADLLSHDQLLTERREQKVFLHFEEEEITFAPTYRFERLTRDKYAYTKQKATGMKYNLPSWCDRVLWKSYPLVHVVCQSYGSTSDIMTSDHSPVFATFEAGVTSQFVSKNGPGTVDSQGQIEFLRCYATLKTKSQTKFYLEFHSSCLESFVKSQEGENEEGSEGELVVKFGETLPKLKPIISDPEYLLDQHILISIKSSDSDESYGEGCIALRLEATETQLPIYTPLTHHGELTGHFQGEIKLQTSQGKTREKLYDFVKTERDESSGPKTLKSLTSHDPMKQWEVTSRAPPCSGSSITEIINPNYMGVGPFGPPMPLHVKQTLSPDQQPTAWSYDQPPKDSPLGPCRGESPPTPPGQPPISPKKFLPSTANRGLPPRTQESRPSDLGKNAGDTLPQEDLPLTKPEMFENPLYGSLSSFPKPAPRKDQESPKMPRKEPPPCPEPGILSPSIVLTKAQEADRGEGPGKQVPAPRLRSFTCSSSAEGRAAGGDKSQGKPKTPVSSQAPVPAKRPIKPSRSEINQQTPPTPTPRPPLPVKSPAVLHLQHSKGRDYRDNTELPHHGKHRPEEGPPGPLGRTAMQ

Gene Information

Entrez Gene ID
3635
Gene Name
inositol polyphosphate-5-phosphatase, 145kDa
Gene Symbol
INPP5D
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005829 TAS:Reactome C cytosol
GO:0016020 IEA:UniProtKB-KW C membrane
GO:0004445 TAS:ProtInc F inositol-polyphosphate 5-phosphatase activity
GO:0034594 IEA:Ensembl F phosphatidylinositol trisphosphate phosphatase activity
GO:0050852 TAS:Reactome P T cell receptor signaling pathway
GO:0006915 IEA:UniProtKB-KW P apoptotic process
GO:0007596 TAS:Reactome P blood coagulation
GO:0008340 IEA:Ensembl P determination of adult lifespan
GO:0016064 IEA:Ensembl P immunoglobulin mediated immune response
GO:0043647 TAS:Reactome P inositol phosphate metabolic process
GO:0035556 IEA:Ensembl P intracellular signal transduction
GO:0050900 TAS:Reactome P leukocyte migration
GO:0030889 IEA:Ensembl P negative regulation of B cell proliferation
GO:0045779 IEA:Ensembl P negative regulation of bone resorption
GO:0050777 IEA:Ensembl P negative regulation of immune response
GO:0045409 IEA:Ensembl P negative regulation of interleukin-6 biosynthetic process
GO:0045656 IEA:Ensembl P negative regulation of monocyte differentiation
GO:0045659 IEA:Ensembl P negative regulation of neutrophil differentiation
GO:0045671 IEA:Ensembl P negative regulation of osteoclast differentiation
GO:0009968 IEA:Ensembl P negative regulation of signal transduction
GO:0006796 TAS:ProtInc P phosphate-containing compound metabolic process
GO:0006661 TAS:Reactome P phosphatidylinositol biosynthetic process
GO:0046856 IEA:InterPro P phosphatidylinositol dephosphorylation
GO:0006644 TAS:Reactome P phospholipid metabolic process
GO:0045579 IEA:Ensembl P positive regulation of B cell differentiation
GO:0043065 IEA:Ensembl P positive regulation of apoptotic process
GO:0045648 IEA:Ensembl P positive regulation of erythrocyte differentiation
GO:0007165 TAS:ProtInc P signal transduction
GO:0044281 TAS:Reactome P small molecule metabolic process

KEGG Pathway Links

KEGG Pathway ID Description
hsa04662 B cell receptor signaling pathway
hsa04664 Fc epsilon RI signaling pathway
hsa04666 Fc gamma R-mediated phagocytosis

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_150312 Synthesis of IP3 and IP4 in the cytosol

Domain Information

InterPro Annotations

Accession Description
IPR005135 Endonuclease/exonuclease/phosphatase
IPR000300 Inositol polyphosphate-related phosphatase
IPR000980 SH2 domain

UniProt Annotations

Entry Information

Gene Name
inositol polyphosphate-5-phosphatase, 145kDa
Protein Entry
SHIP1_HUMAN
UniProt ID
Q92835
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q92835-1; Sequence=Displayed; Name=2; IsoId=Q92835-2; Sequence=VSP_027978; Name=3; Synonyms=SIP-110; IsoId=Q92835-3; Sequence=VSP_027977, VSP_027979;
Catalytic Activity 1-phosphatidyl-1D-myo-inositol 3,4,5- triphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 3,4- diphosphate + phosphate. {ECO
Domain The NPXY sequence motif found in many tyrosine- phosphorylated proteins is required for the specific binding of the PID domain.
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).
Enzyme Regulation Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane.
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.
Interaction P31994:FCGR2B; NbExp=2; IntAct=EBI-1380477, EBI-724784; Q96B97:SH3KBP1; NbExp=6; IntAct=EBI-1380477, EBI-346595;
Ptm 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. {ECO
Sequence Caution Sequence=AAC50454.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ;
Similarity Belongs to the inositol 1,4,5-trisphosphate 5- phosphatase family.
Similarity Contains 1 SH2 domain. {ECO
Subcellular Location Cytoplasm . Membrane ; Peripheral membrane protein . 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).
Subunit 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 (By similarity).
Tissue Specificity Specifically expressed in immune and hematopoietic cells. Expressed in bone marrow and blood cells. Levels vary considerably within this compartment. Present in at least 74% of immature CD34+ cells, whereas within the more mature population of CD33+ cells, it is present in only 10% of cells. Present in the majority of T-cells, while it is present in a minority of B-cells (at protein level). {ECO

Identical and Related Proteins

Unique RefSeq proteins for LMP006659 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
64085167 RefSeq NP_001017915 1189 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform a
40254823 RefSeq NP_005532 1188 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform b

Identical Sequences to LMP006659 proteins

Reference Database Accession Length Protein Name
GI:40254823 GenBank AAB53573.1 1188 SH2-containing inositol 5-phosphatase [Homo sapiens]
GI:64085167 GenBank AAD00081.1 1189 signaling inositol polyphosphate phosphatase SHIP II [Homo sapiens]
GI:40254823 GenBank AAH99920.1 1188 Inositol polyphosphate-5-phosphatase, 145kDa [Homo sapiens]
GI:40254823 GenBank AAI13581.1 1188 Inositol polyphosphate-5-phosphatase, 145kDa [Homo sapiens]
GI:40254823 GenBank AAI13583.1 1188 Inositol polyphosphate-5-phosphatase, 145kDa [Homo sapiens]
GI:40254823 GenBank AIC63062.1 1188 INPP5D, partial [synthetic construct]
GI:64085167 SwissProt Q92835.2 1189 RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1; AltName: Full=Inositol polyphosphate-5-phosphatase of 145 kDa; Short=SIP-145; AltName: Full=SH2 domain-containing inositol 5'-phosphatase 1; Short=SH2 domain-containing inositol phosphatase 1; Short=SHIP-1; AltName: Full=p150Ship; Short=hp51CN [Homo sapiens]

Related Sequences to LMP006659 proteins

Reference Database Accession Length Protein Name
GI:40254823 EMBL CAA67071.1 1188 inositol polyphosphate 5- phosphatase [Homo sapiens]
GI:64085167 GenBank AAB53573.1 1188 SH2-containing inositol 5-phosphatase [Homo sapiens]
GI:40254823 GenBank AAD00081.1 1189 signaling inositol polyphosphate phosphatase SHIP II [Homo sapiens]
GI:40254823 GenBank AAE68035.1 1187 Sequence 8 from patent US 6218162
GI:40254823 GenBank AAE72726.1 1187 Sequence 8 from patent US 6238903
GI:64085167 GenBank AAH99920.1 1188 Inositol polyphosphate-5-phosphatase, 145kDa [Homo sapiens]
GI:64085167 GenBank AAI13581.1 1188 Inositol polyphosphate-5-phosphatase, 145kDa [Homo sapiens]
GI:64085167 GenBank AAI13583.1 1188 Inositol polyphosphate-5-phosphatase, 145kDa [Homo sapiens]
GI:64085167 GenBank AIC63062.1 1188 INPP5D, partial [synthetic construct]
GI:64085167 RefSeq NP_005532.2 1188 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform b [Homo sapiens]
GI:40254823 RefSeq NP_001017915.1 1189 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform a [Homo sapiens]
GI:40254823 SwissProt Q92835.2 1189 RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1; AltName: Full=Inositol polyphosphate-5-phosphatase of 145 kDa; Short=SIP-145; AltName: Full=SH2 domain-containing inositol 5'-phosphatase 1; Short=SH2 domain-containing inositol phosphatase 1; Short=SHIP-1; AltName: Full=p150Ship; Short=hp51CN [Homo sapiens]