dbPAF Protein Information


Tag Content
dbPAF ID dbPAF-0000937
Uniprot Accession O15357; SHIP2_HUMAN; B2RTX5; Q13577; Q13578;
Genbank Protein ID NP_001558.3; XP_011543301.1;
Genbank Nucleotide ID NM_001567.3; XM_011544999.1;
Protein Name Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Protein Synonyms/Alias Inositol polyphosphate phosphatase-like protein 1;INPPL-1;Protein 51C;SH2 domain-containing inositol 5'-phosphatase 2;SH2 domain-containing inositol phosphatase 2;SHIP-2;
Gene Name INPPL1
Gene Synonyms/Alias SHIP2;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)
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. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (PubMed:21624956). Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification.
Phosphorylation Sites
dbPAF PTMs: 56 (View all)
PositionPeptidesSourceReferences ( PMIDs )
43ARAGRDGSFLVRDSEcurated20873877
49GSFLVRDSESVAGAFPhosphoSitePlus22135298
62AFALCVLYQKHVHTYPhosphoSitePlus22135298
132PPDDRDASDGEDEKPdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;curated17081983; 16381945; 23193290; 21770892; 19651622; 18452278;
154STSISAPTGPSSPLPcurated23663014
157ISAPTGPSSPLPAPEcurated25627689; 23663014
158SAPTGPSSPLPAPETdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;SysPTM 2.0;curated18669648; 16381945; 23193290; 18988627; 22135298; 19366988;
165SPLPAPETPTAPAAEdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;SysPTM 2.0;UniProt;curated18669648; 16381945; 23193290; 18988627; 22135298; 19366988;
167LPAPETPTAPAAESAdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;curated18669648; 16381945; 23193290; 18988627; 22135298; 22817900
182PNGLSTVSHDYLKGSPhosphoSitePlus22135298
185LSTVSHDYLKGSYGLPhosphoSitePlus22135298
189SHDYLKGSYGLDLEAPhosphoSitePlus22135298
190HDYLKGSYGLDLEAVPhosphoSitePlus;curated22135298; 22817900
240SKVFDQQSSPMVTRLdbPTM 3.0;HPRD 9;curated18691976; 16381945; 23193290; 18988627; 22817900
241KVFDQQSSPMVTRLLdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;UniProt;curated18669648; 18691976; 16381945; 23193290; 20068231; 22115753;
290LKALQDMSSTAPPAPdbPTM 3.0;HPRD 9;curated20068231; 16381945; 23193290; 18988627
291KALQDMSSTAPPAPQdbPTM 3.0;HPRD 9;curated20068231; 16381945; 23193290; 18988627
352LLRRQRDSQEDWTTFPhosphoSitePlus;curated22135298; 23917254
622DIQEILNYISRKEFEPhosphoSitePlus22135298
661EISFPPTYRYERGSRPhosphoSitePlus;curated22135298; 22817900
Sequence
(Fasta)
MASACGAPGP GGALGSQAPS WYHRDLSRAA AEELLARAGR DGSFLVRDSE SVAGAFALCV 60
LYQKHVHTYR ILPDGEDFLA VQTSQGVPVR RFQTLGELIG LYAQPNQGLV CALLLPVEGE 120
REPDPPDDRD ASDGEDEKPP LPPRSGSTSI SAPTGPSSPL PAPETPTAPA AESAPNGLST 180
VSHDYLKGSY GLDLEAVRGG ASHLPHLTRT LATSCRRLHS EVDKVLSGLE ILSKVFDQQS 240
SPMVTRLLQQ QNLPQTGEQE LESLVLKLSV LKDFLSGIQK KALKALQDMS STAPPAPQPS 300
TRKAKTIPVQ AFEVKLDVTL GDLTKIGKSQ KFTLSVDVEG GRLVLLRRQR DSQEDWTTFT 360
HDRIRQLIKS QRVQNKLGVV FEKEKDRTQR KDFIFVSARK REAFCQLLQL MKNKHSKQDE 420
PDMISVFIGT WNMGSVPPPK NVTSWFTSKG LGKTLDEVTV TIPHDIYVFG TQENSVGDRE 480
WLDLLRGGLK ELTDLDYRPI AMQSLWNIKV AVLVKPEHEN RISHVSTSSV KTGIANTLGN 540
KGAVGVSFMF NGTSFGFVNC HLTSGNEKTA RRNQNYLDIL RLLSLGDRQL NAFDISLRFT 600
HLFWFGDLNY RLDMDIQEIL NYISRKEFEP LLRVDQLNLE REKHKVFLRF SEEEISFPPT 660
YRYERGSRDT YAWHKQKPTG VRTNVPSWCD RILWKSYPET HIICNSYGCT DDIVTSDHSP 720
VFGTFEVGVT SQFISKKGLS KTSDQAYIEF ESIEAIVKTA SRTKFFIEFY STCLEEYKKS 780
FENDAQSSDN INFLKVQWSS RQLPTLKPIL ADIEYLQDQH LLLTVKSMDG YESYGECVVA 840
LKSMIGSTAQ QFLTFLSHRG EETGNIRGSM KVRVPTERLG TRERLYEWIS IDKDEAGAKS 900
KAPSVSRGSQ EPRSGSRKPA FTEASCPLSR LFEEPEKPPP TGRPPAPPRA APREEPLTPR 960
LKPEGAPEPE GVAAPPPKNS FNNPAYYVLE GVPHQLLPPE PPSPARAPVP SATKNKVAIT 1020
VPAPQLGHHR HPRVGEGSSS DEESGGTLPP PDFPPPPLPD SAIFLPPSLD PLPGPVVRGR 1080
GGAEARGPPP PKAHPRPPLP PGPSPASTFL GEVASGDDRS CSVLQMAKTL SEVDYAPAGP 1140
ARSALLPGPL ELQPPRGLPS DYGRPLSFPP PRIRESIQED LAEEAPCLQG GRASGLGEAG 1200
MSAWLRAIGL ERYEEGLVHN GWDDLEFLSD ITEEDLEEAG VQDPAHKRLL LDTLQLSK 1259
Keyword

KW-0002--3D-structure
KW-0009--Actin-binding
KW-0025--Alternative splicing
KW-0130--Cell adhesion
KW-0966--Cell projection
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0206--Cytoskeleton
KW-0219--Diabetes mellitus
KW-0225--Disease mutation
KW-0378--Hydrolase
KW-0391--Immunity
KW-0472--Membrane
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0727--SH2 domain
KW-0729--SH3-binding

Interpro

IPR005135--Endo/exonuclease/phosphatase
IPR000300--IPPc
IPR001660--SAM
IPR013761--SAM/pointed
IPR000980--SH2

PROSITE

PS50105--SAM_DOMAIN
PS50001--SH2

Pfam

PF03372--Exo_endo_phos
PF00536--SAM_1
PF00017--SH2

Gene Ontology

GO:0005737--C:cytoplasm
GO:0005856--C:cytoskeleton
GO:0005829--C:cytosol
GO:0030175--C:filopodium
GO:0005794--C:Golgi apparatus
GO:0030027--C:lamellipodium
GO:0005886--C:plasma membrane
GO:0016787--F:hydrolase activity
GO:0042169--F:SH2 domain binding
GO:0007015--P:actin filament organization
GO:0007155--P:cell adhesion
GO:0001958--P:endochondral ossification
GO:0006897--P:endocytosis
GO:0006006--P:glucose metabolic process
GO:0002376--P:immune system process
GO:0043647--P:inositol phosphate metabolic process
GO:0008285--P:negative regulation of cell proliferation
GO:0010629--P:negative regulation of gene expression
GO:0006661--P:phosphatidylinositol biosynthetic process
GO:0046856--P:phosphatidylinositol dephosphorylation
GO:0006644--P:phospholipid metabolic process
GO:0009791--P:post-embryonic development
GO:0032868--P:response to insulin
GO:0097178--P:ruffle assembly
GO:0044281--P:small molecule metabolic process