dbPAF Protein Information
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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)
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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 |
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Keyword | KW-0002--3D-structure |
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Interpro | IPR005135--Endo/exonuclease/phosphatase |
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PROSITE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pfam | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Gene Ontology | GO:0005737--C:cytoplasm |