Search Results

Overview

Uniprot ID	O15357
Protein Name	Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Gene Name	INPPL1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
1014	APVPSATKNKVAITV
325	VTLGDLTKIGKSQKF

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 (PubMed:16824732). Required for correct mitotic spindle orientation and therefore progression of mitosis (By similarity). Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear (PubMed:9660833). While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking (By similarity). Confers resistance to dietary obesity (By similarity). May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane (By similarity). Part of a signaling pathway that regulates actin cytoskeleton remodeling (PubMed:11739414, PubMed:12676785). 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 (PubMed:15668240). 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 (PubMed:12235291). Required for HGF-mediated lamellipodium formation, cell scattering and spreading (PubMed:15735664). Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation (PubMed:17135240). 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 (By similarity). Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A) (PubMed:12690104). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems (PubMed:11016922). Involved in EGF signaling pathway (PubMed:11349134). Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3 (PubMed:11349134). Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity (PubMed:11349134). Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1 (By similarity). In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling (By similarity). Plays a role in the localization of AURKA and NEDD9/HEF1 to the basolateral membrane at interphase in polarized cysts, thereby mediates cell cycle homeostasis, cell polarization and cilia assembly (By similarity). Additionally promotion of cilia growth is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2 (By similarity). Promotes formation of apical membrane-initiation sites during the initial stages of lumen formation via Rho family-induced actin filament organization and CTNNB1 localization to cell-cell contacts (By similarity). 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 (PubMed:23273569)

Protein Sequence

10 MASACGAPGP 20 GGALGSQAPS 30 WYHRDLSRAA 40 AEELLARAGR 50 DGSFLVRDSE 60 SVAGAFALCV 70 LYQKHVHTYR 80 ILPDGEDFLA 90 VQTSQGVPVR 100 RFQTLGELIG 110 LYAQPNQGLV 120 CALLLPVEGE 130 REPDPPDDRD 140 ASDGEDEKPP 150 LPPRSGSTSI 160 SAPTGPSSPL 170 PAPETPTAPA 180 AESAPNGLST 190 VSHDYLKGSY 200 GLDLEAVRGG 210 ASHLPHLTRT 220 LATSCRRLHS 230 EVDKVLSGLE 240 ILSKVFDQQS 250 SPMVTRLLQQ 260 QNLPQTGEQE 270 LESLVLKLSV 280 LKDFLSGIQK 290 KALKALQDMS 300 STAPPAPQPS 310 TRKAKTIPVQ 320 AFEVKLDVTL 330 GDLTKIGKSQ 340 KFTLSVDVEG 350 GRLVLLRRQR 360 DSQEDWTTFT 370 HDRIRQLIKS 380 QRVQNKLGVV 390 FEKEKDRTQR 400 KDFIFVSARK 410 REAFCQLLQL 420 MKNKHSKQDE 430 PDMISVFIGT 440 WNMGSVPPPK 450 NVTSWFTSKG 460 LGKTLDEVTV 470 TIPHDIYVFG 480 TQENSVGDRE 490 WLDLLRGGLK 500 ELTDLDYRPI 510 AMQSLWNIKV 520 AVLVKPEHEN 530 RISHVSTSSV 540 KTGIANTLGN 550 KGAVGVSFMF 560 NGTSFGFVNC 570 HLTSGNEKTA 580 RRNQNYLDIL 590 RLLSLGDRQL 600 NAFDISLRFT 610 HLFWFGDLNY 620 RLDMDIQEIL 630 NYISRKEFEP 640 LLRVDQLNLE 650 REKHKVFLRF 660 SEEEISFPPT 670 YRYERGSRDT 680 YAWHKQKPTG 690 VRTNVPSWCD 700 RILWKSYPET 710 HIICNSYGCT 720 DDIVTSDHSP 730 VFGTFEVGVT 740 SQFISKKGLS 750 KTSDQAYIEF 760 ESIEAIVKTA 770 SRTKFFIEFY 780 STCLEEYKKS 790 FENDAQSSDN 800 INFLKVQWSS 810 RQLPTLKPIL 820 ADIEYLQDQH 830 LLLTVKSMDG 840 YESYGECVVA 850 LKSMIGSTAQ 860 QFLTFLSHRG 870 EETGNIRGSM 880 KVRVPTERLG 890 TRERLYEWIS 900 IDKDEAGAKS 910 KAPSVSRGSQ 920 EPRSGSRKPA 930 FTEASCPLSR 940 LFEEPEKPPP 950 TGRPPAPPRA 960 APREEPLTPR 970 LKPEGAPEPE 980 GVAAPPPKNS 990 FNNPAYYVLE 1000 GVPHQLLPPE 1010 PPSPARAPVP 1020 SATKNKVAIT 1030 VPAPQLGHHR 1040 HPRVGEGSSS 1050 DEESGGTLPP 1060 PDFPPPPLPD 1070 SAIFLPPSLD 1080 PLPGPVVRGR 1090 GGAEARGPPP 1100 PKAHPRPPLP 1110 PGPSPASTFL 1120 GEVASGDDRS 1130 CSVLQMAKTL 1140 SEVDYAPAGP 1150 ARSALLPGPL 1160 ELQPPRGLPS 1170 DYGRPLSFPP 1180 PRIRESIQED 1190 LAEEAPCLQG 1200 GRASGLGEAG 1210 MSAWLRAIGL 1220 ERYEEGLVHN 1230 GWDDLEFLSD 1240 ITEEDLEEAG 1250 VQDPAHKRLL LDTLQLSK

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0009925	basal plasma membrane
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0030175	filopodium
Cellular Component	GO:0030027	lamellipodium
Cellular Component	GO:0016607	nuclear speck
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0000922	spindle pole
Molecular Function	GO:0003779	actin binding
Molecular Function	GO:0004445	inositol-polyphosphate 5-phosphatase activity
Molecular Function	GO:0034485	phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity
Molecular Function	GO:0042169	SH2 domain binding
Molecular Function	GO:0017124	SH3 domain binding
Biological Process	GO:0007015	actin filament organization
Biological Process	GO:0007155	cell adhesion
Biological Process	GO:0001958	endochondral ossification
Biological Process	GO:0006897	endocytosis
Biological Process	GO:0000132	establishment of mitotic spindle orientation
Biological Process	GO:0002376	immune system process
Biological Process	GO:0043569	negative regulation of insulin-like growth factor receptor signaling pathway
Biological Process	GO:0006661	phosphatidylinositol biosynthetic process
Biological Process	GO:0046856	phosphatidylinositol dephosphorylation
Biological Process	GO:0110053	regulation of actin filament organization
Biological Process	GO:0050776	regulation of immune response
Biological Process	GO:0032880	regulation of protein localization

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[3] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.