Overview
| Uniprot ID | Q92835 |
|---|
| Protein Name | Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 |
|---|
| Gene Name | INPP5D |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 349 |
KKILQLIKSQKFLNK |
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:10764818, PubMed:8723348, PubMed:8769125). Also, is able to hydrolyze the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3), 1D-myo-inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate (PubMed:10764818, PubMed:40969890, PubMed:8769125, PubMed:9108392). 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 (PubMed:16682172). 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
Protein Sequence
10
MVPCWNHGNI
20
TRSKAEELLS
30
RTGKDGSFLV
40
RASESISRAY
50
ALCVLYRNCV
60
YTYRILPNED
70
DKFTVQASEG
80
VSMRFFTKLD
90
QLIEFYKKEN
100
MGLVTHLQYP
110
VPLEEEDTGD
120
DPEEDTVESV
130
VSPPELPPRN
140
IPLTASSCEA
150
KEVPFSNENP
160
RATETSRPSL
170
SETLFQRLQS
180
MDTSGLPEEH
190
LKAIQDYLST
200
QLAQDSEFVK
210
TGSSSLPHLK
220
KLTTLLCKEL
230
YGEVIRTLPS
240
LESLQRLFDQ
250
QLSPGLRPRP
260
QVPGEANPIN
270
MVSKLSQLTS
280
LLSSIEDKVK
290
ALLHEGPESP
300
HRPSLIPPVT
310
FEVKAESLGI
320
PQKMQLKVDV
330
ESGKLIIKKS
340
KDGSEDKFYS
350
HKKILQLIKS
360
QKFLNKLVIL
370
VETEKEKILR
380
KEYVFADSKK
390
REGFCQLLQQ
400
MKNKHSEQPE
410
PDMITIFIGT
420
WNMGNAPPPK
430
KITSWFLSKG
440
QGKTRDDSAD
450
YIPHDIYVIG
460
TQEDPLSEKE
470
WLEILKHSLQ
480
EITSVTFKTV
490
AIHTLWNIRI
500
VVLAKPEHEN
510
RISHICTDNV
520
KTGIANTLGN
530
KGAVGVSFMF
540
NGTSLGFVNS
550
HLTSGSEKKL
560
RRNQNYMNIL
570
RFLALGDKKL
580
SPFNITHRFT
590
HLFWFGDLNY
600
RVDLPTWEAE
610
TIIQKIKQQQ
620
YADLLSHDQL
630
LTERREQKVF
640
LHFEEEEITF
650
APTYRFERLT
660
RDKYAYTKQK
670
ATGMKYNLPS
680
WCDRVLWKSY
690
PLVHVVCQSY
700
GSTSDIMTSD
710
HSPVFATFEA
720
GVTSQFVSKN
730
GPGTVDSQGQ
740
IEFLRCYATL
750
KTKSQTKFYL
760
EFHSSCLESF
770
VKSQEGENEE
780
GSEGELVVKF
790
GETLPKLKPI
800
ISDPEYLLDQ
810
HILISIKSSD
820
SDESYGEGCI
830
ALRLEATETQ
840
LPIYTPLTHH
850
GELTGHFQGE
860
IKLQTSQGKT
870
REKLYDFVKT
880
ERDESSGPKT
890
LKSLTSHDPM
900
KQWEVTSRAP
910
PCSGSSITEI
920
INPNYMGVGP
930
FGPPMPLHVK
940
QTLSPDQQPT
950
AWSYDQPPKD
960
SPLGPCRGES
970
PPTPPGQPPI
980
SPKKFLPSTA
990
NRGLPPRTQE
1000
SRPSDLGKNA
1010
GDTLPQEDLP
1020
LTKPEMFENP
1030
LYGSLSSFPK
1040
PAPRKDQESP
1050
KMPRKEPPPC
1060
PEPGILSPSI
1070
VLTKAQEADR
1080
GEGPGKQVPA
1090
PRLRSFTCSS
1100
SAEGRAAGGD
1110
KSQGKPKTPV
1120
SSQAPVPAKR
1130
PIKPSRSEIN
1140
QQTPPTPTPR
1150
PPLPVKSPAV
1160
LHLQHSKGRD
1170
YRDNTELPHH
1180
GKHRPEEGPP
GPLGRTAMQ
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005856 |
cytoskeleton |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0045121 |
membrane raft |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Molecular Function |
GO:0052659 |
inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity |
| Molecular Function |
GO:0004445 |
inositol-polyphosphate 5-phosphatase activity |
| Molecular Function |
GO:0016314 |
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity |
| Molecular Function |
GO:0034485 |
phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity |
| Molecular Function |
GO:0004439 |
phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity |
| Molecular Function |
GO:0017124 |
SH3 domain binding |
| Biological Process |
GO:0006915 |
apoptotic process |
| Biological Process |
GO:0045779 |
negative regulation of bone resorption |
| Biological Process |
GO:0045953 |
negative regulation of natural killer cell mediated cytotoxicity |
| Biological Process |
GO:0045659 |
negative regulation of neutrophil differentiation |
| Biological Process |
GO:0009968 |
negative regulation of signal transduction |
| Biological Process |
GO:0006796 |
phosphate-containing compound metabolic process |
| Biological Process |
GO:0006661 |
phosphatidylinositol biosynthetic process |
| Biological Process |
GO:0046856 |
phosphatidylinositol dephosphorylation |
| Biological Process |
GO:0045579 |
positive regulation of B cell differentiation |
| Biological Process |
GO:0050776 |
regulation of immune response |
| Biological Process |
GO:0007165 |
signal transduction |
| Biological Process |
GO:0050852 |
T cell receptor signaling pathway |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.