UniProtKB - Q96PE3 (INP4A_HUMAN)
Protein
Inositol polyphosphate-4-phosphatase type I A
Gene
INPP4A
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (PubMed:20463662, PubMed:15716355). Catalyzes also inositol 1,3,4-trisphosphate and inositol 1,4-bisphosphate (By similarity). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:30071275) (By similarity). May protect neurons from excitotoxic cell death by regulating the synaptic localization of cell surface N-methyl-D-aspartate-type glutamate receptors (NMDARs) and NMDAR-mediated excitatory postsynaptic current (By similarity).By similarity3 Publications
Displays no 4-phosphatase activity for PtdIns(3,4)P2, Ins(3,4)P2, or Ins(1,3,4)P3.1 Publication
Catalytic activityi
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + phosphate2 PublicationsEC:3.1.3.662 PublicationsThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forwardBy similarity direction.
- 1D-myo-inositol 1,3,4-trisphosphate + H2O = 1D-myo-inositol 1,3-bisphosphate + phosphateBy similarityThis reaction proceeds in the forwardBy similarity direction.
: phosphatidylinositol signaling pathway Pathwayi
This protein is involved in the pathway phosphatidylinositol signaling pathway, which is part of Signal transduction.2 PublicationsView all proteins of this organism that are known to be involved in the pathway phosphatidylinositol signaling pathway and in Signal transduction.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 895 | Phosphocysteine intermediate1 Publication | 1 |
GO - Molecular functioni
- phosphatidylinositol-3,4-bisphosphate 4-phosphatase activity Source: GO_Central
- phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity Source: UniProtKB-EC
GO - Biological processi
- inositol phosphate metabolic process Source: Reactome
- phosphatidylinositol biosynthetic process Source: Reactome
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Hydrolase |
Enzyme and pathway databases
BioCyci | MetaCyc:HS00551-MONOMER |
BRENDAi | 3.1.3.66, 2681 |
PathwayCommonsi | Q96PE3 |
Reactomei | R-HSA-1660499, Synthesis of PIPs at the plasma membrane R-HSA-1660516, Synthesis of PIPs at the early endosome membrane R-HSA-1855183, Synthesis of IP2, IP, and Ins in the cytosol |
UniPathwayi | UPA00944 |
Chemistry databases
SwissLipidsi | SLP:000000900 |
Names & Taxonomyi
Protein namesi | Recommended name: Inositol polyphosphate-4-phosphatase type I AImportedAlternative name(s): Inositol polyphosphate 4-phosphatase type I1 Publication Type I inositol 3,4-bisphosphate 4-phosphatase (EC:3.1.3.663 Publications) |
Gene namesi | Name:INPP4A |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000040933.15 |
HGNCi | HGNC:6074, INPP4A |
MIMi | 600916, gene |
neXtProti | NX_Q96PE3 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication
Nucleus
- Nucleus 1 Publication
Endosome
- Early endosome membrane 1 Publication
- Recycling endosome membrane 1 Publication
Other locations
- Cytoplasm 1 Publication
- postsynaptic density By similarity
Note: Translocates to the plasma membrane upon EGF stimulation (PubMed:15716355). Shuttles between the cytoplasm and the nucleus, depending on the cell cycle stage, with highest amounts detected in the nucleus during the G0/G1phase (PubMed:30071275).2 Publications
Cytosol
- cytosol Source: Reactome
Endosome
- early endosome membrane Source: UniProtKB-SubCell
- recycling endosome membrane Source: UniProtKB-SubCell
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: UniProtKB
- postsynaptic density Source: UniProtKB
Keywords - Cellular componenti
Cell junction, Cell membrane, Cytoplasm, Endosome, Membrane, Nucleus, SynapsePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 731 | D → N: Complete loss of lipid phosphatase activity. 1 Publication | 1 | |
Mutagenesisi | 895 | C → S: Does not rescue the wortmannin-induced dilation of endosomes due to accumulation of (PtdIns(3,4)P2). 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 3631 |
MalaCardsi | INPP4A |
OpenTargetsi | ENSG00000040933 |
PharmGKBi | PA29882 |
Miscellaneous databases
Pharosi | Q96PE3, Tbio |
Polymorphism and mutation databases
BioMutai | INPP4A |
DMDMi | 73920059 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000190232 | 1 – 977 | Inositol polyphosphate-4-phosphatase type I AAdd BLAST | 977 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 355 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 487 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q96PE3 |
jPOSTi | Q96PE3 |
MassIVEi | Q96PE3 |
MaxQBi | Q96PE3 |
PaxDbi | Q96PE3 |
PeptideAtlasi | Q96PE3 |
PRIDEi | Q96PE3 |
ProteomicsDBi | 77678 [Q96PE3-1] 77679 [Q96PE3-2] 77680 [Q96PE3-3] 77681 [Q96PE3-4] |
PTM databases
DEPODi | INPP4A |
iPTMneti | Q96PE3 |
MetOSitei | Q96PE3 |
PhosphoSitePlusi | Q96PE3 |
Expressioni
Tissue specificityi
Isoform 1 is expressed in the platelets, MEG-01 megakaryocytes and Jurkat T-cells. Isoform 2 is expressed in the brain.1 Publication
Gene expression databases
Bgeei | ENSG00000040933, Expressed in dorsolateral prefrontal cortex and 232 other tissues |
ExpressionAtlasi | Q96PE3, baseline and differential |
Genevisiblei | Q96PE3, HS |
Organism-specific databases
HPAi | ENSG00000040933, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with INPP5F.
1 PublicationProtein-protein interaction databases
BioGRIDi | 109843, 9 interactors |
IntActi | Q96PE3, 4 interactors |
MINTi | Q96PE3 |
STRINGi | 9606.ENSP00000074304 |
Miscellaneous databases
RNActi | Q96PE3, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 153 | C2PROSITE-ProRule annotationAdd BLAST | 128 |
Sequence similaritiesi
Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.Curated
Phylogenomic databases
eggNOGi | KOG4428, Eukaryota |
GeneTreei | ENSGT00940000157360 |
HOGENOMi | CLU_007802_0_0_1 |
InParanoidi | Q96PE3 |
OMAi | RMWAHND |
OrthoDBi | 129165at2759 |
PhylomeDBi | Q96PE3 |
TreeFami | TF325637 |
Family and domain databases
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR035892, C2_domain_sf IPR039034, INPP4 |
PANTHERi | PTHR12187, PTHR12187, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q96PE3-1) [UniParc]FASTAAdd to basket
Also known as: Alpha-3
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MTAREHSPRH GARARAMQRA STIDVAADML GLSLAGNIQD PDEPILEFSL
60 70 80 90 100
ACSELHTPSL DRKPNSFVAV SVTTPPQAFW TKHAQTEIIE GTNNPIFLSS
110 120 130 140 150
IAFFQDSLIN QMTQVKLSVY DVKDRSQGTM YLLGSGTFIV KDLLQDRHHR
160 170 180 190 200
LHLTLRSAES DRVGNITVIG WQMEEKSDQR PPVTRSVDTV NGRMVLPVDE
210 220 230 240 250
SLTEALGIRS KYASLRKDTL LKSVFGGAIC RMYRFPTTDG NHLRILEQMA
260 270 280 290 300
ESVLSLHVPR QFVKLLLEED AARVCELEEL GELSPCWESL RRQIVTQYQT
310 320 330 340 350
IILTYQENLT DLHQYRGPSF KASSLKADKK LEFVPTNLHI QRMRVQDDGG
360 370 380 390 400
SDQNYDIVTI GAPAAHCQGF KSGGLRKKLH KFEETKKHFE ECCTSSGCQS
410 420 430 440 450
IIYIPQDVVR AKEIIAQINT LKTQVSYYAE RLSRAAKDRS ATGLERTLAI
460 470 480 490 500
LADKTRQLVT VCDCKLLANS IHGLNAARPD YIASKASPTS TEEEQVMLRN
510 520 530 540 550
DQDTLMARWT GRNSRSSLQV DWHEEEWEKV WLNVDKSLEC IIQRVDKLLQ
560 570 580 590 600
KERLHGEGCE DVFPCAGSCT SKKGNPDSHA YWIRPEDPFC DVPSSPCPST
610 620 630 640 650
MPSTACHPHL TTHCSPPPEE SSPGEWSEAL YPLLTTLTDC VAMMSDKAKK
660 670 680 690 700
AMVFLLMQDS APTIATYLSL QYRRDVVFCQ TLTALICGFI IKLRNCLHDD
710 720 730 740 750
GFLRQLYTIG LLAQFESLLS TYGEELAMLE DMSLGIMDLR NVTFKVTQAT
760 770 780 790 800
SSASADMLPV ITGNRDGFNV RVPLPGPLFD ALPREIQSGM LLRVQPVLFN
810 820 830 840 850
VGINEQQTLA ERFGDTSLQE VINVESLVRL NSYFEQFKEV LPEDCLPRSR
860 870 880 890 900
SQTCLPELLR FLGQNVHARK NKNVDILWQA AEICRRLNGV RFTSCKSAKD
910 920 930 940 950
RTAMSVTLEQ CLILQHEHGM APQVFTQALE CMRSEGCRRE NTMKNVGSRK
960 970
YAFNSLQLKA FPKHYRPPEG TYGKVET
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB8ZZB2 | B8ZZB2_HUMAN | Inositol polyphosphate-4-phosphatas... | INPP4A | 306 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 767 | G → E in AAH28361 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_059359 | 604 | T → A. Corresponds to variant dbSNP:rs2278206Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_015240 | 389 – 393 | Missing in isoform 3. 1 Publication | 5 | |
Alternative sequenceiVSP_015241 | 574 – 613 | GNPDS…HLTTH → D in isoform 2 and isoform 4. 2 PublicationsAdd BLAST | 40 | |
Alternative sequenceiVSP_015242 | 935 – 977 | EGCRR…GKVET → IGTREVVTQKNLSGLVPIRD LRLDPSLLCSIPLLALSPNL LIVWLFLSIAYLVTKLRCK in isoform 4. 1 PublicationAdd BLAST | 43 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U26398 mRNA Translation: AAB01068.1 U96919 mRNA Translation: AAB72150.1 AF368319 mRNA Translation: AAK58870.1 AC010134 Genomic DNA Translation: AAX93230.1 BC028361 mRNA Translation: AAH28361.1 |
CCDSi | CCDS46369.1 [Q96PE3-1] CCDS46370.1 [Q96PE3-2] CCDS46371.1 [Q96PE3-3] CCDS46372.1 [Q96PE3-4] |
PIRi | B57487 |
RefSeqi | NP_001127696.1, NM_001134224.1 [Q96PE3-1] NP_001127697.1, NM_001134225.1 [Q96PE3-3] NP_001557.1, NM_001566.2 [Q96PE3-4] NP_004018.1, NM_004027.2 [Q96PE3-2] XP_016859487.1, XM_017003998.1 |
Genome annotation databases
Ensembli | ENST00000074304; ENSP00000074304; ENSG00000040933 [Q96PE3-1] ENST00000409016; ENSP00000386704; ENSG00000040933 [Q96PE3-2] ENST00000409540; ENSP00000387294; ENSG00000040933 [Q96PE3-4] ENST00000409851; ENSP00000386777; ENSG00000040933 [Q96PE3-3] ENST00000523221; ENSP00000427722; ENSG00000040933 [Q96PE3-1] |
GeneIDi | 3631 |
KEGGi | hsa:3631 |
UCSCi | uc002syx.4, human [Q96PE3-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U26398 mRNA Translation: AAB01068.1 U96919 mRNA Translation: AAB72150.1 AF368319 mRNA Translation: AAK58870.1 AC010134 Genomic DNA Translation: AAX93230.1 BC028361 mRNA Translation: AAH28361.1 |
CCDSi | CCDS46369.1 [Q96PE3-1] CCDS46370.1 [Q96PE3-2] CCDS46371.1 [Q96PE3-3] CCDS46372.1 [Q96PE3-4] |
PIRi | B57487 |
RefSeqi | NP_001127696.1, NM_001134224.1 [Q96PE3-1] NP_001127697.1, NM_001134225.1 [Q96PE3-3] NP_001557.1, NM_001566.2 [Q96PE3-4] NP_004018.1, NM_004027.2 [Q96PE3-2] XP_016859487.1, XM_017003998.1 |
3D structure databases
SMRi | Q96PE3 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109843, 9 interactors |
IntActi | Q96PE3, 4 interactors |
MINTi | Q96PE3 |
STRINGi | 9606.ENSP00000074304 |
Chemistry databases
SwissLipidsi | SLP:000000900 |
PTM databases
DEPODi | INPP4A |
iPTMneti | Q96PE3 |
MetOSitei | Q96PE3 |
PhosphoSitePlusi | Q96PE3 |
Polymorphism and mutation databases
BioMutai | INPP4A |
DMDMi | 73920059 |
Proteomic databases
EPDi | Q96PE3 |
jPOSTi | Q96PE3 |
MassIVEi | Q96PE3 |
MaxQBi | Q96PE3 |
PaxDbi | Q96PE3 |
PeptideAtlasi | Q96PE3 |
PRIDEi | Q96PE3 |
ProteomicsDBi | 77678 [Q96PE3-1] 77679 [Q96PE3-2] 77680 [Q96PE3-3] 77681 [Q96PE3-4] |
Protocols and materials databases
Antibodypediai | 41266, 99 antibodies |
DNASUi | 3631 |
Genome annotation databases
Ensembli | ENST00000074304; ENSP00000074304; ENSG00000040933 [Q96PE3-1] ENST00000409016; ENSP00000386704; ENSG00000040933 [Q96PE3-2] ENST00000409540; ENSP00000387294; ENSG00000040933 [Q96PE3-4] ENST00000409851; ENSP00000386777; ENSG00000040933 [Q96PE3-3] ENST00000523221; ENSP00000427722; ENSG00000040933 [Q96PE3-1] |
GeneIDi | 3631 |
KEGGi | hsa:3631 |
UCSCi | uc002syx.4, human [Q96PE3-1] |
Organism-specific databases
CTDi | 3631 |
DisGeNETi | 3631 |
EuPathDBi | HostDB:ENSG00000040933.15 |
GeneCardsi | INPP4A |
HGNCi | HGNC:6074, INPP4A |
HPAi | ENSG00000040933, Low tissue specificity |
MalaCardsi | INPP4A |
MIMi | 600916, gene |
neXtProti | NX_Q96PE3 |
OpenTargetsi | ENSG00000040933 |
PharmGKBi | PA29882 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4428, Eukaryota |
GeneTreei | ENSGT00940000157360 |
HOGENOMi | CLU_007802_0_0_1 |
InParanoidi | Q96PE3 |
OMAi | RMWAHND |
OrthoDBi | 129165at2759 |
PhylomeDBi | Q96PE3 |
TreeFami | TF325637 |
Enzyme and pathway databases
UniPathwayi | UPA00944 |
BioCyci | MetaCyc:HS00551-MONOMER |
BRENDAi | 3.1.3.66, 2681 |
PathwayCommonsi | Q96PE3 |
Reactomei | R-HSA-1660499, Synthesis of PIPs at the plasma membrane R-HSA-1660516, Synthesis of PIPs at the early endosome membrane R-HSA-1855183, Synthesis of IP2, IP, and Ins in the cytosol |
Miscellaneous databases
BioGRID-ORCSi | 3631, 7 hits in 843 CRISPR screens |
ChiTaRSi | INPP4A, human |
GeneWikii | INPP4A |
GenomeRNAii | 3631 |
Pharosi | Q96PE3, Tbio |
PROi | PR:Q96PE3 |
RNActi | Q96PE3, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000040933, Expressed in dorsolateral prefrontal cortex and 232 other tissues |
ExpressionAtlasi | Q96PE3, baseline and differential |
Genevisiblei | Q96PE3, HS |
Family and domain databases
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR035892, C2_domain_sf IPR039034, INPP4 |
PANTHERi | PTHR12187, PTHR12187, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | INP4A_HUMAN | |
Accessioni | Q96PE3Primary (citable) accession number: Q96PE3 Secondary accession number(s): O15326 Q8TC02 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 30, 2005 |
Last sequence update: | December 1, 2001 | |
Last modified: | December 2, 2020 | |
This is version 135 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations