INP4B_HUMAN
ID INP4B_HUMAN Reviewed; 924 AA.
AC O15327; Q2TAI2; Q5XLE7; Q6IN59; Q6PJB4;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 4.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Inositol polyphosphate 4-phosphatase type II;
DE AltName: Full=Type II inositol 3,4-bisphosphate 4-phosphatase;
DE EC=3.1.3.66 {ECO:0000269|PubMed:24591580};
GN Name=INPP4B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP PHE-311.
RC TISSUE=Brain;
RX PubMed=9295334; DOI=10.1074/jbc.272.38.23859;
RA Norris F.A., Atkins R.C., Majerus P.W.;
RT "The cDNA cloning and characterization of inositol polyphosphate 4-
RT phosphatase type II. Evidence for conserved alternative splicing in the 4-
RT phosphatase family.";
RL J. Biol. Chem. 272:23859-23864(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RA Shearn C.T., Joseph R.E., Norris F.A.;
RT "Characterization of stubby: a natural C2 domain containing spliceoform of
RT type II inositol polyphosphate 4-phosphatases.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION.
RX PubMed=19647222; DOI=10.1016/j.ccr.2009.06.006;
RA Gewinner C., Wang Z.C., Richardson A., Teruya-Feldstein J.,
RA Etemadmoghadam D., Bowtell D., Barretina J., Lin W.M., Rameh L.,
RA Salmena L., Pandolfi P.P., Cantley L.C.;
RT "Evidence that inositol polyphosphate 4-phosphatase type II is a tumor
RT suppressor that inhibits PI3K signaling.";
RL Cancer Cell 16:115-125(2009).
RN [7]
RP CATALYTIC ACTIVITY, FUNCTION, AND MUTAGENESIS OF CYS-842; LYS-843; LYS-846
RP AND ASP-847.
RX PubMed=24070612; DOI=10.1016/j.bbrc.2013.09.077;
RA Lopez S.M., Hodgson M.C., Packianathan C., Bingol-Ozakpinar O., Uras F.,
RA Rosen B.P., Agoulnik I.U.;
RT "Determinants of the tumor suppressor INPP4B protein and lipid phosphatase
RT activities.";
RL Biochem. Biophys. Res. Commun. 440:277-282(2013).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24591580; DOI=10.1073/pnas.1311029111;
RA Maekawa M., Terasaka S., Mochizuki Y., Kawai K., Ikeda Y., Araki N.,
RA Skolnik E.Y., Taguchi T., Arai H.;
RT "Sequential breakdown of 3-phosphorylated phosphoinositides is essential
RT for the completion of macropinocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E978-E987(2014).
CC -!- FUNCTION: Catalyzes the hydrolysis of the 4-position phosphate of
CC phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and
CC inositol 3,4-trisphosphate (PubMed:24070612, PubMed:24591580). Plays a
CC role in the late stages of macropinocytosis by dephosphorylating
CC phosphatidylinositol 3,4-bisphosphate in membrane ruffles
CC (PubMed:24591580). The lipid phosphatase activity is critical for tumor
CC suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by
CC dephosphorylating phosphoinositides and thereby modulating cell cycle
CC progression and cell survival (PubMed:19647222, PubMed:24070612).
CC {ECO:0000269|PubMed:19647222, ECO:0000269|PubMed:24070612,
CC ECO:0000269|PubMed:24591580}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3-phosphate) + phosphate; Xref=Rhea:RHEA:17193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57658,
CC ChEBI:CHEBI:58088; EC=3.1.3.66;
CC Evidence={ECO:0000269|PubMed:19647222, ECO:0000269|PubMed:24070612,
CC ECO:0000305|PubMed:24591580};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17194;
CC Evidence={ECO:0000305|PubMed:24070612};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4-trisphosphate + H2O = 1D-myo-inositol
CC 1,3-bisphosphate + phosphate; Xref=Rhea:RHEA:43392,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58414,
CC ChEBI:CHEBI:83242; Evidence={ECO:0000269|PubMed:24070612};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43393;
CC Evidence={ECO:0000305|PubMed:24070612};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 3,4-bisphosphate + H2O = 1D-myo-inositol 3-
CC phosphate + phosphate; Xref=Rhea:RHEA:43388, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58401, ChEBI:CHEBI:83241;
CC Evidence={ECO:0000250|UniProtKB:Q9QWG5};
CC -!- ACTIVITY REGULATION: Strongly inhibited by inositol hexakisphosphate.
CC {ECO:0000250|UniProtKB:Q9QWG5}.
CC -!- PATHWAY: Signal transduction; phosphatidylinositol signaling pathway.
CC {ECO:0000250|UniProtKB:Q9QWG5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O15327-1; Sequence=Displayed;
CC Name=2; Synonyms=stubby;
CC IsoId=O15327-2; Sequence=VSP_047696, VSP_047697;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels occurring in
CC the skeletal muscle and heart. {ECO:0000269|PubMed:9295334}.
CC -!- SIMILARITY: Belongs to the inositol 3,4-bisphosphate 4-phosphatase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH72447.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; U96922; AAB72153.1; -; mRNA.
DR EMBL; AY753912; AAV28485.1; -; mRNA.
DR EMBL; AC093860; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138657; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC139720; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX05081.1; -; Genomic_DNA.
DR EMBL; BC017924; AAH17924.1; -; mRNA.
DR EMBL; BC072447; AAH72447.1; ALT_SEQ; mRNA.
DR EMBL; BC110918; AAI10919.1; -; mRNA.
DR EMBL; BC133005; AAI33006.1; -; mRNA.
DR CCDS; CCDS3757.1; -. [O15327-1]
DR RefSeq; NP_001095139.1; NM_001101669.2. [O15327-1]
DR RefSeq; NP_001317969.1; NM_001331040.1.
DR RefSeq; NP_003857.2; NM_003866.3. [O15327-1]
DR AlphaFoldDB; O15327; -.
DR BioGRID; 114348; 6.
DR IntAct; O15327; 1.
DR STRING; 9606.ENSP00000425487; -.
DR SwissLipids; SLP:000000898; -.
DR DEPOD; INPP4B; -.
DR iPTMnet; O15327; -.
DR PhosphoSitePlus; O15327; -.
DR BioMuta; INPP4B; -.
DR EPD; O15327; -.
DR jPOST; O15327; -.
DR MassIVE; O15327; -.
DR MaxQB; O15327; -.
DR PaxDb; O15327; -.
DR PeptideAtlas; O15327; -.
DR PRIDE; O15327; -.
DR ProteomicsDB; 48591; -. [O15327-1]
DR ProteomicsDB; 65839; -.
DR ABCD; O15327; 1 sequenced antibody.
DR Antibodypedia; 27309; 134 antibodies from 27 providers.
DR DNASU; 8821; -.
DR Ensembl; ENST00000262992.9; ENSP00000262992.4; ENSG00000109452.13. [O15327-1]
DR Ensembl; ENST00000506217.5; ENSP00000424057.1; ENSG00000109452.13. [O15327-2]
DR Ensembl; ENST00000508116.5; ENSP00000423954.1; ENSG00000109452.13. [O15327-1]
DR Ensembl; ENST00000513000.5; ENSP00000425487.1; ENSG00000109452.13. [O15327-1]
DR GeneID; 8821; -.
DR KEGG; hsa:8821; -.
DR MANE-Select; ENST00000262992.9; ENSP00000262992.4; NM_001101669.3; NP_001095139.1.
DR UCSC; uc003iix.5; human. [O15327-1]
DR CTD; 8821; -.
DR DisGeNET; 8821; -.
DR GeneCards; INPP4B; -.
DR HGNC; HGNC:6075; INPP4B.
DR HPA; ENSG00000109452; Low tissue specificity.
DR MIM; 607494; gene.
DR neXtProt; NX_O15327; -.
DR OpenTargets; ENSG00000109452; -.
DR PharmGKB; PA29883; -.
DR VEuPathDB; HostDB:ENSG00000109452; -.
DR eggNOG; KOG4428; Eukaryota.
DR GeneTree; ENSGT00940000157587; -.
DR HOGENOM; CLU_007802_1_0_1; -.
DR InParanoid; O15327; -.
DR OMA; CNEMSEQ; -.
DR OrthoDB; 129165at2759; -.
DR PhylomeDB; O15327; -.
DR TreeFam; TF325637; -.
DR BioCyc; MetaCyc:HS03227-MON; -.
DR BRENDA; 3.1.3.66; 2681.
DR PathwayCommons; O15327; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-HSA-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR SignaLink; O15327; -.
DR SIGNOR; O15327; -.
DR UniPathway; UPA00944; -.
DR BioGRID-ORCS; 8821; 11 hits in 1071 CRISPR screens.
DR ChiTaRS; INPP4B; human.
DR GeneWiki; INPP4B; -.
DR GenomeRNAi; 8821; -.
DR Pharos; O15327; Tbio.
DR PRO; PR:O15327; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O15327; protein.
DR Bgee; ENSG00000109452; Expressed in sperm and 169 other tissues.
DR ExpressionAtlas; O15327; baseline and differential.
DR Genevisible; O15327; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0017161; F:inositol-1,3,4-trisphosphate 4-phosphatase activity; TAS:Reactome.
DR GO; GO:0052828; F:inositol-3,4-bisphosphate 4-phosphatase activity; TAS:Reactome.
DR GO; GO:0016316; F:phosphatidylinositol-3,4-bisphosphate 4-phosphatase activity; IBA:GO_Central.
DR GO; GO:0034597; F:phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IEA:Ensembl.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR039034; INPP4.
DR PANTHER; PTHR12187; PTHR12187; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Lipid metabolism; Reference proteome.
FT CHAIN 1..924
FT /note="Inositol polyphosphate 4-phosphatase type II"
FT /id="PRO_0000190235"
FT DOMAIN 23..165
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 481..516
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 546..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..503
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 125..131
FT /note="VRTSVLP -> IANSSRI (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_047696"
FT VAR_SEQ 132..924
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_047697"
FT VARIANT 311
FT /note="Y -> F (in dbSNP:rs1064226)"
FT /evidence="ECO:0000269|PubMed:9295334"
FT /id="VAR_023324"
FT MUTAGEN 842
FT /note="C->S: Abolished phosphotyrosine phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:24070612"
FT MUTAGEN 843
FT /note="K->M: Increased phosphotyrosine phosphatase
FT activity. Does not alter lipid phosphatase activity for the
FT substrate phosphatidylinositol(3,4)P2, but reduced
FT hydrolysis of inositol(1,3,4)P3 by about 70%."
FT /evidence="ECO:0000269|PubMed:24070612"
FT MUTAGEN 846
FT /note="K->M: Does not alter phosphotyrosine phosphatase
FT activity. Abolished lipid phosphatase activity."
FT /evidence="ECO:0000269|PubMed:24070612"
FT MUTAGEN 847
FT /note="D->E: Significantly reduces phosphotyrosine
FT phosphatase activity. Not able to dephosphorylate
FT phosphatidylinositol(3,4)P2 but retains approximately 35%
FT of activity towards Inosotol(1,3,4)P3."
FT /evidence="ECO:0000269|PubMed:24070612"
FT CONFLICT 319
FT /note="S -> A (in Ref. 1; AAB72153)"
FT /evidence="ECO:0000305"
FT CONFLICT 683
FT /note="A -> P (in Ref. 1; AAB72153)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 924 AA; 104738 MW; 57DE9D98E0168D41 CRC64;
MEIKEEGASE EGQHFLPTAQ ANDPGDCQFT SIQKTPNEPQ LEFILACKDL VAPVRDRKLN
TLVQISVIHP VEQSLTRYSS TEIVEGTRDP LFLTGVTFPS EYPIYEETKI KLTVYDVKDK
SHDTVRTSVL PEHKDPPPEV GRSFLGYASF KVGELLKSKE QLLVLSLRTS DGGKVVGTIE
VSVVKMGEIE DGEADHITTD VQGQKCALVC ECTAPESVSG KDNLPFLNSV LKNPVCKLYR
FPTSDNKWMR IREQMSESIL SFHIPKELIS LHIKEDLCRN QEIKELGELS PHWDNLRKNV
LTHCDQMVNM YQDILTELSK ETGSSFKSSS SKGEKTLEFV PINLHLQRMQ VHSPHLKDAL
YDVITVGAPA AHFQGFKNGG LRKLLHRFET ERRNTGYQFI YYSPENTAKA KEVLSNINQL
QPLIATHADL LLNSASQHSP DSLKNSLKML SEKTELFVHA FKDQLVRSAL LALYTARPGG
ILKKPPSPKS STEESSPQDQ PPVMRGQDSI PHHSDYDEEE WDRVWANVGK SLNCIIAMVD
KLIERDGGSE GSGGNNDGEK EPSLTDAIPS HPREDWYEQL YPLILTLKDC MGEVVNRAKQ
SLTFVLLQEL AYSLPQCLML TLRRDIVFSQ ALAGLVCGFI IKLQTSLYDP GFLQQLHTVG
LIVQYEGLLS TYSDEIGMLE DMAVGISDLK KVAFKIIEAK SNDVLPVITG RREHYVVEVK
LPARMFESLP LQIKEGQLLH VYPVLFNVGI NEQQTLAERF GDVSLQESIN QENFELLQEY
YKIFMEKMPP DYISHFQEQN DLKALLENLL QNIQSKKRKN VEIMWLAATI CRKLNGIRFT
CCKSAKDRTS MSVTLEQCSI LRDEHQLHKD FFIRALDCMR REGCRIENVL KNIKCRKYAF
NMLQLMAFPK YYRPPEGTYG KADT
