INP4B_RAT
ID INP4B_RAT Reviewed; 928 AA.
AC Q9QWG5; O35825;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Type II inositol 3,4-bisphosphate 4-phosphatase;
DE EC=3.1.3.66 {ECO:0000269|PubMed:9295334};
DE AltName: Full=Inositol polyphosphate 4-phosphatase type II;
GN Name=Inpp4b;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND FUNCTION.
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).
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-bisphosphate (PubMed:9295334). Plays a role in the late
CC stages of macropinocytosis by dephosphorylating phosphatidylinositol
CC 3,4-bisphosphate in membrane ruffles (By similarity). The lipid
CC phosphatase activity is critical for tumor suppressor function.
CC Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating
CC phosphoinositides and thereby modulating cell cycle progression and
CC cell survival (By similarity). {ECO:0000250|UniProtKB:O15327,
CC ECO:0000269|PubMed:9295334}.
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:9295334};
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:0000269|PubMed:9295334};
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:9295334};
CC -!- ACTIVITY REGULATION: Strongly inhibited by inositol hexakisphosphate.
CC {ECO:0000269|PubMed:9295334}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=39 uM for inositol 3,4-bisphosphate {ECO:0000269|PubMed:9295334};
CC KM=34 uM for inositol 1,3,4-trisphosphate
CC {ECO:0000269|PubMed:9295334};
CC Vmax=26 umol/min/mg enzyme with inositol 3,4-bisphosphate as
CC substrate {ECO:0000269|PubMed:9295334};
CC Vmax=22 umol/min/mg enzyme with inositol 1,3,4-trisphosphate as
CC substrate {ECO:0000269|PubMed:9295334};
CC pH dependence:
CC Optimum pH is 7-8. {ECO:0000269|PubMed:9295334};
CC -!- PATHWAY: Signal transduction; phosphatidylinositol signaling pathway.
CC {ECO:0000269|PubMed:9295334}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q9QWG5-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q9QWG5-2; Sequence=VSP_015249;
CC -!- MISCELLANEOUS: [Isoform 2]: Inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the inositol 3,4-bisphosphate 4-phosphatase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U96920; AAB72151.1; -; mRNA.
DR EMBL; U96921; AAB72152.1; -; mRNA.
DR RefSeq; NP_446369.1; NM_053917.1. [Q9QWG5-2]
DR RefSeq; XP_008770684.1; XM_008772462.2. [Q9QWG5-2]
DR RefSeq; XP_008770686.1; XM_008772464.2. [Q9QWG5-1]
DR RefSeq; XP_017456652.1; XM_017601163.1. [Q9QWG5-2]
DR RefSeq; XP_017456653.1; XM_017601164.1. [Q9QWG5-1]
DR AlphaFoldDB; Q9QWG5; -.
DR SMR; Q9QWG5; -.
DR STRING; 10116.ENSRNOP00000025013; -.
DR SwissLipids; SLP:000000896; -.
DR iPTMnet; Q9QWG5; -.
DR PhosphoSitePlus; Q9QWG5; -.
DR PaxDb; Q9QWG5; -.
DR Ensembl; ENSRNOT00000024981; ENSRNOP00000024981; ENSRNOG00000018382. [Q9QWG5-1]
DR Ensembl; ENSRNOT00000025013; ENSRNOP00000025013; ENSRNOG00000018382. [Q9QWG5-2]
DR GeneID; 116699; -.
DR KEGG; rno:116699; -.
DR CTD; 8821; -.
DR RGD; 620470; Inpp4b.
DR eggNOG; KOG4428; Eukaryota.
DR GeneTree; ENSGT00940000157587; -.
DR HOGENOM; CLU_007802_1_0_1; -.
DR InParanoid; Q9QWG5; -.
DR OMA; CNEMSEQ; -.
DR OrthoDB; 129165at2759; -.
DR PhylomeDB; Q9QWG5; -.
DR TreeFam; TF325637; -.
DR BRENDA; 3.1.3.66; 5301.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-RNO-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR UniPathway; UPA00944; -.
DR PRO; PR:Q9QWG5; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000018382; Expressed in heart and 17 other tissues.
DR Genevisible; Q9QWG5; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0017161; F:inositol-1,3,4-trisphosphate 4-phosphatase activity; IEA:RHEA.
DR GO; GO:0052828; F:inositol-3,4-bisphosphate 4-phosphatase activity; IEA:RHEA.
DR GO; GO:0008289; F:lipid binding; ISO:RGD.
DR GO; GO:0034593; F:phosphatidylinositol bisphosphate phosphatase activity; ISO:RGD.
DR GO; GO:0034594; F:phosphatidylinositol trisphosphate phosphatase activity; ISO:RGD.
DR GO; GO:0016316; F:phosphatidylinositol-3,4-bisphosphate 4-phosphatase activity; IDA:RGD.
DR GO; GO:0034597; F:phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IDA:MGI.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:MGI.
DR GO; GO:0046850; P:regulation of bone remodeling; ISO:RGD.
DR GO; GO:0046822; P:regulation of nucleocytoplasmic transport; ISO:RGD.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; ISO:RGD.
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..928
FT /note="Type II inositol 3,4-bisphosphate 4-phosphatase"
FT /id="PRO_0000190239"
FT DOMAIN 23..165
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..23
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 548..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..516
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 885..928
FT /note="REGCRIENVLKNIKCRRYAFNMLQLMAFPKCYRPPEGTYGKADT -> SRQT
FT QGALNESDDPETGCLSDNKPTSRHFYPVALLLVSSHLLVVWLILSLALLLAKYQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:9295334"
FT /id="VSP_015249"
SQ SEQUENCE 928 AA; 105245 MW; 973EB2EEA58E6430 CRC64;
MEIKEEGTSE EGQHFLPAAQ ANDPEDIQFT SIQKSPNEPQ LEFILACKDL VAPVSDRKLN
TVVQVSVIHP VEQTLTRYSS TEIVEGTKDP LFLTGVTFPS DYPIYEETRI KLTVYDVKDK
PHDTIRTSVL PEHKDPPPEV ARSFLGCASF KVGELLKSKE QLLSLSLRTS DGGKVVGTIE
VSLVKMGEIE DGDTDHITTD VQGQKCALVY DSTAPESLSG KENLPFMNAV LRNPVCKLYR
FPTSDNKWMR IREQMSESIL SFHIPKELIS LHIKEDLCRN QELKELGDLS PHWDNLRNNV
LSHCDQMVTM YQDILTELSK ETGSSFKSSS SKGEKTLEFV PINLHLQRMQ VHSPHLKDAL
YDVITVGAPA AHFQGFKNGG LRKLLHRFET ERRNTGYQFI YYSPENTAKA KEVLSSINQL
QPLVATHADL LLTSASQHSP DSLRSSLKLL SEKTELFVHA FKDQLVRSAL LALYTARPGG
ILRKPPSPKV STEEKSSQHD SPQQLRRQDS IPHHSDYDEE EWDRVWANVG KSLNCIIAKV
DKLIERDSRN DKSTGGDSSK DGDADPNLED SLTSHPREDW YEQLHPLILT LKECMAEVVN
RAKQSLTFVL LQELAYSLPQ CLMLTLRRDI VFSQALAGLV CGFIIKLHTS LHDPGFLQQL
HTVGLIVQYE GLLSTYSDEI GMLEDMAVGI SDLRKVAFKI TEATSNDVLP VLTGRREHYV
VEVKLPATVF ESLPLQIKEG QLLHVYPVLF NVGINEQQTL AERFGDVSLQ ESINQENFEL
VQEYYSIFME KMPPDYISHF QEQNDLKGLL DNLHQNIQAK KRKNVEIMWL AATICRKLNG
IRFTCCKSAK DRTSMSVTLE QCSILRDEHQ LHKDFFIRAL DCMRREGCRI ENVLKNIKCR
RYAFNMLQLM AFPKCYRPPE GTYGKADT
