PI42B_RAT
ID PI42B_RAT Reviewed; 416 AA.
AC O88377;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 beta {ECO:0000305};
DE EC=2.7.1.149 {ECO:0000269|PubMed:9685379};
DE AltName: Full=1-phosphatidylinositol 5-phosphate 4-kinase 2-beta;
DE AltName: Full=Diphosphoinositide kinase 2-beta;
DE AltName: Full=Phosphatidylinositol 5-phosphate 4-kinase type II beta;
DE Short=PI(5)P 4-kinase type II beta;
DE Short=PIP4KII-beta;
DE AltName: Full=Phosphatidylinositol-phosphate kinase IIgamma;
DE Short=PIPKIIgamma;
DE AltName: Full=PtdIns(5)P-4-kinase isoform 2-beta;
GN Name=Pip4k2b {ECO:0000312|RGD:621710}; Synonyms=Pip5k2b;
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], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Brain;
RX PubMed=9685379; DOI=10.1074/jbc.273.32.20292;
RA Itoh T., Ijuin T., Takenawa T.;
RT "A novel phosphatidylinositol-5-phosphate 4-kinase (phosphatidylinositol-
RT phosphate kinase IIgamma) is phosphorylated in the endoplasmic reticulum in
RT response to mitogenic signals.";
RL J. Biol. Chem. 273:20292-20299(1998).
CC -!- FUNCTION: Participates in the biosynthesis of phosphatidylinositol 4,5-
CC bisphosphate (PubMed:9685379). Preferentially utilizes GTP, rather than
CC ATP, for PI(5)P phosphorylation and its activity reflects changes in
CC direct proportion to the physiological GTP concentration. Its GTP-
CC sensing activity is critical for metabolic adaptation (By similarity).
CC PIP4Ks negatively regulate insulin signaling through a catalytic-
CC independent mechanism. They interact with PIP5Ks and suppress PIP5K-
CC mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to
CC PtdIns(3,4,5)P3 (By similarity). {ECO:0000250|UniProtKB:P78356,
CC ECO:0000269|PubMed:9685379}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-
CC phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:12280,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57795,
CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.149;
CC Evidence={ECO:0000269|PubMed:9685379};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12281;
CC Evidence={ECO:0000305|PubMed:9685379};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-
CC phosphate) + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:55992,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83423,
CC ChEBI:CHEBI:84968, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P78356};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55993;
CC Evidence={ECO:0000250|UniProtKB:P78356};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-
CC phosphate) + GTP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-4,5-bisphosphate) + GDP + H(+); Xref=Rhea:RHEA:55964,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:83423, ChEBI:CHEBI:84968;
CC Evidence={ECO:0000250|UniProtKB:P78356};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55965;
CC Evidence={ECO:0000250|UniProtKB:P78356};
CC -!- SUBUNIT: Homodimer. Binds TNFRSF1A. Interacts with PIP4K2A; the
CC interaction suppresses ubiquitination by the SPOP/CUL3 complex (By
CC similarity). Probably interacts with PIP5K1A; the interaction inhibits
CC PIP5K1A kinase activity (By similarity). {ECO:0000250|UniProtKB:P78356,
CC ECO:0000250|UniProtKB:Q8TBX8}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Cell membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Nucleus {ECO:0000250}.
CC Cytoplasm {ECO:0000250}. Note=Associated with the plasma membrane and
CC the endoplasmic reticulum. {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the SPOP/CUL3 complex. Ubiquitination is
CC stimulated by PtdIns5P levels. {ECO:0000250|UniProtKB:P78356}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000250|UniProtKB:P78356}.
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DR EMBL; AF033355; AAC40203.1; -; mRNA.
DR RefSeq; NP_446002.1; NM_053550.1.
DR AlphaFoldDB; O88377; -.
DR SMR; O88377; -.
DR BioGRID; 250135; 1.
DR IntAct; O88377; 1.
DR STRING; 10116.ENSRNOP00000017989; -.
DR iPTMnet; O88377; -.
DR PhosphoSitePlus; O88377; -.
DR SwissPalm; O88377; -.
DR jPOST; O88377; -.
DR PaxDb; O88377; -.
DR PRIDE; O88377; -.
DR Ensembl; ENSRNOT00000017989; ENSRNOP00000017989; ENSRNOG00000013030.
DR GeneID; 89812; -.
DR KEGG; rno:89812; -.
DR CTD; 8396; -.
DR RGD; 621710; Pip4k2b.
DR eggNOG; KOG0229; Eukaryota.
DR GeneTree; ENSGT00940000159874; -.
DR HOGENOM; CLU_004312_7_0_1; -.
DR InParanoid; O88377; -.
DR OMA; MKSHENA; -.
DR OrthoDB; 1562683at2759; -.
DR PhylomeDB; O88377; -.
DR TreeFam; TF354315; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-6811555; PI5P Regulates TP53 Acetylation.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-8847453; Synthesis of PIPs in the nucleus.
DR PRO; PR:O88377; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000013030; Expressed in skeletal muscle tissue and 18 other tissues.
DR Genevisible; O88377; RN.
DR GO; GO:0005776; C:autophagosome; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; ISS:UniProtKB.
DR GO; GO:0016309; F:1-phosphatidylinositol-5-phosphate 4-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:1902635; P:1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:0090217; P:negative regulation of 1-phosphatidylinositol-4-phosphate 5-kinase activity; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISO:RGD.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:2000786; P:positive regulation of autophagosome assembly; ISO:RGD.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR Gene3D; 3.30.800.10; -; 1.
DR InterPro; IPR023610; PInositol-4-P-5-kinase.
DR InterPro; IPR002498; PInositol-4-P-5-kinase_core.
DR InterPro; IPR027484; PInositol-4-P-5-kinase_N.
DR PANTHER; PTHR23086; PTHR23086; 1.
DR Pfam; PF01504; PIP5K; 1.
DR SMART; SM00330; PIPKc; 1.
DR PROSITE; PS51455; PIPK; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell membrane; Cytoplasm; Endoplasmic reticulum;
KW GTP-binding; Kinase; Lipid metabolism; Membrane; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT CHAIN 2..416
FT /note="Phosphatidylinositol 5-phosphate 4-kinase type-2
FT beta"
FT /id="PRO_0000185472"
FT DOMAIN 38..415
FT /note="PIPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781"
FT REGION 64..70
FT /note="Required for interaction with PIP5K1A"
FT /evidence="ECO:0000250|UniProtKB:Q8TBX8"
FT BINDING 202..204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT BINDING 203..204
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT BINDING 214
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT BINDING 369
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT MOD_RES 8
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 94
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48426"
FT MOD_RES 150
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P78356"
FT MOD_RES 322
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80XI4"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78356"
SQ SEQUENCE 416 AA; 47264 MW; 9481AC50CBB6C196 CRC64;
MSSNCTSTTA VAVAPLSASK TKTKKKHFVC QKVKLFRASE PILSVLMWGV NHTINELSNV
PVPVMLMPDD FKAYSKIKVD NHLFNKENLP SRFKFKEYCP MVFRNLRERF GIDDQDYQNS
VTRSAPINSD SQGRCGTRFL TTYDRRFVIK TVSSEDVAEM HNILKKYHQF IVECHGNTLL
PQFLGMYRLT VDGVETYMVV TRNVFSHRLT VHRKYDLKGS TVAREASDKE KAKDLPTFKD
NDFLNEGQKL RVGEESKKNF LEKLKRDVEF LAQLKIMDYS LLVGIHDVDR AEQEETEVED
RAEEEECEND GVGGGLLCSY GTPPDSPGNL LSFPRFFGPG EFDPSVDVYA MKSHESAPKK
EVYFMAIIDI LTPYDAKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFNEF MSNILT
