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 27-MAR-2024, entry version 150. 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}. 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; 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; 10116-ENSRNOP00000017989; -. DR Ensembl; ENSRNOT00000017989.4; ENSRNOP00000017989.3; ENSRNOG00000013030.4. DR Ensembl; ENSRNOT00055056425; ENSRNOP00055046531; ENSRNOG00055032651. DR Ensembl; ENSRNOT00060045585; ENSRNOP00060037842; ENSRNOG00060026321. DR Ensembl; ENSRNOT00065053691; ENSRNOP00065044137; ENSRNOG00065031143. DR GeneID; 89812; -. DR KEGG; rno:89812; -. DR AGR; RGD:621710; -. 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; HEKWDIK; -. DR OrthoDB; 5481504at2759; -. 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 cell types or tissues. 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; IBA:GO_Central. 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: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 CDD; cd17310; PIPKc_PIP5K2B; 1. DR Gene3D; 3.30.810.10; 2-Layer Sandwich; 2. DR Gene3D; 3.30.800.10; Phosphatidylinositol Phosphate Kinase II Beta; 1. DR InterPro; IPR027483; PInositol-4-P-4/5-kinase_C_sf. DR InterPro; IPR002498; PInositol-4-P-4/5-kinase_core. DR InterPro; IPR027484; PInositol-4-P-5-kinase_N. DR InterPro; IPR023610; PInositol-4/5-P-5/4-kinase. DR PANTHER; PTHR23086:SF22; PHOSPHATIDYLINOSITOL 5-PHOSPHATE 4-KINASE TYPE-2 BETA; 1. DR PANTHER; PTHR23086; PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASE; 1. DR Pfam; PF01504; PIP5K; 1. DR SMART; SM00330; PIPKc; 1. DR SUPFAM; SSF56104; SAICAR synthase-like; 1. DR PROSITE; PS51455; PIPK; 1. DR Genevisible; O88377; RN. 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 //