ID PI42A_RAT Reviewed; 406 AA. AC Q9R0I8; DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 114. DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha; DE EC=2.7.1.149; DE AltName: Full=1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha; DE AltName: Full=Diphosphoinositide kinase 2-alpha; DE AltName: Full=PIPK2 alpha; DE AltName: Full=Phosphatidylinositol 5-phosphate 4-kinase type II alpha; DE Short=PI(5)P 4-kinase type II alpha; DE Short=PIP4KII-alpha; DE AltName: Full=PtdIns(5)P-4-kinase isoform 2-alpha; GN Name=Pip4k2a {ECO:0000312|RGD:621708}; GN Synonyms=Pip4ka {ECO:0000303|PubMed:21847559}, Pip5k2a; 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]. RA Kudo M., Saito S., Kondo H.; RT "Rattus rat phosphatidylinositol 5-phosphate 4-kinase alpha, complete RT cds."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [2] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ACTIVITY REGULATION, RP PHOSPHORYLATION, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20204506; DOI=10.1007/s11064-010-0146-y; RA Huang Z., Anderson R.E., Cao W., Wiechmann A.F., Rajala R.V.S.; RT "Light-induced tyrosine phosphorylation of rod outer segment membrane RT proteins regulate the translocation, membrane binding and activation of RT type II alpha phosphatidylinositol-5-phosphate 4-kinase."; RL Neurochem. Res. 36:627-635(2011). RN [3] RP FUNCTION IN INSULIN-MEDIATED GLUCOSE UPTAKE. RX PubMed=21847559; DOI=10.1007/s00424-011-1008-4; RA Grainger D.L., Tavelis C., Ryan A.J., Hinchliffe K.A.; RT "Involvement of phosphatidylinositol 5-phosphate in insulin-stimulated RT glucose uptake in the L6 myotube model of skeletal muscle."; RL Pflugers Arch. 462:723-732(2011). CC -!- FUNCTION: Catalyzes the phosphorylation of phosphatidylinositol 5- CC phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, CC to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Has both CC ATP- and GTP-dependent kinase activities. May exert its function by CC regulating the levels of PtdIns5P, which functions in the cytosol by CC increasing AKT activity and in the nucleus signals through ING2 (By CC similarity). May regulate the pool of cytosolic PtdIns5P in response to CC the activation of tyrosine phosphorylation (PubMed:20204506). Required CC for lysosome-peroxisome membrane contacts and intracellular cholesterol CC transport through modulating peroxisomal PtdIns(4,5)P2 level (By CC similarity). In collaboration with PIP4K2B, has a role in mediating CC autophagy in times of nutrient stress (By similarity). Required for CC autophagosome-lysosome fusion and the regulation of cellular lipid CC metabolism (By similarity). Negatively regulates insulin signaling CC through a catalytic-independent mechanism. PIP4Ks interact with PIP5Ks CC and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin- CC dependent conversion to PtdIns(3,4,5)P3 (PubMed:21847559). May be CC involved in thrombopoiesis, and the terminal maturation of CC megakaryocytes and regulation of their size (By similarity). CC {ECO:0000250|UniProtKB:O70172, ECO:0000250|UniProtKB:P48426, CC ECO:0000269|PubMed:20204506, ECO:0000269|PubMed:21847559}. 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:20204506}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12281; CC Evidence={ECO:0000305|PubMed:20204506}; 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:P48426}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55993; CC Evidence={ECO:0000250|UniProtKB:P48426}; 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:P48426}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55965; CC Evidence={ECO:0000250|UniProtKB:P48426}; CC -!- ACTIVITY REGULATION: In rod outer segments, activated by light. CC {ECO:0000269|PubMed:20204506}. CC -!- SUBUNIT: Homodimer. Interacts with PIP4K2B; the interaction may CC regulate localization to the nucleus (By similarity). Probably CC interacts with PIP5K1A; the interaction inhibits PIP5K1A kinase CC activity (By similarity). {ECO:0000250|UniProtKB:P48426, CC ECO:0000250|UniProtKB:Q8TBX8}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O70172}. CC Nucleus {ECO:0000250|UniProtKB:P48426}. Lysosome CC {ECO:0000250|UniProtKB:O70172}. Cytoplasm CC {ECO:0000250|UniProtKB:P48426}. Photoreceptor inner segment CC {ECO:0000250|UniProtKB:O70172}. Cell projection, cilium, photoreceptor CC outer segment {ECO:0000250|UniProtKB:O70172}. Note=May translocate from CC the cytosol to the cell membrane upon activation of tyrosine CC phosphorylation. May translocate from the inner to the outer segments CC of the rod photoreceptor cells in response to light (By similarity). CC Localization to the nucleus is modulated by the interaction with CC PIP4K2B (By similarity). {ECO:0000250|UniProtKB:O70172, CC ECO:0000250|UniProtKB:P48426}. CC -!- PTM: Phosphorylated in tyrosines. Phosphorylation is induced by light CC and increases kinase activity. {ECO:0000269|PubMed:20204506}. 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; AB032899; BAA85160.1; -; mRNA. DR RefSeq; NP_446378.1; NM_053926.2. DR AlphaFoldDB; Q9R0I8; -. DR SMR; Q9R0I8; -. DR BioGRID; 250590; 1. DR IntAct; Q9R0I8; 1. DR iPTMnet; Q9R0I8; -. DR PhosphoSitePlus; Q9R0I8; -. DR SwissPalm; Q9R0I8; -. DR jPOST; Q9R0I8; -. DR PaxDb; 10116-ENSRNOP00000022375; -. DR Ensembl; ENSRNOT00000022375.8; ENSRNOP00000022375.8; ENSRNOG00000016670.8. DR Ensembl; ENSRNOT00055018504; ENSRNOP00055014889; ENSRNOG00055010925. DR Ensembl; ENSRNOT00060035398; ENSRNOP00060029092; ENSRNOG00060020405. DR Ensembl; ENSRNOT00065004375; ENSRNOP00065003122; ENSRNOG00065003110. DR GeneID; 116723; -. DR KEGG; rno:116723; -. DR UCSC; RGD:621708; rat. DR AGR; RGD:621708; -. DR CTD; 5305; -. DR RGD; 621708; Pip4k2a. DR eggNOG; KOG0229; Eukaryota. DR GeneTree; ENSGT00940000156508; -. DR InParanoid; Q9R0I8; -. DR OMA; MFTREIT; -. DR OrthoDB; 5481504at2759; -. DR PhylomeDB; Q9R0I8; -. 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:Q9R0I8; -. DR Proteomes; UP000002494; Chromosome 17. DR GO; GO:0005776; C:autophagosome; ISO:RGD. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0001917; C:photoreceptor inner segment; IEA:UniProtKB-SubCell. DR GO; GO:0001750; C:photoreceptor outer segment; IEA:UniProtKB-SubCell. 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; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. 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:0035855; P:megakaryocyte development; ISO:RGD. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB. 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 GO; GO:0090119; P:vesicle-mediated cholesterol transport; ISS:UniProtKB. DR CDD; cd17309; PIPKc_PIP5K2A; 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:SF21; PHOSPHATIDYLINOSITOL 5-PHOSPHATE 4-KINASE TYPE-2 ALPHA; 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. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Cell membrane; Cell projection; Cytoplasm; KW Kinase; Lipid metabolism; Lysosome; Membrane; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P48426" FT CHAIN 2..406 FT /note="Phosphatidylinositol 5-phosphate 4-kinase type-2 FT alpha" FT /id="PRO_0000185468" FT DOMAIN 33..405 FT /note="PIPK" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781" FT REGION 59..65 FT /note="Required for interaction with PIP5K1A" FT /evidence="ECO:0000250|UniProtKB:Q8TBX8" FT REGION 287..328 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 288..302 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P48426" FT MOD_RES 3 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P48426" FT MOD_RES 14 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48426" FT MOD_RES 89 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48426" FT MOD_RES 145 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48426" SQ SEQUENCE 406 AA; 46210 MW; CA54529BC7FD8622 CRC64; MATPSNLGSS VLASKTKTKK KHFVAQKVKL FRASDPLLSV LMWGVNHSIN ELSHVQIPVM LMPDDFKAYS KIKVDNHLFN KENMPSHFKF KEYCPMVFRN LRERFGIDDQ DFQNSLTRSA PLPNDSQARS GARFHTSYDK RYVIKTITSE DVAEMHNILK KYHQYIVECH GVTLLPQFLG MYRLNVDGVE IYVIVTRNVF SHRLSVYRKY DLKGSTVARE ASDKEKAKEL PTLKDNDFIN EGQKIYIDDS NKKIFLEKLK KDVEFLAQLK LMDYSLLVGI HDVERAEQEE VECEENEGEE EGESDGAHPI GTPPDSPGNT LNSSPPLAPG EFDPNIDVYA IKCHENAPRK EVYFMAIIDI LTHYDAKKKA AHAAKTVKHG AGAEISTVNP EQYSKRFLDF IGHILT //