ID PI42C_RAT Reviewed; 420 AA. AC O88370; DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 27-MAR-2024, entry version 125. DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma {ECO:0000305}; DE EC=2.7.1.149 {ECO:0000269|PubMed:9685379}; DE AltName: Full=Phosphatidylinositol 5-phosphate 4-kinase type II gamma; DE Short=PI(5)P 4-kinase type II gamma; DE Short=PIP4KII-gamma; GN Name=Pip4k2c {ECO:0000312|RGD:621711}; Synonyms=Pip5k2c; 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], PHOSPHORYLATION, TISSUE SPECIFICITY, FUNCTION, RP AND CATALYTIC ACTIVITY. 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: Phosphatidylinositol 5-phosphate 4-kinase with low enzymatic CC activity (PubMed:9685379). May be a GTP sensor, has higher GTP- CC dependent kinase activity than ATP-dependent kinase activity (By CC similarity). PIP4Ks negatively regulate insulin signaling through a CC catalytic-independent mechanism. They interact with PIP5Ks and suppress CC PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion CC to PtdIns(3,4,5)P3 (By similarity). {ECO:0000250|UniProtKB:Q8TBX8, 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:Q8TBX8}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55993; CC Evidence={ECO:0000250|UniProtKB:Q8TBX8}; 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:Q8TBX8}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55965; CC Evidence={ECO:0000250|UniProtKB:Q8TBX8}; CC -!- SUBUNIT: Interacts with PIP5K1A; the interaction inhibits PIP5K1A CC kinase activity. {ECO:0000250|UniProtKB:Q8TBX8}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:9685379}. Cytoplasm {ECO:0000269|PubMed:9685379}. CC -!- TISSUE SPECIFICITY: Widely expressed, with the most abundant expression CC in kidney. {ECO:0000269|PubMed:9685379}. CC -!- PTM: Phosphorylated, phosphorylation is induced by EGF. CC {ECO:0000269|PubMed:9685379}. 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; AF030558; AAC40202.1; -; mRNA. DR RefSeq; NP_536728.2; NM_080480.2. DR AlphaFoldDB; O88370; -. DR SMR; O88370; -. DR STRING; 10116.ENSRNOP00000061758; -. DR iPTMnet; O88370; -. DR PhosphoSitePlus; O88370; -. DR jPOST; O88370; -. DR PaxDb; 10116-ENSRNOP00000061758; -. DR GeneID; 140607; -. DR KEGG; rno:140607; -. DR UCSC; RGD:621711; rat. DR AGR; RGD:621711; -. DR CTD; 79837; -. DR RGD; 621711; Pip4k2c. DR VEuPathDB; HostDB:ENSRNOG00000005138; -. DR eggNOG; KOG0229; Eukaryota. DR InParanoid; O88370; -. DR OrthoDB; 5481504at2759; -. DR PhylomeDB; O88370; -. 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:O88370; -. DR Proteomes; UP000002494; Chromosome 7. DR Bgee; ENSRNOG00000005138; Expressed in adult mammalian kidney and 19 other cell types or tissues. DR ExpressionAtlas; O88370; baseline and differential. DR GO; GO:0005776; C:autophagosome; ISO:RGD. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0043229; C:intracellular organelle; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0016308; F:1-phosphatidylinositol-4-phosphate 5-kinase activity; IDA:RGD. DR GO; GO:0016309; F:1-phosphatidylinositol-5-phosphate 4-kinase activity; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:1902635; P:1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process; ISS:UniProtKB. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; NAS: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; ISO:RGD. 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:SF35; PHOSPHATIDYLINOSITOL 5-PHOSPHATE 4-KINASE TYPE-2 GAMMA; 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; O88370; RN. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Cytoplasm; Endoplasmic reticulum; Kinase; KW Lipid metabolism; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q8TBX8" FT CHAIN 2..420 FT /note="Phosphatidylinositol 5-phosphate 4-kinase type-2 FT gamma" FT /id="PRO_0000285753" FT DOMAIN 43..419 FT /note="PIPK" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00781" FT REGION 69..75 FT /note="Required for interaction with PIP5K1A" FT /evidence="ECO:0000250|UniProtKB:Q8TBX8" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q8TBX8" FT MOD_RES 26 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8TBX8" FT MOD_RES 349 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8TBX8" SQ SEQUENCE 420 AA; 47049 MW; BDB07F67FA81E943 CRC64; MASSSVPPAT APAAAGGPGP GFGFASKTKK KHFVQQKVKV FRAADPLVGV FLWGVAHSIN ELSQVPPPVM LLPDDFKASS KIKVNNHLFH RENLPSHFKF KEYCPQVFRN LRDRFAIDDH DYLVSLTRSP PSETEGSDGR FLISYDRTLV IKEVSSEDIA DMHSNLSNYH QYIVKCHGNT LLPQFLGMYR VSVENEDSYM LVMRNMFSHR LPVHRKYDLK GSLVSREASD KEKVKELPTL KDMDFLNKNQ KVYIGEEEKK VFLEKLKRDV EFLVQLKIMD YSLLLGIHDI IRGSEPEEEG PVREEESEWD GDCNLTGPPA LVGSYGTSPE GIGGYIHSHR PLGPGEFESF IDVYAIRSAE GAPEGGVFHG LIDILTQYDA KKKAAHAAKT VKHGAGAEIS TVHPEQYAKR FLDFISNIFA //