PI42A_RAT
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 03-AUG-2022, entry version 106.
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 STRING; 10116.ENSRNOP00000022375; -.
DR iPTMnet; Q9R0I8; -.
DR PhosphoSitePlus; Q9R0I8; -.
DR SwissPalm; Q9R0I8; -.
DR jPOST; Q9R0I8; -.
DR PRIDE; Q9R0I8; -.
DR Ensembl; ENSRNOT00000022375; ENSRNOP00000022375; ENSRNOG00000016670.
DR GeneID; 116723; -.
DR KEGG; rno:116723; -.
DR UCSC; RGD:621708; rat.
DR CTD; 5305; -.
DR RGD; 621708; Pip4k2a.
DR eggNOG; KOG0229; Eukaryota.
DR GeneTree; ENSGT00940000156508; -.
DR InParanoid; Q9R0I8; -.
DR OrthoDB; 1562683at2759; -.
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: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: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 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; 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
