PI42A_PIG
ID PI42A_PIG Reviewed; 406 AA.
AC O13010;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha {ECO:0000305};
DE EC=2.7.1.149 {ECO:0000250|UniProtKB:P48426};
DE AltName: Full=1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha;
DE AltName: Full=Diphosphoinositide kinase 2-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; Synonyms=PIP5K2A;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RA Schechinger W., Schleicher E.D.;
RT "Phosphatidyl-inositol-4-phosphate-5-kinase (PIP-kinase).";
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). May be
CC involved in thrombopoiesis, and the terminal maturation of
CC megakaryocytes and regulation of their size (By similarity). May
CC negatively regulate insulin-stimulated glucose uptake by lowering the
CC levels of PtdIns5P (By similarity). {ECO:0000250|UniProtKB:O70172,
CC ECO:0000250|UniProtKB:P48426, ECO:0000250|UniProtKB:Q9R0I8}.
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:0000250|UniProtKB:P48426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12281;
CC Evidence={ECO:0000250|UniProtKB:P48426};
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:0000250|UniProtKB:Q9R0I8}.
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:0000250|UniProtKB:Q9R0I8}.
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; U96135; AAB53645.1; -; mRNA.
DR RefSeq; NP_001182710.1; NM_001195781.1.
DR STRING; 9823.ENSSSCP00000011817; -.
DR PaxDb; O13010; -.
DR PeptideAtlas; O13010; -.
DR PRIDE; O13010; -.
DR GeneID; 100520446; -.
DR KEGG; ssc:100520446; -.
DR CTD; 5305; -.
DR eggNOG; KOG0229; Eukaryota.
DR InParanoid; O13010; -.
DR OrthoDB; 1562683at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
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; IEA:UniProtKB-SubCell.
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; 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: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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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 2: Evidence at transcript 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_0000185467"
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..331
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; 46189 MW; 24EE8DA70E36C596 CRC64;
MATPGNLGSS VLASKTKTKK KHFVAQKVKL FRASDPLLSV LMWGVNHSIN ELSHVQIPVM
LMPDDFKAYS KIKVDNHLFN KENMPSHFKF KEYCPMVFRN LRERFGIDDQ DFQNSLTRSA
PLPNDSXARS GARFHTSYDR RYVIKTITSE DVAEMHNILK NYHQHIVECH GITLLPQFLG
MYRLNVDGVE IYVIVTRNVF SHRLSVYRKY DLKGSTVARE ASDKEKAKEL PTLKDNDFIN
EGQKIYIDDN XKKVFLEKLK KDVEFLAQLK LMDYSLLVGI HDVERAEQEE VECEENDGEE
EGESDGTHPV GTPPDSPGNT LNSSPPLAPG EFDPNIDVYG IKCHENSPRK EVYFMAIIDI
LTHYDAKKKA AHAAKXVKHG AGAEISTVNP EQYSKRFLDF IGHILT
