PI4KA_RAT
ID PI4KA_RAT Reviewed; 2096 AA.
AC O08662; A0A0G2K2J3;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Phosphatidylinositol 4-kinase alpha;
DE Short=PI4-kinase alpha;
DE Short=PI4K-alpha;
DE Short=PtdIns-4-kinase alpha;
DE EC=2.7.1.67 {ECO:0000269|PubMed:8662589};
GN Name=Pi4ka; Synonyms=Pik4ca;
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] OF 53-2096, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=8662589; DOI=10.1074/jbc.271.20.12088;
RA Nakagawa T., Goto K., Kondo H.;
RT "Cloning, expression, and localization of 230-kDa phosphatidylinositol 4-
RT kinase.";
RL J. Biol. Chem. 271:12088-12094(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP GENE STRUCTURE.
RX PubMed=23229899; DOI=10.1083/jcb.201206095;
RA Nakatsu F., Baskin J.M., Chung J., Tanner L.B., Shui G., Lee S.Y.,
RA Pirruccello M., Hao M., Ingolia N.T., Wenk M.R., De Camilli P.;
RT "PtdIns4P synthesis by PI4KIIIalpha at the plasma membrane and its impact
RT on plasma membrane identity.";
RL J. Cell Biol. 199:1003-1016(2012).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-254; SER-259 AND SER-1430,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Acts on phosphatidylinositol (PtdIns) in the first committed
CC step in the production of the second messenger inositol-1,4,5,-
CC trisphosphate. {ECO:0000269|PubMed:8662589}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:19877, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58178, ChEBI:CHEBI:456216;
CC EC=2.7.1.67; Evidence={ECO:0000269|PubMed:8662589};
CC -!- ACTIVITY REGULATION: Activated by Triton X-100, insensitive to
CC inhibition by adenosine and inhibited by wortmannin (PubMed:8662589).
CC The PI4K complex acts as a regulator of phosphatidylinositol 4-
CC phosphate (PtdIns(4)P) synthesis (By similarity). Interaction with
CC TMEM150A regulates PtdIns(4)P synthesis (By similarity).
CC {ECO:0000250|UniProtKB:P42356, ECO:0000269|PubMed:8662589}.
CC -!- SUBUNIT: Component of a phosphatidylinositol 4-kinase (PI4K) complex,
CC composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and
CC FAM126 (FAM126A or FAM126B). Interacts with TMEM150A; regulating
CC recruitment to the plasma membrane. Interacts with TTC7A.
CC {ECO:0000250|UniProtKB:P42356}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P42356}. Cell
CC membrane {ECO:0000250|UniProtKB:P42356}. Note=Localization to the
CC plasma membrane is mediated by the PI4K complex and association with
CC EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and FAM126 (FAM126A or
CC FAM126B). Localization to the plasma membrane is regulated by TMEM150A.
CC {ECO:0000250|UniProtKB:P42356}.
CC -!- TISSUE SPECIFICITY: Detected in the brain, kidney and lung. Less
CC intensely expressed in the small intestine, uterus, adrenal gland,
CC heart, skeletal muscle, thymus, spleen and testis.
CC {ECO:0000269|PubMed:8662589}.
CC -!- DEVELOPMENTAL STAGE: In brain of prenatal day 18 embryos, the
CC expression is detected throughout the mantle zone of fore-, mid-, and
CC hind brain. In the cerebrum, the expression is intense in the cortical
CC plate and weak in the ventricular zone. At P49, expressed in the gray
CC matter of the entire brain by hippocampal pyramidal cells, dentate
CC granule cells, and cerebellar granule cells and to a lower extent by
CC olfactory mitral and granule cells and the cerebral cortex. Weakly
CC expressed in the diencephalon and brain stem and not detected in the
CC cerebellar medulla. Expression is much higher in the fetal brain than
CC the adult brain, especially in the brain stem.
CC {ECO:0000269|PubMed:8662589}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type III PI4K
CC subfamily. {ECO:0000305}.
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DR EMBL; D83538; BAA19614.1; -; mRNA.
DR EMBL; AC111344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_071637.1; NM_022301.1.
DR AlphaFoldDB; O08662; -.
DR SMR; O08662; -.
DR BioGRID; 248988; 3.
DR IntAct; O08662; 8.
DR MINT; O08662; -.
DR STRING; 10116.ENSRNOP00000059384; -.
DR CarbonylDB; O08662; -.
DR iPTMnet; O08662; -.
DR PhosphoSitePlus; O08662; -.
DR jPOST; O08662; -.
DR PaxDb; O08662; -.
DR PRIDE; O08662; -.
DR GeneID; 64161; -.
DR KEGG; rno:64161; -.
DR CTD; 5297; -.
DR RGD; 621213; Pi4ka.
DR eggNOG; KOG0902; Eukaryota.
DR OrthoDB; 1147978at2759; -.
DR Reactome; R-RNO-1483248; Synthesis of PIPs at the ER membrane.
DR Reactome; R-RNO-1660514; Synthesis of PIPs at the Golgi membrane.
DR PRO; PR:O08662; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; IDA:RGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004430; F:1-phosphatidylinositol 4-kinase activity; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; ISO:RGD.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0051702; P:biological process involved in interaction with symbiont; ISO:RGD.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; ISO:RGD.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; ISO:RGD.
DR GO; GO:0046786; P:viral replication complex formation and maintenance; ISO:RGD.
DR GO; GO:0039694; P:viral RNA genome replication; ISO:RGD.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR045495; PI4K_N.
DR InterPro; IPR015433; PI_Kinase.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR Pfam; PF19274; PI4K_N; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cytoplasm; Kinase; Lipid metabolism; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2096
FT /note="Phosphatidylinositol 4-kinase alpha"
FT /id="PRO_0000425713"
FT DOMAIN 1524..1712
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 1802..2080
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1808..1814
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1948..1956
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1967..1991
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42356"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42356"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42356"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q3L2"
FT MOD_RES 254
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42356"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42356"
FT MOD_RES 1430
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 186
FT /note="R -> K (in Ref. 1; BAA19614)"
FT /evidence="ECO:0000305"
FT CONFLICT 631..633
FT /note="Missing (in Ref. 1; BAA19614)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2096 AA; 236920 MW; 8CB6D0DA792F9694 CRC64;
MAAAGARGTG GSGSSSGSST SRGFYFNTVL SLARSLAVQR PASLEKVQKL LCMCPVDFHG
IFQLDERRRD AVIALGIFLI ESDLQHKDCI VPYLLRLLRG LPKVYWVEES TARKGRGNLP
VAESFSFCLV TLLSDVACRD PSLRDEILEA LLQVLHVLLG MCQALEIQEK EYLCKYAIPC
LIGISRSFGR YSNSEESLLS KLFPKVPPHS LRIPEELEGV RRRSFNDFRS ILPSNLLTVC
QEGTLKRKTS SVSSISQVSP ERGMPPPSSP GGSAFHYFEA SCLPDGTTLE PEYYFSTISS
SFSVSPLFNG ITYKEFYIPL EMLRELLNLV KKIVEEPVLK SLDAAVARVM EANPSADLYY
TTFSDPVYLT MFKMLRDTLY YMKDLPTSFV KEIHDFVLEQ FNMSQGELQK ILHDADRIHS
EMSPLKLRCQ ANAACVDLMV WAVKDEQGAE NLCIKLSEKL QSKTSSKVII AHLPLLICCL
QGLGRLCERF PVVVHSVTPS LRDFLVIPSP VLVKLYKYHS QYHTVAGSDI KISVTNEHSE
STLNVLPGKK NQPSMYEQLR DIAIDNICRC LKAGLTVDPV IVEAFLASLS NRLYISQESD
KDAHLIPDHT IRALGHIAVA LRDTPKVMEP ILQILQQKFC QPPSPLDVLI IDQLGCLVIT
GNQYIYQEVW NLFQQISVKA SSVVYSATKD YKDHGYRHCS LAVINALANI AANIQEEHLV
DELLMNLLEL FVQLGLEGKR ASERASEKGP ALKASSSAGN LGVLIPVIAV LTRRLPPIKE
AKPRLQKLFR DFWLYSVLMG FAVEGSGLWP EEWYEGVCEI ATKSPLLTFP SKEPLRSVLQ
YNSAMKNDTV TPAELNELRS TIINLLDPPP EVSALINKLD FAMSTYLLSV YRLEYMRVLR
STDPDRFQVM FCYFEDKAIQ KDKSGMMQCV IAVADKVFDA FLNMMAEKAK TKENEEELER
HAQFLLVNFN HIHKRIRRVA DKYLSGLVDK FPHLLWSGTV LKTMLDILQT LSLSLSADIH
KDQPYYDIPD APYRITVPDT YEARESIVKD FAARCGMILQ EAMKWAPTVT KSHLQEYLNK
HQNWVSGLSQ HTGLAMATES ILHFAGYNKQ NTTLGVTQLT ERPACVKKDY SNFMASLNLR
NRYAGEVHGM IRFSGATGQM SDLNKMMVQD LITALDHSHP QHYTQAMFKL TAMLISSKDC
DPQLLHHLCW GPLRMFNEHG METALACWEW LLAGKNGVEV PFMREMAGAW HMTVEQKFGL
FSAETKEADP LAASEASQPR PCPPEVTPHY IWIDFLVQRF EIAKYCSSDQ VEIFSSLLQR
SMSLHIGGAR GSMNRHVAAI GPRFKLLTLG LSLLHADVVP NATIRNVLRE KIYSTAFDYF
SCPPKFPTQG EKRLREDISI MIKFWTAMFS DKKYLTASQL VPPDNQDTRS NLDITVGSRQ
QATQGWINTY PLSSGMSTIS KKSGMSKKTN RGSQLHKYYM KRRTLLLSLL ATEIERLITW
YNPLSAPELE LDQAGENSVA NWRSKYISLS EKQWKDNVNL AWTISPYLAV QLPARFKNTE
AIGNEVTRLV RLDPGAVSDV PEAIKFLVTW HTIDADAPEL SHVLCWAPTD PPTGLSYFSS
MYPPHPLTAQ YGVKVLRSFP PDAILFYIPQ IVQALRYDKM GYVREYILWA AAKSQLLAHQ
FIWNMKTNIY LDEEGHQKDP DIGDLLEQLV EEITGSLSGP AKDFYQREFD FFNKITNVSA
IIKPYPKGDE RKKACLSALS EVKVQPGCYL PSNPEAIVLD IDYKSGTPMQ SAAKAPYLAK
FKVKRCGVSE LEKEGLQCRS DTEDECRRQE ADGKKICWQA AIFKVGDDCR QDMLALQIID
LFKNIFQLVG LDLFVFPYRV VATAPGCGVI ECIPDCTSRD QLGRQTDFGM YDYFTRQYGD
ESTLAFQQAR YNFIRSMAAY SLLLFLLQIK DRHNGNIMLD KKGHIIHIDF GFMFESSPGG
NLGWEPDIKL TDEMVMIMGG KMEATPFKWF MEMCVRGYLA VRPYMDAVVS LVTLMLDTGL
PCFRGQTIKL LKHRFSPNMT EREAANFIMK IIQNCFLSNR SRTYDMIQYY QNDIPY
