ID PI4KA_MOUSE Reviewed; 2105 AA.
AC E9Q3L2; Q3UVT5; Q6DIC7; Q7TNG2; Q80Y45;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 2.
DT 27-MAR-2024, entry version 89.
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:0000250|UniProtKB:P42356};
GN Name=Pi4ka {ECO:0000312|MGI:MGI:2448506}; Synonyms=Pik4, Pik4ca;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 56-2105.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH75629.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH75629.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1441-2105.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE23184.1};
RC TISSUE=Diencephalon {ECO:0000312|EMBL:BAE23184.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-260; SER-263 AND SER-1439,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259; SER-260; SER-262;
RP SER-263; SER-268 AND SER-1439, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP GENE STRUCTURE, AND DISRUPTION PHENOTYPE.
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).
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:0000250|UniProtKB:P42356}.
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:0000250|UniProtKB:P42356};
CC -!- ACTIVITY REGULATION: Activated by Triton X-100, insensitive to
CC inhibition by adenosine and inhibited by wortmannin (By similarity).
CC The PI4K complex acts as a regulator of phosphatidylinositol 4-
CC phosphate (PtdIns(4)P) synthesis. Interaction with TMEM150A regulates
CC PtdIns(4)P synthesis (By similarity). {ECO:0000250|UniProtKB:O08662,
CC ECO:0000250|UniProtKB:P42356}.
CC -!- SUBUNIT: Component of a phosphatidylinositol 4-kinase (PI4K) complex,
CC composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and
CC HYCC (HYCC1 or HYCC2). Interacts with TMEM150A; regulating recruitment
CC 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 HYCC (HYCC1 or HYCC2).
CC Localization to the plasma membrane is regulated by TMEM150A.
CC {ECO:0000250|UniProtKB:P42356}.
CC -!- DISRUPTION PHENOTYPE: Early embryonic lethality. Conditional knockout
CC mice show a dramatic depletion of cellular phosphatidylinositol 4-
CC phosphate (PtdIns(4)P). {ECO:0000269|PubMed:23229899}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type III PI4K
CC subfamily. {ECO:0000305}.
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DR EMBL; AC110573; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC049252; AAH49252.1; -; mRNA.
DR EMBL; BC055479; AAH55479.1; -; mRNA.
DR EMBL; BC075629; AAH75629.1; -; mRNA.
DR EMBL; AK136942; BAE23184.1; -; mRNA.
DR RefSeq; NP_001001983.2; NM_001001983.2.
DR RefSeq; XP_006522097.1; XM_006522034.1.
DR AlphaFoldDB; E9Q3L2; -.
DR SMR; E9Q3L2; -.
DR IntAct; E9Q3L2; 9.
DR MINT; E9Q3L2; -.
DR STRING; 10090.ENSMUSP00000156049; -.
DR GlyGen; E9Q3L2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; E9Q3L2; -.
DR PhosphoSitePlus; E9Q3L2; -.
DR SwissPalm; E9Q3L2; -.
DR EPD; E9Q3L2; -.
DR jPOST; E9Q3L2; -.
DR PaxDb; 10090-ENSMUSP00000036162; -.
DR PeptideAtlas; E9Q3L2; -.
DR ProteomicsDB; 289418; -.
DR Pumba; E9Q3L2; -.
DR DNASU; 224020; -.
DR Ensembl; ENSMUST00000232232.3; ENSMUSP00000156049.3; ENSMUSG00000041720.15.
DR GeneID; 224020; -.
DR KEGG; mmu:224020; -.
DR UCSC; uc007ykq.2; mouse.
DR UCSC; uc007ykr.2; mouse.
DR AGR; MGI:2448506; -.
DR CTD; 5297; -.
DR MGI; MGI:2448506; Pi4ka.
DR eggNOG; KOG0902; Eukaryota.
DR GeneTree; ENSGT00550000074798; -.
DR HOGENOM; CLU_000893_2_0_1; -.
DR InParanoid; E9Q3L2; -.
DR OrthoDB; 147843at2759; -.
DR TreeFam; TF102041; -.
DR Reactome; R-MMU-1483248; Synthesis of PIPs at the ER membrane.
DR Reactome; R-MMU-1660514; Synthesis of PIPs at the Golgi membrane.
DR BioGRID-ORCS; 224020; 19 hits in 80 CRISPR screens.
DR ChiTaRS; Pi4ka; mouse.
DR PRO; PR:E9Q3L2; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; E9Q3L2; Protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004430; F:1-phosphatidylinositol 4-kinase activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0044788; P:modulation by host of viral process; ISO:MGI.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IMP:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0140754; P:reorganization of cellular membranes to establish viral sites of replication; ISO:MGI.
DR CDD; cd00871; PI4Ka; 1.
DR CDD; cd05167; PI4Kc_III_alpha; 1.
DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1.
DR Gene3D; 1.25.40.70; Phosphatidylinositol 3-kinase, accessory domain (PIK); 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:SF15; PHOSPHATIDYLINOSITOL 4-KINASE ALPHA; 1.
DR PANTHER; PTHR10048; PHOSPHATIDYLINOSITOL KINASE; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR Pfam; PF19274; PI4K_N; 2.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; ARM repeat; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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..2105
FT /note="Phosphatidylinositol 4-kinase alpha"
FT /id="PRO_0000435632"
FT DOMAIN 1533..1721
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 1811..2089
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1817..1823
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1957..1965
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1976..2000
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42356"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42356"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42356"
FT MOD_RES 1439
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT CONFLICT 861
FT /note="P -> L (in Ref. 2; AAH75629)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2105 AA; 237042 MW; 25EB66874330ED51 CRC64;
MAAAGARGGG GGGGGGGGGG SGSSSGSSTS RGFYFNTVLS LARSLAVQRP ASLEKVQKLL
CMCPVDFHGI FQLDERRRDA VIALGIFLIE SDLQHKDCVV PYLLRLLRGL PKVYWVEEST
ARKGRGNLPV AESFSFCLVT LLSDVACRDP SLRDEILEAI LQVLHVLLGM CQALEIQEKE
YLCKYAIPCL IGISRSFGRY SNSEESLLSK LFPKVSPHSL RIPEELEGVR RRSFNDFRSI
LPSNLLTVCQ EGTLKRKTSS VSSISQVSPE RGIPPPSSPG GSAFHYFEAS CLPDGTALEP
EYYFSTISSS FSISPLFNGI TYKEFCIPLE MLRELLNLVK KIVEEPVLKS LDAIVAGVME
ANPSADLYYT TFSDPLYLTM FKMLRDTLYY MKDLPTSFVK EIHDFVLEQF NMSQGELQKI
LHDADRIHSE MSPLKLRCQA NAACVDLMVW AVKDEQGAEN LCIKLSEKLQ SKTSSKVIIA
HLPLLICCLQ GLGRLCERFP VVVHSVTPSL RDFLVIPSPV LVKLYKYHSQ YHTVAGSDIK
ISVTNEHSES TLNVLPGKKN QPSMYEQLRD IAIDNICRCL KAGLTVDPVI VEAFLASLSN
RLYISQESDK DAHLIPDHTI RALGHIAVAL RDTPKVMEPI LQILQQKFCQ PPSPLDVLII
DQLGCLVITG NQYIYQEVWN LFQQISVKAS SVVYSATKDY KDHGYRHCSL AVINALANIA
ANIQEEHLVD ELLMNLLELF VQLGLEGKRA SERASEKGPA LKASSSAGNL GVLIPVIAVL
TRRLPPIKEA KPRLQKLFRD FWLYSVLMGF AVEGSGLWPE EWYEGVCEIA TKSPLLTFPS
KEPLRSVLQY NSAMKNDTVT PAELSELRST IINLLDPPPE VSALINKLDF AMSTYLLSVY
RLEYMRVLRS TDPDRFQVMF CYFEDKAIQK DKSGMMQCVI AVADKVFDAF LNMMAEKAKT
KENEEELERH AQFLLVNFNH IHKRIRRVAD KYLSGLVDKF PHLLWSGTVL KTMLDILQTL
SLSLSADIHK DQPYYDIPDA PYRITVPDTY EARESIVKDF AARCGMILQE AMKWAPTVTK
SHLQEYLNKH QNWVSGLSQH TGLAMATESI LHFAGYNKQN TTLGATQLTE RPACVKKDYS
NFMASLNLRN RYAGEVHGMI RFSGATGQMS DLNKMMVQDL ITALDHSHPQ HYTQAMFKLT
AMLISSKDCD PQLLHHLCWG PLRMFNEHGM ETALACWEWL LAGKNGVEVP FMREMAGAWH
MTVEQKFGLF SVETKEADPL AASEASQPRP CPPEVTPHYI WIDFLVQRFE IAKYCSSDQV
EIFSSLLQRS MSLNIGGARG SMNRHVAAIG PRFKLLTLGL SLLHADVVPN ATIRNVLREK
IYSTAFDYFS CPPKFPTQGE KRLREDISIM IKFWTAMFSD KKYLTASQLV PPDNQDTRSN
LDITVGSRQQ ATQGWINTYP LSSGMSTISK KSGMSKKTNR GSQLHKYYMK RRTLLLSLLA
TEIERLITWY NPLSAPELEL DQAGENSVAN WRSKYISLSE KQWKDNVNLA WSISPYLAVQ
LPARFKNTEA IGNEVTRLVR LDPGAVSDVP EAIKFLVTWH TIDADAPELS HVLCWAPTDP
PTGLSYFSSM YPPHPLTAQY GVKVLRSFPP DAILFYIPQI VQALRYDKMG YVREYILWAA
AKSQLLAHQF IWNMKTNIYL DEEGHQKDPD IGDLLEQLVE EITGSLSGPA KDFYQREFDF
FNKITNVSAI IKPYPKGDER KKACLSALSE VKVQPGCYLP SNPEAIVLDI DYKSGTPMQS
AAKAPYLAKF KVKRCGVSEL EKEGLQCRSD AEDECFSQEA DGKKICWQAA IFKVGDDCRQ
DMLALQIIDL FKNIFQLVGL DLFVFPYRVV ATAPGCGVIE CIPDCTSRDQ LGRQTDFGMY
DYFTRQYGDE STLAFQQARY NFIRSMAAYS LLLFLLQIKD RHNGNIMLDK KGHIIHIDFG
FMFESSPGGN LGWEPDIKLT DEMVMIMGGK MEATPFKWFM EMCVRGYLAV RPYMDAVVSL
VTLMLDTGLP CFRGQTIKLL KHRFSPNMTE REAANFIMKV IQNCFLSNRS RTYDMIQYYQ
NDIPY
//
