Full text data of PI4KA
PI4KA
(PIK4, PIK4CA)
[Confidence: low (only semi-automatic identification from reviews)]
Phosphatidylinositol 4-kinase alpha; PI4-kinase alpha; PI4K-alpha; PtdIns-4-kinase alpha; 2.7.1.67
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Phosphatidylinositol 4-kinase alpha; PI4-kinase alpha; PI4K-alpha; PtdIns-4-kinase alpha; 2.7.1.67
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P42356
ID PI4KA_HUMAN Reviewed; 2044 AA.
AC P42356; Q7Z625; Q9UPG2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-DEC-2008, sequence version 3.
DT 22-JAN-2014, entry version 128.
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;
GN Name=PI4KA; Synonyms=PIK4, PIK4CA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=7961848;
RA Wong K., Cantley L.C.;
RT "Cloning and characterization of a human phosphatidylinositol 4-
RT kinase.";
RL J. Biol. Chem. 269:28878-28884(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=10101268; DOI=10.1016/S1388-1981(99)00029-3;
RA Gehrmann T., Guelkan H., Suer S., Herberg F.W., Balla A.,
RA Vereb G. Jr., Mayr G.W., Heilmeyer L.M.G. Jr.;
RT "Functional expression and characterisation of a new human
RT phosphatidylinositol 4-kinase PI4K230.";
RL Biochim. Biophys. Acta 1437:341-356(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1142-2044 (ISOFORM 1).
RC TISSUE=Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199; SER-202; SER-204
RP AND SER-207, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207 AND SER-1378, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Acts on phosphatidylinositol (PtdIns) in the first
CC committed step in the production of the second messenger inositol-
CC 1,4,5,-trisphosphate.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol = ADP +
CC 1-phosphatidyl-1D-myo-inositol 4-phosphate.
CC -!- ENZYME REGULATION: This is a type II PtdIns-4-kinase activated by
CC detergents such as triton and inhibited by adenosine.
CC -!- INTERACTION:
CC P27958:- (xeno); NbExp=4; IntAct=EBI-723050, EBI-8753518;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PI4K230;
CC IsoId=P42356-1; Sequence=Displayed;
CC Name=2; Synonyms=PI4K97;
CC IsoId=P42356-2; Sequence=VSP_008805;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously. Highest levels in
CC placenta and brain. Little or no expression in lung, liver,
CC pancreas, testis or leukocytes.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type III PI4K
CC subfamily.
CC -!- SIMILARITY: Contains 1 PI3K/PI4K domain.
CC -!- SIMILARITY: Contains 1 PIK helical domain.
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DR EMBL; L36151; AAA56839.1; -; mRNA.
DR EMBL; AF012872; AAD13352.1; -; mRNA.
DR EMBL; AC007050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC018120; AAH18120.2; -; mRNA.
DR EMBL; BC053654; AAH53654.1; -; mRNA.
DR PIR; A55404; A55404.
DR RefSeq; NP_002641.1; NM_002650.2.
DR UniGene; Hs.529438; -.
DR UniGene; Hs.731386; -.
DR ProteinModelPortal; P42356; -.
DR SMR; P42356; 1446-2018.
DR IntAct; P42356; 16.
DR MINT; MINT-1388461; -.
DR STRING; 9606.ENSP00000255882; -.
DR BindingDB; P42356; -.
DR ChEMBL; CHEMBL3667; -.
DR GuidetoPHARMACOLOGY; 2148; -.
DR PhosphoSite; P42356; -.
DR DMDM; 218512114; -.
DR PaxDb; P42356; -.
DR PRIDE; P42356; -.
DR DNASU; 5297; -.
DR Ensembl; ENST00000414196; ENSP00000402981; ENSG00000241973.
DR Ensembl; ENST00000572273; ENSP00000458238; ENSG00000241973.
DR GeneID; 5297; -.
DR KEGG; hsa:5297; -.
DR CTD; 5297; -.
DR GeneCards; GC22M021061; -.
DR HGNC; HGNC:8983; PI4KA.
DR HPA; CAB009092; -.
DR MIM; 600286; gene.
DR neXtProt; NX_P42356; -.
DR PharmGKB; PA162399305; -.
DR eggNOG; COG5032; -.
DR HOVERGEN; HBG052742; -.
DR InParanoid; P42356; -.
DR KO; K00888; -.
DR PhylomeDB; P42356; -.
DR BioCyc; MetaCyc:HS13481-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P42356; -.
DR ChiTaRS; PI4KA; human.
DR GeneWiki; PI4KA; -.
DR GenomeRNAi; 5297; -.
DR NextBio; 20474; -.
DR PRO; PR:P42356; -.
DR ArrayExpress; P42356; -.
DR Bgee; P42356; -.
DR CleanEx; HS_PI4KA; -.
DR Genevestigator; P42356; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005798; C:Golgi-associated vesicle; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:RefGenome.
DR GO; GO:0004430; F:1-phosphatidylinositol 4-kinase activity; IBA:RefGenome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
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.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR001263; PInositide-3_kin_accessory_dom.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 6.
DR SUPFAM; SSF56112; SSF56112; 2.
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 Alternative splicing; ATP-binding; Complete proteome; Kinase;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Transferase.
FT CHAIN 1 2044 Phosphatidylinositol 4-kinase alpha.
FT /FTId=PRO_0000088827.
FT DOMAIN 1472 1660 PIK helical.
FT DOMAIN 1788 2021 PI3K/PI4K.
FT REGION 1661 1793 Pleckstrin homology (PH) domain
FT conferring phosphoinositide binding
FT specificity (By similarity).
FT MOD_RES 199 199 Phosphoserine.
FT MOD_RES 202 202 Phosphoserine.
FT MOD_RES 204 204 Phosphoserine.
FT MOD_RES 207 207 Phosphoserine.
FT MOD_RES 1378 1378 Phosphoserine.
FT VAR_SEQ 1 1190 Missing (in isoform 2).
FT /FTId=VSP_008805.
FT VARIANT 322 322 M -> V (in dbSNP:rs17819211).
FT /FTId=VAR_050531.
FT VARIANT 1793 1793 V -> L (in dbSNP:rs2539908).
FT /FTId=VAR_059549.
FT CONFLICT 380 380 N -> S (in Ref. 2; AAD13352).
FT CONFLICT 1889 1889 S -> I (in Ref. 4; AAH53654).
SQ SEQUENCE 2044 AA; 231319 MW; 7516EE4AA1E66465 CRC64;
MCPVDFHGIF QLDERRRDAV IALGIFLIES DLQHKDCVVP YLLRLLKGLP KVYWVEESTA
RKGRGALPVA ESFSFCLVTL LSDVAYRDPS LRDEILEVLL QVLHVLLGMC QALEIQDKEY
LCKYAIPCLI GISRAFGRYS NMEESLLSKL FPKIPPHSLR VLEELEGVRR RSFNDFRSIL
PSNLLTVCQE GTLKRKTSSV SSISQVSPER GMPPPSSPGG SAFHYFEASC LPDGTALEPE
YYFSTISSSF SVSPLFNGVT YKEFNIPLEM LRELLNLVKK IVEEAVLKSL DAIVASVMEA
NPSADLYYTS FSDPLYLTMF KMLRDTLYYM KDLPTSFVKE IHDFVLEQFN TSQGELQKIL
HDADRIHNEL SPLKLRCQAN AACVDLMVWA VKDEQGAENL CIKLSEKLQS KTSSKVIIAH
LPLLICCLQG LGRLCERFPV VVHSVTPSLR DFLVIPSPVL VKLYKYHSQY HTVAGNDIKI
SVTNEHSEST LNVMSGKKSQ PSMYEQLRDI AIDNICRCLK AGLTVDPVIV EAFLASLSNR
LYISQESDKD AHLIPDHTIR ALGHIAVALR DTPKVMEPIL QILQQKFCQP PSPLDVLIID
QLGCLVITGN QYIYQEVWNL FQQISVKASS VVYSATKDYK DHGYRHCSLA VINALANIAA
NIQDEHLVDE LLMNLLELFV QLGLEGKRAS ERASEKGPAL KASSSAGNLG VLIPVIAVLT
RRLPPIKEAK PRLQKLFRDF WLYSVLMGFA VEGSGLWPEE WYEGVCEIAT KSPLLTFPSK
EPLRSVLQYN SAMKNDTVTP AELSELRSTI INLLDPPPEV SALINKLDFA MSTYLLSVYR
LEYMRVLRST DPDRFQVMFC YFEDKAIQKD KSGMMQCVIA VADKVFDAFL NMMADKAKTK
ENEEELERHA QFLLVNFNHI HKRIRRVADK YLSGLVDKFP HLLWSGTVLK TMLDILQTLS
LSLSADIHKD QPYYDIPDAP YRITVPDTYE ARESIVKDFA ARCGMILQEA MKWAPTVTKS
HLQEYLNKHQ NWVSGLSQHT GLAMATESIL HFAGYNKQNT TLGATQLSER PACVKKDYSN
FMASLNLRNR YAGEVYGMIR FSGTTGQMSD LNKMMVQDLH SALDRSHPQH YTQAMFKLTA
MLISSKDCDP QLLHHLCWGP LRMFNEHGME TALACWEWLL AGKDGVEVPF MREMAGAWHM
TVEQKFGLFS AEIKEADPLA ASEASQPKPC PPEVTPHYIW IDFLVQRFEI AKYCSSDQVE
IFSSLLQRSM SLNIGGAKGS MNRHVAAIGP RFKLLTLGLS LLHADVVPNA TIRNVLREKI
YSTAFDYFSC PPKFPTQGEK RLREDISIMI KFWTAMFSDK KYLTASQLVP PDNQDTRSNL
DITVGSRQQA TQGWINTYPL SSGMSTISKK SGMSKKTNRG SQLHKYYMKR RTLLLSLLAT
EIERLITWYN PLSAPELELD QAGENSVANW RSKYISLSEK QWKDNVNLAW SISPYLAVQL
PARFKNTEAI GNEVTRLVRL DPGAVSDVPE AIKFLVTWHT IDADAPELSH VLCWAPTDPP
TGLSYFSSMY PPHPLTAQYG VKVLRSFPPD AILFYIPQIV QALRYDKMGY VREYILWAAS
KSQLLAHQFI WNMKTNIYLD EEGHQKDPDI GDLLDQLVEE ITGSLSGPAK DFYQREFDFF
NKITNVSAII KPYPKGDERK KACLSALSEV KVQPGCYLPS NPEAIVLDID YKSGTPMQSA
AKAPYLAKFK VKRCGVSELE KEGLRCRSDS EDECSTQEAD GQKISWQAAI FKVGDDCRQD
MLALQIIDLF KNIFQLVGLD LFVFPYRVVA TAPGCGVIEC IPDCTSRDQL GRQTDFGMYD
YFTRQYGDES TLAFQQARYN FIRSMAAYSL LLFLLQIKDR HNGNIMLDKK GHIIHIDFGF
MFESSPGGNL GWEPDIKLTD EMVMIMGGKM EATPFKWFME MCVRGYLAVR PYMDAVVSLV
TLMLDTGLPC FRGQTIKLLK HRFSPNMTER EAANFIMKVI QSCFLSNRSR TYDMIQYYQN
DIPY
//
ID PI4KA_HUMAN Reviewed; 2044 AA.
AC P42356; Q7Z625; Q9UPG2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-DEC-2008, sequence version 3.
DT 22-JAN-2014, entry version 128.
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;
GN Name=PI4KA; Synonyms=PIK4, PIK4CA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=7961848;
RA Wong K., Cantley L.C.;
RT "Cloning and characterization of a human phosphatidylinositol 4-
RT kinase.";
RL J. Biol. Chem. 269:28878-28884(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=10101268; DOI=10.1016/S1388-1981(99)00029-3;
RA Gehrmann T., Guelkan H., Suer S., Herberg F.W., Balla A.,
RA Vereb G. Jr., Mayr G.W., Heilmeyer L.M.G. Jr.;
RT "Functional expression and characterisation of a new human
RT phosphatidylinositol 4-kinase PI4K230.";
RL Biochim. Biophys. Acta 1437:341-356(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1142-2044 (ISOFORM 1).
RC TISSUE=Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199; SER-202; SER-204
RP AND SER-207, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207 AND SER-1378, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Acts on phosphatidylinositol (PtdIns) in the first
CC committed step in the production of the second messenger inositol-
CC 1,4,5,-trisphosphate.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol = ADP +
CC 1-phosphatidyl-1D-myo-inositol 4-phosphate.
CC -!- ENZYME REGULATION: This is a type II PtdIns-4-kinase activated by
CC detergents such as triton and inhibited by adenosine.
CC -!- INTERACTION:
CC P27958:- (xeno); NbExp=4; IntAct=EBI-723050, EBI-8753518;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PI4K230;
CC IsoId=P42356-1; Sequence=Displayed;
CC Name=2; Synonyms=PI4K97;
CC IsoId=P42356-2; Sequence=VSP_008805;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously. Highest levels in
CC placenta and brain. Little or no expression in lung, liver,
CC pancreas, testis or leukocytes.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type III PI4K
CC subfamily.
CC -!- SIMILARITY: Contains 1 PI3K/PI4K domain.
CC -!- SIMILARITY: Contains 1 PIK helical domain.
CC -----------------------------------------------------------------------
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DR EMBL; L36151; AAA56839.1; -; mRNA.
DR EMBL; AF012872; AAD13352.1; -; mRNA.
DR EMBL; AC007050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC018120; AAH18120.2; -; mRNA.
DR EMBL; BC053654; AAH53654.1; -; mRNA.
DR PIR; A55404; A55404.
DR RefSeq; NP_002641.1; NM_002650.2.
DR UniGene; Hs.529438; -.
DR UniGene; Hs.731386; -.
DR ProteinModelPortal; P42356; -.
DR SMR; P42356; 1446-2018.
DR IntAct; P42356; 16.
DR MINT; MINT-1388461; -.
DR STRING; 9606.ENSP00000255882; -.
DR BindingDB; P42356; -.
DR ChEMBL; CHEMBL3667; -.
DR GuidetoPHARMACOLOGY; 2148; -.
DR PhosphoSite; P42356; -.
DR DMDM; 218512114; -.
DR PaxDb; P42356; -.
DR PRIDE; P42356; -.
DR DNASU; 5297; -.
DR Ensembl; ENST00000414196; ENSP00000402981; ENSG00000241973.
DR Ensembl; ENST00000572273; ENSP00000458238; ENSG00000241973.
DR GeneID; 5297; -.
DR KEGG; hsa:5297; -.
DR CTD; 5297; -.
DR GeneCards; GC22M021061; -.
DR HGNC; HGNC:8983; PI4KA.
DR HPA; CAB009092; -.
DR MIM; 600286; gene.
DR neXtProt; NX_P42356; -.
DR PharmGKB; PA162399305; -.
DR eggNOG; COG5032; -.
DR HOVERGEN; HBG052742; -.
DR InParanoid; P42356; -.
DR KO; K00888; -.
DR PhylomeDB; P42356; -.
DR BioCyc; MetaCyc:HS13481-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P42356; -.
DR ChiTaRS; PI4KA; human.
DR GeneWiki; PI4KA; -.
DR GenomeRNAi; 5297; -.
DR NextBio; 20474; -.
DR PRO; PR:P42356; -.
DR ArrayExpress; P42356; -.
DR Bgee; P42356; -.
DR CleanEx; HS_PI4KA; -.
DR Genevestigator; P42356; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005798; C:Golgi-associated vesicle; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:RefGenome.
DR GO; GO:0004430; F:1-phosphatidylinositol 4-kinase activity; IBA:RefGenome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
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.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR001263; PInositide-3_kin_accessory_dom.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 6.
DR SUPFAM; SSF56112; SSF56112; 2.
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 Alternative splicing; ATP-binding; Complete proteome; Kinase;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Transferase.
FT CHAIN 1 2044 Phosphatidylinositol 4-kinase alpha.
FT /FTId=PRO_0000088827.
FT DOMAIN 1472 1660 PIK helical.
FT DOMAIN 1788 2021 PI3K/PI4K.
FT REGION 1661 1793 Pleckstrin homology (PH) domain
FT conferring phosphoinositide binding
FT specificity (By similarity).
FT MOD_RES 199 199 Phosphoserine.
FT MOD_RES 202 202 Phosphoserine.
FT MOD_RES 204 204 Phosphoserine.
FT MOD_RES 207 207 Phosphoserine.
FT MOD_RES 1378 1378 Phosphoserine.
FT VAR_SEQ 1 1190 Missing (in isoform 2).
FT /FTId=VSP_008805.
FT VARIANT 322 322 M -> V (in dbSNP:rs17819211).
FT /FTId=VAR_050531.
FT VARIANT 1793 1793 V -> L (in dbSNP:rs2539908).
FT /FTId=VAR_059549.
FT CONFLICT 380 380 N -> S (in Ref. 2; AAD13352).
FT CONFLICT 1889 1889 S -> I (in Ref. 4; AAH53654).
SQ SEQUENCE 2044 AA; 231319 MW; 7516EE4AA1E66465 CRC64;
MCPVDFHGIF QLDERRRDAV IALGIFLIES DLQHKDCVVP YLLRLLKGLP KVYWVEESTA
RKGRGALPVA ESFSFCLVTL LSDVAYRDPS LRDEILEVLL QVLHVLLGMC QALEIQDKEY
LCKYAIPCLI GISRAFGRYS NMEESLLSKL FPKIPPHSLR VLEELEGVRR RSFNDFRSIL
PSNLLTVCQE GTLKRKTSSV SSISQVSPER GMPPPSSPGG SAFHYFEASC LPDGTALEPE
YYFSTISSSF SVSPLFNGVT YKEFNIPLEM LRELLNLVKK IVEEAVLKSL DAIVASVMEA
NPSADLYYTS FSDPLYLTMF KMLRDTLYYM KDLPTSFVKE IHDFVLEQFN TSQGELQKIL
HDADRIHNEL SPLKLRCQAN AACVDLMVWA VKDEQGAENL CIKLSEKLQS KTSSKVIIAH
LPLLICCLQG LGRLCERFPV VVHSVTPSLR DFLVIPSPVL VKLYKYHSQY HTVAGNDIKI
SVTNEHSEST LNVMSGKKSQ PSMYEQLRDI AIDNICRCLK AGLTVDPVIV EAFLASLSNR
LYISQESDKD AHLIPDHTIR ALGHIAVALR DTPKVMEPIL QILQQKFCQP PSPLDVLIID
QLGCLVITGN QYIYQEVWNL FQQISVKASS VVYSATKDYK DHGYRHCSLA VINALANIAA
NIQDEHLVDE LLMNLLELFV QLGLEGKRAS ERASEKGPAL KASSSAGNLG VLIPVIAVLT
RRLPPIKEAK PRLQKLFRDF WLYSVLMGFA VEGSGLWPEE WYEGVCEIAT KSPLLTFPSK
EPLRSVLQYN SAMKNDTVTP AELSELRSTI INLLDPPPEV SALINKLDFA MSTYLLSVYR
LEYMRVLRST DPDRFQVMFC YFEDKAIQKD KSGMMQCVIA VADKVFDAFL NMMADKAKTK
ENEEELERHA QFLLVNFNHI HKRIRRVADK YLSGLVDKFP HLLWSGTVLK TMLDILQTLS
LSLSADIHKD QPYYDIPDAP YRITVPDTYE ARESIVKDFA ARCGMILQEA MKWAPTVTKS
HLQEYLNKHQ NWVSGLSQHT GLAMATESIL HFAGYNKQNT TLGATQLSER PACVKKDYSN
FMASLNLRNR YAGEVYGMIR FSGTTGQMSD LNKMMVQDLH SALDRSHPQH YTQAMFKLTA
MLISSKDCDP QLLHHLCWGP LRMFNEHGME TALACWEWLL AGKDGVEVPF MREMAGAWHM
TVEQKFGLFS AEIKEADPLA ASEASQPKPC PPEVTPHYIW IDFLVQRFEI AKYCSSDQVE
IFSSLLQRSM SLNIGGAKGS MNRHVAAIGP RFKLLTLGLS LLHADVVPNA TIRNVLREKI
YSTAFDYFSC PPKFPTQGEK RLREDISIMI KFWTAMFSDK KYLTASQLVP PDNQDTRSNL
DITVGSRQQA TQGWINTYPL SSGMSTISKK SGMSKKTNRG SQLHKYYMKR RTLLLSLLAT
EIERLITWYN PLSAPELELD QAGENSVANW RSKYISLSEK QWKDNVNLAW SISPYLAVQL
PARFKNTEAI GNEVTRLVRL DPGAVSDVPE AIKFLVTWHT IDADAPELSH VLCWAPTDPP
TGLSYFSSMY PPHPLTAQYG VKVLRSFPPD AILFYIPQIV QALRYDKMGY VREYILWAAS
KSQLLAHQFI WNMKTNIYLD EEGHQKDPDI GDLLDQLVEE ITGSLSGPAK DFYQREFDFF
NKITNVSAII KPYPKGDERK KACLSALSEV KVQPGCYLPS NPEAIVLDID YKSGTPMQSA
AKAPYLAKFK VKRCGVSELE KEGLRCRSDS EDECSTQEAD GQKISWQAAI FKVGDDCRQD
MLALQIIDLF KNIFQLVGLD LFVFPYRVVA TAPGCGVIEC IPDCTSRDQL GRQTDFGMYD
YFTRQYGDES TLAFQQARYN FIRSMAAYSL LLFLLQIKDR HNGNIMLDKK GHIIHIDFGF
MFESSPGGNL GWEPDIKLTD EMVMIMGGKM EATPFKWFME MCVRGYLAVR PYMDAVVSLV
TLMLDTGLPC FRGQTIKLLK HRFSPNMTER EAANFIMKVI QSCFLSNRSR TYDMIQYYQN
DIPY
//
MIM
600286
*RECORD*
*FIELD* NO
600286
*FIELD* TI
*600286 PHOSPHATIDYLINOSITOL 4-KINASE, CATALYTIC, ALPHA; PI4KA
;;PIK4CA;;
PI4K-ALPHA;;
read morePHOSPHATIDYLINOSITOL 4-KINASE, TYPE III, ALPHA;;
PI4KIII-ALPHA
*FIELD* TX
Phosphatidylinositol (PI) 4-kinase catalyzes the first committed step in
the biosynthesis of phosphatidylinositol 4,5-bisphosphate. Several forms
of mammalian PI 4-kinases have been purified, characterized, and
classified into types II and III. The type II enzymes have an apparent
molecular mass of approximately 55 kD, are highly stimulated by
detergent, and are inhibited by adenosine. The type III enzymes have an
apparent molecular mass of greater than 200 kD, are less stimulated by
detergent, and are not inhibited by adenosine (summary by Nakagawa et
al., 1996).
CLONING
By PCR and by screening human placenta and fetal brain cDNA libraries,
Wong and Cantley (1994) cloned cDNAs encoding a PI 4-kinase, which they
named PI4K-alpha. The predicted 854-amino acid protein has a calculated
molecular mass of 97 kD. It contains an ankyrin repeat, a lipid kinase
unique domain, a pleckstrin-homology domain, and a lipid kinase
catalytic domain. PI4K-alpha has high amino acid sequence similarity to
the yeast PI 4-kinases STT4 and PIK1; it has less amino acid sequence
similarity to the catalytic domains of mammalian and yeast PI 3-kinases
(e.g., 171834) and to the yeast TOR family of proteins. The enzymatic
properties of PI4K-alpha were characteristic of type II PI 4-kinases. By
Northern blot analysis, 7.5- and 3.5-kb PI4K-alpha transcripts were
detected in all human tissues examined, with the highest levels in
placenta and brain.
Nakagawa et al. (1996) cloned a PI 4-kinase cDNA from a rat brain cDNA
library. The C-terminal amino acid sequence of the predicted 2,041-amino
acid rat PI 4-kinase is 98% similar to the amino acid sequence of
PI4K-alpha, the human PI 4-kinase cDNA described by Wong and Cantley
(1994). Northern blot analysis of adult rat tissues detected a 7.8-kb
transcript in all tissues examined, except liver. Based on their similar
amino acid sequences and mRNA expression patterns, Nakagawa et al.
(1996) suggested that PI4K-alpha and the rat PI 4-kinase represent
alternatively spliced forms of the same molecule. The N-terminal region
of the rat PI 4-kinase, which is absent in PI4K-alpha, contains 2
proline-rich regions and an SH3 domain. Western blot analysis of lysates
from transfected mammalian cells indicated that the rat PI 4-kinase has
a molecular mass of approximately 230 kD. Nakagawa et al. (1996) found
that the rat PI 4-kinase has the enzymatic properties of type III PI
4-kinases. By in situ hybridization, they detected rat PI 4-kinase mRNA
in the gray matter of the brain, with expression higher in fetal brain
than in adult brain. Immunohistochemistry demonstrated that the protein
is associated with the membranes of Golgi vesicles and vacuoles.
GENE FUNCTION
Hammond et al. (2012) used a combination of pharmacologic and chemical
genetic approaches to probe the function of plasma membrane
phosphatidylinositol 4-phosphate (PI4P), most of which was not required
for the synthesis or functions of PI(4,5)P2. However, depletion of both
lipids was required to prevent plasma membrane targeting of proteins
that interact with acidic lipids or activation of the transient receptor
potential vanilloid-1 cation channel. Therefore, PI4P contributes to the
pool of polyanionic lipids that define plasma membrane identity and to
some functions previously attributed specifically to PI(4,5)P2, which
may be fulfilled by a more general polyanionic lipid requirement.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PI4KA
gene to chromosome 22 (TMAP RH78571).
*FIELD* RF
1. Hammond, G. R. V.; Fischer, M. J.; Anderson, K. E.; Holdich, J.;
Koteci, A.; Balla, T.; Irvine, R. F.: PI4P and PI(4,5)P2 are essential
but independent lipid determinants of membrane identity. Science 337:
727-730, 2012.
2. Nakagawa, T.; Goto, K.; Kondo, H.: Cloning, expression, and localization
of 230-kDa phosphatidylinositol 4-kinase. J. Biol. Chem. 271: 12088-12094,
1996.
3. Wong, K.; Cantley, L. C.: Cloning and characterization of a human
phosphatidylinositol 4-kinase. J. Biol. Chem. 269: 28878-28884,
1994.
*FIELD* CN
Ada Hamosh - updated: 8/29/2012
Patti M. Sherman - updated: 6/30/1998
*FIELD* CD
Victor A. McKusick: 1/6/1995
*FIELD* ED
alopez: 09/04/2012
terry: 8/29/2012
alopez: 2/4/2009
carol: 3/18/2008
mgross: 12/8/2005
carol: 7/10/1998
psherman: 7/8/1998
carol: 6/30/1998
psherman: 6/30/1998
alopez: 9/26/1997
alopez: 9/8/1997
alopez: 9/5/1997
alopez: 6/5/1997
carol: 1/6/1995
*RECORD*
*FIELD* NO
600286
*FIELD* TI
*600286 PHOSPHATIDYLINOSITOL 4-KINASE, CATALYTIC, ALPHA; PI4KA
;;PIK4CA;;
PI4K-ALPHA;;
read morePHOSPHATIDYLINOSITOL 4-KINASE, TYPE III, ALPHA;;
PI4KIII-ALPHA
*FIELD* TX
Phosphatidylinositol (PI) 4-kinase catalyzes the first committed step in
the biosynthesis of phosphatidylinositol 4,5-bisphosphate. Several forms
of mammalian PI 4-kinases have been purified, characterized, and
classified into types II and III. The type II enzymes have an apparent
molecular mass of approximately 55 kD, are highly stimulated by
detergent, and are inhibited by adenosine. The type III enzymes have an
apparent molecular mass of greater than 200 kD, are less stimulated by
detergent, and are not inhibited by adenosine (summary by Nakagawa et
al., 1996).
CLONING
By PCR and by screening human placenta and fetal brain cDNA libraries,
Wong and Cantley (1994) cloned cDNAs encoding a PI 4-kinase, which they
named PI4K-alpha. The predicted 854-amino acid protein has a calculated
molecular mass of 97 kD. It contains an ankyrin repeat, a lipid kinase
unique domain, a pleckstrin-homology domain, and a lipid kinase
catalytic domain. PI4K-alpha has high amino acid sequence similarity to
the yeast PI 4-kinases STT4 and PIK1; it has less amino acid sequence
similarity to the catalytic domains of mammalian and yeast PI 3-kinases
(e.g., 171834) and to the yeast TOR family of proteins. The enzymatic
properties of PI4K-alpha were characteristic of type II PI 4-kinases. By
Northern blot analysis, 7.5- and 3.5-kb PI4K-alpha transcripts were
detected in all human tissues examined, with the highest levels in
placenta and brain.
Nakagawa et al. (1996) cloned a PI 4-kinase cDNA from a rat brain cDNA
library. The C-terminal amino acid sequence of the predicted 2,041-amino
acid rat PI 4-kinase is 98% similar to the amino acid sequence of
PI4K-alpha, the human PI 4-kinase cDNA described by Wong and Cantley
(1994). Northern blot analysis of adult rat tissues detected a 7.8-kb
transcript in all tissues examined, except liver. Based on their similar
amino acid sequences and mRNA expression patterns, Nakagawa et al.
(1996) suggested that PI4K-alpha and the rat PI 4-kinase represent
alternatively spliced forms of the same molecule. The N-terminal region
of the rat PI 4-kinase, which is absent in PI4K-alpha, contains 2
proline-rich regions and an SH3 domain. Western blot analysis of lysates
from transfected mammalian cells indicated that the rat PI 4-kinase has
a molecular mass of approximately 230 kD. Nakagawa et al. (1996) found
that the rat PI 4-kinase has the enzymatic properties of type III PI
4-kinases. By in situ hybridization, they detected rat PI 4-kinase mRNA
in the gray matter of the brain, with expression higher in fetal brain
than in adult brain. Immunohistochemistry demonstrated that the protein
is associated with the membranes of Golgi vesicles and vacuoles.
GENE FUNCTION
Hammond et al. (2012) used a combination of pharmacologic and chemical
genetic approaches to probe the function of plasma membrane
phosphatidylinositol 4-phosphate (PI4P), most of which was not required
for the synthesis or functions of PI(4,5)P2. However, depletion of both
lipids was required to prevent plasma membrane targeting of proteins
that interact with acidic lipids or activation of the transient receptor
potential vanilloid-1 cation channel. Therefore, PI4P contributes to the
pool of polyanionic lipids that define plasma membrane identity and to
some functions previously attributed specifically to PI(4,5)P2, which
may be fulfilled by a more general polyanionic lipid requirement.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PI4KA
gene to chromosome 22 (TMAP RH78571).
*FIELD* RF
1. Hammond, G. R. V.; Fischer, M. J.; Anderson, K. E.; Holdich, J.;
Koteci, A.; Balla, T.; Irvine, R. F.: PI4P and PI(4,5)P2 are essential
but independent lipid determinants of membrane identity. Science 337:
727-730, 2012.
2. Nakagawa, T.; Goto, K.; Kondo, H.: Cloning, expression, and localization
of 230-kDa phosphatidylinositol 4-kinase. J. Biol. Chem. 271: 12088-12094,
1996.
3. Wong, K.; Cantley, L. C.: Cloning and characterization of a human
phosphatidylinositol 4-kinase. J. Biol. Chem. 269: 28878-28884,
1994.
*FIELD* CN
Ada Hamosh - updated: 8/29/2012
Patti M. Sherman - updated: 6/30/1998
*FIELD* CD
Victor A. McKusick: 1/6/1995
*FIELD* ED
alopez: 09/04/2012
terry: 8/29/2012
alopez: 2/4/2009
carol: 3/18/2008
mgross: 12/8/2005
carol: 7/10/1998
psherman: 7/8/1998
carol: 6/30/1998
psherman: 6/30/1998
alopez: 9/26/1997
alopez: 9/8/1997
alopez: 9/5/1997
alopez: 6/5/1997
carol: 1/6/1995