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Protein

Phosphatidylinositol 4-kinase alpha

Gene

PI4KA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate.2 Publications

Catalytic activityi

ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate.1 Publication

Enzyme regulationi

Activated by Triton X-100, insensitive to inhibition by adenosine and inhibited by wortmannin (By similarity). Isoform 2 is activated by detergents such as Triton X-100 and inhibited by adenosine (PubMed:7961848). The PI4K complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns4P) synthesis (PubMed:23229899, PubMed:26571211). Interaction with TMEM150A regulates PtdIns4P synthesis (PubMed:25608530).By similarity4 Publications

Kineticsi

  1. KM=300 µM for ATP1 Publication

    GO - Molecular functioni

    • 1-phosphatidylinositol 4-kinase activity Source: UniProtKB
    • ATP binding Source: UniProtKB-KW
    • cadherin binding Source: BHF-UCL
    • kinase activity Source: MGI

    GO - Biological processi

    • actin cytoskeleton organization Source: GO_Central
    • multi-organism membrane organization Source: ParkinsonsUK-UCL
    • phosphatidylinositol biosynthetic process Source: Reactome
    • phosphatidylinositol-mediated signaling Source: GO_Central
    • phosphatidylinositol phosphorylation Source: UniProtKB
    • phosphorylation Source: MGI
    • signal transduction Source: ProtInc
    • viral replication complex formation and maintenance Source: ParkinsonsUK-UCL
    • viral RNA genome replication Source: ParkinsonsUK-UCL

    Keywordsi

    Molecular functionKinase, Transferase
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS13481-MONOMER
    ReactomeiR-HSA-1483248 Synthesis of PIPs at the ER membrane
    R-HSA-1660514 Synthesis of PIPs at the Golgi membrane
    SABIO-RKiP42356

    Chemistry databases

    SwissLipidsiSLP:000000895
    SLP:000000902 [P42356-2]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositol 4-kinase alpha (EC:2.7.1.671 Publication)
    Short name:
    PI4-kinase alpha
    Short name:
    PI4K-alpha
    Short name:
    PtdIns-4-kinase alpha
    Gene namesi
    Name:PI4KA
    Synonyms:PIK4, PIK4CA
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 22

    Organism-specific databases

    HGNCiHGNC:8983 PI4KA
    MIMi600286 gene
    neXtProtiNX_P42356

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis (PMGYCHA)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of polymicrogyria, a malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. PMGYCHA patients manifest perisylvian polymicrogyria, cerebellar hypoplasia or dysplasia, and variable contractures of the limbs or fingers.
    See also OMIM:616531
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0746401854D → N in PMGYCHA; loss of kinase activity; no effect on protein abundance. 1 PublicationCorresponds to variant dbSNP:rs747119727EnsemblClinVar.1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi5297
    MalaCardsiPI4KA
    MIMi616531 phenotype
    OpenTargetsiENSG00000241973
    PharmGKBiPA162399305

    Chemistry databases

    ChEMBLiCHEMBL3667
    GuidetoPHARMACOLOGYi2148

    Polymorphism and mutation databases

    BioMutaiPI4KA
    DMDMi218512114

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000888271 – 2102Phosphatidylinositol 4-kinase alphaAdd BLAST2102

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei230PhosphoserineCombined sources1
    Modified residuei256PhosphoserineCombined sources1
    Modified residuei257PhosphoserineCombined sources1
    Modified residuei259PhosphoserineBy similarity1
    Modified residuei260PhosphoserineCombined sources1
    Modified residuei262PhosphoserineCombined sources1
    Modified residuei265PhosphoserineCombined sources1
    Modified residuei429PhosphoserineCombined sources1
    Modified residuei1154PhosphotyrosineCombined sources1
    Modified residuei1436PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiP42356
    MaxQBiP42356
    PaxDbiP42356
    PeptideAtlasiP42356
    PRIDEiP42356
    ProteomicsDBi55512
    55513 [P42356-2]

    PTM databases

    iPTMnetiP42356
    PhosphoSitePlusiP42356
    SwissPalmiP42356

    Expressioni

    Tissue specificityi

    Expressed ubiquitously. Highest levels in placenta and brain. Little or no expression in lung, liver, pancreas, testis or leukocytes.2 Publications

    Gene expression databases

    CleanExiHS_PI4KA
    ExpressionAtlasiP42356 baseline and differential

    Organism-specific databases

    HPAiCAB009092
    HPA075515

    Interactioni

    Subunit structurei

    Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and FAM126 (FAM126A or FAM126B) (PubMed:23229899, PubMed:24417819, PubMed:26571211). Interacts with TMEM150A; regulating recruitment to the plasma membrane (PubMed:25608530).4 Publications

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    Protein-protein interaction databases

    CORUMiP42356
    IntActiP42356, 27 interactors
    MINTiP42356
    STRINGi9606.ENSP00000458238

    Chemistry databases

    BindingDBiP42356

    Structurei

    3D structure databases

    ProteinModelPortaliP42356
    SMRiP42356
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini1530 – 1718PIK helicalPROSITE-ProRule annotationAdd BLAST189
    Domaini1846 – 2079PI3K/PI4KPROSITE-ProRule annotationAdd BLAST234

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG0902 Eukaryota
    COG5032 LUCA
    GeneTreeiENSGT00550000074798
    HOVERGENiHBG052742
    InParanoidiP42356
    KOiK00888
    OMAiCMCPVDF
    TreeFamiTF102041

    Family and domain databases

    Gene3Di1.10.1070.11, 1 hit
    InterProiView protein in InterPro
    IPR016024 ARM-type_fold
    IPR011009 Kinase-like_dom_sf
    IPR000403 PI3/4_kinase_cat_dom
    IPR036940 PI3/4_kinase_cat_sf
    IPR018936 PI3/4_kinase_CS
    IPR015433 PI_Kinase
    IPR001263 PInositide-3_kin_accessory_dom
    PANTHERiPTHR10048 PTHR10048, 1 hit
    PfamiView protein in Pfam
    PF00454 PI3_PI4_kinase, 1 hit
    PF00613 PI3Ka, 1 hit
    SMARTiView protein in SMART
    SM00145 PI3Ka, 1 hit
    SM00146 PI3Kc, 1 hit
    SUPFAMiSSF48371 SSF48371, 6 hits
    SSF56112 SSF56112, 2 hits
    PROSITEiView protein in PROSITE
    PS00915 PI3_4_KINASE_1, 1 hit
    PS00916 PI3_4_KINASE_2, 1 hit
    PS50290 PI3_4_KINASE_3, 1 hit
    PS51545 PIK_HELICAL, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P42356-1) [UniParc]FASTAAdd to basket
    Also known as: PI4K2301 Publication

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MAAAPARGGG GGGGGGGGCS GSGSSASRGF YFNTVLSLAR SLAVQRPASL
    60 70 80 90 100
    EKVQKLLCMC PVDFHGIFQL DERRRDAVIA LGIFLIESDL QHKDCVVPYL
    110 120 130 140 150
    LRLLKGLPKV YWVEESTARK GRGALPVAES FSFCLVTLLS DVAYRDPSLR
    160 170 180 190 200
    DEILEVLLQV LHVLLGMCQA LEIQDKEYLC KYAIPCLIGI SRAFGRYSNM
    210 220 230 240 250
    EESLLSKLFP KIPPHSLRVL EELEGVRRRS FNDFRSILPS NLLTVCQEGT
    260 270 280 290 300
    LKRKTSSVSS ISQVSPERGM PPPSSPGGSA FHYFEASCLP DGTALEPEYY
    310 320 330 340 350
    FSTISSSFSV SPLFNGVTYK EFNIPLEMLR ELLNLVKKIV EEAVLKSLDA
    360 370 380 390 400
    IVASVMEANP SADLYYTSFS DPLYLTMFKM LRDTLYYMKD LPTSFVKEIH
    410 420 430 440 450
    DFVLEQFNTS QGELQKILHD ADRIHNELSP LKLRCQANAA CVDLMVWAVK
    460 470 480 490 500
    DEQGAENLCI KLSEKLQSKT SSKVIIAHLP LLICCLQGLG RLCERFPVVV
    510 520 530 540 550
    HSVTPSLRDF LVIPSPVLVK LYKYHSQYHT VAGNDIKISV TNEHSESTLN
    560 570 580 590 600
    VMSGKKSQPS MYEQLRDIAI DNICRCLKAG LTVDPVIVEA FLASLSNRLY
    610 620 630 640 650
    ISQESDKDAH LIPDHTIRAL GHIAVALRDT PKVMEPILQI LQQKFCQPPS
    660 670 680 690 700
    PLDVLIIDQL GCLVITGNQY IYQEVWNLFQ QISVKASSVV YSATKDYKDH
    710 720 730 740 750
    GYRHCSLAVI NALANIAANI QDEHLVDELL MNLLELFVQL GLEGKRASER
    760 770 780 790 800
    ASEKGPALKA SSSAGNLGVL IPVIAVLTRR LPPIKEAKPR LQKLFRDFWL
    810 820 830 840 850
    YSVLMGFAVE GSGLWPEEWY EGVCEIATKS PLLTFPSKEP LRSVLQYNSA
    860 870 880 890 900
    MKNDTVTPAE LSELRSTIIN LLDPPPEVSA LINKLDFAMS TYLLSVYRLE
    910 920 930 940 950
    YMRVLRSTDP DRFQVMFCYF EDKAIQKDKS GMMQCVIAVA DKVFDAFLNM
    960 970 980 990 1000
    MADKAKTKEN EEELERHAQF LLVNFNHIHK RIRRVADKYL SGLVDKFPHL
    1010 1020 1030 1040 1050
    LWSGTVLKTM LDILQTLSLS LSADIHKDQP YYDIPDAPYR ITVPDTYEAR
    1060 1070 1080 1090 1100
    ESIVKDFAAR CGMILQEAMK WAPTVTKSHL QEYLNKHQNW VSGLSQHTGL
    1110 1120 1130 1140 1150
    AMATESILHF AGYNKQNTTL GATQLSERPA CVKKDYSNFM ASLNLRNRYA
    1160 1170 1180 1190 1200
    GEVYGMIRFS GTTGQMSDLN KMMVQDLHSA LDRSHPQHYT QAMFKLTAML
    1210 1220 1230 1240 1250
    ISSKDCDPQL LHHLCWGPLR MFNEHGMETA LACWEWLLAG KDGVEVPFMR
    1260 1270 1280 1290 1300
    EMAGAWHMTV EQKFGLFSAE IKEADPLAAS EASQPKPCPP EVTPHYIWID
    1310 1320 1330 1340 1350
    FLVQRFEIAK YCSSDQVEIF SSLLQRSMSL NIGGAKGSMN RHVAAIGPRF
    1360 1370 1380 1390 1400
    KLLTLGLSLL HADVVPNATI RNVLREKIYS TAFDYFSCPP KFPTQGEKRL
    1410 1420 1430 1440 1450
    REDISIMIKF WTAMFSDKKY LTASQLVPPD NQDTRSNLDI TVGSRQQATQ
    1460 1470 1480 1490 1500
    GWINTYPLSS GMSTISKKSG MSKKTNRGSQ LHKYYMKRRT LLLSLLATEI
    1510 1520 1530 1540 1550
    ERLITWYNPL SAPELELDQA GENSVANWRS KYISLSEKQW KDNVNLAWSI
    1560 1570 1580 1590 1600
    SPYLAVQLPA RFKNTEAIGN EVTRLVRLDP GAVSDVPEAI KFLVTWHTID
    1610 1620 1630 1640 1650
    ADAPELSHVL CWAPTDPPTG LSYFSSMYPP HPLTAQYGVK VLRSFPPDAI
    1660 1670 1680 1690 1700
    LFYIPQIVQA LRYDKMGYVR EYILWAASKS QLLAHQFIWN MKTNIYLDEE
    1710 1720 1730 1740 1750
    GHQKDPDIGD LLDQLVEEIT GSLSGPAKDF YQREFDFFNK ITNVSAIIKP
    1760 1770 1780 1790 1800
    YPKGDERKKA CLSALSEVKV QPGCYLPSNP EAIVLDIDYK SGTPMQSAAK
    1810 1820 1830 1840 1850
    APYLAKFKVK RCGVSELEKE GLRCRSDSED ECSTQEADGQ KISWQAAIFK
    1860 1870 1880 1890 1900
    VGDDCRQDML ALQIIDLFKN IFQLVGLDLF VFPYRVVATA PGCGVIECIP
    1910 1920 1930 1940 1950
    DCTSRDQLGR QTDFGMYDYF TRQYGDESTL AFQQARYNFI RSMAAYSLLL
    1960 1970 1980 1990 2000
    FLLQIKDRHN GNIMLDKKGH IIHIDFGFMF ESSPGGNLGW EPDIKLTDEM
    2010 2020 2030 2040 2050
    VMIMGGKMEA TPFKWFMEMC VRGYLAVRPY MDAVVSLVTL MLDTGLPCFR
    2060 2070 2080 2090 2100
    GQTIKLLKHR FSPNMTEREA ANFIMKVIQS CFLSNRSRTY DMIQYYQNDI

    PY
    Length:2,102
    Mass (Da):236,830
    Last modified:February 17, 2016 - v4
    Checksum:iED4C3C9EA79E6B5D
    GO
    Isoform 2 (identifier: P42356-2) [UniParc]FASTAAdd to basket
    Also known as: PI4K971 Publication

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1248: Missing.

    Show »
    Length:854
    Mass (Da):96,984
    Checksum:iF519168FA721644E
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti438N → S in AAD13352 (PubMed:10101268).Curated1
    Sequence conflicti1947S → I in AAH53654 (PubMed:15489334).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_050531380M → V. Corresponds to variant dbSNP:rs17819211Ensembl.1
    Natural variantiVAR_0595491851V → L. Corresponds to variant dbSNP:rs2539908Ensembl.1
    Natural variantiVAR_0746401854D → N in PMGYCHA; loss of kinase activity; no effect on protein abundance. 1 PublicationCorresponds to variant dbSNP:rs747119727EnsemblClinVar.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0088051 – 1248Missing in isoform 2. 1 PublicationAdd BLAST1248

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L36151 mRNA Translation: AAA56839.1
    AC007050 Genomic DNA No translation available.
    AC007308 Genomic DNA No translation available.
    AF012872 mRNA Translation: AAD13352.1
    BC018120 mRNA Translation: AAH18120.2
    BC053654 mRNA Translation: AAH53654.1
    CCDSiCCDS33603.2 [P42356-1]
    PIRiA55404
    RefSeqiNP_477352.3, NM_058004.3 [P42356-1]
    UniGeneiHs.529438
    Hs.731386

    Genome annotation databases

    EnsembliENST00000255882; ENSP00000255882; ENSG00000241973 [P42356-1]
    GeneIDi5297
    KEGGihsa:5297

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiPI4KA_HUMAN
    AccessioniPrimary (citable) accession number: P42356
    Secondary accession number(s): Q7Z625, Q9UPG2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: February 17, 2016
    Last modified: June 20, 2018
    This is version 173 of the entry and version 4 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 22
      Human chromosome 22: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

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