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Protein

Phosphatidylinositol 4-kinase alpha

Gene

PI4KA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Ligandi

    ATP-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-RKP42356.

    Chemistry

    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.

    Subcellular locationi

    GO - Cellular componenti

    • cell-cell adherens junction Source: BHF-UCL
    • cytoplasm Source: UniProtKB
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • focal adhesion Source: UniProtKB
    • Golgi-associated vesicle membrane Source: UniProtKB
    • membrane Source: UniProtKB
    • plasma membrane Source: UniProtKB
    Complete GO annotation...

    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1854 – 18541D → N in PMGYCHA; loss of kinase activity; no effect on protein abundance. 1 Publication
    Corresponds to variant rs747119727 [ dbSNP | Ensembl ].
    VAR_074640

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi616531. phenotype.
    PharmGKBiPA162399305.

    Chemistry

    ChEMBLiCHEMBL3038509.
    GuidetoPHARMACOLOGYi2148.

    Polymorphism and mutation databases

    BioMutaiPI4KA.
    DMDMi218512114.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 21022102Phosphatidylinositol 4-kinase alphaPRO_0000088827Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei230 – 2301PhosphoserineCombined sources
    Modified residuei256 – 2561PhosphoserineCombined sources
    Modified residuei257 – 2571PhosphoserineCombined sources
    Modified residuei259 – 2591PhosphoserineBy similarity
    Modified residuei260 – 2601PhosphoserineCombined sources
    Modified residuei262 – 2621PhosphoserineCombined sources
    Modified residuei265 – 2651PhosphoserineCombined sources
    Modified residuei429 – 4291PhosphoserineCombined sources
    Modified residuei1154 – 11541PhosphotyrosineCombined sources
    Modified residuei1436 – 14361PhosphoserineCombined sources

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiP42356.
    MaxQBiP42356.
    PaxDbiP42356.
    PeptideAtlasiP42356.
    PRIDEiP42356.

    PTM databases

    iPTMnetiP42356.
    PhosphoSiteiP42356.
    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

    BgeeiENSG00000241973.
    CleanExiHS_PI4KA.

    Organism-specific databases

    HPAiCAB009092.

    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

    WithEntry#Exp.IntActNotes
    P279587EBI-723050,EBI-8753518From a different organism.
    Q99IB85EBI-723050,EBI-6927873From a different organism.

    GO - Molecular functioni

    • cadherin binding involved in cell-cell adhesion Source: BHF-UCL

    Protein-protein interaction databases

    IntActiP42356. 23 interactions.
    MINTiMINT-1388461.
    STRINGi9606.ENSP00000458238.

    Chemistry

    BindingDBiP42356.

    Structurei

    3D structure databases

    ProteinModelPortaliP42356.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1530 – 1718189PIK helicalPROSITE-ProRule annotationAdd
    BLAST
    Domaini1846 – 2079234PI3K/PI4KPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation
    Contains 1 PIK helical domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG0902. Eukaryota.
    COG5032. LUCA.
    GeneTreeiENSGT00550000074798.
    HOVERGENiHBG052742.
    InParanoidiP42356.
    KOiK00888.
    OMAiFPKIPPH.
    TreeFamiTF102041.

    Family and domain databases

    Gene3Di1.10.1070.11. 1 hit.
    1.25.40.70. 1 hit.
    InterProiIPR016024. ARM-type_fold.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR015433. PI_Kinase.
    IPR001263. PInositide-3_kin_accessory_dom.
    [Graphical view]
    PANTHERiPTHR10048. PTHR10048. 5 hits.
    PfamiPF00454. PI3_PI4_kinase. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view]
    SMARTiSM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 6 hits.
    SSF56112. SSF56112. 2 hits.
    PROSITEiPS00915. 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.
    [Graphical view]

    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti438 – 4381N → S in AAD13352 (PubMed:10101268).Curated
    Sequence conflicti1947 – 19471S → I in AAH53654 (PubMed:15489334).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti380 – 3801M → V.
    Corresponds to variant rs17819211 [ dbSNP | Ensembl ].
    VAR_050531
    Natural varianti1851 – 18511V → L.
    Corresponds to variant rs2539908 [ dbSNP | Ensembl ].
    VAR_059549
    Natural varianti1854 – 18541D → N in PMGYCHA; loss of kinase activity; no effect on protein abundance. 1 Publication
    Corresponds to variant rs747119727 [ dbSNP | Ensembl ].
    VAR_074640

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 12481248Missing in isoform 2. 1 PublicationVSP_008805Add
    BLAST

    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

    Cross-referencesi

    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.

    3D structure databases

    ProteinModelPortaliP42356.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiP42356. 23 interactions.
    MINTiMINT-1388461.
    STRINGi9606.ENSP00000458238.

    Chemistry

    BindingDBiP42356.
    ChEMBLiCHEMBL3038509.
    GuidetoPHARMACOLOGYi2148.
    SwissLipidsiSLP:000000895.
    SLP:000000902. [P42356-2]

    PTM databases

    iPTMnetiP42356.
    PhosphoSiteiP42356.
    SwissPalmiP42356.

    Polymorphism and mutation databases

    BioMutaiPI4KA.
    DMDMi218512114.

    Proteomic databases

    EPDiP42356.
    MaxQBiP42356.
    PaxDbiP42356.
    PeptideAtlasiP42356.
    PRIDEiP42356.

    Protocols and materials databases

    DNASUi5297.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi5297.
    GeneCardsiPI4KA.
    HGNCiHGNC:8983. PI4KA.
    HPAiCAB009092.
    MIMi600286. gene.
    616531. phenotype.
    neXtProtiNX_P42356.
    PharmGKBiPA162399305.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0902. Eukaryota.
    COG5032. LUCA.
    GeneTreeiENSGT00550000074798.
    HOVERGENiHBG052742.
    InParanoidiP42356.
    KOiK00888.
    OMAiFPKIPPH.
    TreeFamiTF102041.

    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-RKP42356.

    Miscellaneous databases

    ChiTaRSiPI4KA. human.
    GeneWikiiPI4KA.
    PROiP42356.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000241973.
    CleanExiHS_PI4KA.

    Family and domain databases

    Gene3Di1.10.1070.11. 1 hit.
    1.25.40.70. 1 hit.
    InterProiIPR016024. ARM-type_fold.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR015433. PI_Kinase.
    IPR001263. PInositide-3_kin_accessory_dom.
    [Graphical view]
    PANTHERiPTHR10048. PTHR10048. 5 hits.
    PfamiPF00454. PI3_PI4_kinase. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view]
    SMARTiSM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 6 hits.
    SSF56112. SSF56112. 2 hits.
    PROSITEiPS00915. 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.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPI4KA_HUMAN
    AccessioniPrimary (citable) accession number: P42356
    Secondary accession number(s): Q7Z625, Q9UPG2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: February 17, 2016
    Last modified: September 7, 2016
    This is version 157 of the entry and version 4 of the sequence. [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

    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. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.