ID   P4K2B_HUMAN             Reviewed;         481 AA.
AC   Q8TCG2; Q9NUW2;
DT   01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   02-JUN-2021, entry version 133.
DE   RecName: Full=Phosphatidylinositol 4-kinase type 2-beta;
DE            EC=2.7.1.67;
DE   AltName: Full=Phosphatidylinositol 4-kinase type II-beta;
DE            Short=PI4KII-BETA;
GN   Name=PI4K2B;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION, SUBCELLULAR
RP   LOCATION, AND VARIANT PRO-78.
RX   PubMed=11923287; DOI=10.1074/jbc.m111807200;
RA   Balla A., Tuymetova G., Barshishat M., Geiszt M., Balla T.;
RT   "Characterization of type II phosphatidylinositol 4-kinase isoforms reveals
RT   association of the enzymes with endosomal vesicular compartments.";
RL   J. Biol. Chem. 277:20041-20050(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND
RP   VARIANT PRO-78.
RC   TISSUE=Brain;
RX   PubMed=12324459; DOI=10.1074/jbc.m206860200;
RA   Wei Y.J., Sun H.Q., Yamamoto M., Wlodarski P., Kunii K., Martinez M.,
RA   Barylko B., Albanesi J.P., Yin H.L.;
RT   "Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral
RT   membrane protein that is recruited to the plasma membrane and activated by
RT   Rac-GTP.";
RL   J. Biol. Chem. 277:46586-46593(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Hong W.;
RT   "Beta isoform of human type II phosphatidylinositol 4-kinase
RT   (PI4KIIbeta).";
RL   Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-78.
RC   TISSUE=Placenta;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-78.
RC   TISSUE=Skin;
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   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-17, AND
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [8]
RP   VARIANT [LARGE SCALE ANALYSIS] PRO-78, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
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).
CC   -!- FUNCTION: Together with PI4K2A and the type III PI4Ks (PIK4CA and
CC       PIK4CB) it contributes to the overall PI4-kinase activity of the cell.
CC       This contribution may be especially significant in plasma membrane,
CC       endosomal and Golgi compartments. The phosphorylation of
CC       phosphatidylinositol (PI) to PI4P is the first committed step in the
CC       generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor
CC       of the second messenger inositol 1,4,5-trisphosphate (InsP3).
CC       Contributes to the production of InsP3 in stimulated cells and is
CC       likely to be involved in the regulation of vesicular trafficking.
CC       {ECO:0000269|PubMed:11923287}.
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;
CC   -!- ACTIVITY REGULATION: Recruited and activated by membrane association.
CC       Binding to the microsomal membrane has been shown to enhance its
CC       activity. {ECO:0000269|PubMed:12324459}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane. Note=Mostly cytoplasmic but
CC       also found associated with the plasma membrane, the Golgi and
CC       endosomes. Compared to PI4K2A, a larger fraction of PI4K2B is cytosolic
CC       due to a smaller extent of palmitoylation. Translocates to membranes
CC       where it is recruited by PDGF stimulation by a Rac-GTP-dependent
CC       mechanism.
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:11923287}.
CC   -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. Type II PI4K
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AY065990; AAL47580.1; -; mRNA.
DR   EMBL; AF411320; AAL04154.1; -; mRNA.
DR   EMBL; AY091514; AAM12049.1; -; mRNA.
DR   EMBL; AK001967; BAA92006.1; -; mRNA.
DR   EMBL; BC051749; AAH51749.1; -; mRNA.
DR   CCDS; CCDS3433.1; -.
DR   RefSeq; NP_060793.2; NM_018323.3.
DR   PDB; 4WTV; X-ray; 1.90 A; A/B=90-165, A/B=176-450.
DR   PDBsum; 4WTV; -.
DR   SMR; Q8TCG2; -.
DR   BioGRID; 120587; 35.
DR   IntAct; Q8TCG2; 24.
DR   STRING; 9606.ENSP00000264864; -.
DR   ChEMBL; CHEMBL3220; -.
DR   DrugBank; DB02709; Resveratrol.
DR   DrugCentral; Q8TCG2; -.
DR   GuidetoPHARMACOLOGY; 2499; -.
DR   iPTMnet; Q8TCG2; -.
DR   PhosphoSitePlus; Q8TCG2; -.
DR   SwissPalm; Q8TCG2; -.
DR   BioMuta; PI4K2B; -.
DR   DMDM; 74715788; -.
DR   EPD; Q8TCG2; -.
DR   jPOST; Q8TCG2; -.
DR   MassIVE; Q8TCG2; -.
DR   MaxQB; Q8TCG2; -.
DR   PaxDb; Q8TCG2; -.
DR   PeptideAtlas; Q8TCG2; -.
DR   PRIDE; Q8TCG2; -.
DR   ProteomicsDB; 74134; -.
DR   Antibodypedia; 1318; 182 antibodies.
DR   DNASU; 55300; -.
DR   Ensembl; ENST00000264864; ENSP00000264864; ENSG00000038210.
DR   GeneID; 55300; -.
DR   KEGG; hsa:55300; -.
DR   UCSC; uc003grk.3; human.
DR   CTD; 55300; -.
DR   DisGeNET; 55300; -.
DR   GeneCards; PI4K2B; -.
DR   HGNC; HGNC:18215; PI4K2B.
DR   HPA; ENSG00000038210; Tissue enhanced (intestine).
DR   MIM; 612101; gene.
DR   neXtProt; NX_Q8TCG2; -.
DR   OpenTargets; ENSG00000038210; -.
DR   PharmGKB; PA142671173; -.
DR   VEuPathDB; HostDB:ENSG00000038210.12; -.
DR   eggNOG; KOG2381; Eukaryota.
DR   GeneTree; ENSGT00390000010434; -.
DR   HOGENOM; CLU_032516_1_0_1; -.
DR   InParanoid; Q8TCG2; -.
DR   OMA; ECGVFPE; -.
DR   OrthoDB; 1273723at2759; -.
DR   PhylomeDB; Q8TCG2; -.
DR   TreeFam; TF314740; -.
DR   BioCyc; MetaCyc:HS00529-MONOMER; -.
DR   BRENDA; 2.7.1.67; 2681.
DR   PathwayCommons; Q8TCG2; -.
DR   Reactome; R-HSA-1483248; Synthesis of PIPs at the ER membrane.
DR   Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR   Reactome; R-HSA-1660514; Synthesis of PIPs at the Golgi membrane.
DR   Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR   SignaLink; Q8TCG2; -.
DR   SIGNOR; Q8TCG2; -.
DR   BioGRID-ORCS; 55300; 7 hits in 995 CRISPR screens.
DR   ChiTaRS; PI4K2B; human.
DR   GeneWiki; PI4K2B; -.
DR   GenomeRNAi; 55300; -.
DR   Pharos; Q8TCG2; Tbio.
DR   PRO; PR:Q8TCG2; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q8TCG2; protein.
DR   Bgee; ENSG00000038210; Expressed in secondary oocyte and 202 other tissues.
DR   ExpressionAtlas; Q8TCG2; baseline and differential.
DR   Genevisible; Q8TCG2; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005768; C:endosome; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR   GO; GO:0004430; F:1-phosphatidylinositol 4-kinase activity; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0007032; P:endosome organization; IBA:GO_Central.
DR   GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR   GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR   GO; GO:0046854; P:phosphatidylinositol phosphorylation; IBA:GO_Central.
DR   InterPro; IPR039756; Lsb6/PI4K2.
DR   InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR   PANTHER; PTHR12865; PTHR12865; 1.
DR   Pfam; PF00454; PI3_PI4_kinase; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cytoplasm; Kinase; Membrane; Nucleotide-binding;
KW   Phosphoprotein; Reference proteome; Transferase.
FT   CHAIN           1..481
FT                   /note="Phosphatidylinositol 4-kinase type 2-beta"
FT                   /id="PRO_0000285164"
FT   DOMAIN          129..436
FT                   /note="PI3K/PI4K"
FT   NP_BIND         127..133
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT   NP_BIND         257..260
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT   REGION          1..82
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          153..155
FT                   /note="Important for substrate binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT   REGION          161..174
FT                   /note="Important for interaction with membranes"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT   REGION          264..272
FT                   /note="Important for interaction with membranes"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT   REGION          357..366
FT                   /note="Important for interaction with membranes"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT   COMPBIAS        1..16
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         148
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT   BINDING         344
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BTU6"
FT   MOD_RES         12
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19369195"
FT   MOD_RES         17
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19369195"
FT   MOD_RES         45
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VARIANT         78
FT                   /note="S -> P (in dbSNP:rs313549)"
FT                   /evidence="ECO:0000269|PubMed:11923287,
FT                   ECO:0000269|PubMed:12324459, ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334, ECO:0007744|PubMed:19690332"
FT                   /id="VAR_031974"
FT   HELIX           104..118
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   STRAND          124..130
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   STRAND          134..137
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   STRAND          143..149
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           185..199
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   STRAND          207..212
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   STRAND          252..258
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           266..272
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   TURN            273..275
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           280..299
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   STRAND          307..314
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   STRAND          337..342
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   STRAND          356..358
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           363..366
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           368..371
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           376..386
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           389..403
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           411..433
FT                   /evidence="ECO:0007829|PDB:4WTV"
FT   HELIX           438..441
FT                   /evidence="ECO:0007829|PDB:4WTV"
SQ   SEQUENCE   481 AA;  54744 MW;  B4E16257E0AEC026 CRC64;
     MEDPSEPDRL ASADGGSPEE EEDGEREPLL PRIAWAHPRR GAPGSAVRLL DAAGEEGEAG
     DEELPLPPGD VGVSRSSSAE LDRSRPAVSV TIGTSEMNAF LDDPEFADIM LRAEQAIEVG
     IFPERISQGS SGSYFVKDPK RKIIGVFKPK SEEPYGQLNP KWTKYVHKVC CPCCFGRGCL
     IPNQGYLSEA GAYLVDNKLH LSIVPKTKVV WLVSETFNYN AIDRAKSRGK KYALEKVPKV
     GRKFHRIGLP PKIGSFQLFV EGYKEAEYWL RKFEADPLPE NIRKQFQSQF ERLVILDYII
     RNTDRGNDNW LVRYEKQKCE KEIDHKESKW IDDEEFLIKI AAIDNGLAFP FKHPDEWRAY
     PFHWAWLPQA KVPFSEEIRN LILPYISDMN FVQDLCEDLY ELFKTDKGFD KATFESQMSV
     MRGQILNLTQ ALRDGKSPFQ LVQIPCVIVE RSQGGSQGRI VHLSNSFTQT VNCRKPFFSS
     W
//