LOCUS       NP_001275701            1486 aa            linear   PRI 29-APR-2025
DEFINITION  phosphatidylinositol 3-kinase C2 domain-containing subunit gamma
            isoform 1 [Homo sapiens].
ACCESSION   NP_001275701
VERSION     NP_001275701.1
DBSOURCE    REFSEQ: accession NM_001288772.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 1486)
  AUTHORS   Koch,P.A., Dornan,G.L., Hessenberger,M. and Haucke,V.
  TITLE     The molecular mechanisms mediating class II PI 3-kinase function in
            cell physiology
  JOURNAL   FEBS J 288 (24), 7025-7042 (2021)
   PUBMED   33387369
  REMARK    GeneRIF: The molecular mechanisms mediating class II PI 3-kinase
            function in cell physiology.
            Review article
REFERENCE   2  (residues 1 to 1486)
  AUTHORS   Yoshioka,K.
  TITLE     Class II phosphatidylinositol 3-kinase isoforms in vesicular
            trafficking
  JOURNAL   Biochem Soc Trans 49 (2), 893-901 (2021)
   PUBMED   33666217
  REMARK    GeneRIF: Class II phosphatidylinositol 3-kinase isoforms in
            vesicular trafficking.
            Review article
REFERENCE   3  (residues 1 to 1486)
  AUTHORS   Freitag,A., Prajwal,P., Shymanets,A., Harteneck,C., Nurnberg,B.,
            Schachtele,C., Kubbutat,M., Totzke,F. and Laufer,S.A.
  TITLE     Development of first lead structures for phosphoinositide
            3-kinase-C2gamma inhibitors
  JOURNAL   J Med Chem 58 (1), 212-221 (2015)
   PUBMED   24983663
  REMARK    GeneRIF: Data indicate substituents of benzensulfonamide and
            pyrazine as phosphoinositide 3-kinase-C2gamma (PI3K-C2GAMMA)
            inhibitors.
REFERENCE   4  (residues 1 to 1486)
  AUTHORS   Wang,Q., Xiang,B., Deng,W., Wu,J., Li,M., Ma,X., Wang,Y., Jiang,L.,
            McAlonan,G., Chua,S.E., Sham,P.C., Hu,X. and Li,T.
  TITLE     Genome-wide association analysis with gray matter volume as a
            quantitative phenotype in first-episode treatment-naive patients
            with schizophrenia
  JOURNAL   PLoS One 8 (9), e75083 (2013)
   PUBMED   24086445
  REMARK    Erratum:[PLoS One. 2015 Apr 07;10(4):e0122945. doi:
            10.1371/journal.pone.0122945. PMID: 25848962]
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 1486)
  AUTHORS   Shia,W.C., Ku,T.H., Tsao,Y.M., Hsia,C.H., Chang,Y.M., Huang,C.H.,
            Chung,Y.C., Hsu,S.L., Liang,K.W. and Hsu,F.R.
  TITLE     Genetic copy number variants in myocardial infarction patients with
            hyperlipidemia
  JOURNAL   BMC Genomics 12 Suppl 3 (Suppl 3), S23 (2011)
   PUBMED   22369086
REFERENCE   6  (residues 1 to 1486)
  AUTHORS   Ono,F., Nakagawa,T., Saito,S., Owada,Y., Sakagami,H., Goto,K.,
            Suzuki,M., Matsuno,S. and Kondo,H.
  TITLE     A novel class II phosphoinositide 3-kinase predominantly expressed
            in the liver and its enhanced expression during liver regeneration
  JOURNAL   J Biol Chem 273 (13), 7731-7736 (1998)
   PUBMED   9516481
REFERENCE   7  (residues 1 to 1486)
  AUTHORS   Misawa,H., Ohtsubo,M., Copeland,N.G., Gilbert,D.J., Jenkins,N.A.
            and Yoshimura,A.
  TITLE     Cloning and characterization of a novel class II phosphoinositide
            3-kinase containing C2 domain
  JOURNAL   Biochem Biophys Res Commun 244 (2), 531-539 (1998)
   PUBMED   9514948
REFERENCE   8  (residues 1 to 1486)
  AUTHORS   Borgatti,P., Zauli,G., Cantley,L.C. and Capitani,S.
  TITLE     Extracellular HIV-1 Tat protein induces a rapid and selective
            activation of protein kinase C (PKC)-alpha, and -epsilon and -zeta
            isoforms in PC12 cells
  JOURNAL   Biochem Biophys Res Commun 242 (2), 332-337 (1998)
   PUBMED   9446795
REFERENCE   9  (residues 1 to 1486)
  AUTHORS   Borgatti,P., Zauli,G., Colamussi,M.L., Gibellini,D., Previati,M.,
            Cantley,L.L. and Capitani,S.
  TITLE     Extracellular HIV-1 Tat protein activates phosphatidylinositol 3-
            and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells
  JOURNAL   Eur J Immunol 27 (11), 2805-2811 (1997)
   PUBMED   9394803
REFERENCE   10 (residues 1 to 1486)
  AUTHORS   Milani,D., Mazzoni,M., Borgatti,P., Zauli,G., Cantley,L. and
            Capitani,S.
  TITLE     Extracellular human immunodeficiency virus type-1 Tat protein
            activates phosphatidylinositol 3-kinase in PC12 neuronal cells
  JOURNAL   J Biol Chem 271 (38), 22961-22964 (1996)
   PUBMED   8798481
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC087240.17, AC092851.9,
            KF455618.1, AC087236.11 and AC091815.7.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: The protein encoded by this gene belongs to the
            phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in
            signaling pathways involved in cell proliferation, oncogenic
            transformation, cell survival, cell migration, and intracellular
            protein trafficking. This protein contains a lipid kinase catalytic
            domain as well as a C-terminal C2 domain, a characteristic of class
            II PI3-kinases. C2 domains act as calcium-dependent phospholipid
            binding motifs that mediate translocation of proteins to membranes,
            and may also mediate protein-protein interactions. This gene may
            play a role in several diseases, including type II diabetes.
            Alternative splicing results in multiple transcript variants.
            [provided by RefSeq, Jan 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            CDS exon combination :: BC144134.1 [ECO:0000331]
            RNAseq introns       :: single sample supports all introns
                                    SAMEA2142586, SAMEA2145774 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000538779.6/ ENSP00000445381.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1486
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12p12.3"
     Protein         1..1486
                     /product="phosphatidylinositol 3-kinase C2
                     domain-containing subunit gamma isoform 1"
                     /EC_number="2.7.1.137"
                     /EC_number="2.7.1.154"
                     /note="PTDINS-3-kinase C2 gamma;
                     phosphatidylinositol-4-phosphate 3-kinase C2
                     domain-containing subunit gamma;
                     phosphatidylinositol-4-phosphate 3-kinase C2
                     domain-containing gamma polypeptide;
                     phosphoinositide-3-kinase, class 2, gamma polypeptide;
                     phosphatidylinositol 3-kinase C2 domain-containing subunit
                     gamma"
                     /calculated_mol_wt=170552
     Region          287..369
                     /region_name="PI3K_rbd"
                     /note="PI3-kinase family, ras-binding domain; cl02484"
                     /db_xref="CDD:413336"
     Region          520..678
                     /region_name="C2A_PI3K_class_II"
                     /note="C2 domain first repeat present in class II
                     phosphatidylinositol 3-kinases (PI3Ks); cd04012"
                     /db_xref="CDD:175979"
     Region          692..860
                     /region_name="PI3Ka_II"
                     /note="Phosphoinositide 3-kinase (PI3K) class II,
                     accessory domain (PIK domain); PIK domain is conserved in
                     all PI3 and PI4-kinases. Its role is unclear but it has
                     been suggested to be involved in substrate presentation.
                     In general, class II PI3-kinases...; cd00869"
                     /db_xref="CDD:238441"
     Region          866..1219
                     /region_name="PI3Kc_C2_gamma"
                     /note="Catalytic domain of Class II Phosphoinositide
                     3-kinase gamma; cd05177"
                     /db_xref="CDD:270721"
     Region          935..941
                     /region_name="G-loop.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00269"
                     /note="propagated from UniProtKB/Swiss-Prot (O75747.4)"
     Site            order(936,938..940,942,960,962,965,996,1008..1011,1016,
                     1019,1079,1081,1091..1092)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:270721"
     Region          1071..1079
                     /region_name="Catalytic loop.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00269"
                     /note="propagated from UniProtKB/Swiss-Prot (O75747.4)"
     Site            1071..1079
                     /site_type="active"
                     /note="catalytic loop [active]"
                     /db_xref="CDD:270721"
     Region          1090..1116
                     /region_name="Activation loop.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00269"
                     /note="propagated from UniProtKB/Swiss-Prot (O75747.4)"
     Site            1092..1116
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:270721"
     Region          1248..1348
                     /region_name="PX_PI3K_C2_gamma"
                     /note="The phosphoinositide binding Phox Homology Domain
                     of the Gamma Isoform of Class II Phosphoinositide
                     3-Kinases; cd06896"
                     /db_xref="CDD:132806"
     Site            order(1279..1281,1304..1305,1317)
                     /site_type="other"
                     /note="putative phosphoinositide binding site [chemical
                     binding]"
                     /db_xref="CDD:132806"
     Region          1370..1482
                     /region_name="C2B_PI3K_class_II"
                     /note="C2 domain second repeat present in class II
                     phosphatidylinositol 3-kinases (PI3Ks); cd08381"
                     /db_xref="CDD:176027"
     Site            1419..1429
                     /site_type="active"
                     /note="nuclear localization signal [active]"
                     /db_xref="CDD:176027"
     CDS             1..1486
                     /gene="PIK3C2G"
                     /gene_synonym="PI3K-C2-gamma; PI3K-C2GAMMA"
                     /coded_by="NM_001288772.2:139..4599"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS73452.1"
                     /db_xref="GeneID:5288"
                     /db_xref="HGNC:HGNC:8973"
                     /db_xref="MIM:609001"
ORIGIN      
        1 mayswqtdpn pneshekqye hqeflfvnqp hsssqvslgf dqivdeisgk iphyeseide
       61 ntffvptapk wdstghslne ahqislneft sksrelswhq vskapaigfs psvlpkpqnt
      121 nkecswgspi gkhhgaddsr fsilapsfts ldkinlekel enenhnyhig fessipptns
      181 sfssdfmpke enkrsghvni vepslmllkg slqpgmwest wqkniesigc siqlvevpqs
      241 sntslasfcn kvkkireryh aadvnfnsgk iwstttafpy qlfsktkfni hifidnstqp
      301 lhfmpcanyl vkdliaeilh fctndqllpk dhilsvcgse eflqndhclg shkmfqkdks
      361 viqlhlqksr eapgklsrkh eedhsqfyln qllefmhiwk vsrqclltli rkydfhlkyl
      421 lktqenvyni ieevkkicsv lgcvetkqit davnelslil qrkgenfyqs setsakglie
      481 kvttelstsi yqlinvycns fyadfqpvnv prctsylnpg lpshlsftvy aahnipetwv
      541 hsykafsftc wltyagkklc qvrnyrnipd kklffflvnw netinfplei kslpresmlt
      601 vklfgiacat nnanllawtc lplfpkeksi lgsmlfsmtl qseppvemit pgvwdvsqps
      661 pvtlqidfpa tgweymkpds eenrsnleep lkecikhiar lsqkqtplll seekkrylwf
      721 yrfycnnenc slplvlgsap gwdertvsem htilrrwtfs qplealgllt ssfpdqeirk
      781 vavqqldnll ndelleylpq lvqavkfewn lesplvqlll hrslqsiqva hrlywllkna
      841 eneayfkswy qkllaalqfc agkalndefs keqklikilg digervksas dhqrqevlkk
      901 eigrleeffq dvntchlpln palcikgidh dacsyftsna lplkitfina npmgknisii
      961 fkagddlrqd mlvlqliqvm dniwlqegld mqmiiyrcls tgkdqglvqm vpdavtlaki
     1021 hrhsgligpl kentikkwfs qhnhlkadye kalrnffysc agwcvvtfil gvcdrhndni
     1081 mltksghmfh idfgkflgha qtfggikrdr apfiftseme yfiteggknp qhfqdfvelc
     1141 crayniirkh sqlllnllem mlyaglpels giqdlkyvyn nlrpqdtdle atshftkkik
     1201 eslecfpvkl nnlihtlaqm saispaksts qtfpqescll sttrsierat ilgfskkssn
     1261 lyliqvthsn netslteksf eqfsklhsql qkqfasltlp efphwwhlpf tnsdhrrfrd
     1321 lnhymeqiln vshevtnsdc vlsfflseav qqtveesspv ylgekfpdkk pkvqlvisye
     1381 dvkltilvkh mknihlpdgs apsahvefyl lpypsevrrr ktksvpkctd ptyneivvyd
     1441 evtelqghvl mlivksktvf vgainirlcs vpldkekwyp lgnsii
//
