P3C2G_MOUSE
ID P3C2G_MOUSE Reviewed; 1506 AA.
AC O70167; O70168;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma {ECO:0000305|PubMed:9514948};
DE Short=PI3K-C2-gamma;
DE Short=PtdIns-3-kinase C2 subunit gamma;
DE EC=2.7.1.137 {ECO:0000269|PubMed:9514948};
DE EC=2.7.1.154 {ECO:0000269|PubMed:9514948};
DE AltName: Full=Phosphoinositide 3-kinase-C2-gamma;
GN Name=Pik3c2g;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RC TISSUE=Liver, and Lymphoid tissue;
RX PubMed=9514948; DOI=10.1006/bbrc.1998.8294;
RA Misawa H., Ohtsubo M., Copeland N.G., Gilbert D.J., Jenkins N.A.,
RA Yoshimura A.;
RT "Cloning and characterization of a novel class II phosphoinositide 3-kinase
RT containing C2 domain.";
RL Biochem. Biophys. Res. Commun. 244:531-539(1998).
RN [2]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20536348; DOI=10.3109/10428191003754624;
RA Yu W., Sun X., Tang H., Tao Y., Dai Z.;
RT "Inhibition of class II phosphoinositide 3-kinase gamma expression by
RT p185(Bcr-Abl) contributes to impaired chemotaxis and aberrant homing of
RT leukemic cells.";
RL Leuk. Lymphoma 51:1098-1107(2010).
CC -!- FUNCTION: Generates phosphatidylinositol 3-phosphate (PtdIns3P) and
CC phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as
CC second messengers (PubMed:9514948). May play a role in SDF1A-stimulated
CC chemotaxis. {ECO:0000269|PubMed:20536348, ECO:0000269|PubMed:9514948}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-
CC phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:18373,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57658,
CC ChEBI:CHEBI:58178, ChEBI:CHEBI:456216; EC=2.7.1.154;
CC Evidence={ECO:0000269|PubMed:9514948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18374;
CC Evidence={ECO:0000305|PubMed:9514948};
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-3-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216;
CC EC=2.7.1.137; Evidence={ECO:0000269|PubMed:9514948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000305|PubMed:9514948};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:9514948}; Peripheral
CC membrane protein {ECO:0000269|PubMed:9514948}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O70167-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O70167-2; Sequence=VSP_004706, VSP_004707;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in liver. Also found in
CC kidney, lung and lymphoid tissue. Down-regulated in BeF3 cells
CC expressing the BCR-ABL oncogene p185. {ECO:0000269|PubMed:20536348,
CC ECO:0000269|PubMed:9514948}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00879, ECO:0000255|PROSITE-ProRule:PRU00880}.
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DR EMBL; AB008791; BAA25427.1; -; mRNA.
DR EMBL; AB008792; BAA25428.1; -; mRNA.
DR PIR; JC5985; JC5985.
DR RefSeq; NP_997566.1; NM_207683.2.
DR AlphaFoldDB; O70167; -.
DR SMR; O70167; -.
DR STRING; 10090.ENSMUSP00000107499; -.
DR iPTMnet; O70167; -.
DR PhosphoSitePlus; O70167; -.
DR PaxDb; O70167; -.
DR PRIDE; O70167; -.
DR ProteomicsDB; 294093; -. [O70167-1]
DR ProteomicsDB; 294094; -. [O70167-2]
DR DNASU; 18705; -.
DR GeneID; 18705; -.
DR KEGG; mmu:18705; -.
DR UCSC; uc029wch.1; mouse. [O70167-1]
DR CTD; 5288; -.
DR MGI; MGI:1203730; Pik3c2g.
DR eggNOG; KOG0905; Eukaryota.
DR InParanoid; O70167; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; O70167; -.
DR BRENDA; 2.7.1.137; 3474.
DR BRENDA; 2.7.1.154; 3474.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-1660514; Synthesis of PIPs at the Golgi membrane.
DR BioGRID-ORCS; 18705; 0 hits in 66 CRISPR screens.
DR ChiTaRS; Pik3c2g; mouse.
DR PRO; PR:O70167; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O70167; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:UniProtKB.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; IMP:UniProtKB.
DR GO; GO:0044788; P:modulation by host of viral process; ISO:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR CDD; cd05177; PI3Kc_C2_gamma; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 2.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR037707; PI3K-C2-gamma_dom.
DR InterPro; IPR002420; PI3K-type_C2_dom.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR000341; PI3K_Ras-bd_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00792; PI3K_C2; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR Pfam; PF00787; PX; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00142; PI3K_C2; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 2.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS51547; C2_PI3K; 1.
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; PS51546; PI3K_RBD; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Chemotaxis; Kinase; Lipid metabolism;
KW Membrane; Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..1506
FT /note="Phosphatidylinositol 3-kinase C2 domain-containing
FT subunit gamma"
FT /id="PRO_0000088800"
FT DOMAIN 285..371
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 541..689
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 704..880
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 949..1227
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 1260..1372
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 1381..1506
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 955..961
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1091..1099
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 1110..1136
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT VAR_SEQ 1..853
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004706"
FT VAR_SEQ 854..855
FT /note="YW -> MG (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004707"
SQ SEQUENCE 1506 AA; 171580 MW; 2D802A2B5449B672 CRC64;
MAYSWQTEPN RTEPQEDGSD TQQFHHTNQH LSSRQVRLGF DQLVEEINNK TPLSESEKEE
DTYFVPDAPN LGSKWPSIYE THPRYFSEFT SQSPDSSQLR FGKLSAIGFN PAVLPTHQLI
HEGASWRNPS GKYHGIEYPR FDALPPSSTG QGECNPQGQS GTKHHNYCGE HEGNLPHHHS
SYSIDSIPNR EKRRSGDVNL VEPSLEFSKD SFLPRTSENV SVESTEPIGC PIEIVEVPQG
SNKNLASFCN KVKKIRESYH ASDINSNSGK IWAITTAYPS RLFADTKFRV KISIDNSAQL
LLLMPHANYL VKDLIAEILL LCANEPLSPK EYLLSVCGSE EFLQMDHSLG SHKIFQKNKS
VIQLHLQKNR DTPGKLSRKS EDDHSPFHLN QLLEFTHIWK ISRQCLSTVM KKYNLHVEHL
LKPQKDMEEK HLSSMVSGNQ HTSQPHVNNV LEEVKNICSV LGCIETKQVS DAVKELNLIL
QRPSQNFHQN SETSKKGFIE RVTAELSRSI YQLIDVYCSS FCTDFQPVHT PGGVSHVHAG
LQSHLSFTVC SLHNVPETWA HSYKAFSFSC WLTYAGKKLC QVKSCRPLPV TKSFSLLVNW
NEIINFPLEI KSLPRESMLV IKLFGIDSAT HSTNLLAWTC LPLFPRQESV LGSRLFSVTL
QSEPPIEMIA PGVWDGSQPS PLTLQIDFPD AGWEYLKPES EENRTDHEEP PRECLKHIAK
LSQKKSPLLL SEEKRRYLWF YRLYCNNENS SLPLVLGSAP GWDEETVSEM HAILRRWTFS
HPWEALGLLT SRFPDQDIRE VAVQQLDTLL TDELLDCLPQ LVQAVKFEWN LESPLVELLP
RRPLQSIRVA HCLYWLLRDA QGEAYFKSWY QELLAALQFC AGEALNEELS KEQKLVKLLG
DIGEKVKSAS DPQRKDVLKK EIGSLEEFFK DIKTCHLPLN PALCIKGIDR DACSYFTSNA
SPLKITFINA NPMGKNISVI FKAGDDLRQD MLALQIIQVM DNAWLQEGLD MQMITYGCLS
TGRAQGFIEM VPDAVTLAKI HLHSGLIGPL KENTIKKWFS QHNHLKEDYE KALRNFFYSC
AGWCVVTFIL GVCDRHNDNI MLTKSGHMFH IDFGKFLGHA QTFGGIKRDR APFIFTSEME
YFITEGGKNI QHFQDFVELC CRAYNIVRKH SQLILSLLEM MLHAGLPELR GIEDLKYVHN
NLRPQDTDLE ATSHFTKKIK ESLECFPVKL NNLIHTLAQM PALSLAKPAP QTLLQESCIL
NKTRTIQRVT ILGFSKTHSN LYLMEVTCSD NRRSLTKKSF EQFYRLHSQM QKQFSSLALP
EFPHWWHLPF TDSDHKRIRD LSHYVEQVLR GSYEVANSDC VLSFFLSEHI QPTLEDSPFV
DPGENSLDKS PKVQLLMTYE DSRLTILVKH LKNIHLPDGS VPSAHVEIYL LPHPSEVRRK
KTKCVPKCTD PTYNEIVVYD EVLGLQGHVL MLIVKSKTVF VGAVNIQLCS VPLNEEKWYP
LGNSII
