PI3R6_MOUSE
ID PI3R6_MOUSE Reviewed; 756 AA.
AC Q3U6Q4; Q3TBT5; Q3UAY4; Q8K323;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Phosphoinositide 3-kinase regulatory subunit 6;
DE AltName: Full=Phosphoinositide 3-kinase gamma adapter protein of 87 kDa;
DE AltName: Full=p84 PI3K adapter protein;
DE Short=p84 PIKAP;
DE AltName: Full=p87 PI3K adapter protein;
DE Short=p87PIKAP;
GN Name=Pik3r6;
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] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP INTERACTION WITH PDE3B AND PIK3CG, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=16476736; DOI=10.1074/jbc.m512502200;
RA Voigt P., Dorner M.B., Schaefer M.;
RT "Characterization of p87PIKAP, a novel regulatory subunit of
RT phosphoinositide 3-kinase gamma that is highly expressed in heart and
RT interacts with PDE3B.";
RL J. Biol. Chem. 281:9977-9986(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [5]
RP INTERACTION WITH PIK3CG, AND FUNCTION.
RX PubMed=15797027; DOI=10.1016/j.cub.2005.02.020;
RA Suire S., Coadwell J., Ferguson G.J., Davidson K., Hawkins P., Stephens L.;
RT "p84, a new Gbetagamma-activated regulatory subunit of the type IB
RT phosphoinositide 3-kinase p110gamma.";
RL Curr. Biol. 15:566-570(2005).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19906996; DOI=10.1073/pnas.0905506106;
RA Kurig B., Shymanets A., Bohnacker T., Prajwal X., Brock C., Ahmadian M.R.,
RA Schaefer M., Gohla A., Harteneck C., Wymann M.P., Jeanclos E., Nurnberg B.;
RT "Ras is an indispensable coregulator of the class IB phosphoinositide 3-
RT kinase p87/p110gamma.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20312-20317(2009).
CC -!- FUNCTION: Regulatory subunit of the PI3K gamma complex. Acts as an
CC adapter to drive activation of PIK3CG by beta-gamma G protein dimers.
CC The PIK3CG:PIK3R6 heterodimer is much less sensitive to beta-gamma G
CC proteins than PIK3CG:PIK3R5 and its membrane recruitment and beta-gamma
CC G protein dimer-dependent activation requires HRAS bound to PIK3CG.
CC Recruits of the PI3K gamma complex to a PDE3B:RAPGEF3 signaling complex
CC involved in angiogenesis; signaling seems to involve RRAS.
CC {ECO:0000269|PubMed:15797027, ECO:0000269|PubMed:16476736,
CC ECO:0000269|PubMed:19906996}.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit (PIK3CG) and a regulatory
CC (PIK3R6) subunit. The binding of PIK3R6 to PIK3CG may exclude the
CC binding of PIK3R5 to PIK3CG (PubMed:16476736, PubMed:15797027).
CC Interacts with beta-gamma G protein dimers (PubMed:16476736). Interacts
CC with PDE3B and RAPGEF3; form a signaling complex that regulates
CC phosphatidylinositol 3-kinase gamma in angiogenesis (By similarity).
CC {ECO:0000250|UniProtKB:Q5UE93, ECO:0000269|PubMed:15797027,
CC ECO:0000269|PubMed:16476736}.
CC -!- INTERACTION:
CC Q3U6Q4; Q9JHG7: Pik3cg; NbExp=4; IntAct=EBI-4303950, EBI-644372;
CC Q3U6Q4; P48736: PIK3CG; Xeno; NbExp=6; IntAct=EBI-4303950, EBI-1030384;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16476736}. Cell
CC membrane {ECO:0000269|PubMed:19906996}; Peripheral membrane protein
CC {ECO:0000269|PubMed:19906996}. Note=Translocated to the plasma membrane
CC in a Ras-dependent manner (PubMed:19906996).
CC {ECO:0000269|PubMed:19906996}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3U6Q4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3U6Q4-2; Sequence=VSP_018257;
CC Name=3;
CC IsoId=Q3U6Q4-3; Sequence=VSP_018255, VSP_018256;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart. In a lower extent, also
CC expressed in brain, spleen, lung, liver, kidney, prostate, thyroid,
CC salivary gland, dendritic cells, macrophages and neutrophils.
CC {ECO:0000269|PubMed:16476736}.
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DR EMBL; AY753194; AAV30089.1; -; mRNA.
DR EMBL; DQ295832; ABB97395.1; -; mRNA.
DR EMBL; AK151178; BAE30180.1; -; mRNA.
DR EMBL; AK153039; BAE31670.1; -; mRNA.
DR EMBL; AK171063; BAE42222.1; -; mRNA.
DR EMBL; BC028998; AAH28998.1; -; mRNA.
DR EMBL; AL606831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS24866.1; -. [Q3U6Q4-2]
DR CCDS; CCDS36186.1; -. [Q3U6Q4-1]
DR RefSeq; NP_001004435.1; NM_001004435.3. [Q3U6Q4-2]
DR RefSeq; NP_001075035.1; NM_001081566.2. [Q3U6Q4-1]
DR AlphaFoldDB; Q3U6Q4; -.
DR SMR; Q3U6Q4; -.
DR CORUM; Q3U6Q4; -.
DR DIP; DIP-60179N; -.
DR IntAct; Q3U6Q4; 4.
DR STRING; 10090.ENSMUSP00000099673; -.
DR iPTMnet; Q3U6Q4; -.
DR PhosphoSitePlus; Q3U6Q4; -.
DR EPD; Q3U6Q4; -.
DR MaxQB; Q3U6Q4; -.
DR PaxDb; Q3U6Q4; -.
DR PRIDE; Q3U6Q4; -.
DR ProteomicsDB; 289560; -. [Q3U6Q4-1]
DR ProteomicsDB; 289561; -. [Q3U6Q4-2]
DR ProteomicsDB; 289562; -. [Q3U6Q4-3]
DR Antibodypedia; 74162; 99 antibodies from 26 providers.
DR DNASU; 104709; -.
DR Ensembl; ENSMUST00000060441; ENSMUSP00000052522; ENSMUSG00000046207. [Q3U6Q4-1]
DR Ensembl; ENSMUST00000102613; ENSMUSP00000099673; ENSMUSG00000046207. [Q3U6Q4-2]
DR GeneID; 104709; -.
DR KEGG; mmu:104709; -.
DR UCSC; uc007jnq.1; mouse. [Q3U6Q4-3]
DR UCSC; uc007jnr.2; mouse. [Q3U6Q4-1]
DR UCSC; uc007jns.2; mouse. [Q3U6Q4-2]
DR CTD; 146850; -.
DR MGI; MGI:2144613; Pik3r6.
DR VEuPathDB; HostDB:ENSMUSG00000046207; -.
DR eggNOG; ENOG502QSK4; Eukaryota.
DR GeneTree; ENSGT00530000063753; -.
DR HOGENOM; CLU_023662_0_0_1; -.
DR InParanoid; Q3U6Q4; -.
DR OMA; QQPVYFN; -.
DR OrthoDB; 171539at2759; -.
DR PhylomeDB; Q3U6Q4; -.
DR TreeFam; TF102035; -.
DR BRENDA; 2.7.1.137; 3474.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-392451; G beta:gamma signalling through PI3Kgamma.
DR BioGRID-ORCS; 104709; 4 hits in 75 CRISPR screens.
DR PRO; PR:Q3U6Q4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q3U6Q4; protein.
DR Bgee; ENSMUSG00000046207; Expressed in granulocyte and 118 other tissues.
DR Genevisible; Q3U6Q4; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005944; C:phosphatidylinositol 3-kinase complex, class IB; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IEA:GOC.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IMP:CACAO.
DR GO; GO:0042269; P:regulation of natural killer cell mediated cytotoxicity; ISO:MGI.
DR InterPro; IPR019522; PIK3R5/6.
DR PANTHER; PTHR15593; PTHR15593; 1.
DR Pfam; PF10486; PI3K_1B_p101; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Angiogenesis; Cell membrane; Cytoplasm; Membrane;
KW Reference proteome.
FT CHAIN 1..756
FT /note="Phosphoinositide 3-kinase regulatory subunit 6"
FT /id="PRO_0000234339"
FT REGION 570..589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 716..738
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 271..305
FT /note="DLLQDRLPSIPLPSPYITFHLWTDQEQLWKELVLF -> KRGPAGDLPRETA
FT IRRGGRQRARLDRMRFPEEPED (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018255"
FT VAR_SEQ 306..756
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018256"
FT VAR_SEQ 463..466
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16476736"
FT /id="VSP_018257"
FT CONFLICT 710
FT /note="S -> G (in Ref. 2; BAE30180)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 756 AA; 84663 MW; 5F3B56982C514876 CRC64;
MESSDVELDF QRSVQAVLRE LNTPNPALQS NQGMWRWSLH KKVERNPGKS SILVRILLRE
LEKAESEDGR RVIIPLLLTL MSVLTKATGI PEDLYHRAYT FCTRLLTLPA PYSTVALDCA
IRLKTETAVP GTLYQRTVIA EQNLISELYP YQERVFLFVD PELVSASVCS ALLLEIQAAQ
EQQTPEACMR HVVSHALQAA LGEACHTGAL NRKLQASSRR VLEYYFHAVV AAIEQVASED
SPSRLGHLEK MEEIYCSLLG PATTRRHCVG DLLQDRLPSI PLPSPYITFH LWTDQEQLWK
ELVLFLRPRS QLRLSADLDA LDLQGFRLDR DLARVSTDSG IERDLPLGSD ELPDPSSSEM
ERAALQRKGG IKKRVWPPDF FMPGSWDGPP GLHRRTGRPS GDGELLPGVS RVHTARVLVL
GDDRMLGRLA QAYYRLRKRE TKKFCLTPRL SLQLYYIPVL APQVTGQDPE ASRKPELGEL
ASFLGRVDPW YESTVNTLCP AILKLAEMPP YLDTSRTVDP FILDVITYYV RMGTQPIYFQ
LYKVKIFTSL SHDPTEDIFL TELKVKIQDS KSPKEGSSPR RRGAAEGTGA ELSMCYQKAL
LSHRPREVTV SLRATGLVLK AIPAGDTEVS GFFHCTSPNA ASATDCSCLH VSVTEVVKSS
NLAGRSFTTS TNTFRTSSIQ VQSQDQRLLT LWLDKDGRRT FRDVVRFEVS PCPEPCSRTQ
KSKTSALNSH GQETEKNMAK PNSLLMPINT FSGIIQ
