PI3R5_HUMAN
ID PI3R5_HUMAN Reviewed; 880 AA.
AC Q8WYR1; B0LPH4; D3DTS3; Q5G936; Q5G938; Q5G939; Q8IZ23; Q9Y2Y2;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Phosphoinositide 3-kinase regulatory subunit 5;
DE Short=PI3-kinase regulatory subunit 5;
DE AltName: Full=PI3-kinase p101 subunit;
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase regulatory subunit;
DE Short=PtdIns-3-kinase regulatory subunit;
DE AltName: Full=Protein FOAP-2;
DE AltName: Full=PtdIns-3-kinase p101;
DE AltName: Full=p101-PI3K;
GN Name=PIK3R5;
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] (ISOFORM 1).
RA Yazaki M., Fujii Y., Tsuritani K., Yajima Y., Amemiya T., Ukai Y.,
RA Naito K., Kawaguchi A., Takayama K.;
RT "Molecular cloning of a human novel gene, FOAP-2, which are highly
RT expressed in macrophages.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Stephens L., Hawkins P.T., Braselmann S.;
RT "G-beta gamma regulated phosphatidylinositol 3-kinase.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Blood;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-369 (ISOFORM 1).
RC TISSUE=Peripheral blood leukocyte, and Spleen;
RA Reichwald K., Gausmann U., Karagyozov L., Platzer M.;
RT "Identification of alternative transcripts of human P101-PI3K.";
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP INTERACTION WITH PIK3CG, AND TISSUE SPECIFICITY.
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458 AND SER-507, 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 [9]
RP TISSUE SPECIFICITY, AND VARIANT AOA3 SER-629.
RX PubMed=22065524; DOI=10.1002/humu.21650;
RA Tassan N.A., Khalil D., Shinwari J., Sharif L.A., Bavi P., Abduljaleel Z.,
RA Abu Dhaim N., Magrashi A., Bobis S., Ahmed H., Alahmed S., Bohlega S.;
RT "A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor
RT apraxia.";
RL Hum. Mutat. 33:351-354(2012).
RN [10]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-28.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Regulatory subunit of the PI3K gamma complex. Required for
CC recruitment of the catalytic subunit to the plasma membrane via
CC interaction with beta-gamma G protein dimers. Required for G protein-
CC mediated activation of PIK3CG (By similarity). {ECO:0000250}.
CC -!- ACTIVITY REGULATION: Greatly activated by G gamma proteins.
CC {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit (PIK3CG/p120) and a
CC regulatory (PIK3R5a/p101) subunit. Interacts with beta-gamma G protein
CC dimers. {ECO:0000269|PubMed:15797027}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O02696}. Cytoplasm
CC {ECO:0000250|UniProtKB:O02696}. Cell membrane
CC {ECO:0000250|UniProtKB:O02696}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O02696}. Note=Predominantly localized in the
CC nucleus in absence of PIK3CG/p120. Colocalizes with PIK3CG/p120 in the
CC cytoplasm. Translocated to the plasma membrane in a beta-gamma G
CC protein-dependent manner. {ECO:0000250|UniProtKB:O02696}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WYR1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WYR1-2; Sequence=VSP_016388;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with high expression in
CC fetal brain compared to adult brain. Abundant expression is observed in
CC cerebellum, cerebral cortex, cerebral meninges, and vermis cerebelli.
CC {ECO:0000269|PubMed:15797027, ECO:0000269|PubMed:22065524}.
CC -!- DOMAIN: The heterodimerization region allows the binding to the
CC catalytic subunit.
CC -!- DISEASE: Ataxia-oculomotor apraxia 3 (AOA3) [MIM:615217]: An autosomal
CC recessive disease characterized by cerebellar ataxia, oculomotor
CC apraxia, areflexia and peripheral neuropathy.
CC {ECO:0000269|PubMed:22065524}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AB028925; BAB82464.1; -; mRNA.
DR EMBL; AF128881; AAD33397.1; -; mRNA.
DR EMBL; EU332864; ABY87553.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90035.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90036.1; -; Genomic_DNA.
DR EMBL; BC028212; AAH28212.1; -; mRNA.
DR EMBL; AY725851; AAW63121.1; -; mRNA.
DR EMBL; AY725852; AAW63122.1; -; mRNA.
DR EMBL; AY725853; AAW63123.1; -; mRNA.
DR EMBL; AY725854; AAW63124.1; -; mRNA.
DR CCDS; CCDS11147.1; -. [Q8WYR1-1]
DR CCDS; CCDS73986.1; -. [Q8WYR1-2]
DR RefSeq; NP_001136105.1; NM_001142633.2. [Q8WYR1-1]
DR RefSeq; NP_001238780.1; NM_001251851.1. [Q8WYR1-2]
DR RefSeq; NP_001238781.1; NM_001251852.1. [Q8WYR1-2]
DR RefSeq; NP_001238782.1; NM_001251853.1. [Q8WYR1-2]
DR RefSeq; NP_001238784.1; NM_001251855.1. [Q8WYR1-2]
DR RefSeq; NP_055123.2; NM_014308.3. [Q8WYR1-1]
DR AlphaFoldDB; Q8WYR1; -.
DR SMR; Q8WYR1; -.
DR BioGRID; 117079; 7.
DR ComplexPortal; CPX-5986; Phosphatidylinositol 3-kinase complex class IB, p110gamma/p101.
DR IntAct; Q8WYR1; 7.
DR STRING; 9606.ENSP00000392812; -.
DR BindingDB; Q8WYR1; -.
DR ChEMBL; CHEMBL3430881; -.
DR iPTMnet; Q8WYR1; -.
DR PhosphoSitePlus; Q8WYR1; -.
DR BioMuta; PIK3R5; -.
DR DMDM; 74716480; -.
DR MassIVE; Q8WYR1; -.
DR MaxQB; Q8WYR1; -.
DR PaxDb; Q8WYR1; -.
DR PeptideAtlas; Q8WYR1; -.
DR PRIDE; Q8WYR1; -.
DR ProteomicsDB; 75194; -. [Q8WYR1-1]
DR ProteomicsDB; 75195; -. [Q8WYR1-2]
DR Antibodypedia; 24754; 456 antibodies from 31 providers.
DR DNASU; 23533; -.
DR Ensembl; ENST00000447110.6; ENSP00000392812.1; ENSG00000141506.15. [Q8WYR1-1]
DR Ensembl; ENST00000581552.5; ENSP00000462433.1; ENSG00000141506.15. [Q8WYR1-1]
DR Ensembl; ENST00000611902.4; ENSP00000477795.1; ENSG00000141506.15. [Q8WYR1-2]
DR Ensembl; ENST00000616147.4; ENSP00000484211.1; ENSG00000141506.15. [Q8WYR1-2]
DR Ensembl; ENST00000623421.3; ENSP00000485280.1; ENSG00000141506.15. [Q8WYR1-2]
DR GeneID; 23533; -.
DR KEGG; hsa:23533; -.
DR MANE-Select; ENST00000447110.6; ENSP00000392812.1; NM_001142633.3; NP_001136105.1.
DR UCSC; uc002glt.4; human. [Q8WYR1-1]
DR CTD; 23533; -.
DR DisGeNET; 23533; -.
DR GeneCards; PIK3R5; -.
DR HGNC; HGNC:30035; PIK3R5.
DR HPA; ENSG00000141506; Tissue enhanced (bone).
DR MalaCards; PIK3R5; -.
DR MIM; 611317; gene.
DR MIM; 615217; phenotype.
DR neXtProt; NX_Q8WYR1; -.
DR OpenTargets; ENSG00000141506; -.
DR Orphanet; 64753; Spinocerebellar ataxia with axonal neuropathy type 2.
DR PharmGKB; PA134890823; -.
DR VEuPathDB; HostDB:ENSG00000141506; -.
DR eggNOG; ENOG502QV4A; Eukaryota.
DR GeneTree; ENSGT00530000063753; -.
DR HOGENOM; CLU_337590_0_0_1; -.
DR InParanoid; Q8WYR1; -.
DR OMA; PWEDSTN; -.
DR OrthoDB; 220934at2759; -.
DR PhylomeDB; Q8WYR1; -.
DR TreeFam; TF102035; -.
DR BioCyc; MetaCyc:HS13887-MON; -.
DR PathwayCommons; Q8WYR1; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR SignaLink; Q8WYR1; -.
DR BioGRID-ORCS; 23533; 19 hits in 1071 CRISPR screens.
DR ChiTaRS; PIK3R5; human.
DR GeneWiki; PIK3R5; -.
DR GenomeRNAi; 23533; -.
DR Pharos; Q8WYR1; Tbio.
DR PRO; PR:Q8WYR1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8WYR1; protein.
DR Bgee; ENSG00000141506; Expressed in granulocyte and 130 other tissues.
DR ExpressionAtlas; Q8WYR1; baseline and differential.
DR Genevisible; Q8WYR1; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; IC:ComplexPortal.
DR GO; GO:0005944; C:phosphatidylinositol 3-kinase complex, class IB; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; IC:ComplexPortal.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR InterPro; IPR019522; PIK3R5/6.
DR PANTHER; PTHR15593; PTHR15593; 1.
DR Pfam; PF10486; PI3K_1B_p101; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Cytoplasm;
KW Disease variant; Membrane; Neurodegeneration; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..880
FT /note="Phosphoinositide 3-kinase regulatory subunit 5"
FT /id="PRO_0000058421"
FT REGION 25..101
FT /note="Heterodimerization"
FT /evidence="ECO:0000250"
FT REGION 315..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 454..510
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 565..601
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 653..753
FT /note="Interaction with beta-gamma G protein dimers"
FT /evidence="ECO:0000250"
FT COMPBIAS 315..335
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 471..485
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 573..587
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O02696"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 1..386
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016388"
FT VARIANT 28
FT /note="R -> C (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs371789171)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036227"
FT VARIANT 629
FT /note="P -> S (in AOA3; dbSNP:rs61761068)"
FT /evidence="ECO:0000269|PubMed:22065524"
FT /id="VAR_067052"
FT CONFLICT 15
FT /note="H -> L (in Ref. 6; AAW63122)"
FT /evidence="ECO:0000305"
FT CONFLICT 29
FT /note="R -> C (in Ref. 6; AAW63122)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="L -> Q (in Ref. 6; AAW63122)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="F -> L (in Ref. 6; AAW63122)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="V -> E (in Ref. 6; AAW63122)"
FT /evidence="ECO:0000305"
FT CONFLICT 220..297
FT /note="AKTLAELEDIFTETAEAQELASGIGDAAEARRWLRTKLQAVGEKAGFPGVLD
FT TAKPGKLHTIPIPVARCYTYSWSQDS -> TLQNQGSSIPSPSLSPGATPTAGARTALT
FT SCRKSCSRNRSCSSQGSWEMMKRRKRRRRRWRRTWKLMGTVPREIPCSP (in Ref.
FT 6; AAW63122)"
FT /evidence="ECO:0000305"
FT CONFLICT 299..368
FT /note="DILQEILLKEQELLQPGILGDDEEEEEEEEEVEEDLETDGHCAERDSLLSTS
FT SLASHDSTLSLASSQASG -> GNIEGDPGPRRPDSAGLASLQTSCRKSCSRNRSYSSQ
FT GSWEMMKRRERRRRRWRRTWKLTGTVPREIPCS (in Ref. 6; AAW63121)"
FT /evidence="ECO:0000305"
FT CONFLICT 674
FT /note="V -> L (in Ref. 2; AAD33397)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 880 AA; 97348 MW; 70E356773B148A8A CRC64;
MQPGATTCTE DRIQHALERC LHGLSLSRRS TSWSAGLCLN CWSLQELVSR DPGHFLILLE
QILQKTREVQ EKGTYDLLTP LALLFYSTVL CTPHFPPDSD LLLKAASTYH RFLTWPVPYC
SICQELLTFI DAELKAPGIS YQRLVRAEQG LPIRSHRSST VTVLLLNPVE VQAEFLAVAN
KLSTPGHSPH SAYTTLLLHA FQATFGAHCD VPGLHCRLQA KTLAELEDIF TETAEAQELA
SGIGDAAEAR RWLRTKLQAV GEKAGFPGVL DTAKPGKLHT IPIPVARCYT YSWSQDSFDI
LQEILLKEQE LLQPGILGDD EEEEEEEEEV EEDLETDGHC AERDSLLSTS SLASHDSTLS
LASSQASGPA LSRHLLTSFV SGLSDGMDSG YVEDSEESSS EWPWRRGSQE RRGHRRPGQK
FIRIYKLFKS TSQLVLRRDS RSLEGSSDTA LPLRRAGSLC SPLDEPVSPP SRAQRSRSLP
QPKLGTQLPS WLLAPASRPQ RRRPFLSGDE DPKASTLRVV VFGSDRISGK VARAYSNLRR
LENNRPLLTR FFKLQFFYVP VKRSHGTSPG ACPPPRSQTP SPPTDSPRHA SPGELGTTPW
EESTNDISHY LGMLDPWYER NVLGLMHLPP EVLCQQSLKA EAQALEGSPT QLPILADMLL
YYCRFAARPV LLQVYQTELT FITGEKTTEI FIHSLELGHS AATRAIKASG PGSKRLGIDG
DREAVPLTLQ IIYSKGAISG RSRWSNLEKV CTSVNLNKAC RKQEELDSSM EALTLNLTEV
VKRQNSKSKK GFNQISTSQI KVDKVQIIGS NSCPFAVCLD QDERKILQSV VRCEVSPCYK
PEKSDLSSPP QTPPDLPAQA APDLCSLLCL PIMTFSGALP
