P85A_PONAB
ID P85A_PONAB Reviewed; 724 AA.
AC Q5R685; Q5RDU5;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Phosphatidylinositol 3-kinase regulatory subunit alpha;
DE Short=PI3-kinase regulatory subunit alpha;
DE Short=PI3K regulatory subunit alpha;
DE Short=PtdIns-3-kinase regulatory subunit alpha;
DE AltName: Full=Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha;
DE Short=PI3-kinase subunit p85-alpha;
DE Short=PtdIns-3-kinase regulatory subunit p85-alpha;
GN Name=PIK3R1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Binds to activated (phosphorylated) protein-Tyr kinases,
CC through its SH2 domain, and acts as an adapter, mediating the
CC association of the p110 catalytic unit to the plasma membrane.
CC Necessary for the insulin-stimulated increase in glucose uptake and
CC glycogen synthesis in insulin-sensitive tissues. Plays an important
CC role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF,
CC KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling.
CC Modulates the cellular response to ER stress by promoting nuclear
CC translocation of XBP1 in a ER stress- and/or insulin-dependent manner
CC during metabolic overloading in the liver and hence plays a role in
CC glucose tolerance improvement (By similarity).
CC {ECO:0000250|UniProtKB:P26450, ECO:0000250|UniProtKB:P27986}.
CC -!- SUBUNIT: Heterodimer of a regulatory subunit PIK3R1 and a p110
CC catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts (via SH2
CC domains) with CCDC88A/GIV (tyrosine-phosphorylated form); the
CC interaction enables recruitment of PIK3R1 to the EGFR receptor,
CC enhancing PI3K activity and cell migration (By similarity). Interacts
CC with phosphorylated LAT, LAX1, TRAT1 and LIME1 upon TCR and/or BCR
CC activation. Interacts with CBLB. The SH2 domains interact with the YTHM
CC motif of phosphorylated INSR in vitro. Also interacts with tyrosine-
CC phosphorylated IGF1R in vitro. Interacts with CD28 and CD3Z upon T-cell
CC activation. Interacts with SOCS7. Interacts with IRS1 and
CC phosphorylated IRS4. Interacts with NISCH, RUFY3 and HCST. Interacts
CC with AXL, FASLG, FER, FGR, HCK, KIT and BCR. Interacts with PDGFRA
CC (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated).
CC Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated).
CC Interacts with ERBB4 (phosphorylated). Interacts (via SH2 domain) with
CC TEK/TIE2 (tyrosine phosphorylated). Interacts with LYN (via SH3
CC domain); this enhances enzyme activity. Interacts with NTRK1
CC (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1.
CC Interacts with PIK3R2; the interaction is dissociated in an insulin-
CC dependent manner. Interacts with XBP1; the interaction is direct and
CC induces translocation of XBP1 into the nucleus in a ER stress- and/or
CC insulin-dependent but PI3K-independent manner (By similarity).
CC Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By
CC similarity). Interacts with APPL1 and APPL2 (By similarity). Interacts
CC with SRC (By similarity). Interacts with ALOX5; this interaction
CC bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the
CC production of reactive oxygen species (ROS) (By similarity).
CC {ECO:0000250|UniProtKB:P23727, ECO:0000250|UniProtKB:P26450,
CC ECO:0000250|UniProtKB:P27986, ECO:0000250|UniProtKB:Q63787}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5R685-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5R685-2; Sequence=VSP_037230, VSP_037231;
CC -!- DOMAIN: The SH3 domain mediates the binding to CBLB. {ECO:0000250}.
CC -!- PTM: Polyubiquitinated in T-cells by CBLB; which does not promote
CC proteasomal degradation but impairs association with CD28 and CD3Z upon
CC T-cell activation. {ECO:0000250}.
CC -!- PTM: Phosphorylated. Tyrosine phosphorylated in response to signaling
CC by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated by CSF1R.
CC Phosphorylated on tyrosine residues by TEK/TIE2. Dephosphorylated by
CC PTPRJ. Phosphorylated by PIK3CA at Ser-608; phosphorylation is
CC stimulated by insulin and PDGF. The relevance of phosphorylation by
CC PIK3CA is however unclear. Phosphorylated in response to KIT and
CC KITLG/SCF. Phosphorylated by FGR and ERBB4 (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PI3K p85 subunit family. {ECO:0000305}.
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DR EMBL; CR857802; CAH90062.1; -; mRNA.
DR EMBL; CR860609; CAH92731.1; -; mRNA.
DR RefSeq; NP_001126593.1; NM_001133121.1. [Q5R685-1]
DR RefSeq; NP_001128767.1; NM_001135295.1.
DR AlphaFoldDB; Q5R685; -.
DR BMRB; Q5R685; -.
DR SMR; Q5R685; -.
DR STRING; 9601.ENSPPYP00000017341; -.
DR Ensembl; ENSPPYT00000036528; ENSPPYP00000031504; ENSPPYG00000015520. [Q5R685-2]
DR GeneID; 100173589; -.
DR GeneID; 100189665; -.
DR KEGG; pon:100173589; -.
DR CTD; 5295; -.
DR eggNOG; KOG4637; Eukaryota.
DR GeneTree; ENSGT00940000155553; -.
DR InParanoid; Q5R685; -.
DR OrthoDB; 737926at2759; -.
DR Proteomes; UP000001595; Chromosome 5.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0033120; P:positive regulation of RNA splicing; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR CDD; cd12924; iSH2_PIK3R1; 1.
DR CDD; cd09930; SH2_cSH2_p85_like; 1.
DR CDD; cd09942; SH2_nSH2_p85_like; 1.
DR CDD; cd11910; SH3_PI3K_p85alpha; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR044124; ISH2_PIK3R1.
DR InterPro; IPR032498; PI3K_P85_iSH2.
DR InterPro; IPR035591; PI3K_p85alpha_SH3.
DR InterPro; IPR035020; PI3kinase_P85_cSH2.
DR InterPro; IPR035022; PI3kinase_P85_nSH2.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF16454; PI3K_P85_iSH2; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF00017; SH2; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00324; RhoGAP; 1.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50001; SH2; 2.
DR PROSITE; PS50002; SH3; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Alternative splicing; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; SH2 domain; SH3 domain; Stress response;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT CHAIN 2..724
FT /note="Phosphatidylinositol 3-kinase regulatory subunit
FT alpha"
FT /id="PRO_0000373801"
FT DOMAIN 3..79
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 113..301
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 333..428
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 624..718
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 80..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..98
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 467
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P26450"
FT MOD_RES 580
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23727"
FT VAR_SEQ 1..270
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_037230"
FT VAR_SEQ 271..304
FT /note="MLFRFSAASSDNTENLIKVIEILISTEWNERQPA -> MYNTVWNMEDLDLE
FT YAKTDINCGTDLMFYIEMDP (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_037231"
FT CONFLICT 550
FT /note="K -> R (in Ref. 1; CAH90062)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 724 AA; 83596 MW; D6A95EFC075F04D2 CRC64;
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP EEIGWLNGYN
ETTGERGDFP GTYVEYIGRK KISPPTPKPR PPRPLPVAPG SSKTEADVEQ QALTLPDLAE
QLAPPDIAPP LLIKLVEAIE KKGLECSTLY RTQSSSNLAE LRQLLDCDTA SVDLEMIDVH
VLADAFKRYL LDLPNPVIPA AVYSEMISLA QEVQSSEEYI QLLKKLIRSP SIPHQYWLTL
QYLLKHFFKL SQTSSKNLLN ARVLSEIFSP MLFRFSAASS DNTENLIKVI EILISTEWNE
RQPAPALPPK PPKPTTVANN GMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA
STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFNS VVELINHYRN ESLAQYNPKL
DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEEY TRTSQEIQMK
RTAIEAFNET IKIFEEQCQT QERYSKEYIE KFKREGNEKE IQRIMHNYDK LKSRISEIID
SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN
ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE SSKQGCYACS
VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH TSLVQHNDSL NVTLAYPVYA
QQRR
