BCAP_CHICK
ID BCAP_CHICK Reviewed; 800 AA.
AC Q9DDT2; Q9DDL3;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Phosphoinositide 3-kinase adapter protein 1;
DE AltName: Full=B-cell adapter for phosphoinositide 3-kinase;
DE AltName: Full=B-cell phosphoinositide 3-kinase adapter protein 1;
GN Name=PIK3AP1; Synonyms=BCAP;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 293-303;
RP 492-505; 560-566; 599-612 AND 614-624, FUNCTION IN B-CELL RECEPTOR
RP SIGNALING, SUBCELLULAR LOCATION, INTERACTION WITH PIK3R1, PHOSPHORYLATION
RP AT TYR-266; TYR-423; TYR-448 AND TYR-463, AND MUTAGENESIS OF TYR-266;
RP TYR-423; TYR-448 AND TYR-463.
RX PubMed=11163197; DOI=10.1016/s1074-7613(00)00079-0;
RA Okada T., Maeda A., Iwamatsu A., Gotoh K., Kurosaki T.;
RT "BCAP: the tyrosine kinase substrate that connects B cell receptor to
RT phosphoinositide 3-kinase activation.";
RL Immunity 13:817-827(2000).
RN [2]
RP FUNCTION.
RX PubMed=11781242; DOI=10.1182/blood.v99.2.584;
RA Inabe K., Kurosaki T.;
RT "Tyrosine phosphorylation of B-cell adaptor for phosphoinositide 3-kinase
RT is required for Akt activation in response to CD19 engagement.";
RL Blood 99:584-589(2002).
RN [3]
RP FUNCTION.
RX PubMed=12627965; DOI=10.1021/bi0205911;
RA Qin S., Chock P.B.;
RT "Implication of phosphatidylinositol 3-kinase membrane recruitment in
RT hydrogen peroxide-induced activation of PI3K and Akt.";
RL Biochemistry 42:2995-3003(2003).
CC -!- FUNCTION: Signaling adapter that contributes to B-cell development by
CC linking B-cell receptor (BCR) signaling to the phosphoinositide 3-
CC kinase (PI3K)-Akt signaling pathway. Has a complementary role to the
CC BCR coreceptor CD19, coupling BCR and PI3K activation by providing a
CC docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-
CC like receptor (TLR) signaling to PI3K activation, a process preventing
CC excessive inflammatory cytokine production. Also involved in the
CC activation of PI3K in natural killer cells. May be involved in the
CC survival of mature B-cells via activation of REL.
CC {ECO:0000269|PubMed:11163197, ECO:0000269|PubMed:11781242,
CC ECO:0000269|PubMed:12627965}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts (phosphorylated on
CC tyrosine residues within YXXM motifs) with PIK3R1 (via SH2 domain);
CC required for BCR- and TLR-mediated activation of phosphoinositide 3-
CC kinase. {ECO:0000250, ECO:0000269|PubMed:11163197}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11163197}. Cell
CC membrane {ECO:0000305|PubMed:11163197}; Peripheral membrane protein
CC {ECO:0000305|PubMed:11163197}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9DDT2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9DDT2-2; Sequence=VSP_034244;
CC -!- DOMAIN: The DBB domain is required for dimerization. {ECO:0000250}.
CC -!- PTM: Constitutively phosphorylated (By similarity). Phosphorylated on
CC tyrosine residues within the YXXM motifs by BTK and SYK. Isoform 1 and
CC isoform 2 are phosphorylated on tyrosine residues, most likely within
CC the YXXM motifs, via CD19 activation. {ECO:0000250,
CC ECO:0000269|PubMed:11163197}.
CC -!- MISCELLANEOUS: [Isoform 2]: It is unsure whether this isoform is
CC produced by alternative splicing or alternative initiation.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF293805; AAG48583.1; -; mRNA.
DR EMBL; AF315784; AAG48619.1; -; mRNA.
DR RefSeq; NP_989681.1; NM_204350.1. [Q9DDT2-1]
DR AlphaFoldDB; Q9DDT2; -.
DR SMR; Q9DDT2; -.
DR BioGRID; 675276; 1.
DR STRING; 9031.ENSGALP00000008882; -.
DR iPTMnet; Q9DDT2; -.
DR PaxDb; Q9DDT2; -.
DR Ensembl; ENSGALT00000008896; ENSGALP00000008882; ENSGALG00000005547. [Q9DDT2-1]
DR Ensembl; ENSGALT00000088192; ENSGALP00000062022; ENSGALG00000005547. [Q9DDT2-2]
DR GeneID; 374268; -.
DR KEGG; gga:374268; -.
DR CTD; 118788; -.
DR VEuPathDB; HostDB:geneid_374268; -.
DR eggNOG; ENOG502QS94; Eukaryota.
DR GeneTree; ENSGT00390000008787; -.
DR HOGENOM; CLU_012993_0_0_1; -.
DR InParanoid; Q9DDT2; -.
DR OMA; IIMKCKL; -.
DR OrthoDB; 280243at2759; -.
DR PhylomeDB; Q9DDT2; -.
DR Reactome; R-GGA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-GGA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-GGA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR PRO; PR:Q9DDT2; -.
DR Proteomes; UP000000539; Chromosome 6.
DR Bgee; ENSGALG00000005547; Expressed in spleen and 13 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0043549; P:regulation of kinase activity; IMP:BHF-UCL.
DR GO; GO:0042325; P:regulation of phosphorylation; IMP:BHF-UCL.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034154; P:toll-like receptor 7 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR GO; GO:0031929; P:TOR signaling; IMP:BHF-UCL.
DR Gene3D; 3.40.50.10140; -; 1.
DR InterPro; IPR017893; DBB_domain.
DR InterPro; IPR041340; PIK3AP1_TIR.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR Pfam; PF14545; DBB; 1.
DR Pfam; PF18567; TIR_3; 1.
DR SMART; SM01282; DBB; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51376; DBB; 1.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Coiled coil; Cytoplasm;
KW Direct protein sequencing; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..800
FT /note="Phosphoinositide 3-kinase adapter protein 1"
FT /id="PRO_0000341275"
FT DOMAIN 8..145
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT DOMAIN 185..321
FT /note="DBB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00707"
FT REGION 10..144
FT /note="Necessary and sufficient to mediate inhibition of
FT NF-kappa-B downstream of activated TLRs"
FT /evidence="ECO:0000250"
FT REGION 527..548
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 702..800
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 643..663
FT /evidence="ECO:0000255"
FT COMPBIAS 713..742
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 763..780
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 266
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11163197"
FT MOD_RES 423
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000305|PubMed:11163197"
FT MOD_RES 448
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000305|PubMed:11163197"
FT MOD_RES 463
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000305|PubMed:11163197"
FT VAR_SEQ 1..168
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11163197"
FT /id="VSP_034244"
FT MUTAGEN 266
FT /note="Y->F: Fails to bind PIK3R1 in a BCR-signaling
FT dependent manner; when associated with Y-423; Y-448 and Y-
FT 463."
FT /evidence="ECO:0000269|PubMed:11163197"
FT MUTAGEN 423
FT /note="Y->F: Fails to bind PIK3R1 in a BCR-signaling
FT dependent manner; when associated with Y-266; Y-448 and Y-
FT 463."
FT /evidence="ECO:0000269|PubMed:11163197"
FT MUTAGEN 448
FT /note="Y->F: Fails to bind PIK3R1 in a BCR-signaling
FT dependent manner; when associated with Y-266; Y-423 and Y-
FT 463."
FT /evidence="ECO:0000269|PubMed:11163197"
FT MUTAGEN 463
FT /note="Y->F: Fails to bind PIK3R1 in a BCR-signaling
FT dependent manner; when associated with Y-266; Y-423 and Y-
FT 448."
FT /evidence="ECO:0000269|PubMed:11163197"
SQ SEQUENCE 800 AA; 90156 MW; E506D0CFE5E558ED CRC64;
MTASGTHGGY DVLILYASDA AEWCQYLQNL FLSTRHIRKH HIQSYQLEGE SAISDQELDL
FNRSRSIIIL LSAELVQNFY CPPVLQSLQE ALWPPHKVVK LFCGVTDCDD YLTFFKDWYQ
WQELTYDDEP DAYLEAVKKA ISEDSGCDSV TDTETEDEKT SVYSCQLAMN EEHESSKSTG
EHLVVQPDHI RCGVQTTVYI IMKCRLDDKV KTEVEFSPEN SSSVRVLAEL ENEYTISVEA
PNLTSGTVPL QIYSGDLMVG ETSVTYHTDM EEISSLLANA ANPVQFMCQA FKIVPYSIEA
LDKLLTESLK KNIPASGLHL FGINQLEEDD MTTNQRDEEL PTLLHFSARY GLKNLTALLL
TCPGALQAYS VANKYGHYPN TIAEKHGFKD LRQFIDEYVE TADMLKSHIK EELMQGEEDE
SVYESMAHLS TDLLMKCSLN PGSDEELYES MAGFVPGAPE DLYVEMLQSK PDTPISGDEI
SLTVKDSMLR KFLEGGSTDA PDSGEGVSQQ YGEDLYYSVE KDTFPQEMAS RPPVPVPRPE
SSSPQPDNEL YISKVFAQKA QRPENLYVPR GKVRKETIVR PVRDLSQSSI YDPFAGMKTP
GQRQLITLQE QVKMGILNVD EAVLHFKEWQ LNQKKRSESF RFQQENLKRL RDSITRRQME
KQKSGKSADL EITVPIRRSH NTLGKPECGI YEYAPRKNIF PPKKELKRGD WKTESTSSTT
SSASNRSSTR SILSVSSGME GDSEDNEVSE ASRSRSPIPS QAERLPLPLP ERPPRVPPRG
ASRPVNCEGF YPPPVPPRGR
