Q6ZUJ8 (BCAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphoinositide 3-kinase adapter protein 1

Alternative name(s):
B-cell adapter for phosphoinositide 3-kinase
B-cell phosphoinositide 3-kinase adapter protein 1

Gene names

Name:	PIK3AP1
Synonyms:	BCAP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	805 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL. Ref.5
Subunit structure	Homooligomer By similarity. Interacts (phosphorylated on tyrosine residues within YXXM motifs) with PIK3R1 (via SH2 domain); required for BCR- and TLR-mediated activation of phosphoinositide 3-kinase. Interacts (via polyproline C-terminal region) with ABI1 (via SH3 domain); the interaction promotes phosphorylation of PIK3AP1 by ABL1. May interact with MYD88 and TIRAP By similarity. Ref.5 Ref.6
Subcellular location	Cytoplasm By similarity. Cell membrane By similarity; Peripheral membrane protein By similarity.
Tissue specificity	Expressed in natural killer (NK) cells. Ref.6
Domain	The DBB domain is required for dimerization By similarity.
Post-translational modification	Constitutively phosphorylated. Phosphorylated on tyrosine residues in C-terminus region by ABL1. Phosphorylated on tyrosine residues within the YXXM motifs by BTK and SYK By similarity. Isoform 1 and isoform 2 are phosphorylated on tyrosine residues, most likely within the YXXM motifs, via CD19 activation By similarity. Toll-like receptor activation induces appearance of a phosphorylated form associated with membranes By similarity. Ref.5
Sequence similarities	Contains 1 DBB domain.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of phosphatidylinositol 3-kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB toll-like receptor 2 signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB toll-like receptor 4 signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB toll-like receptor 7 signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB toll-like receptor 9 signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	phosphatidylinositol 3-kinase regulatory subunit binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6ZUJ8-1)

Also known as: BCAP-L;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6ZUJ8-2)

Also known as: BCAP-S;

The sequence of this isoform differs from the canonical sequence as follows:
     1-178: Missing.

Isoform 3 (identifier: Q6ZUJ8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: MAASGVPRGC...GPEASFSAED → MRFFTSVACY...TGAKHVPGSS
     58-458: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 805	805	Phosphoinositide 3-kinase adapter protein 1		PRO_0000341273
Regions
	Domain	181 – 317	137	DBB
	Region	10 – 144	135	Necessary and sufficent to mediate inhibition of NF-kappa-B downstream of activated TLRs; may mediate interaction with MYD88 and TIRAP By similarity
	Coiled coil	645 – 667	23	Potential
	Compositional bias	760 – 802	43	Pro-rich
Amino acid modifications
	Modified residue	263	1	Phosphotyrosine By similarity
	Modified residue	419	1	Phosphotyrosine; by SYK By similarity
	Modified residue	444	1	Phosphotyrosine; by SYK By similarity
	Modified residue	459	1	Phosphotyrosine; by SYK By similarity
	Modified residue	513	1	Phosphotyrosine; by ABL1 Ref.5
	Modified residue	553	1	Phosphotyrosine; by ABL1 Ref.5
	Modified residue	570	1	Phosphotyrosine; by ABL1 Ref.5
	Modified residue	594	1	Phosphotyrosine; by ABL1 Ref.5
	Modified residue	694	1	Phosphotyrosine; by ABL1 Ref.5
Natural variations
	Alternative sequence	1 – 178	178	Missing in isoform 2.		VSP_034238
	Alternative sequence	1 – 57	57	MAASG…FSAED → MRFFTSVACYGSCLFASELL IRCKDWLKGRPALFTALLAC VLYLCEWTGAKHVPGSS in isoform 3.		VSP_034239
	Alternative sequence	58 – 458	401	Missing in isoform 3.		VSP_034240
	Natural variant	21	1	E → K. Ref.1 Corresponds to variant rs17112076 [ dbSNP | Ensembl ].		VAR_044035
	Natural variant	83	1	A → S. Ref.2 Corresponds to variant rs3748229 [ dbSNP | Ensembl ].		VAR_044036
	Natural variant	551	1	E → K. Corresponds to variant rs3748233 [ dbSNP | Ensembl ].		VAR_044037
	Natural variant	638	1	K → R. Corresponds to variant rs12784975 [ dbSNP | Ensembl ].		VAR_044038
Experimental info
	Sequence conflict	726	1	T → P in BAC03996. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (BCAP-L) [UniParc]. Last modified July 22, 2008. Version 2. Checksum: DF1025A37905AEA7	FASTA	805	90,398
	10 20 30 40 50 60 MAASGVPRGC DILIVYSPDA EEWCQYLQTL FLSSRQVRSQ KILTHRLGPE ASFSAEDLSL 70 80 90 100 110 120 FLSTRCVVVL LSAELVQHFH KPALLPLLQR AFHPPHRVVR LLCGVRDSEE FLDFFPDWAH 130 140 150 160 170 180 WQELTCDDEP ETYVAAVKKA ISEDSGCDSV TDTEPEDEKV VSYSKQQNLP TVTSPGNLMV 190 200 210 220 230 240 VQPDRIRCGA ETTVYVIVRC KLDDRVATEA EFSPEDSPSV RMEAKVENEY TISVKAPNLS 250 260 270 280 290 300 SGNVSLKIYS GDLVVCETVI SYYTDMEEIG NLLSNAANPV EFMCQAFKIV PYNTETLDKL 310 320 330 340 350 360 LTESLKNNIP ASGLHLFGIN QLEEEDMMTN QRDEELPTLL HFAAKYGLKN LTALLLTCPG 370 380 390 400 410 420 ALQAYSVANK HGHYPNTIAE KHGFRDLRQF IDEYVETVDM LKSHIKEELM HGEEADAVYE 430 440 450 460 470 480 SMAHLSTDLL MKCSLNPGCD EDLYESMAAF VPAATEDLYV EMLQASTSNP IPGDGFSRAT 490 500 510 520 530 540 KDSMIRKFLE GNSMGMTNLE RDQCHLGQEE DVYHTVDDDE AFSVDLASRP PVPVPRPETT 550 560 570 580 590 600 APGAHQLPDN EPYIFKVFAE KSQERPGNFY VSSESIRKGP PVRPWRDRPQ SSIYDPFAGM 610 620 630 640 650 660 KTPGQRQLIT LQEQVKLGIV NVDEAVLHFK EWQLNQKKRS ESFRFQQENL KRLRDSITRR 670 680 690 700 710 720 QREKQKSGKQ TDLEITVPIR HSQHLPAKVE FGVYESGPRK SVIPPRTELR RGDWKTDSTS 730 740 750 760 770 780 STASSTSNRS STRSLLSVSS GMEGDNEDNE VPEVTRSRSP GPPQVDGTPT MSLERPPRVP 790 800 PRAASQRPPT RETFHPPPPV PPRGR
	Isoform 2 (BCAP-S) [UniParc]. Checksum: A2D7C2496537C129	FASTA	627	70,412
	10 20 30 40 50 60 MVVQPDRIRC GAETTVYVIV RCKLDDRVAT EAEFSPEDSP SVRMEAKVEN EYTISVKAPN 70 80 90 100 110 120 LSSGNVSLKI YSGDLVVCET VISYYTDMEE IGNLLSNAAN PVEFMCQAFK IVPYNTETLD 130 140 150 160 170 180 KLLTESLKNN IPASGLHLFG INQLEEEDMM TNQRDEELPT LLHFAAKYGL KNLTALLLTC 190 200 210 220 230 240 PGALQAYSVA NKHGHYPNTI AEKHGFRDLR QFIDEYVETV DMLKSHIKEE LMHGEEADAV 250 260 270 280 290 300 YESMAHLSTD LLMKCSLNPG CDEDLYESMA AFVPAATEDL YVEMLQASTS NPIPGDGFSR 310 320 330 340 350 360 ATKDSMIRKF LEGNSMGMTN LERDQCHLGQ EEDVYHTVDD DEAFSVDLAS RPPVPVPRPE 370 380 390 400 410 420 TTAPGAHQLP DNEPYIFKVF AEKSQERPGN FYVSSESIRK GPPVRPWRDR PQSSIYDPFA 430 440 450 460 470 480 GMKTPGQRQL ITLQEQVKLG IVNVDEAVLH FKEWQLNQKK RSESFRFQQE NLKRLRDSIT 490 500 510 520 530 540 RRQREKQKSG KQTDLEITVP IRHSQHLPAK VEFGVYESGP RKSVIPPRTE LRRGDWKTDS 550 560 570 580 590 600 TSSTASSTSN RSSTRSLLSV SSGMEGDNED NEVPEVTRSR SPGPPQVDGT PTMSLERPPR 610 620 VPPRAASQRP PTRETFHPPP PVPPRGR
	Isoform 3 [UniParc]. Checksum: EDBB28E0023875E9	FASTA	404	45,484
	10 20 30 40 50 60 MRFFTSVACY GSCLFASELL IRCKDWLKGR PALFTALLAC VLYLCEWTGA KHVPGSSYVE 70 80 90 100 110 120 MLQASTSNPI PGDGFSRATK DSMIRKFLEG NSMGMTNLER DQCHLGQEED VYHTVDDDEA 130 140 150 160 170 180 FSVDLASRPP VPVPRPETTA PGAHQLPDNE PYIFKVFAEK SQERPGNFYV SSESIRKGPP 190 200 210 220 230 240 VRPWRDRPQS SIYDPFAGMK TPGQRQLITL QEQVKLGIVN VDEAVLHFKE WQLNQKKRSE 250 260 270 280 290 300 SFRFQQENLK RLRDSITRRQ REKQKSGKQT DLEITVPIRH SQHLPAKVEF GVYESGPRKS 310 320 330 340 350 360 VIPPRTELRR GDWKTDSTSS TASSTSNRSS TRSLLSVSSG MEGDNEDNEV PEVTRSRSPG 370 380 390 400 PPQVDGTPTM SLERPPRVPP RAASQRPPTR ETFHPPPPVP PRGR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT LYS-21. Tissue: Spleen and Synovium.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-83. Tissue: Fetal liver.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[5]	"Identification of B cell adaptor for PI3-kinase (BCAP) as an Abl interactor 1-regulated substrate of Abl kinases." Maruoka M., Suzuki J., Kawata S., Yoshida K., Hirao N., Sato S., Goff S.P., Takeya T., Tani K., Shishido T. FEBS Lett. 579:2986-2990(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ABI1, PHOSPHORYLATION AT TYR-513; TYR-553; TYR-570; TYR-594 AND TYR-694.
[6]	"Enhanced NK cell development and function in BCAP-deficient mice." Macfarlane A.W. IV, Yamazaki T., Fang M., Sigal L.J., Kurosaki T., Campbell K.S. Blood 112:131-140(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIK3R1, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK092883 mRNA. Translation: BAC03996.1. AK125635 mRNA. Translation: BAC86227.1. BX648550 mRNA. No translation available. AL358235, AL138765, AL591364 Genomic DNA. Translation: CAH71154.2. AL591364, AL358235, AL138765 Genomic DNA. Translation: CAH73440.2. AL591364, AL358235, AL138765 Genomic DNA. Translation: CAH73441.2. AL138765, AL591364 Genomic DNA. Translation: CAI13579.2. AL138765, AL358235, AL591364 Genomic DNA. Translation: CAI13581.2. AL138765 Genomic DNA. Translation: CAI13586.1. BC029917 mRNA. Translation: AAH29917.1.
IPI	IPI00180939. IPI00643527. IPI00783519.
RefSeq	NP_689522.2. NM_152309.2.
UniGene	Hs.310456.
3D structure databases
ProteinModelPortal	Q6ZUJ8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6ZUJ8. 4 interactions.
MINT	MINT-7009152.
STRING	9606.ENSP00000339826.
PTM databases
PhosphoSite	Q6ZUJ8.
Polymorphism databases
DMDM	205830907.
Proteomic databases
PaxDb	Q6ZUJ8.
PRIDE	Q6ZUJ8.
Protocols and materials databases
DNASU	118788.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000339364; ENSP00000339826; ENSG00000155629. ENST00000371109; ENSP00000360150; ENSG00000155629. ENST00000371110; ENSP00000360151; ENSG00000155629.
GeneID	118788.
KEGG	hsa:118788.
UCSC	uc001kmo.3. human. uc001kmp.3. human.
Organism-specific databases
CTD	118788.
GeneCards	GC10M098343.
H-InvDB	HIX0201490.
HGNC	HGNC:30034. PIK3AP1.
HPA	CAB026136.
MIM	607942. gene.
neXtProt	NX_Q6ZUJ8.
PharmGKB	PA134979629.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG70048.
HOGENOM	HOG000095183.
HOVERGEN	HBG104426.
InParanoid	Q6ZUJ8.
KO	K12230.
OMA	VRCKLDE.
OrthoDB	EOG447FT3.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
Bgee	Q6ZUJ8.
CleanEx	HS_PIK3AP1.
Genevestigator	Q6ZUJ8.
Family and domain databases
InterPro	IPR017893. DBB_domain. [Graphical view]
PROSITE	PS51376. DBB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	118788.
NextBio	80340.
SOURCE	Search...

Entry information

Entry name

BCAP_HUMAN

Accession

Primary (citable) accession number: Q6ZUJ8
Secondary accession number(s): Q5TB56 , Q5VXJ9, Q8N6J6, Q8NAC8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 22, 2008
Last sequence update:	July 22, 2008
Last modified:	May 29, 2013
This is version 74 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.