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Protein

Phosphoinositide 3-kinase adapter protein 1

Gene

PIK3AP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SIGNORiQ6ZUJ8.

Names & Taxonomyi

Protein namesi
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 namesi
Name:PIK3AP1
Synonyms:BCAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:30034. PIK3AP1.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi118788.
OpenTargetsiENSG00000155629.
PharmGKBiPA134979629.

Polymorphism and mutation databases

BioMutaiPIK3AP1.
DMDMi205830907.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003412731 – 805Phosphoinositide 3-kinase adapter protein 1Add BLAST805

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei263PhosphotyrosineBy similarity1
Modified residuei419Phosphotyrosine; by SYKBy similarity1
Modified residuei444Phosphotyrosine; by SYKBy similarity1
Modified residuei459Phosphotyrosine; by SYKBy similarity1
Modified residuei513Phosphotyrosine; by ABL11 Publication1
Modified residuei553Phosphotyrosine; by ABL11 Publication1
Modified residuei570Phosphotyrosine; by ABL11 Publication1
Modified residuei594Phosphotyrosine; by ABL11 Publication1
Modified residuei642PhosphoserineCombined sources1
Modified residuei694Phosphotyrosine; by ABL11 Publication1
Modified residuei718PhosphoserineCombined sources1

Post-translational modificationi

Constitutively phosphorylated. Phosphorylated on tyrosine residues in C-terminal 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).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6ZUJ8.
MaxQBiQ6ZUJ8.
PaxDbiQ6ZUJ8.
PeptideAtlasiQ6ZUJ8.
PRIDEiQ6ZUJ8.

PTM databases

iPTMnetiQ6ZUJ8.
PhosphoSitePlusiQ6ZUJ8.

Expressioni

Tissue specificityi

Expressed in natural killer (NK) cells.1 Publication

Gene expression databases

BgeeiENSG00000155629.
CleanExiHS_PIK3AP1.
GenevisibleiQ6ZUJ8. HS.

Organism-specific databases

HPAiCAB026136.
HPA038452.

Interactioni

Subunit structurei

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).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi125621. 5 interactors.
IntActiQ6ZUJ8. 7 interactors.
MINTiMINT-7009152.
STRINGi9606.ENSP00000339826.

Structurei

Secondary structure

1805
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi12 – 16Combined sources5
Helixi18 – 20Combined sources3
Helixi21 – 33Combined sources13
Turni35 – 39Combined sources5
Beta strandi42 – 46Combined sources5
Helixi55 – 63Combined sources9
Beta strandi65 – 71Combined sources7
Helixi73 – 79Combined sources7
Helixi85 – 91Combined sources7
Helixi95 – 97Combined sources3
Beta strandi98 – 104Combined sources7
Helixi109 – 113Combined sources5
Helixi118 – 120Combined sources3
Beta strandi121 – 124Combined sources4
Helixi130 – 138Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5FORX-ray2.50A7-142[»]
ProteinModelPortaliQ6ZUJ8.
SMRiQ6ZUJ8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini181 – 317DBBPROSITE-ProRule annotationAdd BLAST137

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni10 – 144Necessary and sufficient to mediate inhibition of NF-kappa-B downstream of activated TLRs; may mediate interaction with MYD88 and TIRAPBy similarityAdd BLAST135

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili645 – 667Sequence analysisAdd BLAST23

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi760 – 802Pro-richAdd BLAST43

Domaini

The DBB domain is required for dimerization.By similarity

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IKKC. Eukaryota.
ENOG4110NCP. LUCA.
GeneTreeiENSGT00390000008787.
HOGENOMiHOG000095183.
HOVERGENiHBG104426.
InParanoidiQ6ZUJ8.
KOiK12230.
OMAiVRCKLDE.
OrthoDBiEOG091G0125.
PhylomeDBiQ6ZUJ8.
TreeFamiTF328570.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiView protein in InterPro
IPR020683. Ankyrin_rpt-contain_dom.
IPR017893. DBB_domain.
PfamiView protein in Pfam
PF14545. DBB. 1 hit.
SMARTiView protein in SMART
SM01282. DBB. 1 hit.
PROSITEiView protein in PROSITE
PS51376. DBB. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6ZUJ8-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MAASGVPRGC DILIVYSPDA EEWCQYLQTL FLSSRQVRSQ KILTHRLGPE
60 70 80 90 100
ASFSAEDLSL FLSTRCVVVL LSAELVQHFH KPALLPLLQR AFHPPHRVVR
110 120 130 140 150
LLCGVRDSEE FLDFFPDWAH WQELTCDDEP ETYVAAVKKA ISEDSGCDSV
160 170 180 190 200
TDTEPEDEKV VSYSKQQNLP TVTSPGNLMV VQPDRIRCGA ETTVYVIVRC
210 220 230 240 250
KLDDRVATEA EFSPEDSPSV RMEAKVENEY TISVKAPNLS SGNVSLKIYS
260 270 280 290 300
GDLVVCETVI SYYTDMEEIG NLLSNAANPV EFMCQAFKIV PYNTETLDKL
310 320 330 340 350
LTESLKNNIP ASGLHLFGIN QLEEEDMMTN QRDEELPTLL HFAAKYGLKN
360 370 380 390 400
LTALLLTCPG ALQAYSVANK HGHYPNTIAE KHGFRDLRQF IDEYVETVDM
410 420 430 440 450
LKSHIKEELM HGEEADAVYE SMAHLSTDLL MKCSLNPGCD EDLYESMAAF
460 470 480 490 500
VPAATEDLYV EMLQASTSNP IPGDGFSRAT KDSMIRKFLE GNSMGMTNLE
510 520 530 540 550
RDQCHLGQEE DVYHTVDDDE AFSVDLASRP PVPVPRPETT APGAHQLPDN
560 570 580 590 600
EPYIFKVFAE KSQERPGNFY VSSESIRKGP PVRPWRDRPQ SSIYDPFAGM
610 620 630 640 650
KTPGQRQLIT LQEQVKLGIV NVDEAVLHFK EWQLNQKKRS ESFRFQQENL
660 670 680 690 700
KRLRDSITRR QREKQKSGKQ TDLEITVPIR HSQHLPAKVE FGVYESGPRK
710 720 730 740 750
SVIPPRTELR RGDWKTDSTS STASSTSNRS STRSLLSVSS GMEGDNEDNE
760 770 780 790 800
VPEVTRSRSP GPPQVDGTPT MSLERPPRVP PRAASQRPPT RETFHPPPPV

PPRGR
Length:805
Mass (Da):90,398
Last modified:July 22, 2008 - v2
Checksum:iDF1025A37905AEA7
GO
Isoform 2 (identifier: Q6ZUJ8-2) [UniParc]FASTAAdd to basket
Also known as: BCAP-S

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

Show »
Length:627
Mass (Da):70,412
Checksum:iA2D7C2496537C129
GO
Isoform 3 (identifier: Q6ZUJ8-3) [UniParc]FASTAAdd to basket

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

Show »
Length:404
Mass (Da):45,484
Checksum:iEDBB28E0023875E9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti726T → P in BAC03996 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04403521E → K1 PublicationCorresponds to variant dbSNP:rs17112076Ensembl.1
Natural variantiVAR_04403683A → S1 PublicationCorresponds to variant dbSNP:rs3748229Ensembl.1
Natural variantiVAR_044037551E → K. Corresponds to variant dbSNP:rs3748233Ensembl.1
Natural variantiVAR_044038638K → R. Corresponds to variant dbSNP:rs12784975Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0342381 – 178Missing in isoform 2. 1 PublicationAdd BLAST178
Alternative sequenceiVSP_0342391 – 57MAASG…FSAED → MRFFTSVACYGSCLFASELL IRCKDWLKGRPALFTALLAC VLYLCEWTGAKHVPGSS in isoform 3. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_03424058 – 458Missing in isoform 3. 1 PublicationAdd BLAST401

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31259.1. [Q6ZUJ8-1]
RefSeqiNP_689522.2. NM_152309.2. [Q6ZUJ8-1]
XP_005269555.1. XM_005269498.1. [Q6ZUJ8-2]
XP_005269556.1. XM_005269499.1. [Q6ZUJ8-2]
UniGeneiHs.310456.

Genome annotation databases

EnsembliENST00000339364; ENSP00000339826; ENSG00000155629. [Q6ZUJ8-1]
ENST00000371109; ENSP00000360150; ENSG00000155629. [Q6ZUJ8-3]
ENST00000371110; ENSP00000360151; ENSG00000155629. [Q6ZUJ8-2]
GeneIDi118788.
KEGGihsa:118788.
UCSCiuc001kmo.4. human. [Q6ZUJ8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31259.1. [Q6ZUJ8-1]
RefSeqiNP_689522.2. NM_152309.2. [Q6ZUJ8-1]
XP_005269555.1. XM_005269498.1. [Q6ZUJ8-2]
XP_005269556.1. XM_005269499.1. [Q6ZUJ8-2]
UniGeneiHs.310456.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5FORX-ray2.50A7-142[»]
ProteinModelPortaliQ6ZUJ8.
SMRiQ6ZUJ8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125621. 5 interactors.
IntActiQ6ZUJ8. 7 interactors.
MINTiMINT-7009152.
STRINGi9606.ENSP00000339826.

PTM databases

iPTMnetiQ6ZUJ8.
PhosphoSitePlusiQ6ZUJ8.

Polymorphism and mutation databases

BioMutaiPIK3AP1.
DMDMi205830907.

Proteomic databases

EPDiQ6ZUJ8.
MaxQBiQ6ZUJ8.
PaxDbiQ6ZUJ8.
PeptideAtlasiQ6ZUJ8.
PRIDEiQ6ZUJ8.

Protocols and materials databases

DNASUi118788.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000339364; ENSP00000339826; ENSG00000155629. [Q6ZUJ8-1]
ENST00000371109; ENSP00000360150; ENSG00000155629. [Q6ZUJ8-3]
ENST00000371110; ENSP00000360151; ENSG00000155629. [Q6ZUJ8-2]
GeneIDi118788.
KEGGihsa:118788.
UCSCiuc001kmo.4. human. [Q6ZUJ8-1]

Organism-specific databases

CTDi118788.
DisGeNETi118788.
GeneCardsiPIK3AP1.
H-InvDBiHIX0201490.
HGNCiHGNC:30034. PIK3AP1.
HPAiCAB026136.
HPA038452.
MIMi607942. gene.
neXtProtiNX_Q6ZUJ8.
OpenTargetsiENSG00000155629.
PharmGKBiPA134979629.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKKC. Eukaryota.
ENOG4110NCP. LUCA.
GeneTreeiENSGT00390000008787.
HOGENOMiHOG000095183.
HOVERGENiHBG104426.
InParanoidiQ6ZUJ8.
KOiK12230.
OMAiVRCKLDE.
OrthoDBiEOG091G0125.
PhylomeDBiQ6ZUJ8.
TreeFamiTF328570.

Enzyme and pathway databases

ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SIGNORiQ6ZUJ8.

Miscellaneous databases

GeneWikiiPIK3AP1.
GenomeRNAii118788.
PROiPR:Q6ZUJ8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155629.
CleanExiHS_PIK3AP1.
GenevisibleiQ6ZUJ8. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiView protein in InterPro
IPR020683. Ankyrin_rpt-contain_dom.
IPR017893. DBB_domain.
PfamiView protein in Pfam
PF14545. DBB. 1 hit.
SMARTiView protein in SMART
SM01282. DBB. 1 hit.
PROSITEiView protein in PROSITE
PS51376. DBB. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiBCAP_HUMAN
AccessioniPrimary (citable) accession number: Q6ZUJ8
Secondary accession number(s): Q5TB56
, Q5VXJ9, Q8N6J6, Q8NAC8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: July 22, 2008
Last modified: March 15, 2017
This is version 109 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.