ID   DAPP1_HUMAN             Reviewed;         280 AA.
AC   Q9UN19; Q8TCK5; Q9UHF2;
DT   05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 182.
DE   RecName: Full=Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide;
DE            Short=hDAPP1;
DE   AltName: Full=B lymphocyte adapter protein Bam32;
DE   AltName: Full=B-cell adapter molecule of 32 kDa;
GN   Name=DAPP1; Synonyms=BAM32; ORFNames=HSPC066;
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), TISSUE SPECIFICITY, INTERACTION
RP   WITH PTDINS(3,4,5)P3 AND PTDINS(3,4)P2, AND MUTAGENESIS OF LYS-173 AND
RP   TRP-250.
RX   PubMed=10432293; DOI=10.1042/bj3420007;
RA   Dowler S., Currie R.A., Downes C.P., Alessi D.R.;
RT   "DAPP1: a dual adaptor for phosphotyrosine and 3-phosphoinositides.";
RL   Biochem. J. 342:7-12(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, PHOSPHORYLATION,
RP   SUBCELLULAR LOCATION, INTERACTION WITH PLCG2, AND MUTAGENESIS OF ARG-61;
RP   ARG-184 AND LYS-197.
RX   PubMed=10770799; DOI=10.1084/jem.191.8.1319;
RA   Marshall A.J., Niiro H., Lerner C.G., Yun T.J., Thomas S., Disteche C.M.,
RA   Clark E.A.;
RT   "A novel B lymphocyte-associated adaptor protein, Bam32, regulates antigen
RT   receptor signaling downstream of phosphatidylinositol 3-kinase.";
RL   J. Exp. Med. 191:1319-1332(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Zhang W., Wan T., Cao X.;
RT   "Molecular cloning of a protein-tyrosine phosphatase D.";
RL   Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Umbilical cord blood;
RX   PubMed=11042152; DOI=10.1101/gr.140200;
RA   Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA   Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA   Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT   "Cloning and functional analysis of cDNAs with open reading frames for 300
RT   previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT   cells.";
RL   Genome Res. 10:1546-1560(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Urinary bladder wart;
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 [LARGE SCALE MRNA] OF 216-280 (ISOFORM 1).
RC   TISSUE=Lymph node;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 162-261 IN COMPLEX WITH INOSITOL
RP   1,3,4,5-3 TETRAKISPHOSPHATE, AND X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF
RP   157-262.
RX   PubMed=10983984; DOI=10.1016/s1097-2765(00)00037-x;
RA   Ferguson K.M., Kavran J.M., Sankaran V.G., Fournier E., Isakoff S.J.,
RA   Skolnik E.Y., Lemmon M.A.;
RT   "Structural basis for discrimination of 3-phosphoinositides by pleckstrin
RT   homology domains.";
RL   Mol. Cell 6:373-384(2000).
CC   -!- FUNCTION: May act as a B-cell-associated adapter that regulates B-cell
CC       antigen receptor (BCR)-signaling downstream of PI3K.
CC       {ECO:0000269|PubMed:10770799}.
CC   -!- SUBUNIT: Interacts with PtdIns(3,4,5)P3 and PLCG2. In vitro, interacts
CC       with PtdIns(3,4)P2. {ECO:0000269|PubMed:10432293,
CC       ECO:0000269|PubMed:10770799, ECO:0000269|PubMed:10983984}.
CC   -!- INTERACTION:
CC       Q9UN19; O95704: APBB3; NbExp=2; IntAct=EBI-3918199, EBI-286427;
CC       Q9UN19; Q9NVQ4-2: FAIM; NbExp=3; IntAct=EBI-3918199, EBI-12039347;
CC       Q9UN19; Q16595: FXN; NbExp=6; IntAct=EBI-3918199, EBI-949340;
CC       Q9UN19; P42858: HTT; NbExp=9; IntAct=EBI-3918199, EBI-466029;
CC       Q9UN19; Q99732: LITAF; NbExp=3; IntAct=EBI-3918199, EBI-725647;
CC       Q9UN19; Q8TBZ3: WDR20; NbExp=3; IntAct=EBI-3918199, EBI-2511486;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10770799}. Membrane
CC       {ECO:0000269|PubMed:10770799}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:10770799}. Note=Membrane-associated after cell
CC       stimulation leading to its translocation.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=hBam1;
CC         IsoId=Q9UN19-1; Sequence=Displayed;
CC       Name=2; Synonyms=hBam2;
CC         IsoId=Q9UN19-2; Sequence=VSP_010699;
CC   -!- TISSUE SPECIFICITY: Highly expressed in placenta and lung, followed by
CC       brain, heart, kidney, liver, pancreas and skeletal muscle. Expressed by
CC       B-lymphocytes, but not T-lymphocytes or nonhematopoietic cells.
CC       {ECO:0000269|PubMed:10432293}.
CC   -!- INDUCTION: Upon B-cell activation.
CC   -!- PTM: Phosphorylated on tyrosine residues.
CC       {ECO:0000269|PubMed:10770799}.
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DR   EMBL; AF163254; AAD49697.1; -; mRNA.
DR   EMBL; AF161551; AAF29038.1; -; mRNA.
DR   EMBL; AF186022; AAF14578.1; -; mRNA.
DR   EMBL; AF178987; AAF44351.1; -; mRNA.
DR   EMBL; BC012924; AAH12924.1; -; mRNA.
DR   EMBL; AL713793; CAD28547.1; -; mRNA.
DR   CCDS; CCDS47112.1; -. [Q9UN19-1]
DR   RefSeq; NP_001293080.1; NM_001306151.1.
DR   RefSeq; NP_055210.2; NM_014395.2. [Q9UN19-1]
DR   PDB; 1FAO; X-ray; 1.80 A; A=148-273.
DR   PDB; 1FB8; X-ray; 2.40 A; A=148-273.
DR   PDBsum; 1FAO; -.
DR   PDBsum; 1FB8; -.
DR   AlphaFoldDB; Q9UN19; -.
DR   SMR; Q9UN19; -.
DR   BioGRID; 117981; 25.
DR   IntAct; Q9UN19; 22.
DR   MINT; Q9UN19; -.
DR   STRING; 9606.ENSP00000423602; -.
DR   DrugBank; DB01863; Inositol 1,3,4,5-Tetrakisphosphate.
DR   iPTMnet; Q9UN19; -.
DR   PhosphoSitePlus; Q9UN19; -.
DR   BioMuta; DAPP1; -.
DR   DMDM; 51317293; -.
DR   EPD; Q9UN19; -.
DR   MassIVE; Q9UN19; -.
DR   MaxQB; Q9UN19; -.
DR   PaxDb; 9606-ENSP00000423602; -.
DR   PeptideAtlas; Q9UN19; -.
DR   ProteomicsDB; 85238; -. [Q9UN19-1]
DR   ProteomicsDB; 85239; -. [Q9UN19-2]
DR   Antibodypedia; 25934; 494 antibodies from 37 providers.
DR   DNASU; 27071; -.
DR   Ensembl; ENST00000512369.2; ENSP00000423602.1; ENSG00000070190.13. [Q9UN19-1]
DR   GeneID; 27071; -.
DR   KEGG; hsa:27071; -.
DR   MANE-Select; ENST00000512369.2; ENSP00000423602.1; NM_014395.3; NP_055210.2.
DR   UCSC; uc003hvf.5; human. [Q9UN19-1]
DR   AGR; HGNC:16500; -.
DR   CTD; 27071; -.
DR   DisGeNET; 27071; -.
DR   GeneCards; DAPP1; -.
DR   HGNC; HGNC:16500; DAPP1.
DR   HPA; ENSG00000070190; Tissue enhanced (esophagus, lymphoid tissue).
DR   MIM; 605768; gene.
DR   neXtProt; NX_Q9UN19; -.
DR   OpenTargets; ENSG00000070190; -.
DR   PharmGKB; PA27145; -.
DR   VEuPathDB; HostDB:ENSG00000070190; -.
DR   eggNOG; KOG0017; Eukaryota.
DR   GeneTree; ENSGT00910000144274; -.
DR   HOGENOM; CLU_099070_0_0_1; -.
DR   InParanoid; Q9UN19; -.
DR   OMA; ALGWYHD; -.
DR   OrthoDB; 53565at2759; -.
DR   PhylomeDB; Q9UN19; -.
DR   TreeFam; TF105418; -.
DR   PathwayCommons; Q9UN19; -.
DR   Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR   SignaLink; Q9UN19; -.
DR   SIGNOR; Q9UN19; -.
DR   BioGRID-ORCS; 27071; 5 hits in 1156 CRISPR screens.
DR   EvolutionaryTrace; Q9UN19; -.
DR   GeneWiki; DAPP1; -.
DR   GenomeRNAi; 27071; -.
DR   Pharos; Q9UN19; Tbio.
DR   PRO; PR:Q9UN19; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q9UN19; Protein.
DR   Bgee; ENSG00000070190; Expressed in amniotic fluid and 171 other cell types or tissues.
DR   ExpressionAtlas; Q9UN19; baseline and differential.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR   GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR   GO; GO:0005543; F:phospholipid binding; NAS:UniProtKB.
DR   GO; GO:0006470; P:protein dephosphorylation; NAS:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd10573; PH_DAPP1; 1.
DR   CDD; cd10355; SH2_DAPP1_BAM32_like; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 1.
DR   InterPro; IPR035843; DAPP1_SH2.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR000980; SH2.
DR   InterPro; IPR036860; SH2_dom_sf.
DR   PANTHER; PTHR14336:SF8; DUAL ADAPTER FOR PHOSPHOTYROSINE AND 3-PHOSPHOTYROSINE AND 3-PHOSPHOINOSITIDE; 1.
DR   PANTHER; PTHR14336; TANDEM PH DOMAIN CONTAINING PROTEIN; 1.
DR   Pfam; PF00169; PH; 1.
DR   Pfam; PF00017; SH2; 1.
DR   PRINTS; PR00401; SH2DOMAIN.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00252; SH2; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF55550; SH2 domain; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   PROSITE; PS50001; SH2; 1.
DR   Genevisible; Q9UN19; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Membrane; Phosphoprotein;
KW   Reference proteome; SH2 domain.
FT   CHAIN           1..280
FT                   /note="Dual adapter for phosphotyrosine and 3-
FT                   phosphotyrosine and 3-phosphoinositide"
FT                   /id="PRO_0000079785"
FT   DOMAIN          35..129
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT   DOMAIN          164..259
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT   REGION          1..20
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         139
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QXT1"
FT   MOD_RES         141
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QXT1"
FT   VAR_SEQ         259..280
FT                   /note="SQIRKQLNQGEGTIRSRSFIFK -> VKDKSCILSALCISPEEKTDHK (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10770799"
FT                   /id="VSP_010699"
FT   MUTAGEN         61
FT                   /note="R->K: No change in BCR-induced NFAT activation."
FT                   /evidence="ECO:0000269|PubMed:10770799"
FT   MUTAGEN         173
FT                   /note="K->L: No interaction with 3-phosphoinositides."
FT                   /evidence="ECO:0000269|PubMed:10432293"
FT   MUTAGEN         184
FT                   /note="R->C: No membrane association."
FT                   /evidence="ECO:0000269|PubMed:10770799"
FT   MUTAGEN         197
FT                   /note="K->E: No membrane association."
FT                   /evidence="ECO:0000269|PubMed:10770799"
FT   MUTAGEN         250
FT                   /note="W->L: No interaction with 3-phosphoinositides."
FT                   /evidence="ECO:0000269|PubMed:10432293"
FT   CONFLICT        216..229
FT                   /note="VQFDYSQERVNCFC -> MICNILCSFFCPIS (in Ref. 6)"
FT                   /evidence="ECO:0000305"
FT   STRAND          167..174
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   STRAND          176..178
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   STRAND          181..189
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   STRAND          192..198
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   STRAND          205..209
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   HELIX           210..212
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   STRAND          215..219
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   STRAND          221..232
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   STRAND          235..240
FT                   /evidence="ECO:0007829|PDB:1FAO"
FT   HELIX           244..259
FT                   /evidence="ECO:0007829|PDB:1FAO"
SQ   SEQUENCE   280 AA;  32194 MW;  4A7F686B55146241 CRC64;
     MGRAELLEGK MSTQDPSDLW SRSDGEAELL QDLGWYHGNL TRHAAEALLL SNGCDGSYLL
     RDSNETTGLY SLSVRAKDSV KHFHVEYTGY SFKFGFNEFS SLKDFVKHFA NQPLIGSETG
     TLMVLKHPYP RKVEEPSIYE SVRVHTAMQT GRTEDDLVPT APSLGTKEGY LTKQGGLVKT
     WKTRWFTLHR NELKYFKDQM SPEPIRILDL TECSAVQFDY SQERVNCFCL VFPFRTFYLC
     AKTGVEADEW IKILRWKLSQ IRKQLNQGEG TIRSRSFIFK
//