DAPP1_HUMAN
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 03-AUG-2022, entry version 173.
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; Q9UN19; -.
DR PeptideAtlas; Q9UN19; -.
DR PRIDE; Q9UN19; -.
DR ProteomicsDB; 85238; -. [Q9UN19-1]
DR ProteomicsDB; 85239; -. [Q9UN19-2]
DR Antibodypedia; 25934; 445 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 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; ILRWKMS; -.
DR OrthoDB; 1061200at2759; -.
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 1076 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 170 other tissues.
DR ExpressionAtlas; Q9UN19; baseline and differential.
DR Genevisible; Q9UN19; HS.
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; cd10355; SH2_DAPP1_BAM32_like; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 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 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; SSF55550; SSF55550; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50001; SH2; 1.
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
