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Q9UN19

- DAPP1_HUMAN

UniProt

Q9UN19 - DAPP1_HUMAN

Protein

Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide

Gene

DAPP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    Functioni

    May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K.1 Publication

    GO - Molecular functioni

    1. phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
    2. phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
    3. phospholipid binding Source: UniProtKB

    GO - Biological processi

    1. protein dephosphorylation Source: UniProtKB
    2. signal transduction Source: ProtInc

    Enzyme and pathway databases

    ReactomeiREACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    SignaLinkiQ9UN19.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide
    Short name:
    hDAPP1
    Alternative name(s):
    B lymphocyte adapter protein Bam32
    B-cell adapter molecule of 32 kDa
    Gene namesi
    Name:DAPP1
    Synonyms:BAM32
    ORF Names:HSPC066
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:16500. DAPP1.

    Subcellular locationi

    Cytoplasm 1 Publication. Membrane 1 Publication; Peripheral membrane protein 1 Publication
    Note: Membrane-associated after cell stimulation leading to its translocation.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi61 – 611R → K: No change in BCR-induced NFAT activation. 1 Publication
    Mutagenesisi173 – 1731K → L: No interaction with 3-phosphoinositides. 1 Publication
    Mutagenesisi184 – 1841R → C: No membrane association. 1 Publication
    Mutagenesisi197 – 1971K → E: No membrane association. 1 Publication
    Mutagenesisi250 – 2501W → L: No interaction with 3-phosphoinositides. 1 Publication

    Organism-specific databases

    PharmGKBiPA27145.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 280280Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositidePRO_0000079785Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei139 – 1391PhosphotyrosineBy similarity
    Modified residuei141 – 1411PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated on tyrosine residues.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9UN19.
    PaxDbiQ9UN19.
    PRIDEiQ9UN19.

    PTM databases

    PhosphoSiteiQ9UN19.

    Expressioni

    Tissue specificityi

    Highly expressed in placenta and lung, followed by brain, heart, kidney, liver, pancreas and skeletal muscle. Expressed by B-lymphocytes, but not T-lymphocytes or nonhematopoietic cells.1 Publication

    Inductioni

    Upon B-cell activation.

    Gene expression databases

    ArrayExpressiQ9UN19.
    BgeeiQ9UN19.
    CleanExiHS_DAPP1.
    GenevestigatoriQ9UN19.

    Organism-specific databases

    HPAiCAB033822.
    HPA046074.

    Interactioni

    Subunit structurei

    Interacts with PtdIns(3,4,5)P3 and PLCG2. In vitro, interacts with PtdIns(3,4)P2.3 Publications

    Protein-protein interaction databases

    BioGridi117981. 5 interactions.
    IntActiQ9UN19. 7 interactions.
    MINTiMINT-1499560.
    STRINGi9606.ENSP00000296414.

    Structurei

    Secondary structure

    1
    280
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi167 – 1748
    Beta strandi176 – 1783
    Beta strandi181 – 1899
    Beta strandi192 – 1987
    Beta strandi205 – 2095
    Helixi210 – 2123
    Beta strandi215 – 2195
    Beta strandi221 – 23212
    Beta strandi235 – 2406
    Helixi244 – 25916

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FAOX-ray1.80A148-273[»]
    1FB8X-ray2.40A148-273[»]
    ProteinModelPortaliQ9UN19.
    SMRiQ9UN19. Positions 35-128, 157-262.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UN19.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini35 – 12995SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini164 – 25996PHPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 PH domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG145370.
    HOGENOMiHOG000112147.
    HOVERGENiHBG051297.
    InParanoidiQ9UN19.
    KOiK12229.
    OMAiQRNELKY.
    PhylomeDBiQ9UN19.
    TreeFamiTF105418.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProiIPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR000980. SH2.
    [Graphical view]
    PfamiPF00169. PH. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    SMARTiSM00233. PH. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view]
    SUPFAMiSSF55550. SSF55550. 1 hit.
    PROSITEiPS50003. PH_DOMAIN. 1 hit.
    PS50001. SH2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9UN19-1) [UniParc]FASTAAdd to Basket

    Also known as: hBam1

    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

    MGRAELLEGK MSTQDPSDLW SRSDGEAELL QDLGWYHGNL TRHAAEALLL    50
    SNGCDGSYLL RDSNETTGLY SLSVRAKDSV KHFHVEYTGY SFKFGFNEFS 100
    SLKDFVKHFA NQPLIGSETG TLMVLKHPYP RKVEEPSIYE SVRVHTAMQT 150
    GRTEDDLVPT APSLGTKEGY LTKQGGLVKT WKTRWFTLHR NELKYFKDQM 200
    SPEPIRILDL TECSAVQFDY SQERVNCFCL VFPFRTFYLC AKTGVEADEW 250
    IKILRWKLSQ IRKQLNQGEG TIRSRSFIFK 280
    Length:280
    Mass (Da):32,194
    Last modified:May 1, 2000 - v1
    Checksum:i4A7F686B55146241
    GO
    Isoform 2 (identifier: Q9UN19-2) [UniParc]FASTAAdd to Basket

    Also known as: hBam2

    The sequence of this isoform differs from the canonical sequence as follows:
         259-280: SQIRKQLNQGEGTIRSRSFIFK → VKDKSCILSALCISPEEKTDHK

    Show »
    Length:280
    Mass (Da):32,044
    Checksum:i643DF0A3C4FB32DC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti216 – 22914VQFDY…VNCFC → MICNILCSFFCPIS(PubMed:17974005)CuratedAdd
    BLAST

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei259 – 28022SQIRK…SFIFK → VKDKSCILSALCISPEEKTD HK in isoform 2. 1 PublicationVSP_010699Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF163254 mRNA. Translation: AAD49697.1.
    AF161551 mRNA. Translation: AAF29038.1.
    AF186022 mRNA. Translation: AAF14578.1.
    AF178987 mRNA. Translation: AAF44351.1.
    BC012924 mRNA. Translation: AAH12924.1.
    AL713793 mRNA. Translation: CAD28547.1.
    CCDSiCCDS47112.1. [Q9UN19-1]
    RefSeqiNP_055210.2. NM_014395.2. [Q9UN19-1]
    UniGeneiHs.436271.
    Hs.708484.

    Genome annotation databases

    EnsembliENST00000512369; ENSP00000423602; ENSG00000070190. [Q9UN19-1]
    GeneIDi27071.
    KEGGihsa:27071.
    UCSCiuc003hvf.4. human. [Q9UN19-1]

    Polymorphism databases

    DMDMi51317293.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF163254 mRNA. Translation: AAD49697.1 .
    AF161551 mRNA. Translation: AAF29038.1 .
    AF186022 mRNA. Translation: AAF14578.1 .
    AF178987 mRNA. Translation: AAF44351.1 .
    BC012924 mRNA. Translation: AAH12924.1 .
    AL713793 mRNA. Translation: CAD28547.1 .
    CCDSi CCDS47112.1. [Q9UN19-1 ]
    RefSeqi NP_055210.2. NM_014395.2. [Q9UN19-1 ]
    UniGenei Hs.436271.
    Hs.708484.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1FAO X-ray 1.80 A 148-273 [» ]
    1FB8 X-ray 2.40 A 148-273 [» ]
    ProteinModelPortali Q9UN19.
    SMRi Q9UN19. Positions 35-128, 157-262.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117981. 5 interactions.
    IntActi Q9UN19. 7 interactions.
    MINTi MINT-1499560.
    STRINGi 9606.ENSP00000296414.

    PTM databases

    PhosphoSitei Q9UN19.

    Polymorphism databases

    DMDMi 51317293.

    Proteomic databases

    MaxQBi Q9UN19.
    PaxDbi Q9UN19.
    PRIDEi Q9UN19.

    Protocols and materials databases

    DNASUi 27071.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000512369 ; ENSP00000423602 ; ENSG00000070190 . [Q9UN19-1 ]
    GeneIDi 27071.
    KEGGi hsa:27071.
    UCSCi uc003hvf.4. human. [Q9UN19-1 ]

    Organism-specific databases

    CTDi 27071.
    GeneCardsi GC04P100737.
    H-InvDB HIX0004401.
    HGNCi HGNC:16500. DAPP1.
    HPAi CAB033822.
    HPA046074.
    MIMi 605768. gene.
    neXtProti NX_Q9UN19.
    PharmGKBi PA27145.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG145370.
    HOGENOMi HOG000112147.
    HOVERGENi HBG051297.
    InParanoidi Q9UN19.
    KOi K12229.
    OMAi QRNELKY.
    PhylomeDBi Q9UN19.
    TreeFami TF105418.

    Enzyme and pathway databases

    Reactomei REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    SignaLinki Q9UN19.

    Miscellaneous databases

    EvolutionaryTracei Q9UN19.
    GeneWikii DAPP1.
    GenomeRNAii 27071.
    NextBioi 49659.
    PROi Q9UN19.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UN19.
    Bgeei Q9UN19.
    CleanExi HS_DAPP1.
    Genevestigatori Q9UN19.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProi IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR000980. SH2.
    [Graphical view ]
    Pfami PF00169. PH. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    SMARTi SM00233. PH. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55550. SSF55550. 1 hit.
    PROSITEi PS50003. PH_DOMAIN. 1 hit.
    PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "DAPP1: a dual adaptor for phosphotyrosine and 3-phosphoinositides."
      Dowler S., Currie R.A., Downes C.P., Alessi D.R.
      Biochem. J. 342:7-12(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH PTDINS(3,4,5)P3 AND PTDINS(3,4)P2, MUTAGENESIS OF LYS-173 AND TRP-250.
    2. "A novel B lymphocyte-associated adaptor protein, Bam32, regulates antigen receptor signaling downstream of phosphatidylinositol 3-kinase."
      Marshall A.J., Niiro H., Lerner C.G., Yun T.J., Thomas S., Disteche C.M., Clark E.A.
      J. Exp. Med. 191:1319-1332(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH PLCG2, MUTAGENESIS OF ARG-61; ARG-184 AND LYS-197.
    3. "Molecular cloning of a protein-tyrosine phosphatase D."
      Zhang W., Wan T., Cao X.
      Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
      Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X.
      , Gu J., Chen S.-J., Chen Z.
      Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Umbilical cord blood.
    5. "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 1).
      Tissue: Urinary bladder wart.
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 216-280 (ISOFORM 1).
      Tissue: Lymph node.
    7. "Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains."
      Ferguson K.M., Kavran J.M., Sankaran V.G., Fournier E., Isakoff S.J., Skolnik E.Y., Lemmon M.A.
      Mol. Cell 6:373-384(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 162-261 IN COMPLEX WITH INOSITOL 1,3,4,5-3 TETRAKISPHOSPHATE, X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 157-262.

    Entry informationi

    Entry nameiDAPP1_HUMAN
    AccessioniPrimary (citable) accession number: Q9UN19
    Secondary accession number(s): Q8TCK5, Q9UHF2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 5, 2004
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 123 of the entry and version 1 of the sequence. [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 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3