Q9UN19 (DAPP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	DAPP1
Synonyms:	BAM32
ORF Names:	HSPC066

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	280 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K. Ref.2
Subunit structure	Interacts with PtdIns(3,4,5)P3 and PLCG2. In vitro, interacts with PtdIns(3,4)P2. Ref.1 Ref.2
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Note: Membrane-associated after cell stimulation leading to its translocation. Ref.2
Tissue specificity	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. Ref.1
Induction	Upon B-cell activation.
Post-translational modification	Phosphorylated on tyrosine residues. Ref.2
Sequence similarities	Contains 1 PH domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay PubMed 17823121. Source: UniProtKB
Molecular_function	phosphatidylinositol-3,4,5-trisphosphate binding Inferred from direct assay PubMed 11001876. Source: UniProtKB phosphatidylinositol-3,4-bisphosphate binding Inferred from direct assay PubMed 17823121. Source: UniProtKB protein tyrosine phosphatase activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UN19-1)

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.

Isoform 2 (identifier: Q9UN19-2)

Also known as: hBam2;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 280

280

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

PRO_0000079785

Regions

Domain

35 – 129

95

SH2

Domain

164 – 259

96

PH

Amino acid modifications

Modified residue

139

1

Phosphotyrosine By similarity

Modified residue

141

1

Phosphoserine By similarity

Natural variations

Alternative sequence

259 – 280

22

SQIRK…SFIFK → VKDKSCILSALCISPEEKTD HK in isoform 2.

VSP_010699

Experimental info

Mutagenesis

61

1

R → K: No change in BCR-induced NFAT activation. Ref.2

Mutagenesis

173

1

K → L: No interaction with 3-phosphoinositides. Ref.1

Mutagenesis

184

1

R → C: No membrane association. Ref.2

Mutagenesis

197

1

K → E: No membrane association. Ref.2

Mutagenesis

250

1

W → L: No interaction with 3-phosphoinositides. Ref.1

Sequence conflict

216 – 229

14

VQFDY…VNCFC → MICNILCSFFCPIS Ref.6

Secondary structure

1

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280

Helix Strand Turn

Details...

Beta strand

167 – 174

8

Beta strand

176 – 178

3

Beta strand

181 – 189

9

Beta strand

192 – 198

7

Beta strand

205 – 209

5

Helix

210 – 212

3

Beta strand

215 – 219

5

Beta strand

221 – 232

12

Beta strand

235 – 240

6

Helix

244 – 259

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (hBam1) [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 4A7F686B55146241	FASTA	280	32,194
	10 20 30 40 50 60 MGRAELLEGK MSTQDPSDLW SRSDGEAELL QDLGWYHGNL TRHAAEALLL SNGCDGSYLL 70 80 90 100 110 120 RDSNETTGLY SLSVRAKDSV KHFHVEYTGY SFKFGFNEFS SLKDFVKHFA NQPLIGSETG 130 140 150 160 170 180 TLMVLKHPYP RKVEEPSIYE SVRVHTAMQT GRTEDDLVPT APSLGTKEGY LTKQGGLVKT 190 200 210 220 230 240 WKTRWFTLHR NELKYFKDQM SPEPIRILDL TECSAVQFDY SQERVNCFCL VFPFRTFYLC 250 260 270 280 AKTGVEADEW IKILRWKLSQ IRKQLNQGEG TIRSRSFIFK
	Isoform 2 (hBam2) [UniParc]. Checksum: 643DF0A3C4FB32DC	FASTA	280	32,044
	10 20 30 40 50 60 MGRAELLEGK MSTQDPSDLW SRSDGEAELL QDLGWYHGNL TRHAAEALLL SNGCDGSYLL 70 80 90 100 110 120 RDSNETTGLY SLSVRAKDSV KHFHVEYTGY SFKFGFNEFS SLKDFVKHFA NQPLIGSETG 130 140 150 160 170 180 TLMVLKHPYP RKVEEPSIYE SVRVHTAMQT GRTEDDLVPT APSLGTKEGY LTKQGGLVKT 190 200 210 220 230 240 WKTRWFTLHR NELKYFKDQM SPEPIRILDL TECSAVQFDY SQERVNCFCL VFPFRTFYLC 250 260 270 280 AKTGVEADEW IKILRWKLVK DKSCILSALC ISPEEKTDHK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"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] 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00004301.
IPI00384620.

RefSeq

NP_055210.2. NM_014395.2.

UniGene

Hs.436271.
Hs.708484.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FAO	X-ray	1.80	A	148-273	[»]
1FB8	X-ray	2.40	A	148-273	[»]

ProteinModelPortal

Q9UN19.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UN19. 4 interactions.

MINT

MINT-1499560.

STRING

9606.ENSP00000296414.

PTM databases

PhosphoSite

Q9UN19.

Polymorphism databases

DMDM

51317293.

Proteomic databases

PaxDb

Q9UN19.

PRIDE

Q9UN19.

Protocols and materials databases

DNASU

27071.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000512369; ENSP00000423602; ENSG00000070190.

GeneID

27071.

KEGG

hsa:27071.

UCSC

uc003hvf.4. human.
uc010ilh.3. human.

Organism-specific databases

CTD

27071.

GeneCards

GC04P100737.

H-InvDB

HIX0004401.

HGNC

HGNC:16500. DAPP1.

HPA

CAB033822.

MIM

605768. gene.

neXtProt

NX_Q9UN19.

PharmGKB

PA27145.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG145370.

HOGENOM

HOG000112147.

HOVERGEN

HBG051297.

InParanoid

Q9UN19.

KO

K12229.

OMA

REGTIRS.

OrthoDB

EOG4K9BD5.

PhylomeDB

Q9UN19.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.
pi3kcipathway. Class I PI3K signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

Q9UN19.

CleanEx

HS_DAPP1.

Genevestigator

Q9UN19.

GermOnline

ENSG00000070190. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.
3.30.505.10. 1 hit.

InterPro

IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000980. SH2.
[Graphical view]

Pfam

PF00169. PH. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.

SMART

SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]

PROSITE

PS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UN19.

GenomeRNAi

27071.

NextBio

49659.

SOURCE

Search...

Entry information

Entry name

DAPP1_HUMAN

Accession

Primary (citable) accession number: Q9UN19
Secondary accession number(s): Q8TCK5, Q9UHF2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2004
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 110 of the entry and version 1 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.