Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0004462
UniProt IDP98082
Primary gene name(s)DAB2
Synonym gene name(s)DOC2
Protein nameDisabled homolog 2
Protein functionAdapter protein that functions as clathrin-associated sorting protein, CLASP required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate, PtdIns(4,5P2 and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1, PP1. Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr-419'. Proposed to be involved in modulation of androgen receptor, AR signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm, VE during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor. {ECO:0000269|PubMed:11387212, ECO:0000269|PubMed:12805222, ECO:0000269|PubMed:16267015, ECO:0000269|PubMed:16984970, ECO:0000269|PubMed:19306879, ECO:0000269|PubMed:21995445, ECO:0000269|PubMed:22323290, ECO:0000269|PubMed:22491013}.
Subcellular locationCytoplasm. Cytoplasmic vesicle, clathrin-coated vesicle membrane. Membrane, clathrin-coated pit. Note=Colocalizes with large insert-containing isoforms of MYO6 at clathrin-coated pits/vesicles. During mitosis is progressively displaced from the membrane and translocated to the cytoplasm.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P98082
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
cell proliferation [GO:0008283];
leading edge cell differentiation [GO:0035026];
multicellular organism development [GO:0007275];
negative regulation of androgen receptor signaling pathway [GO:0060766];
negative regulation of apoptotic process [GO:0043066];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
negative regulation of protein binding [GO:0032091];
negative regulation of protein localization to plasma membrane [GO:1903077];
negative regulation of transcription, DNA-templated [GO:0045892];
positive regulation of cell migration [GO:0030335];
positive regulation of clathrin-dependent endocytosis [GO:2000370];
positive regulation of early endosome to late endosome transport [GO:2000643];
positive regulation of endocytosis [GO:0045807];
positive regulation of epithelial to mesenchymal transition [GO:0010718];
positive regulation of pathway-restricted SMAD protein phosphorylation [GO:0010862];
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of SMAD protein import into nucleus [GO:0060391];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transforming growth factor beta receptor signaling pathway [GO:0030511];
positive regulation of Wnt signaling pathway, planar cell polarity pathway [GO:2000096];
protein transport [GO:0015031];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
cargo receptor activity [GO:0038024];
clathrin adaptor activity [GO:0035615];
protein C-terminus binding [GO:0008022];
SMAD binding [GO:0046332]
Gene Ontology
(Cellular Component)
Complete annatation
clathrin-coated vesicle [GO:0030136];
clathrin-coated vesicle membrane [GO:0030665];
coated pit [GO:0005905];
extracellular exosome [GO:0070062];
focal adhesion [GO:0005925];
intracellular membrane-bounded organelle [GO:0043231];
lysosomal membrane [GO:0005765];
nucleolus [GO:0005730];
plasma membrane [GO:0005886]
Protein-protein interaction107971
Phylogenetic treeP98082
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3unknownunknownunknown
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3unknownunknownunknown
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activationunknownunknownunknown
HIV vs. Mock in Latency-0.2705938560044340.5842902091259260.999834320637052
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD3unknownunknownunknown
SAHA vs. IL7unknownunknownunknown
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 1.39337 0.000580925
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.87 1.257 0.854 0.987 0.905
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2LSW NMR - A=24-58.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Nef requires 25496667

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04144 Endocytosis - Homo sapiens (human)
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