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P98078 (DAB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Disabled homolog 2
Alternative name(s):
DOC-2
Mitogen-responsive phosphoprotein
Gene names
Name:Dab2
Synonyms:Doc2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length766 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter 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(4,5)P2) and cargos containg 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. Isoform p96 is involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Isoform p67 is not involved in LDL receptor endocytosis. 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. Isoform p67 may be involved in transcriptional regulation. May act as a tumor suppressor. Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.24 Ref.25

Subunit structure

Interacts (via NPXY motif) with DAB2 (via PID domain). Can interact (via PID domain) with LDLR, APP, APLP1 and APLP2, and weakly with INPP5D (via NPXY motifs); the interaction is impaired by tyrosine phosphorylation of the respective NPXY motifs. Can weakly interact (via PID domain) with LRP1 (via NPXY motif); the interaction is enhanced by tyrosine phosphorylation of the NPXY motif. Interacts with LRP2 (via NPXY motif); the interaction is not affected by tyrosine phosphorylation of the NPXY motif. Interacts with clathrin; in vitro can assemble clathrin triskelia into polyhedral coats. Interacts with AP2A2, ITGB1, ITGB3, ITGB5, PIAS2, DAB2IP, NOSTRIN, FCHO1, DVL3 and EPS15L1. Interacts with SH3KBP1 (via SH3 domains). Interacts with GRB2; competes with SOS1 for binding to GRB2 and the interaction is enhanced by EGF and NT-3 stimulation. Isoform p96 interacts with EPS15 and ITSN1; isoform p67 does not interact with EPS15 and only weakly interacts with ITSN1. Interacts with MAP3K7; the interaction is induced by TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation. Interacts with AXIN1 and PPP1CA; the interactions are mutually exclusive. Interacts with the globular tail of MYO6. Interacts (via DPF motifs) with FCHO2; the interaction is direct and required for DAB2-mediated LDLR endocytosis. Interacts with LRP6; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Associates with the TGF-beta receptor complex Probable. Interacts with SMAD2 and SMAD3; the interactions are enhanced upon TGF-beta stimulation. Interacts with GRB2; the interaction is enhanced by EGF and NT-3 stimulation. Interacts with SRC; the interaction is enhanced by EGF stimulation. Ref.5 Ref.6 Ref.7 Ref.8 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.24 Ref.26 Ref.27

Subcellular location

Cytoplasmic vesicleclathrin-coated vesicle membrane. Membraneclathrin-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 By similarity. Ref.6 Ref.7 Ref.12

Isoform p96: Membraneclathrin-coated pit. Note: Colocalizes with LDLR at clathrin-coated pits. Ref.6 Ref.7 Ref.12

Isoform p67: Cytoplasm. Nucleus. Note: Diffuse localization in the cytoplasm; does not localize to clathrin-coated pits. Ref.6 Ref.7 Ref.12

Tissue specificity

Isoform p96 and isoform p67 are expressed in adult kidney and fibroblasts with isoform p96 being the predominant form. Isoform p67 is the predominant isoform expressedin embryonic visceral endoderm. Ref.19

Developmental stage

At E6.5 specifically expressed in the cells of the visceral endoderm. Ref.9 Ref.11

Domain

The PID domain binds to predominantly non-phosphorylated NPXY internalization motifs present in members of the LDLR and APP family; it also mediates simultaneous binding to phosphatidylinositol 4,5-bisphosphate (Ref.7, Ref.12). Ref.7 Ref.12

The Asn-Pro-Phe (NPF) motifs, which are found in proteins involved in the endocytic pathway, mediate the interaction with the EH domain of EPS15, EPS15R and ITSN1 (Ref.27). Ref.7 Ref.12

Post-translational modification

Phosphorylated on serine residues in response to mitogenic growth-factor stimulation. Phosphorylation during mitosis is leading to membrane displacement By similarity.

Disruption phenotype

Embryonic lethal; embryos arrest prior to gastrulation and show lack of endodermal organization, failure to thin the distal tip visceral endoderm (VE), elongate the extra-embryonic portion of the egg cylinder and properly organize the epiblast. Loss of the specific megalin/LRP2 lipoprotein receptor distribution at the brush border at the apical cell edge in presumptive VE cells. Conditionally mutant mice are overtly normal, but have reduced clathrin-coated pits in kidney proximal tubule cells and excrete specific plasma proteins in the urine, consistent with reduced transport by LRP2 in the proximal tubule. Ref.9 Ref.11

Sequence similarities

Contains 1 PID domain.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Endocytosis
Protein transport
Transport
Wnt signaling pathway
   Cellular componentCoated pit
Cytoplasm
Cytoplasmic vesicle
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   Molecular functionDevelopmental protein
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

activation of JUN kinase activity

Inferred from direct assay Ref.18. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell morphogenesis involved in differentiation

Inferred from mutant phenotype Ref.9. Source: MGI

cellular response to transforming growth factor beta stimulus

Inferred from direct assay Ref.17Ref.18. Source: UniProtKB

clathrin coat assembly

Inferred from direct assay Ref.12. Source: UniProtKB

endoderm development

Inferred from mutant phenotype PubMed 22411869. Source: MGI

excretion

Inferred from mutant phenotype Ref.11. Source: MGI

in utero embryonic development

Inferred from mutant phenotype Ref.9. Source: MGI

myeloid cell differentiation

Inferred from expression pattern Ref.10. Source: UniProtKB

negative regulation of androgen receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.17. Source: UniProtKB

negative regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway

Inferred from mutant phenotype Ref.17. Source: MGI

negative regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

pinocytosis

Inferred from mutant phenotype Ref.19. Source: MGI

positive regulation of SMAD protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of Wnt signaling pathway, planar cell polarity pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell adhesion

Inferred from direct assay Ref.10. Source: UniProtKB

positive regulation of cell migration

Inferred from mutant phenotype Ref.18. Source: UniProtKB

positive regulation of clathrin-mediated endocytosis

Inferred from direct assay Ref.21. Source: UniProtKB

positive regulation of early endosome to late endosome transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial to mesenchymal transition

Inferred from mutant phenotype Ref.17. Source: UniProtKB

positive regulation of integrin-mediated signaling pathway

Inferred from mutant phenotype Ref.17. Source: UniProtKB

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from mutant phenotype Ref.25. Source: UniProtKB

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of receptor recycling

Inferred from mutant phenotype Ref.25. Source: UniProtKB

positive regulation of substrate adhesion-dependent cell spreading

Inferred from direct assay Ref.10. Source: UniProtKB

positive regulation of transcription elongation from RNA polymerase II promoter

Inferred from mutant phenotype Ref.18. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

positive regulation of transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 21146513. Source: MGI

clathrin coat of coated pit

Inferred from direct assay Ref.7. Source: UniProtKB

clathrin-coated vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay Ref.6. Source: MGI

nucleus

Inferred from direct assay Ref.6. Source: MGI

plasma membrane

Inferred from direct assay PubMed 21146513. Source: MGI

transforming growth factor beta receptor homodimeric complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionAP-2 adaptor complex binding

Inferred from direct assay Ref.12. Source: UniProtKB

cargo receptor activity

Inferred from direct assay Ref.21. Source: UniProtKB

clathrin adaptor activity

Inferred from direct assay Ref.21. Source: UniProtKB

clathrin binding

Inferred from direct assay Ref.12. Source: UniProtKB

integrin binding

Inferred from mutant phenotype Ref.17. Source: UniProtKB

phosphatidylinositol binding

Inferred from direct assay Ref.12. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from direct assay Ref.28. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AP2A2O949732EBI-1391846,EBI-1642835From a different organism.
Axin1O356254EBI-1391846,EBI-2365912
DVL3Q929972EBI-1391846,EBI-739789From a different organism.
Eps15P425672EBI-1391846,EBI-443923
Eps15l1Q609022EBI-1391846,EBI-443931
FCHO2Q0JRZ94EBI-1391846,EBI-2609756From a different organism.
GRB2P629934EBI-1391846,EBI-401755From a different organism.
Grb2Q606314EBI-1391846,EBI-1688
MYO6Q9I8D12EBI-1391846,EBI-6307292From a different organism.
MYO6Q9UM544EBI-1391846,EBI-350606From a different organism.
Necap1Q9CR952EBI-1391846,EBI-7592476
NostrinQ6WKZ72EBI-1391846,EBI-1391878
Pias2Q8C5D83EBI-6305891,EBI-6305825
SH3KBP1Q96B979EBI-1391846,EBI-346595From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform p96 (identifier: P98078-1)

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 p93 (identifier: P98078-2)

The sequence of this isoform differs from the canonical sequence as follows:
     209-229: Missing.
Isoform p67 (identifier: P98078-3)

The sequence of this isoform differs from the canonical sequence as follows:
     230-447: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 766765Disabled homolog 2
PRO_0000079771

Regions

Domain45 – 196152PID
Region230 – 447218Required for localization to clathrin-coated pits
Region600 – 730131Sufficient for interaction with GRB2
Region617 – 6259Required for interaction with CSK By similarity
Region647 – 766120Required for interaction with MYO6
Region661 – 6699Required for interaction with GRB2 and CSK By similarity
Region707 – 72317Sufficient for interaction with SH3KBP1 SH3 domain
Motif293 – 2953DPF 1
Motif298 – 3003DPF 2

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue3231Phosphoserine Ref.23
Modified residue3261Phosphoserine; in mitosis By similarity
Modified residue3281Phosphoserine; in mitosis By similarity
Modified residue4011Phosphoserine By similarity
Modified residue7271Phosphoserine Ref.23

Natural variations

Alternative sequence209 – 22921Missing in isoform p93.
VSP_004182
Alternative sequence230 – 447218Missing in isoform p67.
VSP_004183

Experimental info

Mutagenesis531K → A: Abolishes binding to PtdIns(4,5)P2. Ref.21 Ref.28
Mutagenesis531K → Q: Abolishes LDLR endocytosis. Ref.21 Ref.28
Mutagenesis901K → A: Abolishes binding to PtdIns(4,5)P2. Ref.28
Mutagenesis1221S → T: Abolishes LDLR endocytosis. Ref.21 Ref.22
Mutagenesis1221S → Y: Impairs LDLR endocytosis. Ref.21 Ref.22
Mutagenesis2551F → V: Abolishes interaction with ITSN1, fails to internalize integrin beta-1; when associated with V-398, V-589, V-736 and V-765. Ref.27
Mutagenesis2941P → A: Loss of interaction with FCHO2; when associated with A-299. Ref.26
Mutagenesis2991P → A: Loss of interaction with FCHO2; when associated with A-294. Ref.26
Mutagenesis3981F → V: Abolishes interaction with ITSN1, fails to internalize integrin beta-1; when associated with V-255, V-589, V-736 and V-765. Ref.27
Mutagenesis5891F → V: Abolishes interaction with EPS15 and impairs interaction with ITSN1, fails to internalize integrin beta-1; when associated with V-736 and V-765. Abolishes interaction with ITSN1; when associated with V-255, V-398, V-736 and V-765. Ref.27
Mutagenesis7361F → V: Abolishes interaction with EPS15 and impairs interaction with ITSN1, fails to internalize integrin beta-1; when associated with V-589 and V-765. Abolishes interaction with ITSN1; when associated with V-255, V-398, V-589, and V-765. Ref.27
Mutagenesis7651F → V: Abolishes interaction with EPS15 and impairs interaction with ITSN1, fails to internalize integrin beta-1; when associated with V-589 and V-736. Abolishes interaction with ITSN1; when associated with V-255, V-398, V-589 and V-736. Ref.27
Sequence conflict101T → A in AAH06588. Ref.4
Sequence conflict2241D → G in AAH06588. Ref.4
Sequence conflict3381G → V in AAB02646. Ref.1
Sequence conflict3381G → V in AAB02645. Ref.1
Sequence conflict4541L → P in AAB02645. Ref.1
Sequence conflict4541L → P in AAB02646. Ref.1
Sequence conflict4541L → P in AAB02647. Ref.1
Sequence conflict4541L → P in AAG44669. Ref.2
Sequence conflict4901A → P in AAB02645. Ref.1
Sequence conflict4901A → P in AAB02646. Ref.1
Sequence conflict4901A → P in AAB02647. Ref.1
Sequence conflict4901A → P in AAG44669. Ref.2
Sequence conflict5361R → G in BAE32784. Ref.3
Sequence conflict5361R → G in AAH16887. Ref.4
Sequence conflict5361R → G in AAH06588. Ref.4
Sequence conflict5531S → P in AAH06588. Ref.4

Secondary structure

........................ 766
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform p96 [UniParc].

Last modified January 10, 2006. Version 2.
Checksum: 856C946BD43C4B07

FASTA76682,312
        10         20         30         40         50         60 
MSNEVETSTT NGQPDQQAAP KAPSKKEKKK GSEKTDEYLL ARFKGDGVKY KAKLIGIDDV 

        70         80         90        100        110        120 
PDARGDKMSQ DSMMKLKGMA AAGRSQGQHK QRIWVNISLS GIKIIDEKTG VIEHEHPVNK 

       130        140        150        160        170        180 
ISFIARDVTD NRAFGYVCGG EGQHQFFAIK TGQQAEPLVV DLKDLFQVIY NVKKKEEDKK 

       190        200        210        220        230        240 
KVEEANKAEE NGSEALMTLD DQANKLKLGV DQMDLFGDMS TPPDLNSPTE SKDILLVDLN 

       250        260        270        280        290        300 
SEIDTNQNSL RENPFLTNGV TSCSLPRPKP QASFLPENAF SANLNFFPTP NPDPFRDDPF 

       310        320        330        340        350        360 
AQPDQSAPSS FDSLTSPDQK KASLSSSSTP QSKGPLNGDT DYFGQQFDQL SNRTGKPEAQ 

       370        380        390        400        410        420 
GGPWPYPSSQ TQQAVRTQNG VSEREQNGFH IKSSPNPFVG SPPKGLSVPN GVKQDLESSV 

       430        440        450        460        470        480 
QSSAHDSIAI IPPPQSTKPG RGRRTAKSSA NDLLASDIFA SEPPGQMSPT GQPAVPQSNF 

       490        500        510        520        530        540 
LDLFKGNAPA PVGPLVGLGT VPVTPPQAGP WTPVVYSPST TVVPGAIISG QPPSFRQPLV 

       550        560        570        580        590        600 
FGTTPAVQVW NQSPSFATPA SPPPPTVWCP TTSVAPNAWS STSPLGNPFQ SNNIFPPPTM 

       610        620        630        640        650        660 
STQSSPQPMM SSVLATPPQP PPRNGPLKDI PSDAFTGLDP LGDKEVKEVK EMFKDFQLRQ 

       670        680        690        700        710        720 
PPLVPSRKGE TPPSGTSSAF SSYFNNKVGI PQEHVDHDDF DANQLLNKIN EPPKPAPRQG 

       730        740        750        760 
VLLGTKSADN SLENPFSKGF SSSNPSVVSQ PASSDPHRSP FGNPFA 

« Hide

Isoform p93 [UniParc].

Checksum: B47489C90FF80532
Show »

FASTA74580,092
Isoform p67 [UniParc].

Checksum: C21F04C80C860424
Show »

FASTA54858,822

References

« Hide 'large scale' references
[1]"Cloning of a novel phosphoprotein regulated by colony-stimulating factor 1 shares a domain with the Drosophila disabled gene product."
Xu X.-X., Yang W., Jackowski S., Rock C.O.
J. Biol. Chem. 270:14184-14191(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS P67; P93 AND P96).
Strain: BALB/c.
Tissue: Macrophage.
[2]"Chromosomal location of murine disabled-2 gene and structural comparison with its human ortholog."
Sheng Z., Smith E.R., He J., Tuppen J.A., Martin W.D., Dong F.B., Xu X.X.
Gene 268:31-39(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM P96).
Strain: 129/Sv.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P96).
Strain: NOD.
Tissue: Dendritic cell.
[4]"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 P67).
Tissue: Kidney.
[5]"Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2."
Xu X.X., Yi T., Tang B., Lambeth J.D.
Oncogene 16:1561-1569(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB2.
[6]"p67 isoform of mouse disabled 2 protein acts as a transcriptional activator during the differentiation of F9 cells."
Cho S.-Y., Jeon J.W., Lee S.H., Park S.-S.
Biochem. J. 352:645-650(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION (ISOFORM P67), SUBCELLULAR LOCATION (ISOFORM P67), INTERACTION WITH PIAS2.
[7]"Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2."
Morris S.M., Cooper J.A.
Traffic 2:111-123(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LDLR; APP; APLP; APLP2; INPP5D; LRP1 AND AP2A2, DOMAIN.
[8]"DOC-2/DAB2 is the binding partner of myosin VI."
Inoue A., Sato O., Homma K., Ikebe M.
Biochem. Biophys. Res. Commun. 292:300-307(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYO6.
[9]"Disabled-2 is essential for endodermal cell positioning and structure formation during mouse embryogenesis."
Yang D.H., Smith E.R., Roland I.H., Sheng Z., He J., Martin W.D., Hamilton T.C., Lambeth J.D., Xu X.X.
Dev. Biol. 251:27-44(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
[10]"Disabled-2 is transcriptionally regulated by ICSBP and augments macrophage spreading and adhesion."
Rosenbauer F., Kallies A., Scheller M., Knobeloch K.P., Rock C.O., Schwieger M., Stocking C., Horak I.
EMBO J. 21:211-220(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport."
Morris S.M., Tallquist M.D., Rock C.O., Cooper J.A.
EMBO J. 21:1555-1564(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
[12]"Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor."
Mishra S.K., Keyel P.A., Hawryluk M.J., Agostinelli N.R., Watkins S.C., Traub L.M.
EMBO J. 21:4915-4926(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CLATHRIN AND PHOSPHATIDYLINOSITIDES, DOMAIN.
[13]"Interaction of Disabled-1 and the GTPase activating protein Dab2IP in mouse brain."
Homayouni R., Magdaleno S., Keshvara L., Rice D.S., Curran T.
Brain Res. Mol. Brain Res. 115:121-129(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2IP.
[14]"Dab2 links CIN85 with clathrin-mediated receptor internalization."
Kowanetz K., Terzic J., Dikic I.
FEBS Lett. 554:81-87(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SH3KBP1.
[15]"Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling."
Calderwood D.A., Fujioka Y., de Pereda J.M., Garcia-Alvarez B., Nakamoto T., Margolis B., McGlade C.J., Liddington R.C., Ginsberg M.H.
Proc. Natl. Acad. Sci. U.S.A. 100:2272-2277(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGB3 AND ITGB5.
[16]"Cloning and characterization of mouse disabled 2-interacting protein 2, a mouse orthologue of human NOSTRIN."
Choi Y.-J., Cho S.-Y., Kim H.-W., Kim J.-A., Bae S.-H., Park S.-S.
Biochem. Biophys. Res. Commun. 326:594-599(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NOSTRIN.
[17]"Disabled-2 (Dab2) is required for transforming growth factor beta-induced epithelial to mesenchymal transition (EMT)."
Prunier C., Howe P.H.
J. Biol. Chem. 280:17540-17548(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ITGB1.
[18]"Disabled-2 (Dab2) mediates transforming growth factor beta (TGFbeta)-stimulated fibronectin synthesis through TGFbeta-activated kinase 1 and activation of the JNK pathway."
Hocevar B.A., Prunier C., Howe P.H.
J. Biol. Chem. 280:25920-25927(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP3K7.
[19]"Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein."
Maurer M.E., Cooper J.A.
J. Cell Sci. 118:5345-5355(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[20]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH."
Maurer M.E., Cooper J.A.
J. Cell Sci. 119:4235-4246(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-53 AND SER-122.
[22]"A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors."
Keyel P.A., Mishra S.K., Roth R., Heuser J.E., Watkins S.C., Traub L.M.
Mol. Biol. Cell 17:4300-4317(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-122.
[23]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323 AND SER-727, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"Dab2 stabilizes Axin and attenuates Wnt/beta-catenin signaling by preventing protein phosphatase 1 (PP1)-Axin interactions."
Jiang Y., Luo W., Howe P.H.
Oncogene 28:2999-3007(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AXIN1 AND PPP1CA.
[25]"Type II transforming growth factor-beta receptor recycling is dependent upon the clathrin adaptor protein Dab2."
Penheiter S.G., Singh R.D., Repellin C.E., Wilkes M.C., Edens M., Howe P.H., Pagano R.E., Leof E.B.
Mol. Biol. Cell 21:4009-4019(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[26]"FCH domain only-2 organizes clathrin-coated structures and interacts with Disabled-2 for low-density lipoprotein receptor endocytosis."
Mulkearns E.E., Cooper J.A.
Mol. Biol. Cell 23:1330-1342(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCHO2, MUTAGENESIS OF PRO-294 AND PRO-299.
[27]"The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin beta1 endocytosis."
Teckchandani A., Mulkearns E.E., Randolph T.W., Toida N., Cooper J.A.
Mol. Biol. Cell 23:2905-2916(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPS15, EPS15L1 AND ITSN1, MUTAGENESIS OF PHE-255; PHE-398; PHE-589; PHE-736 AND PHE-765.
[28]"Crystal structures of the Dab homology domains of mouse disabled 1 and 2."
Yun M., Keshvara L., Park C.G., Zhang Y.M., Dickerson J.B., Zheng J., Rock C.O., Curran T., Park H.W.
J. Biol. Chem. 278:36572-36581(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 33-191, MUTAGENESIS OF LYS-53 AND LYS-90.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U18869 mRNA. Translation: AAB02646.1.
U18869 mRNA. Translation: AAB02647.1.
U18869 mRNA. Translation: AAB02645.1.
AF260580 Genomic DNA. Translation: AAG44669.1.
AK154716 mRNA. Translation: BAE32784.1.
BC016887 mRNA. Translation: AAH16887.1.
BC006588 mRNA. Translation: AAH06588.1.
RefSeqNP_001008702.1. NM_001008702.2.
NP_001032994.1. NM_001037905.3.
NP_075607.2. NM_023118.5.
XP_006520023.1. XM_006519960.1.
UniGeneMm.240830.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M7EX-ray2.45A/B/C33-191[»]
1P3RX-ray2.10A/B/C33-191[»]
ProteinModelPortalP98078.
SMRP98078. Positions 33-180, 674-711.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199043. 10 interactions.
IntActP98078. 52 interactions.
MINTMINT-259116.

PTM databases

PhosphoSiteP98078.

Proteomic databases

PaxDbP98078.
PRIDEP98078.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000080880; ENSMUSP00000079689; ENSMUSG00000022150.
GeneID13132.
KEGGmmu:13132.
UCSCuc007vde.1. mouse. [P98078-1]

Organism-specific databases

CTD1601.
MGIMGI:109175. Dab2.

Phylogenomic databases

eggNOGNOG328122.
GeneTreeENSGT00520000055585.
HOGENOMHOG000060158.
HOVERGENHBG018945.
InParanoidP98078.
KOK12475.
OrthoDBEOG7HQN7R.
PhylomeDBP98078.
TreeFamTF316724.

Gene expression databases

ArrayExpressP98078.
BgeeP98078.
CleanExMM_DAB2.
GenevestigatorP98078.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR028761. Dab.
IPR011993. PH_like_dom.
IPR006020. PTB/PI_dom.
[Graphical view]
PANTHERPTHR11232:SF1. PTHR11232:SF1. 1 hit.
PfamPF00640. PID. 1 hit.
[Graphical view]
SMARTSM00462. PTB. 1 hit.
[Graphical view]
PROSITEPS01179. PID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP98078.
NextBio283182.
PROP98078.
SOURCESearch...

Entry information

Entry nameDAB2_MOUSE
AccessionPrimary (citable) accession number: P98078
Secondary accession number(s): Q3U3K1, Q91W56, Q923E1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 10, 2006
Last modified: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot