Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Disabled homolog 2

Gene

Dab2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.12 Publications

GO - Molecular functioni

  • AP-2 adaptor complex binding Source: UniProtKB
  • cargo receptor activity Source: UniProtKB
  • clathrin adaptor activity Source: UniProtKB
  • clathrin binding Source: UniProtKB
  • integrin binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol binding Source: UniProtKB
  • protein C-terminus binding Source: MGI
  • SMAD binding Source: MGI

GO - Biological processi

  • activation of JUN kinase activity Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • cell morphogenesis involved in differentiation Source: MGI
  • cellular response to transforming growth factor beta stimulus Source: UniProtKB
  • clathrin coat assembly Source: UniProtKB
  • endoderm development Source: MGI
  • excretion Source: MGI
  • in utero embryonic development Source: MGI
  • leading edge cell differentiation Source: MGI
  • myeloid cell differentiation Source: UniProtKB
  • negative regulation of androgen receptor signaling pathway Source: MGI
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of protein binding Source: MGI
  • negative regulation of protein localization to plasma membrane Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: MGI
  • pinocytosis Source: MGI
  • positive regulation of cell adhesion Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of clathrin-mediated endocytosis Source: UniProtKB
  • positive regulation of early endosome to late endosome transport Source: MGI
  • positive regulation of endocytosis Source: MGI
  • positive regulation of epithelial to mesenchymal transition Source: UniProtKB
  • positive regulation of integrin-mediated signaling pathway Source: UniProtKB
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: UniProtKB
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of receptor internalization Source: CACAO
  • positive regulation of receptor recycling Source: UniProtKB
  • positive regulation of SMAD protein import into nucleus Source: MGI
  • positive regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription elongation from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of transforming growth factor beta receptor signaling pathway Source: MGI
  • positive regulation of Wnt signaling pathway, planar cell polarity pathway Source: MGI
  • protein transport Source: UniProtKB-KW
  • receptor-mediated endocytosis Source: MGI
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Apoptosis, Differentiation, Endocytosis, Protein transport, Transport, Wnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Disabled homolog 2
Alternative name(s):
Adaptor molecule disabled-2
Differentially expressed in ovarian carcinoma 2
Short name:
DOC-2
Mitogen-responsive phosphoprotein
Gene namesi
Name:Dab2
Synonyms:Doc2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:109175. Dab2.

Subcellular locationi

Isoform p96 :
Isoform p67 :
  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Diffuse localization in the cytoplasm; does not localize to clathrin-coated pits.

GO - Cellular componenti

  • apical plasma membrane Source: MGI
  • clathrin-coated vesicle Source: MGI
  • clathrin-coated vesicle membrane Source: UniProtKB-SubCell
  • clathrin coat of coated pit Source: UniProtKB
  • coated pit Source: MGI
  • cytoplasm Source: MGI
  • extracellular exosome Source: MGI
  • focal adhesion Source: MGI
  • intracellular membrane-bounded organelle Source: MGI
  • nucleolus Source: MGI
  • nucleus Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Coated pit, Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi53 – 531K → A: Abolishes binding to PtdIns(4,5)P2. 2 Publications
Mutagenesisi53 – 531K → Q: Abolishes LDLR endocytosis. 2 Publications
Mutagenesisi90 – 901K → A: Abolishes binding to PtdIns(4,5)P2. 1 Publication
Mutagenesisi122 – 1221S → T: Abolishes LDLR endocytosis. 2 Publications
Mutagenesisi122 – 1221S → Y: Impairs LDLR endocytosis. 2 Publications
Mutagenesisi255 – 2551F → V: Abolishes interaction with ITSN1, fails to internalize integrin beta-1; when associated with V-398, V-589, V-736 and V-765. 1 Publication
Mutagenesisi294 – 2941P → A: Loss of interaction with FCHO2; when associated with A-299. 1 Publication
Mutagenesisi299 – 2991P → A: Loss of interaction with FCHO2; when associated with A-294. 1 Publication
Mutagenesisi398 – 3981F → V: Abolishes interaction with ITSN1, fails to internalize integrin beta-1; when associated with V-255, V-589, V-736 and V-765. 1 Publication
Mutagenesisi589 – 5891F → 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. 1 Publication
Mutagenesisi736 – 7361F → 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. 1 Publication
Mutagenesisi765 – 7651F → 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. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 766765Disabled homolog 2PRO_0000079771Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei2 – 21PhosphoserineBy similarity
Modified residuei170 – 1701PhosphotyrosineCombined sources
Modified residuei193 – 1931PhosphoserineCombined sources
Modified residuei323 – 3231PhosphoserineCombined sources
Modified residuei326 – 3261Phosphoserine; in mitosisBy similarity
Modified residuei328 – 3281Phosphoserine; in mitosisBy similarity
Modified residuei401 – 4011PhosphoserineBy similarity
Modified residuei671 – 6711PhosphothreonineCombined sources
Modified residuei727 – 7271PhosphoserineCombined sources
Modified residuei759 – 7591PhosphoserineCombined sources

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP98078.
PaxDbiP98078.
PRIDEiP98078.

PTM databases

iPTMnetiP98078.
PhosphoSiteiP98078.
SwissPalmiP98078.

Expressioni

Tissue specificityi

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 expressed in embryonic visceral endoderm.1 Publication

Developmental stagei

At E6.5 specifically expressed in the cells of the visceral endoderm.2 Publications

Gene expression databases

BgeeiP98078.
CleanExiMM_DAB2.

Interactioni

Subunit structurei

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.Curated14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
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.

GO - Molecular functioni

  • AP-2 adaptor complex binding Source: UniProtKB
  • clathrin adaptor activity Source: UniProtKB
  • clathrin binding Source: UniProtKB
  • integrin binding Source: UniProtKB
  • protein C-terminus binding Source: MGI
  • SMAD binding Source: MGI

Protein-protein interaction databases

BioGridi199043. 11 interactions.
DIPiDIP-39422N.
IntActiP98078. 52 interactions.
MINTiMINT-259116.
STRINGi10090.ENSMUSP00000079689.

Structurei

Secondary structure

1
766
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi36 – 438Combined sources
Beta strandi48 – 6316Combined sources
Helixi66 – 8419Combined sources
Turni85 – 873Combined sources
Beta strandi91 – 988Combined sources
Beta strandi101 – 1066Combined sources
Turni107 – 1093Combined sources
Beta strandi112 – 1165Combined sources
Helixi118 – 1203Combined sources
Beta strandi121 – 1266Combined sources
Beta strandi133 – 1408Combined sources
Beta strandi144 – 15310Combined sources
Helixi156 – 17722Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M7EX-ray2.45A/B/C33-191[»]
1P3RX-ray2.10A/B/C32-191[»]
ProteinModelPortaliP98078.
SMRiP98078. Positions 33-180, 674-711.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP98078.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini45 – 196152PIDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni230 – 447218Required for localization to clathrin-coated pitsAdd
BLAST
Regioni600 – 730131Sufficient for interaction with GRB2Add
BLAST
Regioni617 – 6259Required for interaction with CSKBy similarity
Regioni647 – 766120Required for interaction with MYO6Add
BLAST
Regioni661 – 6699Required for interaction with GRB2 and CSKBy similarity
Regioni707 – 72317Sufficient for interaction with SH3KBP1 SH3 domainAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi293 – 2953DPF 1
Motifi298 – 3003DPF 2

Domaini

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 (PubMed:11247302, PubMed:12234931).2 Publications
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 ITSN1.1 Publication

Sequence similaritiesi

Contains 1 PID domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3535. Eukaryota.
ENOG410XZ1H. LUCA.
HOGENOMiHOG000060158.
HOVERGENiHBG018945.
InParanoidiP98078.
KOiK12475.
OrthoDBiEOG7HQN7R.
PhylomeDBiP98078.
TreeFamiTF316724.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamiPF00640. PID. 1 hit.
[Graphical view]
SMARTiSM00462. PTB. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS01179. PID. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform p96 (identifier: P98078-1) [UniParc]FASTAAdd to basket

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

        10         20         30         40         50
MSNEVETSTT NGQPDQQAAP KAPSKKEKKK GSEKTDEYLL ARFKGDGVKY
60 70 80 90 100
KAKLIGIDDV PDARGDKMSQ DSMMKLKGMA AAGRSQGQHK QRIWVNISLS
110 120 130 140 150
GIKIIDEKTG VIEHEHPVNK ISFIARDVTD NRAFGYVCGG EGQHQFFAIK
160 170 180 190 200
TGQQAEPLVV DLKDLFQVIY NVKKKEEDKK KVEEANKAEE NGSEALMTLD
210 220 230 240 250
DQANKLKLGV DQMDLFGDMS TPPDLNSPTE SKDILLVDLN SEIDTNQNSL
260 270 280 290 300
RENPFLTNGV TSCSLPRPKP QASFLPENAF SANLNFFPTP NPDPFRDDPF
310 320 330 340 350
AQPDQSAPSS FDSLTSPDQK KASLSSSSTP QSKGPLNGDT DYFGQQFDQL
360 370 380 390 400
SNRTGKPEAQ GGPWPYPSSQ TQQAVRTQNG VSEREQNGFH IKSSPNPFVG
410 420 430 440 450
SPPKGLSVPN GVKQDLESSV QSSAHDSIAI IPPPQSTKPG RGRRTAKSSA
460 470 480 490 500
NDLLASDIFA SEPPGQMSPT GQPAVPQSNF LDLFKGNAPA PVGPLVGLGT
510 520 530 540 550
VPVTPPQAGP WTPVVYSPST TVVPGAIISG QPPSFRQPLV FGTTPAVQVW
560 570 580 590 600
NQSPSFATPA SPPPPTVWCP TTSVAPNAWS STSPLGNPFQ SNNIFPPPTM
610 620 630 640 650
STQSSPQPMM SSVLATPPQP PPRNGPLKDI PSDAFTGLDP LGDKEVKEVK
660 670 680 690 700
EMFKDFQLRQ PPLVPSRKGE TPPSGTSSAF SSYFNNKVGI PQEHVDHDDF
710 720 730 740 750
DANQLLNKIN EPPKPAPRQG VLLGTKSADN SLENPFSKGF SSSNPSVVSQ
760
PASSDPHRSP FGNPFA
Length:766
Mass (Da):82,312
Last modified:January 10, 2006 - v2
Checksum:i856C946BD43C4B07
GO
Isoform p93 (identifier: P98078-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     209-229: Missing.

Show »
Length:745
Mass (Da):80,092
Checksum:iB47489C90FF80532
GO
Isoform p67 (identifier: P98078-3) [UniParc]FASTAAdd to basket

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

Show »
Length:548
Mass (Da):58,822
Checksum:iC21F04C80C860424
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti10 – 101T → A in AAH06588 (PubMed:15489334).Curated
Sequence conflicti224 – 2241D → G in AAH06588 (PubMed:15489334).Curated
Sequence conflicti338 – 3381G → V in AAB02646 (PubMed:7775479).Curated
Sequence conflicti338 – 3381G → V in AAB02645 (PubMed:7775479).Curated
Sequence conflicti454 – 4541L → P in AAB02645 (PubMed:7775479).Curated
Sequence conflicti454 – 4541L → P in AAB02646 (PubMed:7775479).Curated
Sequence conflicti454 – 4541L → P in AAB02647 (PubMed:7775479).Curated
Sequence conflicti454 – 4541L → P in AAG44669 (PubMed:11368898).Curated
Sequence conflicti490 – 4901A → P in AAB02645 (PubMed:7775479).Curated
Sequence conflicti490 – 4901A → P in AAB02646 (PubMed:7775479).Curated
Sequence conflicti490 – 4901A → P in AAB02647 (PubMed:7775479).Curated
Sequence conflicti490 – 4901A → P in AAG44669 (PubMed:11368898).Curated
Sequence conflicti536 – 5361R → G in BAE32784 (PubMed:16141072).Curated
Sequence conflicti536 – 5361R → G in AAH16887 (PubMed:15489334).Curated
Sequence conflicti536 – 5361R → G in AAH06588 (PubMed:15489334).Curated
Sequence conflicti553 – 5531S → P in AAH06588 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei209 – 22921Missing in isoform p93. 1 PublicationVSP_004182Add
BLAST
Alternative sequencei230 – 447218Missing in isoform p67. 2 PublicationsVSP_004183Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS37029.1. [P98078-1]
CCDS37030.1. [P98078-3]
CCDS79357.1. [P98078-2]
RefSeqiNP_001008702.1. NM_001008702.2.
NP_001032994.1. NM_001037905.3.
NP_075607.2. NM_023118.5.
XP_006520023.1. XM_006519960.2.
XP_011243626.1. XM_011245324.1.
UniGeneiMm.240830.

Genome annotation databases

GeneIDi13132.
KEGGimmu:13132.
UCSCiuc007vde.1. mouse. [P98078-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS37029.1. [P98078-1]
CCDS37030.1. [P98078-3]
CCDS79357.1. [P98078-2]
RefSeqiNP_001008702.1. NM_001008702.2.
NP_001032994.1. NM_001037905.3.
NP_075607.2. NM_023118.5.
XP_006520023.1. XM_006519960.2.
XP_011243626.1. XM_011245324.1.
UniGeneiMm.240830.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M7EX-ray2.45A/B/C33-191[»]
1P3RX-ray2.10A/B/C32-191[»]
ProteinModelPortaliP98078.
SMRiP98078. Positions 33-180, 674-711.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199043. 11 interactions.
DIPiDIP-39422N.
IntActiP98078. 52 interactions.
MINTiMINT-259116.
STRINGi10090.ENSMUSP00000079689.

PTM databases

iPTMnetiP98078.
PhosphoSiteiP98078.
SwissPalmiP98078.

Proteomic databases

MaxQBiP98078.
PaxDbiP98078.
PRIDEiP98078.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi13132.
KEGGimmu:13132.
UCSCiuc007vde.1. mouse. [P98078-1]

Organism-specific databases

CTDi1601.
MGIiMGI:109175. Dab2.

Phylogenomic databases

eggNOGiKOG3535. Eukaryota.
ENOG410XZ1H. LUCA.
HOGENOMiHOG000060158.
HOVERGENiHBG018945.
InParanoidiP98078.
KOiK12475.
OrthoDBiEOG7HQN7R.
PhylomeDBiP98078.
TreeFamiTF316724.

Miscellaneous databases

ChiTaRSiDab2. mouse.
EvolutionaryTraceiP98078.
NextBioi283182.
PROiP98078.
SOURCEiSearch...

Gene expression databases

BgeeiP98078.
CleanExiMM_DAB2.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamiPF00640. PID. 1 hit.
[Graphical view]
SMARTiSM00462. PTB. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS01179. PID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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/cJ.
    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.
    , 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. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-170; SER-193; THR-671; SER-727 AND SER-759, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen and Testis.
  26. "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.
  27. "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.
  28. "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.
  29. "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.

Entry informationi

Entry nameiDAB2_MOUSE
AccessioniPrimary (citable) accession number: P98078
Secondary accession number(s): Q3U3K1, Q91W56, Q923E1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 10, 2006
Last modified: May 11, 2016
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.