P98082 (DAB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Disabled homolog 2

Alternative name(s):
DOC-2
Differentially-expressed protein 2

Gene names

Name:	DAB2
Synonyms:	DOC2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	770 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the CSF-1 signal transduction pathway By similarity.
Subunit structure	Interacts with the globular tail of MYO6. Interacts with DAB2IP. Interacts with NOSTRIN By similarity. Ref.9
Subcellular location	Cytoplasmic vesicle › clathrin-coated vesicle membrane. Membrane › clathrin-coated pit. Note: Colocalizes with large insert-containing isoforms of MYO6 at clathrin-coated pits/vesicles. Ref.9
Tissue specificity	Expressed in deep invaginations, inclusion cysts and the surface epithelial cells of the ovary. Also expressed in breast epithelial cells, spleen, thymus, prostate, testis, macrophages, fibroblasts, lung epithelial cells, placenta, brain stem, heart and small intestine. Ref.2 Ref.3
Sequence similarities	Contains 1 PID domain.

Ontologies

Keywords
Cellular component	Coated pit Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell proliferation Traceable author statement. Source: ProtInc negative regulation of canonical Wnt receptor signaling pathway Inferred from mutant phenotype. Source: BHF-UCL negative regulation of protein binding Inferred from mutant phenotype. Source: BHF-UCL negative regulation of transcription, DNA-dependent Inferred from mutant phenotype. Source: BHF-UCL positive regulation of Wnt receptor signaling pathway, planar cell polarity pathway Inferred from mutant phenotype. Source: BHF-UCL positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype. Source: BHF-UCL positive regulation of protein phosphorylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	clathrin coated vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell coated pit Inferred from direct assay. Source: UniProtKB
Molecular function	protein C-terminus binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	2	EBI-1171238,EBI-401755
NCK1	P16333	2	EBI-1171238,EBI-389883

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P98082-1)

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 2 (identifier: P98082-2)

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

Isoform 3 (identifier: P98082-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 770	770	Disabled homolog 2		PRO_0000079770
Regions
	Domain	45 – 196	152	PID
	Region	649 – 770	122	Required for interaction with MYO6 By similarity
Amino acid modifications
	Modified residue	151	1	Phosphothreonine Ref.13
	Modified residue	170	1	Phosphotyrosine Ref.13
	Modified residue	221	1	Phosphothreonine Ref.10
	Modified residue	227	1	Phosphoserine Ref.10
	Modified residue	342	1	Phosphotyrosine Ref.11
	Modified residue	393	1	Phosphoserine Ref.11 Ref.12
	Modified residue	394	1	Phosphoserine Ref.11 Ref.12 Ref.14
	Modified residue	401	1	Phosphoserine Ref.10 Ref.12 Ref.13 Ref.14
	Modified residue	729	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	209 – 229	21	Missing in isoform 3.		VSP_038401
	Alternative sequence	230 – 447	218	Missing in isoform 2.		VSP_004181
	Natural variant	586	1	T → I. Corresponds to variant rs700241 [ dbSNP | Ensembl ].		VAR_031705
	Natural variant	634	1	S → N. Corresponds to variant rs3733801 [ dbSNP | Ensembl ].		VAR_050942
Experimental info
	Mutagenesis	684 – 686	3	SYF → AAA: Greatly reduced binding to MYO6. Ref.9
	Sequence conflict	44 – 47	4	KGDG → PRVC in AAA93195. Ref.8
	Sequence conflict	82	1	A → R in AAC50824. Ref.1
	Sequence conflict	82	1	A → R in AAB19032. Ref.1
	Sequence conflict	82	1	A → R in AAA98975. Ref.2
	Sequence conflict	82	1	A → R in AAF23161. Ref.4
	Sequence conflict	82	1	A → R in AAA93195. Ref.8
	Sequence conflict	148	1	A → T in AAA98975. Ref.2
	Sequence conflict	197	1	M → R in AAA98975. Ref.2
	Sequence conflict	230 – 232	3	ESK → VCF in AAF05540. Ref.3
	Sequence conflict	230 – 232	3	ESK → VCF in AAA93195. Ref.8
	Sequence conflict	275	1	L → S in AAC50824. Ref.1
	Sequence conflict	302 – 304	3	QPD → HTR in AAA93195. Ref.8
	Sequence conflict	498	1	L → Q in AAF05540. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 17, 2007. Version 3. Checksum: 5B2F8B510A580A77	FASTA	770	82,448
	10 20 30 40 50 60 MSNEVETSAT NGQPDQQAAP KAPSKKEKKK GPEKTDEYLL 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 NVKKKEEEKK 190 200 210 220 230 240 KIEEASKAVE NGSEALMILD DQTNKLKSGV DQMDLFGDMS TPPDLNSPTE SKDILLVDLN 250 260 270 280 290 300 SEIDTNQNSL RENPFLTNGI TSCSLPRPTP QASFLPENAF SANLNFFPTP NPDPFRDDPF 310 320 330 340 350 360 TQPDQSTPSS FDSLKSPDQK KENSSSSSTP LSNGPLNGDV DYFGQQFDQI SNRTGKQEAQ 370 380 390 400 410 420 AGPWPFSSSQ TQPAVRTQNG VSEREQNGFS VKSSPNPFVG SPPKGLSIQN GVKQDLESSV 430 440 450 460 470 480 QSSPHDSIAI IPPPQSTKPG RGRRTAKSSA NDLLASDIFA PPVSEPSGQA SPTGQPTALQ 490 500 510 520 530 540 PNPLDLFKTS APAPVGPLVG LGGVTVTLPQ AGPWNTASLV FNQSPSMAPG AMMGGQPSGF 550 560 570 580 590 600 SQPVIFGTSP AVSGWNQPSP FAASTPPPVP VVWGPSASVA PNAWSTTSPL GNPFQSNIFP 610 620 630 640 650 660 APAVSTQPPS MHSSLLVTPP QPPPRAGPPK DISSDAFTAL DPLGDKEIKD VKEMFKDFQL 670 680 690 700 710 720 RQPPAVPARK GEQTSSGTLS AFASYFNSKV GIPQENADHD DFDANQLLNK INEPPKPAPR 730 740 750 760 770 QVSLPVTKST DNAFENPFFK DSFGSSQASV ASSQPVSSEM YRDPFGNPFA
	Isoform 2 [UniParc]. Checksum: 2F25868284E3757F	FASTA	552	58,861
	10 20 30 40 50 60 MSNEVETSAT NGQPDQQAAP KAPSKKEKKK GPEKTDEYLL 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 NVKKKEEEKK 190 200 210 220 230 240 KIEEASKAVE NGSEALMILD DQTNKLKSGV DQMDLFGDMS TPPDLNSPTS SANDLLASDI 250 260 270 280 290 300 FAPPVSEPSG QASPTGQPTA LQPNPLDLFK TSAPAPVGPL VGLGGVTVTL PQAGPWNTAS 310 320 330 340 350 360 LVFNQSPSMA PGAMMGGQPS GFSQPVIFGT SPAVSGWNQP SPFAASTPPP VPVVWGPSAS 370 380 390 400 410 420 VAPNAWSTTS PLGNPFQSNI FPAPAVSTQP PSMHSSLLVT PPQPPPRAGP PKDISSDAFT 430 440 450 460 470 480 ALDPLGDKEI KDVKEMFKDF QLRQPPAVPA RKGEQTSSGT LSAFASYFNS KVGIPQENAD 490 500 510 520 530 540 HDDFDANQLL NKINEPPKPA PRQVSLPVTK STDNAFENPF FKDSFGSSQA SVASSQPVSS 550 EMYRDPFGNP FA
	Isoform 3 [UniParc]. Checksum: D52B66BB7CA45240	FASTA	749	80,228
	10 20 30 40 50 60 MSNEVETSAT NGQPDQQAAP KAPSKKEKKK GPEKTDEYLL 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 NVKKKEEEKK 190 200 210 220 230 240 KIEEASKAVE NGSEALMILD DQTNKLKSES KDILLVDLNS EIDTNQNSLR ENPFLTNGIT 250 260 270 280 290 300 SCSLPRPTPQ ASFLPENAFS ANLNFFPTPN PDPFRDDPFT QPDQSTPSSF DSLKSPDQKK 310 320 330 340 350 360 ENSSSSSTPL SNGPLNGDVD YFGQQFDQIS NRTGKQEAQA GPWPFSSSQT QPAVRTQNGV 370 380 390 400 410 420 SEREQNGFSV KSSPNPFVGS PPKGLSIQNG VKQDLESSVQ SSPHDSIAII PPPQSTKPGR 430 440 450 460 470 480 GRRTAKSSAN DLLASDIFAP PVSEPSGQAS PTGQPTALQP NPLDLFKTSA PAPVGPLVGL 490 500 510 520 530 540 GGVTVTLPQA GPWNTASLVF NQSPSMAPGA MMGGQPSGFS QPVIFGTSPA VSGWNQPSPF 550 560 570 580 590 600 AASTPPPVPV VWGPSASVAP NAWSTTSPLG NPFQSNIFPA PAVSTQPPSM HSSLLVTPPQ 610 620 630 640 650 660 PPPRAGPPKD ISSDAFTALD PLGDKEIKDV KEMFKDFQLR QPPAVPARKG EQTSSGTLSA 670 680 690 700 710 720 FASYFNSKVG IPQENADHDD FDANQLLNKI NEPPKPAPRQ VSLPVTKSTD NAFENPFFKD 730 740 SFGSSQASVA SSQPVSSEMY RDPFGNPFA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence, genomic structure, and chromosomal assignment of human DOC-2." Albertsen H.M., Smith S.A., Melis R., Williams B., Holik P., Stevens J., White R. Genomics 33:207-213(1996) [PubMed: 8660969] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]	"DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer." Mok S.C., Chan W.Y., Wong K.-K., Cheung K.K., Lau C.C., Ng S.W., Baldini A., Colitti C.V., Rock C.O., Berkowitz R.S. Oncogene 16:2381-2387(1998) [PubMed: 9620555] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, ALTERNATIVE SPLICING. Tissue: Ovary.
[3]	"Disabled-2 inactivation is an early step in ovarian tumorigenicity." Fazili Z., Sun W., Mittelstaedt S., Cohen C., Xu X.-X. Oncogene 18:3104-3113(1999) [PubMed: 10340382] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
[4]	"Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2)." Sheng Z., He J., Tuppen J.A., Sun W., Fazili Z., Smith E.R., Dong F.B., Xu X.-X. Genomics 70:381-386(2000) [PubMed: 11161789] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 3).
[5]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[8]	"Molecular cloning of differentially expressed genes in human epithelial ovarian cancer." Mok S.C., Wong K.-K., Chan R.K.W., Lau C.C., Tsao S.-W., Knapp R.C., Berkowitz R.S. Gynecol. Oncol. 52:247-252(1994) [PubMed: 8314147] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 44-304 (ISOFORM 1). Tissue: Ovary.
[9]	"Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton." Morris S.M., Arden S.D., Roberts R.C., Kendrick-Jones J., Cooper J.A., Luzio J.P., Buss F. Traffic 3:331-341(2002) [PubMed: 11967127] [Abstract] Cited for: INTERACTION WITH MYO6, SUBCELLULAR LOCATION, MUTAGENESIS OF 684-SER--PHE-686.
[10]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-221; SER-227 AND SER-401, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-342; SER-393 AND SER-394, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393; SER-394 AND SER-401, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-151; TYR-170 AND SER-401, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394 AND SER-401, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U39050 mRNA. Translation: AAC50824.1. U41111 Genomic DNA. Translation: AAB19032.1. U53446 mRNA. Translation: AAA98975.1. AF188298 mRNA. Translation: AAF05540.1. AF205890 Genomic DNA. Translation: AAF23161.1. AC008916 Genomic DNA. No translation available. CH471119 Genomic DNA. Translation: EAW55989.1. BC003064 mRNA. Translation: AAH03064.1. L16886 mRNA. Translation: AAA93195.1.
IPI	IPI00179438. IPI00219298. IPI00954039.
PIR	G02228.
RefSeq	NP_001231800.1. NM_001244871.1. NP_001334.2. NM_001343.3.
UniGene	Hs.481980.
3D structure databases
ProteinModelPortal	P98082.
SMR	P98082. Positions 33-172, 676-713.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-45617N.
IntAct	P98082. 8 interactions.
MINT	MINT-5006053.
STRING	P98082.
PTM databases
PhosphoSite	P98082.
Polymorphism databases
DMDM	145559465.
Proteomic databases
PRIDE	P98082.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320816; ENSP00000313391; ENSG00000153071.
GeneID	1601.
KEGG	hsa:1601.
UCSC	uc003jlw.2. human.
Organism-specific databases
CTD	1601.
GeneCards	GC05M039408.
H-InvDB	HIX0004830.
HGNC	HGNC:2662. DAB2.
HPA	CAB009314.
MIM	601236. gene.
neXtProt	NX_P98082.
PharmGKB	PA27132.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11040.
GeneTree	ENSGT00520000055585.
HOGENOM	HBG755336.
HOVERGEN	HBG018945.
InParanoid	P98082.
OMA	IPQENAD.
OrthoDB	EOG4S1T6R.
PhylomeDB	P98082.
Enzyme and pathway databases
Pathway_Interaction_DB	tgfbrpathway. TGF-beta receptor signaling.
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	P98082.
Bgee	P98082.
CleanEx	HS_DAB2.
Genevestigator	P98082.
GermOnline	ENSG00000153071. Homo sapiens.
Family and domain databases
InterPro	IPR011993. PH_type. IPR006020. PTyr_interaction_dom. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
KO	K12475.
Pfam	PF00640. PID. 1 hit. [Graphical view]
SMART	SM00462. PTB. 1 hit. [Graphical view]
PROSITE	PS01179. PID. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	6566.
SOURCE	Search...

Entry information

Entry name

DAB2_HUMAN

Accession

Primary (citable) accession number: P98082
Secondary accession number(s): A6NES5 , Q13598, Q9BTY0, Q9UK04

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	April 17, 2007
Last modified:	December 14, 2011
This is version 112 of the entry and version 3 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.