Reviewed, UniProtKB/Swiss-Prot P98082 (DAB2_HUMAN)

Names and origin

Protein names

Recommended name:
    Disabled homolog 2
Alternative name(s):
    Differentially-expressed protein 2
    DOC-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.
Sequence processing	The displayed sequence is not processed.
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.
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.
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.
Sequence similarities	Contains 1 PID domain.

Ontologies

Keywords
Cellular component	Coated pit Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell proliferation Ref.4 Traceable author statement. Source: ProtInc
Cellular component	coated pit Inferred from direct assay. Source: UniProtKB cytoplasmic vesicle Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein C-terminus binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FYN	P06241	1	EBI-1171238,EBI-515315
GRB2	P62993	1	EBI-1171238,EBI-401755
NCK1	P16333	1	EBI-1171238,EBI-389883
PIK3R1	P27986	1	EBI-1171238,EBI-79464

Alternative products

This entry describes 2 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.

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
	Modified residue	170	1	Phosphotyrosine
	Modified residue	221	1	Phosphothreonine
	Modified residue	227	1	Phosphoserine
	Modified residue	342	1	Phosphotyrosine
	Modified residue	393	1	Phosphoserine
	Modified residue	394	1	Phosphoserine
	Modified residue	401	1	Phosphoserine
Natural variations
	Alternative sequence	230 – 447	218	Missing in isoform 2.		VSP_004181
	Natural variant	586	1	T → I: dbSNP rs700241.		VAR_031705
Experimental info
	Mutagenesis	684 – 686	3	SYF → AAA: Greatly reduced binding to MYO6
	Sequence conflict	44 – 47	4	KGDG → PRVC in AAA93195. Ref.8
	Sequence conflict	82	1	A → R in AAC50824 and AAB19032. Ref.1
	Sequence conflict	82	1	A → R in AAF23161. Ref.2
	Sequence conflict	82	1	A → R in AAA98975. Ref.4
	Sequence conflict	82	1	A → R in AAA93195. Ref.8
	Sequence conflict	148	1	A → T in AAA98975. Ref.4
	Sequence conflict	197	1	M → R in AAA98975. Ref.4
	Sequence conflict	209 – 229	21	Missing in AAF05540. Ref.3
	Sequence conflict	230 – 232	3	ESK → VCF in AAF05540. Ref.3
	Sequence conflict	230 – 232	3	ESK → VCF in AAA93195. Ref.6
	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		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

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].
[2]	"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].
[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], TISSUE SPECIFICITY.
[4]	"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], TISSUE SPECIFICITY, ALTERNATIVE SPLICING. Tissue: Ovary.
[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]. 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. 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: Epithelium.
[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: Epithelium.
[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: Epithelium.
[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.
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U39050 mRNA. Translation: AAC50824.1. U41111 Genomic DNA. Translation: AAB19032.1. AF205890 Genomic DNA. Translation: AAF23161.1. AF188298 mRNA. Translation: AAF05540.1. U53446 mRNA. Translation: AAA98975.1. AC008916 Genomic DNA. No translation available. CH471119 Genomic DNA. Translation: EAW55989.1. BC003064 mRNA. Translation: AAH03064.1. L16886 mRNA. Translation: AAA93195.1.
PIR	G02228.
RefSeq	NP_001334.2.
UniGene	Hs.481980
3D structure databases
HSSP	HSSP built from PDB template 1NU2 based on UniProtKB P97318.
SMR	P98082. Positions 33-180.
ModBase	Search...
Protein-protein interaction databases
IntAct	P98082.
PTM databases
PhosphoSite	P98082.
Genome annotation databases
Ensembl	ENSG00000153071. Homo sapiens. [Contig view]
GeneID	1601.
KEGG	hsa:1601.
Organism-specific databases
HGNC	HGNC:2662. DAB2.
HPA	CAB009314.
MIM	601236. gene.
PharmGKB	PA27132.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P98082.
HOVERGEN	P98082.
Enzyme and pathway databases
Reactome	REACT_9480. Gap junction trafficking and regulation.
Gene expression databases
ArrayExpress	P98082.
CleanEx	HS_DAB2.
GermOnline	ENSG00000153071. Homo sapiens.
Family and domain databases
InterPro	IPR011993. PH_type. IPR006020. PTB_PID. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
Pfam	PF00640. PID. 1 hit. [Graphical view]
SMART	SM00462. PTB. 1 hit. [Graphical view]
PROSITE	PS01179. PID. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	November 25, 2008
This is version 84 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)