Reviewed, UniProtKB/Swiss-Prot Q8IZD9 (DOCK3_HUMAN)

Names and origin

Protein names

Recommended name:
    Dedicator of cytokinesis protein 3
Alternative name(s):
    Modifier of cell adhesion
    Presenilin-binding protein
      Short name=PBP

Gene names

Name:	DOCK3
Synonyms:	KIAA0299, MOCA

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	2030 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Potential guanine nucleotide exchange factor (GEF). GEF proteins activate some small GTPases by exchanging bound GDP for free GTP. Its interaction with presenilin proteins as well as its ability to stimulate Tau/MAPT phosphorylation suggest that it may be involved in Alzheimer disease. Ectopic expression in nerve cells decreases the secretion of beta-amyloid APBA1 protein and lowers the rate of cell-substratum adhesion, suggesting that it may affect the function of some small GTPase involved in the regulation of actin cytoskeleton or cell adhesion receptors By similarity.
Subunit structure	Interacts with presenilin proteins PSEN1 and PSEN2. Interacts with CRK By similarity.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	In normal brains, it is localized in the neuropil, and occasionally in the pyramidal cells, while in Alzheimer disease brains, it is associated with neurofibrillary tangles. Ref.4
Domain	The DHR-2 domain may mediate some GEF activity By similarity.
Involvement in disease	A chromosomal aberration involving DOCK3 may be a cause of early-onset behavioral/developmental disorder with features of attention deficit-hyperactivity disorder and intellectual disability (ADHD) [MIM:143465]. Inversion inv3(p14:q21). The inversion disrupts DOCK3 and SLC9A9. Ref.2
Sequence similarities	Belongs to the DOCK family. Contains 1 DHR-1 (CZH-1) domain. Contains 1 DHR-2 (CZH-2) domain. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Chromosomal rearrangement
Domain	SH3 domain SH3-binding
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	GTP binding Inferred from electronic annotation. Source: InterPro GTPase binding Inferred from electronic annotation. Source: InterPro SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-1752361,EBI-375543
CRK	P46108	1	EBI-1752361,EBI-886
FYN	P06241	1	EBI-1752361,EBI-515315
GRB2	P62993	1	EBI-1752361,EBI-401755
NCK1	P16333	1	EBI-1752361,EBI-389883
PIK3R1	P27986	1	EBI-1752361,EBI-79464
SRC	P12931	1	EBI-1752361,EBI-621482

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2030	2030	Dedicator of cytokinesis protein 3		PRO_0000189988
Regions
	Domain	6 – 67	62	SH3
	Domain	418 – 654	237	DHR-1
	Domain	1122 – 1630	509	DHR-2
	Motif	1970 – 1976	7	SH3-binding Potential
	Compositional bias	1731 – 1768	38	Ser-rich
Amino acid modifications
	Modified residue	2013	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q8IZD9-1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: FF87E874B926C1C7	FASTA	2,030	233,103
	10 20 30 40 50 60 MWTPTEEEKY GVVICSFRGS VPQGLVLEIG ETVQILEKCE GWYRGVSTKK PNVKGIFPAN 70 80 90 100 110 120 YIHLKKAIVS NRGQYETVVP LEDSIVTEVT ATLQEWASLW KQLYVKHKVD LFYKLRHVMN 130 140 150 160 170 180 ELIDLRRQLL SGHLTQDQVR EVKRHITVRL DWGNEHLGLD LVPRKDFEVV DSDQISVSDL 190 200 210 220 230 240 YKMHLSSRQS VQQSTSQVDT MRPRHGETCR MPVPHHFFLS LKSFTYNTIG EDTDVFFSLY 250 260 270 280 290 300 DMREGKQISE RFLVRLNKNG GPRNPEKIER MCALFTDLSS KDMKRDLYIV AHVIRIGRML 310 320 330 340 350 360 LNDSKKGPPH LHYRRPYGCA VLSILDVLQS LTEVKEEKDF VLKVYTCNNE SEWSQIHENI 370 380 390 400 410 420 IRKSSAKYSA PSASHGLIIS LQLLRGDMEQ IRRENPMIFN RGLAITRKLG FPDVIMPGDI 430 440 450 460 470 480 RNDLYLTLEK GDFERGGKSV QKNIEVTMYV LYADGEILKD CISLGSGEPN RSSYHSFVLY 490 500 510 520 530 540 HSNSPRWGEI IKLPIPIDRF RGSHLRFEFR HCSTKDKGEK KLFGFAFSTL MRDDGTTLSD 550 560 570 580 590 600 DIHELYVYKC DENSTFNNHA LYLGLPCCKE DYNGCPNIPS SLIFQRSTKE SFFISTQLSS 610 620 630 640 650 660 TKLTQNVDLL ALLKWKAFPD RIMDVLGRLR HVSGEEIVKF LQDILDTLFV ILDDNTEKYG 670 680 690 700 710 720 LLVFQSLVFI INLLRDIKYF HFRPVMDTYI QKHFAGALAY KELIRCLKWY MDCSAELIRQ 730 740 750 760 770 780 DHIQEAMRAL EYLFKFIVQS RILYSRATCG MEEEQFRSSI QELFQSIRFV LSLDSRNSET 790 800 810 820 830 840 LLFTQAALLN SFPTIFDELL QMFTVQEVAE FVRGTLGSMP STVHIGQSMD VVKLQSIART 850 860 870 880 890 900 VDSRLFSFSE SRRILLPVVL HHIHLHLRQQ KELLICSGIL GSIFSIVKTS SLEADVMEEV 910 920 930 940 950 960 EMMVESLLDV LLQTLLTIMS KSHAQEAVRG QRCPQCTAEI TGEYVSCLLS LLRQMCDTHF 970 980 990 1000 1010 1020 QHLLDNFQSK DELKEFLLKI FCVFRNLMKM SVFPRDWMVM RLLTSNIIVT TVQYLSSALH 1030 1040 1050 1060 1070 1080 KNFTETDFDF KVWNSYFSLA VLFINQPSLQ LEIITSAKRK KILDKYGDMR VMMAYELFSM 1090 1100 1110 1120 1130 1140 WQNLGEHKIH FIPGMIGPFL GVTLVPQPEV RNIMIPIFHD MMDWEQRKNG NFKQVEAELI 1150 1160 1170 1180 1190 1200 DKLDSMVSEG KGDESYRELF SLLTQLFGPY PSLLEKVEQE TWRETGISFV TSVTRLMERL 1210 1220 1230 1240 1250 1260 LDYRDCMKGE ETENKKIGCT VNLMNFYKSE INKEEMYIRY IHKLCDMHLQ AENYTEAAFT 1270 1280 1290 1300 1310 1320 LLLYCELLQW EDRPLREFLH YPSQTEWQRK EGLCRKIIHY FNKGKSWEFG IPLCRELACQ 1330 1340 1350 1360 1370 1380 YESLYDYQSL SWIRKMEASY YDNIMEQQRL EPEFFRVGFY GRKFPFFLRN KEYVCRGHDY 1390 1400 1410 1420 1430 1440 ERLEAFQQRM LSEFPQAVAM QHPNHPDDAI LQCDAQYLQI YAVTPIPDYV DVLQMDRVPD 1450 1460 1470 1480 1490 1500 RVKSFYRVNN VRKFRYDRPF HKGPKDKENE FKSLWIERTT LTLTHSLPGI SRWFEVERRE 1510 1520 1530 1540 1550 1560 LVEVSPLENA IQVVENKNQE LRSLISQYQH KQVHGNINLL SMCLNGVIDA AVNGGIARYQ 1570 1580 1590 1600 1610 1620 EAFFDKDYIN KHPGDAEKIT QLKELMQEQV HVLGVGLAVH EKFVHPEMRP LHKKLIDQFQ 1630 1640 1650 1660 1670 1680 MMRASLYHEF PGLDKLSPAC SGTSTPRGNV LASHSPMSPE SIKMTHRHSP MNLMGTGRHS 1690 1700 1710 1720 1730 1740 SSSLSSHASS EAGNMVMLGD GSMGDAPEDL YHHMQLAYPN PRYQGSVTNV SVLSSSQASP 1750 1760 1770 1780 1790 1800 SSSSLSSTHS APSQMITSAP SSARGSPSLP DKYRHAREMM LLLPTYRDRP SSAMYPAAIL 1810 1820 1830 1840 1850 1860 ENGQPPNFQR ALFQQVVGAC KPCSDPNLSV AEKGHYSLHF DAFHHPLGDT PPALPARTLR 1870 1880 1890 1900 1910 1920 KSPLHPIPAS PTSPQSGLDG SNSTLSGSAS SGVSSLSESN FGHSSEAPPR TDTMDSMPSQ 1930 1940 1950 1960 1970 1980 AWNADEDLEP PYLPVHYSLS ESAVLDSIKA QPCRSHSAPG CVIPQDPMDP PALPPKPYHP 1990 2000 2010 2020 2030 RLPALEHDEG VLLREETERP RGLHRKAPLP PGSAKEEQAR MAWEHGRGEQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of novel presenilin binding protein." Kashiwa A., Yoshida H., Lee S., Paladino T., Liu Y., Chen Q., Dargusch R., Schubert D., Kimura H. J. Neurochem. 75:109-116(2000) [PubMed: 10854253] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is associated with an attention deficit hyperactivity disorder-like phenotype." De Silva M.G., Elliott K., Dahl H.-H.M., Fitzpatrick E., Wilcox S., Delatycki M., Williamson R., Efron D., Lynch M., Forrest S. J. Med. Genet. 40:733-740(2003) [PubMed: 14569117] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISEASE.
[3]	"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed: 9205841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 124-2030. Tissue: Brain.
[4]	"Presenilin binding protein is associated with neurofibrillary alterations in Alzheimer's disease and stimulates tau phosphorylation." Chen Q., Yoshida H., Schubert D., Maher P., Mallory M., Masliah E. Am. J. Pathol. 159:1597-1602(2001) [PubMed: 11696419] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity." Cote J.-F., Vuori K. J. Cell Sci. 115:4901-4913(2002) [PubMed: 12432077] [Abstract] Cited for: NOMENCLATURE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY145303 mRNA. Translation: AAN12301.1. AY254099 mRNA. Translation: AAP80572.1. AB002297 mRNA. Translation: BAA20759.1.
IPI	IPI00217985.
RefSeq	NP_004938.1.
UniGene	Hs.476284
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IZD9. 8 interactions.
STRING	Q8IZD9.
Proteomic databases
PRIDE	Q8IZD9.
Genome annotation databases
Ensembl	ENST00000266037; ENSP00000266037; ENSG00000088538; Homo sapiens. [Genome view] ENST00000402669; ENSP00000385673; ENSG00000088538; Homo sapiens. [Genome view]
GeneID	1795.
KEGG	hsa:1795.
Organism-specific databases
CTD	1795.
GeneCards	GC03P050687.
H-InvDB	HIX0003327.
HGNC	HGNC:2989. DOCK3.
MIM	143465. phenotype. 603123. gene.
PharmGKB	PA27455.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q8IZD9.
HOVERGEN	Q8IZD9.
Gene expression databases
ArrayExpress	Q8IZD9.
Bgee	Q8IZD9.
CleanEx	HS_DOCK3.
Genevestigator	Q8IZD9.
Family and domain databases
InterPro	IPR010703. DOCK. IPR011511. SH3_2. IPR001452. SH3_domain. [Graphical view]
Pfam	PF06920. Ded_cyto. 1 hit. PF07653. SH3_2. 1 hit. [Graphical view]
ProDom	PD000066. SH3. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00326. SH3. 1 hit. [Graphical view]
PROSITE	PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	7313.
SOURCE	Search...

Entry information

Entry name

DOCK3_HUMAN

Accession

Primary (citable) accession number: Q8IZD9
Secondary accession number(s): O15017

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 3, 2003
Last sequence update:	March 1, 2003
Last modified:	October 13, 2009
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.