UniProtKB - Q8IZD9 (DOCK3_HUMAN)
Protein
Dedicator of cytokinesis protein 3
Gene
DOCK3
Organism
Homo sapiens (Human)
Status
Functioni
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 amyloid-beta 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).By similarity
GO - Molecular functioni
- Rac guanyl-nucleotide exchange factor activity Source: Reactome
- SH3 domain binding Source: UniProtKB-KW
GO - Biological processi
- positive regulation of non-membrane spanning protein tyrosine kinase activity Source: Reactome
- small GTPase mediated signal transduction Source: InterPro
Keywordsi
Molecular function | Guanine-nucleotide releasing factor |
Enzyme and pathway databases
PathwayCommonsi | Q8IZD9 |
Reactomei | R-HSA-9032759, NTRK2 activates RAC1 R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
SIGNORi | Q8IZD9 |
Names & Taxonomyi
Protein namesi | Recommended name: Dedicator of cytokinesis protein 3Alternative name(s): Modifier of cell adhesion Presenilin-binding protein Short name: PBP |
Gene namesi | Name:DOCK3 Synonyms:KIAA0299, MOCA |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2989, DOCK3 |
MIMi | 603123, gene |
neXtProti | NX_Q8IZD9 |
VEuPathDBi | HostDB:ENSG00000088538.12 |
Subcellular locationi
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
A chromosomal aberration involving DOCK3 has been found in a family with early-onset behavioral/developmental disorder with features of attention deficit-hyperactivity disorder and intellectual disability. Inversion inv(3)(p14:q21). The inversion disrupts DOCK3 and SLC9A9.1 Publication
Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia (NEDIDHA)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disease characterized by global developmental delay, hypotonia, ataxic gait, hyporeflexia, poor or absent speech, and variable and mild dysmorphic features.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081831 | 128 – 2030 | Missing in NEDIDHA. 1 PublicationAdd BLAST | 1903 | |
Natural variantiVAR_081832 | 392 | R → Q in NEDIDHA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199600118Ensembl. | 1 | |
Natural variantiVAR_081833 | 1296 | K → R in NEDIDHA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201184598Ensembl. | 1 | |
Natural variantiVAR_081834 | 1674 | M → L in NEDIDHA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs142515812EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 1795 |
MalaCardsi | DOCK3 |
MIMi | 618292, phenotype |
OpenTargetsi | ENSG00000088538 |
Orphaneti | 528084, Non-specific syndromic intellectual disability |
PharmGKBi | PA27455 |
Miscellaneous databases
Pharosi | Q8IZD9, Tbio |
Genetic variation databases
BioMutai | DOCK3 |
DMDMi | 32469734 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000189988 | 1 – 2030 | Dedicator of cytokinesis protein 3Add BLAST | 2030 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1658 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
MassIVEi | Q8IZD9 |
MaxQBi | Q8IZD9 |
PaxDbi | Q8IZD9 |
PeptideAtlasi | Q8IZD9 |
PRIDEi | Q8IZD9 |
ProteomicsDBi | 71332 |
PTM databases
iPTMneti | Q8IZD9 |
PhosphoSitePlusi | Q8IZD9 |
Expressioni
Tissue specificityi
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.1 Publication
Gene expression databases
Bgeei | ENSG00000088538, Expressed in frontal pole and 157 other tissues |
Genevisiblei | Q8IZD9, HS |
Organism-specific databases
HPAi | ENSG00000088538, Tissue enhanced (brain) |
Interactioni
Subunit structurei
Interacts with presenilin proteins PSEN1 and PSEN2.
Interacts with CRK (By similarity).
By similarityBinary interactionsi
Hide detailsQ8IZD9
With | #Exp. | IntAct |
---|---|---|
ARHGAP5 - isoform 1 [Q13017-1] | 2 | EBI-1752361,EBI-25409992 |
HOXA1 [P49639] | 3 | EBI-1752361,EBI-740785 |
NCK1 [P16333] | 3 | EBI-1752361,EBI-389883 |
PLEKHF2 [Q9H8W4] | 3 | EBI-1752361,EBI-742388 |
GO - Molecular functioni
- Rac guanyl-nucleotide exchange factor activity Source: Reactome
- SH3 domain binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 108130, 11 interactors |
IntActi | Q8IZD9, 36 interactors |
STRINGi | 9606.ENSP00000266037 |
Miscellaneous databases
RNActi | Q8IZD9, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 6 – 67 | SH3PROSITE-ProRule annotationAdd BLAST | 62 | |
Domaini | 421 – 599 | C2 DOCK-typePROSITE-ProRule annotationAdd BLAST | 179 | |
Domaini | 1228 – 1635 | DOCKERPROSITE-ProRule annotationAdd BLAST | 408 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 1970 – 1976 | SH3-bindingSequence analysis | 7 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1731 – 1768 | Ser-richAdd BLAST | 38 |
Domaini
The DOCKER domain may mediate some GEF activity.By similarity
Sequence similaritiesi
Belongs to the DOCK family.PROSITE-ProRule annotation
Keywords - Domaini
SH3 domain, SH3-bindingPhylogenomic databases
eggNOGi | KOG1998, Eukaryota |
GeneTreei | ENSGT00940000155514 |
HOGENOMi | CLU_000595_2_0_1 |
InParanoidi | Q8IZD9 |
OMAi | SMHFDAF |
PhylomeDBi | Q8IZD9 |
TreeFami | TF300423 |
Family and domain databases
CDDi | cd08695, C2_Dock-B, 1 hit cd12048, SH3_DOCK3_B, 1 hit |
Gene3Di | 1.20.1270.350, 1 hit 1.20.58.740, 1 hit 1.25.40.410, 1 hit 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR016024, ARM-type_fold IPR037811, C2_Dock-B IPR035892, C2_domain_sf IPR027007, DHR-1_domain IPR027357, DHR-2 IPR026791, DOCK IPR026800, DOCK3 IPR035767, DOCK3_SH3 IPR010703, DOCK_C IPR043161, DOCK_C_lobe_A IPR043162, DOCK_C_lobe_C IPR032376, DOCK_N IPR042455, DOCK_N_sub1 IPR036028, SH3-like_dom_sf IPR001452, SH3_domain |
PANTHERi | PTHR45653, PTHR45653, 1 hit PTHR45653:SF4, PTHR45653:SF4, 1 hit |
Pfami | View protein in Pfam PF06920, DHR-2, 1 hit PF14429, DOCK-C2, 1 hit PF16172, DOCK_N, 1 hit PF07653, SH3_2, 1 hit |
SMARTi | View protein in SMART SM00326, SH3, 1 hit |
SUPFAMi | SSF48371, SSF48371, 1 hit SSF50044, SSF50044, 1 hit |
PROSITEi | View protein in PROSITE PS51650, C2_DOCK, 1 hit PS51651, DOCKER, 1 hit PS50002, SH3, 1 hit |
i Sequence
Sequence statusi: Complete.
Q8IZD9-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MWTPTEEEKY GVVICSFRGS VPQGLVLEIG ETVQILEKCE GWYRGVSTKK
60 70 80 90 100
PNVKGIFPAN YIHLKKAIVS NRGQYETVVP LEDSIVTEVT ATLQEWASLW
110 120 130 140 150
KQLYVKHKVD LFYKLRHVMN ELIDLRRQLL SGHLTQDQVR EVKRHITVRL
160 170 180 190 200
DWGNEHLGLD LVPRKDFEVV DSDQISVSDL YKMHLSSRQS VQQSTSQVDT
210 220 230 240 250
MRPRHGETCR MPVPHHFFLS LKSFTYNTIG EDTDVFFSLY DMREGKQISE
260 270 280 290 300
RFLVRLNKNG GPRNPEKIER MCALFTDLSS KDMKRDLYIV AHVIRIGRML
310 320 330 340 350
LNDSKKGPPH LHYRRPYGCA VLSILDVLQS LTEVKEEKDF VLKVYTCNNE
360 370 380 390 400
SEWSQIHENI IRKSSAKYSA PSASHGLIIS LQLLRGDMEQ IRRENPMIFN
410 420 430 440 450
RGLAITRKLG FPDVIMPGDI RNDLYLTLEK GDFERGGKSV QKNIEVTMYV
460 470 480 490 500
LYADGEILKD CISLGSGEPN RSSYHSFVLY HSNSPRWGEI IKLPIPIDRF
510 520 530 540 550
RGSHLRFEFR HCSTKDKGEK KLFGFAFSTL MRDDGTTLSD DIHELYVYKC
560 570 580 590 600
DENSTFNNHA LYLGLPCCKE DYNGCPNIPS SLIFQRSTKE SFFISTQLSS
610 620 630 640 650
TKLTQNVDLL ALLKWKAFPD RIMDVLGRLR HVSGEEIVKF LQDILDTLFV
660 670 680 690 700
ILDDNTEKYG LLVFQSLVFI INLLRDIKYF HFRPVMDTYI QKHFAGALAY
710 720 730 740 750
KELIRCLKWY MDCSAELIRQ DHIQEAMRAL EYLFKFIVQS RILYSRATCG
760 770 780 790 800
MEEEQFRSSI QELFQSIRFV LSLDSRNSET LLFTQAALLN SFPTIFDELL
810 820 830 840 850
QMFTVQEVAE FVRGTLGSMP STVHIGQSMD VVKLQSIART VDSRLFSFSE
860 870 880 890 900
SRRILLPVVL HHIHLHLRQQ KELLICSGIL GSIFSIVKTS SLEADVMEEV
910 920 930 940 950
EMMVESLLDV LLQTLLTIMS KSHAQEAVRG QRCPQCTAEI TGEYVSCLLS
960 970 980 990 1000
LLRQMCDTHF QHLLDNFQSK DELKEFLLKI FCVFRNLMKM SVFPRDWMVM
1010 1020 1030 1040 1050
RLLTSNIIVT TVQYLSSALH KNFTETDFDF KVWNSYFSLA VLFINQPSLQ
1060 1070 1080 1090 1100
LEIITSAKRK KILDKYGDMR VMMAYELFSM WQNLGEHKIH FIPGMIGPFL
1110 1120 1130 1140 1150
GVTLVPQPEV RNIMIPIFHD MMDWEQRKNG NFKQVEAELI DKLDSMVSEG
1160 1170 1180 1190 1200
KGDESYRELF SLLTQLFGPY PSLLEKVEQE TWRETGISFV TSVTRLMERL
1210 1220 1230 1240 1250
LDYRDCMKGE ETENKKIGCT VNLMNFYKSE INKEEMYIRY IHKLCDMHLQ
1260 1270 1280 1290 1300
AENYTEAAFT LLLYCELLQW EDRPLREFLH YPSQTEWQRK EGLCRKIIHY
1310 1320 1330 1340 1350
FNKGKSWEFG IPLCRELACQ YESLYDYQSL SWIRKMEASY YDNIMEQQRL
1360 1370 1380 1390 1400
EPEFFRVGFY GRKFPFFLRN KEYVCRGHDY ERLEAFQQRM LSEFPQAVAM
1410 1420 1430 1440 1450
QHPNHPDDAI LQCDAQYLQI YAVTPIPDYV DVLQMDRVPD RVKSFYRVNN
1460 1470 1480 1490 1500
VRKFRYDRPF HKGPKDKENE FKSLWIERTT LTLTHSLPGI SRWFEVERRE
1510 1520 1530 1540 1550
LVEVSPLENA IQVVENKNQE LRSLISQYQH KQVHGNINLL SMCLNGVIDA
1560 1570 1580 1590 1600
AVNGGIARYQ EAFFDKDYIN KHPGDAEKIT QLKELMQEQV HVLGVGLAVH
1610 1620 1630 1640 1650
EKFVHPEMRP LHKKLIDQFQ MMRASLYHEF PGLDKLSPAC SGTSTPRGNV
1660 1670 1680 1690 1700
LASHSPMSPE SIKMTHRHSP MNLMGTGRHS SSSLSSHASS EAGNMVMLGD
1710 1720 1730 1740 1750
GSMGDAPEDL YHHMQLAYPN PRYQGSVTNV SVLSSSQASP SSSSLSSTHS
1760 1770 1780 1790 1800
APSQMITSAP SSARGSPSLP DKYRHAREMM LLLPTYRDRP SSAMYPAAIL
1810 1820 1830 1840 1850
ENGQPPNFQR ALFQQVVGAC KPCSDPNLSV AEKGHYSLHF DAFHHPLGDT
1860 1870 1880 1890 1900
PPALPARTLR KSPLHPIPAS PTSPQSGLDG SNSTLSGSAS SGVSSLSESN
1910 1920 1930 1940 1950
FGHSSEAPPR TDTMDSMPSQ AWNADEDLEP PYLPVHYSLS ESAVLDSIKA
1960 1970 1980 1990 2000
QPCRSHSAPG CVIPQDPMDP PALPPKPYHP RLPALEHDEG VLLREETERP
2010 2020 2030
RGLHRKAPLP PGSAKEEQAR MAWEHGRGEQ
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081831 | 128 – 2030 | Missing in NEDIDHA. 1 PublicationAdd BLAST | 1903 | |
Natural variantiVAR_081832 | 392 | R → Q in NEDIDHA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199600118Ensembl. | 1 | |
Natural variantiVAR_081833 | 1296 | K → R in NEDIDHA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201184598Ensembl. | 1 | |
Natural variantiVAR_081834 | 1674 | M → L in NEDIDHA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs142515812EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY145303 mRNA Translation: AAN12301.1 AY254099 mRNA Translation: AAP80572.1 AB002297 mRNA Translation: BAA20759.1 |
CCDSi | CCDS46835.1 |
RefSeqi | NP_004938.1, NM_004947.4 |
Genome annotation databases
Ensembli | ENST00000266037; ENSP00000266037; ENSG00000088538 |
GeneIDi | 1795 |
KEGGi | hsa:1795 |
UCSCi | uc011bds.2, human |
Keywords - Coding sequence diversityi
Chromosomal rearrangementSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY145303 mRNA Translation: AAN12301.1 AY254099 mRNA Translation: AAP80572.1 AB002297 mRNA Translation: BAA20759.1 |
CCDSi | CCDS46835.1 |
RefSeqi | NP_004938.1, NM_004947.4 |
3D structure databases
SMRi | Q8IZD9 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108130, 11 interactors |
IntActi | Q8IZD9, 36 interactors |
STRINGi | 9606.ENSP00000266037 |
PTM databases
iPTMneti | Q8IZD9 |
PhosphoSitePlusi | Q8IZD9 |
Genetic variation databases
BioMutai | DOCK3 |
DMDMi | 32469734 |
Proteomic databases
MassIVEi | Q8IZD9 |
MaxQBi | Q8IZD9 |
PaxDbi | Q8IZD9 |
PeptideAtlasi | Q8IZD9 |
PRIDEi | Q8IZD9 |
ProteomicsDBi | 71332 |
Protocols and materials databases
Antibodypediai | 46085, 76 antibodies |
Genome annotation databases
Ensembli | ENST00000266037; ENSP00000266037; ENSG00000088538 |
GeneIDi | 1795 |
KEGGi | hsa:1795 |
UCSCi | uc011bds.2, human |
Organism-specific databases
CTDi | 1795 |
DisGeNETi | 1795 |
GeneCardsi | DOCK3 |
HGNCi | HGNC:2989, DOCK3 |
HPAi | ENSG00000088538, Tissue enhanced (brain) |
MalaCardsi | DOCK3 |
MIMi | 603123, gene 618292, phenotype |
neXtProti | NX_Q8IZD9 |
OpenTargetsi | ENSG00000088538 |
Orphaneti | 528084, Non-specific syndromic intellectual disability |
PharmGKBi | PA27455 |
VEuPathDBi | HostDB:ENSG00000088538.12 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1998, Eukaryota |
GeneTreei | ENSGT00940000155514 |
HOGENOMi | CLU_000595_2_0_1 |
InParanoidi | Q8IZD9 |
OMAi | SMHFDAF |
PhylomeDBi | Q8IZD9 |
TreeFami | TF300423 |
Enzyme and pathway databases
PathwayCommonsi | Q8IZD9 |
Reactomei | R-HSA-9032759, NTRK2 activates RAC1 R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
SIGNORi | Q8IZD9 |
Miscellaneous databases
BioGRID-ORCSi | 1795, 3 hits in 874 CRISPR screens |
ChiTaRSi | DOCK3, human |
GeneWikii | Dock3 |
GenomeRNAii | 1795 |
Pharosi | Q8IZD9, Tbio |
PROi | PR:Q8IZD9 |
RNActi | Q8IZD9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000088538, Expressed in frontal pole and 157 other tissues |
Genevisiblei | Q8IZD9, HS |
Family and domain databases
CDDi | cd08695, C2_Dock-B, 1 hit cd12048, SH3_DOCK3_B, 1 hit |
Gene3Di | 1.20.1270.350, 1 hit 1.20.58.740, 1 hit 1.25.40.410, 1 hit 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR016024, ARM-type_fold IPR037811, C2_Dock-B IPR035892, C2_domain_sf IPR027007, DHR-1_domain IPR027357, DHR-2 IPR026791, DOCK IPR026800, DOCK3 IPR035767, DOCK3_SH3 IPR010703, DOCK_C IPR043161, DOCK_C_lobe_A IPR043162, DOCK_C_lobe_C IPR032376, DOCK_N IPR042455, DOCK_N_sub1 IPR036028, SH3-like_dom_sf IPR001452, SH3_domain |
PANTHERi | PTHR45653, PTHR45653, 1 hit PTHR45653:SF4, PTHR45653:SF4, 1 hit |
Pfami | View protein in Pfam PF06920, DHR-2, 1 hit PF14429, DOCK-C2, 1 hit PF16172, DOCK_N, 1 hit PF07653, SH3_2, 1 hit |
SMARTi | View protein in SMART SM00326, SH3, 1 hit |
SUPFAMi | SSF48371, SSF48371, 1 hit SSF50044, SSF50044, 1 hit |
PROSITEi | View protein in PROSITE PS51650, C2_DOCK, 1 hit PS51651, DOCKER, 1 hit PS50002, SH3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DOCK3_HUMAN | |
Accessioni | Q8IZD9Primary (citable) accession number: Q8IZD9 Secondary accession number(s): O15017 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 3, 2003 |
Last sequence update: | March 1, 2003 | |
Last modified: | February 10, 2021 | |
This is version 150 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM