DOCK3_MOUSE
ID DOCK3_MOUSE Reviewed; 2027 AA.
AC Q8CIQ7;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Dedicator of cytokinesis protein 3;
DE AltName: Full=Modifier of cell adhesion;
DE AltName: Full=Presenilin-binding protein;
DE Short=PBP;
GN Name=Dock3; Synonyms=Moca;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH PSEN1 AND CRK.
RC TISSUE=Brain;
RX PubMed=10854253; DOI=10.1046/j.1471-4159.2000.0750109.x;
RA Kashiwa A., Yoshida H., Lee S., Paladino T., Liu Y., Chen Q., Dargusch R.,
RA Schubert D., Kimura H.;
RT "Isolation and characterization of novel presenilin binding protein.";
RL J. Neurochem. 75:109-116(2000).
RN [2]
RP FUNCTION, AND INTERACTION WITH PSEN2.
RX PubMed=12093789; DOI=10.1083/jcb.200110151;
RA Chen Q., Kimura H., Schubert D.;
RT "A novel mechanism for the regulation of amyloid precursor protein
RT metabolism.";
RL J. Cell Biol. 158:79-89(2002).
RN [3]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=19129390; DOI=10.1523/jneurosci.3985-08.2009;
RA Chen Q., Peto C.A., Shelton G.D., Mizisin A., Sawchenko P.E., Schubert D.;
RT "Loss of modifier of cell adhesion reveals a pathway leading to axonal
RT degeneration.";
RL J. Neurosci. 29:118-130(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1655, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Potential guanine nucleotide exchange factor (GEF). GEF
CC proteins activate some small GTPases by exchanging bound GDP for free
CC GTP. Its interaction with presenilin proteins as well as its ability to
CC stimulate Tau/MAPT phosphorylation suggest that it may be involved in
CC Alzheimer disease. Ectopic expression in nerve cells decreases the
CC secretion of amyloid-beta APBA1 protein and lowers the rate of cell-
CC substratum adhesion, suggesting that it may affect the function of some
CC small GTPase involved in the regulation of actin cytoskeleton or cell
CC adhesion receptors. {ECO:0000269|PubMed:12093789}.
CC -!- SUBUNIT: Interacts with presenilin proteins PSEN1 and PSEN2. Interacts
CC with CRK. {ECO:0000269|PubMed:10854253, ECO:0000269|PubMed:12093789}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10854253}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, spinal cord, pituitary gland,
CC testis (PubMed:19129390). Not expressed in heart, liver, kidney, spleen
CC and lung. In brain, it is highly expressed in the cerebral cortex and
CC hippocampus, while it is absent in other tissues, except in spinal
CC cord. In the cerebral cortex, it is found within the intermediate (III
CC and IV) and deep (V and VI) layers, whereas it is weakly expressed in
CC superficial layer I. It is also abundant in the piriform cortex. Within
CC the hippocampus, it is expressed in the pyramidal neurons of the CA1,
CC CA2, and CA3 regions and the dentate gyrus.
CC {ECO:0000269|PubMed:10854253, ECO:0000269|PubMed:19129390}.
CC -!- DOMAIN: The DOCKER domain may mediate some GEF activity. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: DOCK3 knockout mice show sensorimotor impairment
CC and structural changes in several brain regions, including the spinal
CC cord and cerebellum. Structural changes are consistent with central
CC axonal dystrophy and include a disorganized cytoskeletons, and abnormal
CC accumulation of autophagic vacuoles associated with impaired axonal
CC transport. Common features of mutant mice are gait abnormalities, limb
CC weakness, ataxia, and an impaired ability to swim.
CC {ECO:0000269|PubMed:19129390}.
CC -!- SIMILARITY: Belongs to the DOCK family. {ECO:0000255|PROSITE-
CC ProRule:PRU00983}.
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DR EMBL; AY145302; AAN12300.1; -; mRNA.
DR AlphaFoldDB; Q8CIQ7; -.
DR SMR; Q8CIQ7; -.
DR CORUM; Q8CIQ7; -.
DR IntAct; Q8CIQ7; 1.
DR MINT; Q8CIQ7; -.
DR STRING; 10090.ENSMUSP00000047652; -.
DR iPTMnet; Q8CIQ7; -.
DR PhosphoSitePlus; Q8CIQ7; -.
DR MaxQB; Q8CIQ7; -.
DR PaxDb; Q8CIQ7; -.
DR PRIDE; Q8CIQ7; -.
DR ProteomicsDB; 279464; -.
DR MGI; MGI:2429763; Dock3.
DR eggNOG; KOG1998; Eukaryota.
DR InParanoid; Q8CIQ7; -.
DR PhylomeDB; Q8CIQ7; -.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9032759; NTRK2 activates RAC1.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR ChiTaRS; Dock3; mouse.
DR PRO; PR:Q8CIQ7; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8CIQ7; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IBA:GO_Central.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR CDD; cd08695; C2_Dock-B; 1.
DR CDD; cd12048; SH3_DOCK3_B; 1.
DR Gene3D; 1.20.1270.350; -; 1.
DR Gene3D; 1.20.58.740; -; 1.
DR Gene3D; 1.25.40.410; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR037811; C2_Dock-B.
DR InterPro; IPR027007; C2_DOCK-type_domain.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR026791; DOCK.
DR InterPro; IPR026800; DOCK3.
DR InterPro; IPR035767; DOCK3_SH3.
DR InterPro; IPR043161; DOCK_C_lobe_A.
DR InterPro; IPR043162; DOCK_C_lobe_C.
DR InterPro; IPR032376; DOCK_N.
DR InterPro; IPR042455; DOCK_N_sub1.
DR InterPro; IPR027357; DOCKER_dom.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR45653; PTHR45653; 1.
DR PANTHER; PTHR45653:SF4; PTHR45653:SF4; 1.
DR Pfam; PF06920; DHR-2; 1.
DR Pfam; PF14429; DOCK-C2; 1.
DR Pfam; PF16172; DOCK_N; 1.
DR Pfam; PF07653; SH3_2; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51650; C2_DOCK; 1.
DR PROSITE; PS51651; DOCKER; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Guanine-nucleotide releasing factor; Phosphoprotein;
KW Reference proteome; SH3 domain; SH3-binding.
FT CHAIN 1..2027
FT /note="Dedicator of cytokinesis protein 3"
FT /id="PRO_0000189989"
FT DOMAIN 6..67
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 421..598
FT /note="C2 DOCK-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00983"
FT DOMAIN 1225..1632
FT /note="DOCKER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00984"
FT REGION 1672..1695
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1731..1768
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1846..1925
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1971..2027
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1967..1973
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 1672..1693
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1731..1765
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1868..1917
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1978..2002
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1655
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 2027 AA; 232910 MW; 006DCE0B4583A1CC CRC64;
MWTPTEEEKY GVVICSFRGS VPQGLVLEIG ETVQILEKCE GWYRGVSTKK PNVKGLFPAN
YIHLKKAIVS NRGQYETVVP LEDSIVTEVT TTLQEWASLW KQLYVKHKVD LFYKLRHVMN
ELIDLRRQLL SGHLTQDQVR EVKRHITVRL DWGNEHLGLD LVPRKDFEVV DSDQISVSDL
YKMHLSSRQS VQQSTSQVDT MRPRHGETCR MPVPYHFFFS LKSFTYNTIG EDSDVFFSLY
DMREGKQISE RFLVRLNKNG GPRNPEKIER MCALFTDLSS KDMKRDLYIV AHVIRIGRML
LNDSKKGPAH LHYRRPYGCA VLSILDVLQS LTELKEEKDF VLKVYTCNNE SEWTQIHENI
IRKSSTKYSA PSASHGLIIS LQLFRGDMEQ IRRENPMIFN RGLAITRKLG FPDVIMPGDI
RNDLYLTLEK GDFERGGKSV QKNIEVTMYV LYADGEILKD CISLGSGEPN RSSYHSFVLY
HSNSPRWGEI IKLPIPIDRF RGSHLRFEFR HCSTKDKGEK KLFGFAFSPL MRDDGTTLSD
DIHELYVYKC DENSTFNNHA LYLGLPCCKE DYNGCPNIPS SLIFQRSKES FFISTQLSST
KLTQNVDLLA LLKWKAFPDR IMDILGRLRH VSGEEIVKFL QDILDTLFVI LDDNTEKYGL
LVFQSLVFII NLLRDIKYFH FRPVMDTYIQ KHFAGALAYK ELIRCLKWYM DCSAELIRQD
HIQEAMRALE YLFKFIVQSR ILYSRATCGM EEEQFRSSIQ ELFQSIRFVL SLDSRNSETL
LFTQAALLNS FPTIFDELLQ MFTVQEVAEF VRGTLGSMPS TVHIGQSMDV VKLQSIARTV
DSRLFSFSES RRILLPVVLH HIHLHLRQQK ELLICSGILG SIFSIVKTSS LEADVMEEVE
MMVESLLDVL LQTLLTIMSK SHAQEAVRGH CPVTAEITGE YVSCLLSLLR QMCDTHFQHL
LDNFQSKDEL KEFLLKIFCV FRNLMKMSVF PRDWMVMRLL TSNIIVTTVQ YLSSALHKNF
TETDFDFKVW NSYFSLAVLF INQPSLQLEI ITSAKRKKIL DKYGDMRVMM AYELFSMWQN
LGEHKIHFIP GMIGPFLGVT LVPQPEVRNI MIPIFHDMMD WEQRKNGNFK QVEAELIDKL
DSMVSEGKGD ESYRELFGLL TQLFGPYPSL LEKVEQETWR ETGISFVTSV TRLMERLLDY
RDCMKGEETE NKKVGCTVNL MNFYKSEINK EEMYIRYIHK LCDMHLQAEN YTEAAFTLLL
YCELLQWEDR PLREFLHYPS QTEWQRKEGL CRKIIHYFNK GKSWEFGIPL CRELACQYES
LYDYQSLSWI RKMEASYYDN IIEQQRLEPE FFRVGFYGRK FPFFLRNKEY VCRGHDYERL
EAFQQRMLSE FPQAVAMQHP NHPDDAILQC DAQYLQIYAV TPIPDYVDVL QMDRVPDRVK
SFYRVNNVRK FRYDRPFHKG PKDKDNEFKS LWIERTTLTL THSLPGISRW FEVERRELVE
VSPLENAIQV VENKNQELRA LISQYQHKQV HGNINLLSMC LNGVIDAAVN GGIARYQEAF
FDKDYITKHP GDAEKISQLK ELMQEQVHVL GVGLAVHEKF VHPEMRPLHK KLIDQFQMMR
ASLYHEFPGL DKLSPACSGT STPRGNVLAS HSPMSPENIK MTHRHSPMNL MGTGRHSSSS
LSSHASSEAG NMMMMGDNSM GEAPEDLYHH MQLAYHNPRY QGSVTNVSVL SSSQASPSSS
SLSSTHSAPS QMITSAPSST RGSPSLPDKY RHAREMMLLL PTHRDRPSSA MYPAAILENG
QPPNFQRALF QQVVGACKPC SDPNLSMAEK GHYSLHFDAF HHPLGDTPPA LPARTLRKSP
LHPIPASPTS PQSGLDGSNS TLSGSASSGV SSLSESNFGH SSEAPPRTDT MDSMPSQAWN
GDEGLEPPYL PVHYSLSESA VLDAIKSQPC RSHSAPGCVL PQDPMDPPAL PPKPYHPRLP
ALEHDEGMLL REEAERPRGL HRKASLPPGS VKEEQARLAW EHGRGEQ
