DOCK4_MOUSE
ID DOCK4_MOUSE Reviewed; 1978 AA.
AC P59764; B2RUG6;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Dedicator of cytokinesis protein 4;
GN Name=Dock4; Synonyms=Kiaa0716;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY (ISOFORM 2), AND DEVELOPMENTAL STAGE (ISOFORM 2).
RX PubMed=16464467; DOI=10.1016/j.jmb.2006.01.017;
RA Yan D., Li F., Hall M.L., Sage C., Hu W.H., Giallourakis C., Upadhyay G.,
RA Ouyang X.M., Du L.L., Bethea J.R., Chen Z.Y., Yajnik V., Liu X.Z.;
RT "An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the
RT inner ear and binds to harmonin (USH1C).";
RL J. Mol. Biol. 357:755-764(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-167, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-193; SER-1608; SER-1616;
RP SER-1640 AND SER-1778, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, and Spleen;
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: Functions as a guanine nucleotide exchange factor (GEF) that
CC promotes the exchange of GDP to GTP, converting inactive GDP-bound
CC small GTPases into their active GTP-bound form. Involved in regulation
CC of adherens junction between cells. Plays a role in cell migration.
CC {ECO:0000250|UniProtKB:Q8N1I0}.
CC -!- FUNCTION: [Isoform 2]: Has a higher guanine nucleotide exchange factor
CC activity compared to other isoforms. {ECO:0000250|UniProtKB:Q8N1I0}.
CC -!- SUBUNIT: Interacts with nucleotide-free Rap1; functions as a guanine
CC nucleotide exchange factor (GEF) for Rap1. Interacts (via DOCKER
CC domain) with RAC1; functions as a guanine nucleotide exchange factor
CC (GEF) for RAC1. Interacts with the SH3 domain of CRK. Interacts with
CC FASLG. Interacts with ELMO2 and EPHA2; mediates activation of RAC1 by
CC EPHA2. Interacts with USH1C (via PDZ 1 domain).
CC {ECO:0000250|UniProtKB:Q8N1I0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8N1I0}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q8N1I0}. Note=Colocalizes
CC with EPHA2, RHOG and CTTN/cortactin at the tip of protrusions in
CC migrating cells. {ECO:0000250|UniProtKB:Q8N1I0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P59764-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P59764-2; Sequence=VSP_060556, VSP_060557;
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in inner ear (at protein
CC level). {ECO:0000269|PubMed:16464467}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 2]: Expressed in the utricular hair
CC bundles at 14.5 dpc (at protein level) (PubMed:16464467). At P1
CC expressed in cochlear hair bundles of the sensory cells extending to
CC the apical surface of the greater epithelial ridge and in the vestibule
CC where it is restricted to hair bundles (at protein level)
CC (PubMed:16464467). {ECO:0000269|PubMed:16464467}.
CC -!- DOMAIN: The DOCKER domain mediates interaction with small GTPases like
CC RAC1 and is required for their activation.
CC {ECO:0000250|UniProtKB:Q8N1I0}.
CC -!- SIMILARITY: Belongs to the DOCK family. {ECO:0000255|PROSITE-
CC ProRule:PRU00983}.
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DR EMBL; AK122353; BAC65635.1; -; mRNA.
DR EMBL; BC141138; AAI41139.1; -; mRNA.
DR CCDS; CCDS25895.1; -. [P59764-1]
DR RefSeq; NP_766391.2; NM_172803.2. [P59764-1]
DR AlphaFoldDB; P59764; -.
DR SMR; P59764; -.
DR BioGRID; 231952; 2.
DR IntAct; P59764; 1.
DR MINT; P59764; -.
DR STRING; 10090.ENSMUSP00000047387; -.
DR iPTMnet; P59764; -.
DR PhosphoSitePlus; P59764; -.
DR SwissPalm; P59764; -.
DR MaxQB; P59764; -.
DR PaxDb; P59764; -.
DR PRIDE; P59764; -.
DR ProteomicsDB; 279798; -. [P59764-1]
DR Antibodypedia; 31488; 141 antibodies from 21 providers.
DR DNASU; 238130; -.
DR Ensembl; ENSMUST00000037488; ENSMUSP00000047387; ENSMUSG00000035954. [P59764-1]
DR GeneID; 238130; -.
DR KEGG; mmu:238130; -.
DR UCSC; uc007nlh.1; mouse. [P59764-1]
DR CTD; 9732; -.
DR MGI; MGI:1918006; Dock4.
DR VEuPathDB; HostDB:ENSMUSG00000035954; -.
DR eggNOG; KOG1998; Eukaryota.
DR eggNOG; KOG3166; Eukaryota.
DR GeneTree; ENSGT00940000155659; -.
DR HOGENOM; CLU_000595_2_0_1; -.
DR InParanoid; P59764; -.
DR OMA; MRDFGHS; -.
DR OrthoDB; 102580at2759; -.
DR PhylomeDB; P59764; -.
DR TreeFam; TF300423; -.
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-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 238130; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Dock4; mouse.
DR PRO; PR:P59764; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P59764; protein.
DR Bgee; ENSMUSG00000035954; Expressed in lateral septal nucleus and 211 other tissues.
DR ExpressionAtlas; P59764; baseline and differential.
DR Genevisible; P59764; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032420; C:stereocilium; IDA:HGNC-UCL.
DR GO; GO:0032421; C:stereocilium bundle; IDA:HGNC-UCL.
DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
DR GO; GO:1904694; P:negative regulation of vascular associated smooth muscle contraction; ISO:MGI.
DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; ISO:MGI.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR CDD; cd08695; C2_Dock-B; 1.
DR CDD; cd12049; SH3_DOCK4_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; IPR037811; C2_Dock-B.
DR InterPro; IPR027007; C2_DOCK-type_domain.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR026791; DOCK.
DR InterPro; IPR037014; DOCK4.
DR InterPro; IPR035769; DOCK4_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:SF7; PTHR45653:SF7; 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; 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 Alternative splicing; Cell membrane; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Reference proteome; SH3 domain; SH3-binding.
FT CHAIN 1..1978
FT /note="Dedicator of cytokinesis protein 4"
FT /id="PRO_0000189991"
FT DOMAIN 6..67
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 401..574
FT /note="C2 DOCK-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00983"
FT DOMAIN 1199..1605
FT /note="DOCKER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00984"
FT REGION 1657..1738
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1751..1978
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1797..1803
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 1657..1708
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1711..1725
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1766..1785
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1806..1883
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 167
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 193
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1608
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1616
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1623
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N1I0"
FT MOD_RES 1627
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N1I0"
FT MOD_RES 1629
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N1I0"
FT MOD_RES 1640
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1778
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1769..1806
FT /note="Missing (in isoform 2)"
FT /id="VSP_060556"
FT VAR_SEQ 1883..1886
FT /note="Missing (in isoform 2)"
FT /id="VSP_060557"
SQ SEQUENCE 1978 AA; 226550 MW; 4A1FC9C71C5A5719 CRC64;
MWIPTEHEKY GVVIASFRGT VPYGLSLEIG DTVQILEKCD GWYRGFALKN PNIKGIFPSS
YVHLKNACVK NKGQFEMVIP TEDSVITEMT STLRDWGTMW KQLYVRNEGD LFHRLWHIMN
EILDLRRQVL VGHLTHDRMK DVKRHITARL DWGNEQLGLD LVPRKEYAMV DPEDISITEL
YRLMEHRHRK KDTPVQASSH HLFVQMKSLM CSNLGEELEV IFSLFDSKEN RPISERFFLR
LNRNGLPKAP DKPERHCSLF VDLGSSELRK DIYITVHIIR IGRMGAGEKK NACSVQYRRP
FGCAVLSIAD LLTGETKDDL VLKVYMCNTE SEWYQIHENI IKKLNARYNL TGSNAGLAVS
LQLLHGDIEQ IRREYSSVFS HGVSITRKLG FSDIIMPGEM RNDLYITVER GEFEKGGKSV
ARNVEVTMFI VDSNGQPLKD FISFGSGEPP ASEYHSFVLY HNNSPRWSEL LKLPIPVDKF
RGSHIRFEFR HCSTKEKGEK KLFGFSFVPL MQEDGRTLPD GTHELIVHKC EENTNLQDTT
RYLKLPFSKV IFLGNNNQTM KATKESFWIT SFLCSTKLTQ NGDMLDLLKW RTHPDKITGC
LSKLKEIDGS EIVKFLQDTL DTLFGILDEN SQKYGSKVFD SLVHIINLLQ DSKFHHFKPV
MDTYIESHFA GALAYRDLIK VLKWYVDRIT EAERQEHIQE VLKAQEYIFK YIVQSRRLFS
LATGGQNEEE FRCCIQELLM SVRFFLSQES KGTGALSQSQ AVFLSSFPAV YSELLKLFDV
REVANLVQDT LGSLPTIMHV DDSLQAIKLQ CIGKTVESQL YTNPDSRYIL LPVVLHHLHI
HLQEQKDLIM CARILSNVFC LIKKNSSEKS VLEEIDVIVA SLLDILLRTI LEITSRPQAS
SSAMRLQFQD VTGEFVACLL SLLRQMTDRH YQQLLNSFST KEELRDFLLQ IFTVFRILIR
PEMFPKDWTV MRLVANNVII TTVLYLSDAL RKNFLNENFD YKIWDSYFYL AVIFINQLCL
QLEMFTPSKK KKVLEKYGDM RVTMGCEIFS MWQNLGEHKL HFIPALIGPF LEVTLIPQPD
LRNVMIPIFH DMMDWEQRRS GNFKQVEAKL IDKLDSLMSE GKGDETYREL FNSIIPLFGP
YPSLLKKIER ETWRESGVSL IATVTRLMER LLDYRDCMKI GEVDGKKIGC TVSLLNFYKT
ELNKEEMYIR YIHKLYDLHL KAQNFTEAAY TLLLYDELLE WSDRPLREFL TYPMQTEWQR
KEHLHLTIIQ NFDRGKCWEN GIILCRKIAE QYESYYDYRN LSKMRMMEAS LYDKIMDQQR
LEPEFFRVGF YGKKFPFFLR NKEFVCRGHD YERLEAFQQR MLNEFPHAIA MQHANQPDET
IFQAEAQYLQ IYAVTPIPES QEVLQREGVP DNIKSFYKVN HIWKFRYDRP FHKGAKDKEN
EFKSLWVERT SLYLVQSLPG ISRWFEVEKR EVVEMSPLEN AIEVLENKNQ QLKTLISQCQ
TRQMQNINPL TMCLNGVIDA AVNGGVSRYQ EAFFVKDYIL SHPEDGEKIA RLRELMLEQA
QILEFGLAVH EKFVPQDMRP LHKKLVDQFF VMKSSFGIQE FPACIQASPV HFPNGSPRVC
RNSAPASMSP DGTRVIPRRS PLSYPAVNRY SSSSLSSQAS AEVSNITGQS ESSDEVFNMQ
PSPSTSSLSS THSASPNVTS SAPSSARASP LLSDKHKHSR ENSCLSPRDR PCSAIYPTPV
EPSQRMLFNH IGDGALPRSD PNLSAPEKAV NPTPSSWSLD SGKEAKNMSD SGKLISPPVP
PRPTQTASPA RHTTSVSPSP AGRSPLKGSV QSFTPSPVEY NSPGLSSNSP VLSGSYSSGI
SSLSRCSTSE TSGFENQANE QSVPVPVPVP VPVPVPSFSG SEEPVRKESK TPPPYSVYER
TLRRPVPLPH SLSIPVTSEP PALPPKPLAA RSSHLENGTR RTEPGPRPRP LPRKVSQL
