DOCK5_MOUSE
ID DOCK5_MOUSE Reviewed; 1868 AA.
AC B2RY04; E9QLI4;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Dedicator of cytokinesis protein 5 {ECO:0000250|UniProtKB:Q9H7D0};
DE AltName: Full=Lens rupture protein 2;
DE AltName: Full=Rupture of lens cataract protein;
GN Name=Dock5 {ECO:0000312|MGI:MGI:2652871};
GN Synonyms=Lr2 {ECO:0000303|PubMed:9230506},
GN Rlc {ECO:0000303|PubMed:9093026};
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2] {ECO:0000312|EMBL:AAI58047.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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] {ECO:0000305}
RP DISEASE.
RX PubMed=9093026; DOI=10.1006/exer.1996.0192;
RA Iida F., Matsushima Y., Hiai H., Uga S., Honda Y.;
RT "Rupture of lens cataract: a novel hereditary recessive cataract model in
RT the mouse.";
RL Exp. Eye Res. 64:107-113(1997).
RN [4] {ECO:0000305}
RP DISEASE.
RX PubMed=9230506; DOI=10.1258/002367797780596338;
RA Song C.-W., Okumoto M., Mori N., Yamate J., Sakuma S., Kim J.-S.,
RA Han S.-S., Hilgers J., Esaki K.;
RT "A new hereditary cataract mouse with lens rupture.";
RL Lab. Anim. 31:248-253(1997).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=18396277; DOI=10.1016/j.exer.2008.02.011;
RA Omi N., Kiyokawa E., Matsuda M., Kinoshita K., Yamada S., Yamada K.,
RA Matsushima Y., Wang Y., Kawai J., Suzuki M., Hayashizaki Y., Hiai H.;
RT "Mutation of Dock5, a member of the guanine exchange factor Dock180
RT superfamily, in the rupture of lens cataract mouse.";
RL Exp. Eye Res. 86:828-834(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1867, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, Spleen, 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: Guanine nucleotide exchange factor (GEF) for Rho and Rac. GEF
CC proteins activate small GTPases by exchanging bound GDP for free GTP
CC (PubMed:18396277). Along with DOCK1, mediates CRK/CRKL regulation of
CC epithelial and endothelial cell spreading and migration on type IV
CC collagen (By similarity). {ECO:0000250|UniProtKB:Q9H7D0,
CC ECO:0000269|PubMed:18396277}.
CC -!- SUBUNIT: Interacts with CRK and CRKL. {ECO:0000250|UniProtKB:Q9H7D0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18396277}. Cell
CC membrane {ECO:0000250|UniProtKB:Q9H7D0}. Note=Associated with the edge
CC of the plasma membrane in intestinal epithelial cells spreading on type
CC IV collagen. {ECO:0000250|UniProtKB:Q9H7D0}.
CC -!- TISSUE SPECIFICITY: Highly expressed in lens, where it predominantly
CC localizes to anterior epithelial cells, and is weakly expressed in lens
CC fiber (at protein level). Expressed in brain, eye, lung, spleen and
CC kidney, but not in thymus or peripheral blood leukocytes.
CC {ECO:0000269|PubMed:18396277}.
CC -!- DEVELOPMENTAL STAGE: In the lens, expressed from 15.5 dpc to maturity.
CC {ECO:0000269|PubMed:18396277}.
CC -!- DOMAIN: The DOCKER domain may mediate some GEF activity.
CC {ECO:0000250|UniProtKB:Q14185}.
CC -!- DISEASE: Note=Defects in Dock5 are the cause of rupture of lens
CC cataract. It affects both eyes and is inherited as an autosomal
CC recessive trait. Homozygotes spontaneously develop opacity of the lens
CC at 35-60 days of age. The initial pathological changes appear at about
CC 35 days of age in the deep layer of the posterior cortex as irregular
CC swelling, condensation, degeneration and fragmentation of the lens
CC fibers, leading to rupture of the lens capsule at the posterior pole at
CC 45-100 days of age. Following rupture, the lens nucleus becomes
CC dislocated behind the lens or occasionally in the anterior chamber.
CC {ECO:0000269|PubMed:9093026, ECO:0000269|PubMed:9230506}.
CC -!- SIMILARITY: Belongs to the DOCK family. {ECO:0000255|PROSITE-
CC ProRule:PRU00983}.
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DR EMBL; AC090431; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093020; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC158046; AAI58047.1; -; mRNA.
DR EMBL; BC158135; AAI58136.1; -; mRNA.
DR EMBL; BC158138; AAI58139.1; -; mRNA.
DR CCDS; CCDS36963.1; -.
DR RefSeq; NP_808448.2; NM_177780.3.
DR AlphaFoldDB; B2RY04; -.
DR SMR; B2RY04; -.
DR BioGRID; 213063; 4.
DR STRING; 10090.ENSMUSP00000036674; -.
DR BindingDB; B2RY04; -.
DR ChEMBL; CHEMBL4739665; -.
DR iPTMnet; B2RY04; -.
DR PhosphoSitePlus; B2RY04; -.
DR EPD; B2RY04; -.
DR jPOST; B2RY04; -.
DR MaxQB; B2RY04; -.
DR PaxDb; B2RY04; -.
DR PeptideAtlas; B2RY04; -.
DR PRIDE; B2RY04; -.
DR ProteomicsDB; 279799; -.
DR Antibodypedia; 2898; 91 antibodies from 16 providers.
DR Ensembl; ENSMUST00000039135; ENSMUSP00000036674; ENSMUSG00000044447.
DR GeneID; 68813; -.
DR KEGG; mmu:68813; -.
DR UCSC; uc007ull.1; mouse.
DR CTD; 80005; -.
DR MGI; MGI:2652871; Dock5.
DR VEuPathDB; HostDB:ENSMUSG00000044447; -.
DR eggNOG; KOG1998; Eukaryota.
DR GeneTree; ENSGT00940000157734; -.
DR HOGENOM; CLU_000595_2_1_1; -.
DR InParanoid; B2RY04; -.
DR OMA; EVQQFSY; -.
DR OrthoDB; 102580at2759; -.
DR PhylomeDB; B2RY04; -.
DR TreeFam; TF300423; -.
DR Reactome; R-MMU-9013149; RAC1 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; 68813; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Dock5; mouse.
DR PRO; PR:B2RY04; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; B2RY04; protein.
DR Bgee; ENSMUSG00000044447; Expressed in epithelium of lens and 210 other tissues.
DR Genevisible; B2RY04; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0007520; P:myoblast fusion; IBA:GO_Central.
DR GO; GO:1904694; P:negative regulation of vascular associated smooth muscle contraction; ISO:MGI.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISS:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
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 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; IPR027007; C2_DOCK-type_domain.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR026791; DOCK.
DR InterPro; IPR030717; DOCK5.
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:SF3; PTHR45653:SF3; 1.
DR Pfam; PF06920; DHR-2; 1.
DR Pfam; PF14429; DOCK-C2; 1.
DR Pfam; PF16172; DOCK_N; 1.
DR Pfam; PF00018; SH3_1; 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 Acetylation; Cataract; Cell membrane; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Reference proteome; SH3 domain.
FT CHAIN 1..1868
FT /note="Dedicator of cytokinesis protein 5"
FT /id="PRO_0000358858"
FT DOMAIN 8..69
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 443..627
FT /note="C2 DOCK-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00983"
FT DOMAIN 1231..1642
FT /note="DOCKER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00984"
FT REGION 1681..1730
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1742..1868
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1681..1696
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1709..1730
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1760..1811
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1842..1856
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7D0"
FT MOD_RES 818
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7D0"
FT MOD_RES 1755
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7D0"
FT MOD_RES 1765
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7D0"
FT MOD_RES 1771
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14185"
FT MOD_RES 1784
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BUR4"
FT MOD_RES 1788
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7D0"
FT MOD_RES 1793
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7D0"
FT MOD_RES 1832
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7D0"
FT MOD_RES 1867
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 49
FT /note="A -> R (in Ref. 2; AAI58047/AAI58136/AAI58139)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1868 AA; 214429 MW; D4AB0D8CD588F73D CRC64;
MARWIPTKRQ KYGVAIYNYN ASQDVELSLQ IGDTVHILEM YEGWYRGYAL QNRSKKGIFP
ETYIHLKEAT VEDGGQHETV IPGELPLVQE LTNTLREWAV IWRKLYVNNK VTLFRQLQQM
TYSLIEWRSQ ILSGTLPKDE LAELKKKVTA KIDHGNRMLG LDLVVRDDNG NILDPDETST
VALFRAHEVA SKRIEEKIQE EKSILQNLDL RGQAIFSTVH TYGLYVNFKN FVCNIGEDAE
LFIALYDPDQ STFISENYLI RWGSNGMPKE IEKLNNLQAV FTDLSSTDLI RPRISLVCQI
VRVGRMELKE GKKHTCGLRR PFGVAVMDIS DIVHGKVDDE EKQHFIPFQQ IAMETYIRQR
QLIMSPLITS HVIGENEPLT SVLNKVIAAK EVNHKGQGLW VSLKLLPGDL TQVQKNFSHL
VDRSTAIARK MGFPEIILPG DVRNDIYVTL IHGEFDKGKK KTPKNVEVTM SVFDEEGNLL
EKAIHPGAGY EGVSEYKSVV YYQVKQPCWY ETVKVFIAIE EVTRCHIRFT FRHRSSQESR
DKSERAFGVA FVKLMNADGT TLQDGRHDLV VYKGDNKKME DAKYYLTLPG TKAELEEKEL
QASKNPSVFT PSKDSTKDSF QIATLICSTK LTQNVDLLGL LNWRSNSQNI KHNLKKLMEV
DGGEIVKFLQ DTLDALFNIM MEMSDNETYD FLVFDALVFI ISLIGDIKFQ HFNPVLETYI
YKHFSATLAH VKLSKVLNFY VANAEDPSKT ELLFAALKAL KYLFRFIIQS RVLYLRFYGQ
SEDGDEFNDS IRQLFLAFNT LMDRPLEEAV KIKGAALKYL PSIINDVKLV FDPMELSVLF
CKFIQSIPDN QLVRQKLNCM TKIVESSLFQ QAECREVLLP LLTDQLSGQL DDHSTKPDHE
ASSQLLSNIL EVLDRTDVGP TSAHVQLIME RLLRRINRTV IGMSRQSPHI GSFVACMIAV
LRQMEDSHYS HYISTFKTRQ DIIDFLMETF IMFKDLIGKN VYAKDWMVMN MTQNRVFLRA
INQFAEVLTK SFMDQASFEL QLWNNYFHLA VAFLTHESLQ LETFSEAKRN KIVKKYGDMR
KEIGFRIRDM WYNLGPHKIK FIPSMVGPIL EVTLTPEVEL RKATIPIFFD MMQCEFNLSG
NGNFHMFENE LITKLDQEVE GGRGDEQYKV LLEKLLLEHC RKHKYLANSG EAFAFLVSSL
LENLLDYRTI IIHDESKENR MSCTVNVLNF YKDKKREDIY IRYLYKLRDL HRDCENYTEA
AYTLLLHAEL LQWSDKPCVP HLLQRDSYYV YTQQELKEKL YQEIISYFDK GKMWEKAIKL
SKELAETYES KVFDYEGLGS LLKKRALFYE NIIKAMRPQP EYFAVGYYGQ GFPSFLRNKI
FIYRGKEYER REDFSLRLLT QFPNAEKMTS TTPPGEDIKS SPKQYLQCFT VKPVMSLPPS
YKDKPVPEQI LNYYRANEVQ QFSYSRPFRK GEKDPENEFA TMWIERTTYR TAYTFPGILK
WFEAKEISVE EISPLENAIE TMELTNERVS NCVQQHAWDH SLSVHPLSML LSGIVDPAVM
GGFSNYEKAF FTEKYLQEHP EDQEKVELLK RLIALQIPLL TEGIRIHGEK LTEQLKPLHA
RLSSCFRELK EKVEKLYGVI TLPPSMTERK PSRAGSMVLP YILSSTLRRL SVTSVASSVI
STSSNSSDNA SSRPGSDGSI LEPLFERRAS SGARVEDLPP KEDSENRISK FKRKDWNLSK
SQVIAEKAPE PDVMSPGKKT QRPKSLQLVD SRLTPFHSPS PLQSTALSPP PLTPKATRTL
SSPSLQTDGL TASVPPPPPP KSKPYESSQR NSAEIAPPLP VRRDSKAPPP PPPKARKSGI
LSSEPGSQ
