PKHG5_MOUSE
ID PKHG5_MOUSE Reviewed; 1073 AA.
AC Q66T02; A2A8B6; A2A8B7; Q66T00; Q6P3B1; Q6ZQ62; Q8R571;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Pleckstrin homology domain-containing family G member 5;
DE Short=PH domain-containing family G member 5;
DE AltName: Full=Synectin-binding RhoA exchange factor;
DE Short=SYX;
GN Name=Plekhg5; Synonyms=Kiaa0720, Syx;
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] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=16467373; DOI=10.1091/mbc.e06-01-0002;
RA Liu M., Horowitz A.;
RT "A PDZ-binding motif as a critical determinant of Rho guanine exchange
RT factor function and cell phenotype.";
RL Mol. Biol. Cell 17:1880-1887(2006).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 576-1073.
RC TISSUE=Brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 596-1073 (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Mammary gland, and Mammary tumor;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-941, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-793; SER-798; THR-909;
RP SER-911; SER-936 AND SER-941, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC 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).
RN [7]
RP FUNCTION IN ANGIOGENESIS, AND SUBCELLULAR LOCATION.
RX PubMed=21543326; DOI=10.1074/jbc.m111.245209;
RA Wu C., Agrawal S., Vasanji A., Drazba J., Sarkaria S., Xie J., Welch C.M.,
RA Liu M., Anand-Apte B., Horowitz A.;
RT "Rab13-dependent trafficking of RhoA is required for directional migration
RT and angiogenesis.";
RL J. Biol. Chem. 286:23511-23520(2011).
RN [8]
RP TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=23777631; DOI=10.1093/hmg/ddt274;
RA Azzedine H., Zavadakova P., Plante-Bordeneuve V., Vaz Pato M., Pinto N.,
RA Bartesaghi L., Zenker J., Poirot O., Bernard-Marissal N.,
RA Arnaud Gouttenoire E., Cartoni R., Title A., Venturini G., Medard J.J.,
RA Makowski E., Schoels L., Claeys K.G., Stendel C., Roos A., Weis J.,
RA Dubourg O., Leal Loureiro J., Stevanin G., Said G., Amato A., Baraban J.,
RA Leguern E., Senderek J., Rivolta C., Chrast R.;
RT "PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive
RT Charcot-Marie-Tooth disease.";
RL Hum. Mol. Genet. 22:4224-4232(2013).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29084947; DOI=10.1038/s41467-017-00689-z;
RA Lueningschroer P., Binotti B., Dombert B., Heimann P., Perez-Lara A.,
RA Slotta C., Thau-Habermann N., R von Collenberg C., Karl F., Damme M.,
RA Horowitz A., Maystadt I., Fuechtbauer A., Fuechtbauer E.M., Jablonka S.,
RA Blum R., Ueceyler N., Petri S., Kaltschmidt B., Jahn R., Kaltschmidt C.,
RA Sendtner M.;
RT "Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic
RT mechanism in motoneuron disease.";
RL Nat. Commun. 8:678-678(2017).
CC -!- FUNCTION: Functions as a guanine exchange factor (GEF) for RAB26 and
CC thus regulates autophagy of synaptic vesicles in axon terminal of
CC motoneurons (PubMed:29084947). Involved in the control of neuronal cell
CC differentiation. Plays a role in angiogenesis through regulation of
CC endothelial cells chemotaxis (PubMed:21543326). Affects also the
CC migration, adhesion, and matrix/bone degradation in macrophages and
CC osteoclasts (By similarity). {ECO:0000250|UniProtKB:O94827,
CC ECO:0000269|PubMed:21543326, ECO:0000269|PubMed:29084947}.
CC -!- SUBUNIT: Interacts with GIPC1/synectin and RHOA. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16467373}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:16467373}. Cell
CC membrane {ECO:0000269|PubMed:16467373}. Cell junction
CC {ECO:0000269|PubMed:21543326}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:21543326}. Note=Predominantly cytoplasmic, however
CC when endothelial cells are stimulated with lysophosphatidic acid,
CC PLEKHG5 is found in perinuclear regions and at the cell membrane
CC (PubMed:16467373). Localizes at cell-cell junctions in quiescent
CC endothelial cells, and relocalizes to cytoplasmic vesicle and the
CC leading edge of lamellipodia in migrating endothelial cells
CC (PubMed:21543326). {ECO:0000269|PubMed:16467373,
CC ECO:0000269|PubMed:21543326}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=SYX1;
CC IsoId=Q66T02-1; Sequence=Displayed;
CC Name=2; Synonyms=SYX2;
CC IsoId=Q66T02-2; Sequence=VSP_028587;
CC -!- TISSUE SPECIFICITY: Expressed in neurons and glial cells of the
CC peripheral nervous system, with highest levels of expression in the
CC brain and sciatic nerve endoneurium. Isoform 2 is expressed at
CC detectable levels only in malignant cells.
CC {ECO:0000269|PubMed:16467373, ECO:0000269|PubMed:23777631}.
CC -!- DEVELOPMENTAL STAGE: Regulated during development, with the highest
CC level at postnatal days 10 to 14, suggesting a role in myelination of
CC the peripheral nervous system. {ECO:0000269|PubMed:23777631}.
CC -!- DISRUPTION PHENOTYPE: Animals develop normally and show no clear
CC neurologic symptoms as adults. However, electrophysiologic studies
CC indicated that mutant mice have decreased motor nerve conduction
CC velocities and delayed compound action potentials. Mutant mice perform
CC slightly less well than control mice in the rotarod test
CC (PubMed:23777631). Deficient mice have no motoneuron loss during their
CC first year. A loss of motoneurons starts at 12 months and this decrease
CC is more prominent in 24-month-old animals. Biogenesis of autophagosomes
CC is impaired in Plekhg5-deficient motoneurons resulting in a reduced
CC number of retrogradely transported autophagosomes (PubMed:29084947).
CC {ECO:0000269|PubMed:23777631, ECO:0000269|PubMed:29084947}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAM24581.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY605057; AAU04953.1; -; mRNA.
DR EMBL; AY605058; AAU04954.1; -; mRNA.
DR EMBL; AL772240; CAM19697.1; -; Genomic_DNA.
DR EMBL; AL611927; CAM19697.1; JOINED; Genomic_DNA.
DR EMBL; AL772240; CAM19699.2; -; Genomic_DNA.
DR EMBL; AL611927; CAM19699.2; JOINED; Genomic_DNA.
DR EMBL; AL611927; CAM24581.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL772240; CAM24581.1; JOINED; Genomic_DNA.
DR EMBL; AL611927; CAM24582.2; -; Genomic_DNA.
DR EMBL; AL772240; CAM24582.2; JOINED; Genomic_DNA.
DR EMBL; AK129198; BAC98008.1; -; mRNA.
DR EMBL; BC023181; AAH23181.1; -; mRNA.
DR EMBL; BC064091; AAH64091.1; -; mRNA.
DR CCDS; CCDS18987.2; -. [Q66T02-1]
DR RefSeq; NP_001272928.1; NM_001285999.1. [Q66T02-1]
DR AlphaFoldDB; Q66T02; -.
DR SMR; Q66T02; -.
DR BioGRID; 234677; 27.
DR ELM; Q66T02; -.
DR IntAct; Q66T02; 10.
DR STRING; 10090.ENSMUSP00000081132; -.
DR iPTMnet; Q66T02; -.
DR PhosphoSitePlus; Q66T02; -.
DR jPOST; Q66T02; -.
DR MaxQB; Q66T02; -.
DR PaxDb; Q66T02; -.
DR PRIDE; Q66T02; -.
DR ProteomicsDB; 289511; -. [Q66T02-1]
DR ProteomicsDB; 289512; -. [Q66T02-2]
DR Antibodypedia; 27380; 153 antibodies from 25 providers.
DR DNASU; 269608; -.
DR Ensembl; ENSMUST00000084115; ENSMUSP00000081132; ENSMUSG00000039713. [Q66T02-2]
DR Ensembl; ENSMUST00000105661; ENSMUSP00000101286; ENSMUSG00000039713. [Q66T02-1]
DR GeneID; 269608; -.
DR KEGG; mmu:269608; -.
DR UCSC; uc008vzh.2; mouse. [Q66T02-1]
DR CTD; 57449; -.
DR MGI; MGI:2652860; Plekhg5.
DR VEuPathDB; HostDB:ENSMUSG00000039713; -.
DR eggNOG; KOG3521; Eukaryota.
DR GeneTree; ENSGT00510000046843; -.
DR InParanoid; Q66T02; -.
DR OMA; EATYIRN; -.
DR OrthoDB; 556467at2759; -.
DR PhylomeDB; Q66T02; -.
DR TreeFam; TF316755; -.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9696264; RND3 GTPase cycle.
DR Reactome; R-MMU-9696273; RND1 GTPase cycle.
DR BioGRID-ORCS; 269608; 7 hits in 72 CRISPR screens.
DR ChiTaRS; Plekhg5; mouse.
DR PRO; PR:Q66T02; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q66T02; protein.
DR Bgee; ENSMUSG00000039713; Expressed in dentate gyrus of hippocampal formation granule cell and 203 other tissues.
DR ExpressionAtlas; Q66T02; baseline and differential.
DR Genevisible; Q66T02; MM.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:MGI.
DR GO; GO:0035767; P:endothelial cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; IDA:MGI.
DR GO; GO:0099575; P:regulation of protein catabolic process at presynapse, modulating synaptic transmission; IDA:SynGO.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR040181; PKHG5/7.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR13217; PTHR13217; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Cell projection;
KW Cytoplasm; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..1073
FT /note="Pleckstrin homology domain-containing family G
FT member 5"
FT /id="PRO_0000307135"
FT DOMAIN 406..598
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 654..754
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 217..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 367..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 762..818
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 833..873
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 899..925
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 993..1046
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..309
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..383
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 791..818
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..865
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 900..917
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1030..1046
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 793
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 798
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 909
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 911
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 936
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 941
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1072..1073
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16467373"
FT /id="VSP_028587"
SQ SEQUENCE 1073 AA; 118924 MW; E34A0B88D61CEE2B CRC64;
MGTGPGVSGR RAAARPSSEL PSPDSQLLWV GGHAHSSDSQ VCHHADCQQL HHRGPLNLCE
TCDSKFHSTL HYDGHVRFDL PPQGSVLARN VSTRSCPPRT SPAADLEEEE EGCTDGKGDR
KSAGLKISKK KARRRHTDDP SKECFTLKFD LNVDIETEIV PAMKKKSLGE VLLPVFERKG
IALGKVDIYL DQSNTPLSLT FEAYRFGGHY LRVKAKPGDE GKVEQGVKDS KSLSLPALRP
SGAGPPVSER VDPQSRRESS LDILAPGRRR KNMSEFLGEA GIPGHEPPAP SSCSLPVGSS
GGTSSGINES WKNRAASRFS GFFSSSPSTS AFSREVDKME QLESKLHAYS LFGLPRMPRR
LRFDHDSWEE EEEDDEEDEE SSGLRLEDSW RELTDGHEKL TRRQCHQQEA VWELLHTEVS
YIRKLRVITN LFLCCLLNLQ ESGLLCEVEA ERLFSNIPEI AKLHRGLWGS VMVPVLEKAR
RTRALLQPSD FLKGFKMFGS LFKPYIRYCM EEEGCMEYMR GLLRDNDLFR AYVTWAEKHQ
QCQRLKLSDM LAKPHQRLTK YPLLLKSVLR KTDDPRTKEA IVTMISSVER FIHHVNTCMR
QRQERQRLAG VVSRIDAYEV VEGSNDEVDK LLKEFLHLDL TAPMPGTSPE ETRQLLLEGS
LRMKEGKDSK MDVYCFLFTD LLLVTKAVKK AERTKVIRPP LLVDKIVCRE LRDPGSFLLI
YLNEFHSAVG AYTFQASSQA LCRSWVDTIY NAQNQLQQLR AQLSAQEHPG SQHLQSLEEE
EDEQEEEGEE SGTSAASSPT ILRKSSNSLD SEHCTSDGST ETLAMVVVEP GATLSSPEFE
GGPVSSQSDE SSLSNTASSV TPTSELLPLG PVDGRSCSMD SAYGTLSPTS LQDFVAPHPV
VEPAPVPQTP SPQPSPRLRR RTPVQLLPRP PRLLKSKSEA SLLQLLSGTP AARGVPPAPS
RSLSELCLIS VAPGVRTQRP LQEGGPGWNG PGMCDPCHGP QLSESENRPS HMTGGPADSA
RRRCREMPSG TMSRVQSEPP SGVSAQHRKL TLAQLYRIRT TLLLNSTLTA SEV
