PKHG5_HUMAN
ID PKHG5_HUMAN Reviewed; 1006 AA.
AC O94827; B3KU07; B7Z2M3; B7Z5X2; F5GZ21; F5H1I0; Q5SY17; Q5T8W5; Q5T8W9;
AC Q6ZNM0; Q7Z436; Q86YD8; Q96BS1;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-APR-2021, sequence version 4.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Pleckstrin homology domain-containing family G member 5;
DE Short=PH domain-containing family G member 5;
DE AltName: Full=Guanine nucleotide exchange factor 720;
DE Short=GEF720;
GN Name=PLEKHG5; Synonyms=KIAA0720;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Brain, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Pancreas, and Skin;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 19-1006 (ISOFORM 1).
RC TISSUE=Lung fibroblast;
RX PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y.,
RA Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.;
RT "Large-scale identification and characterization of human genes that
RT activate NF-kappaB and MAPK signaling pathways.";
RL Oncogene 22:3307-3318(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 102-1006 (ISOFORM 1).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11704860; DOI=10.1038/sj.onc.1204921;
RA De Toledo M., Coulon V., Schmidt S., Fort P., Blangy A.;
RT "The gene for a new brain specific RhoA exchange factor maps to the highly
RT unstable chromosomal region 1p36.2-1p36.3.";
RL Oncogene 20:7307-7317(2001).
RN [9]
RP TISSUE SPECIFICITY.
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 [10]
RP INVOLVEMENT IN CMTRIC.
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 [11]
RP FUNCTION.
RX PubMed=28847484; DOI=10.1016/j.yexcr.2017.08.025;
RA Iwatake M., Nishishita K., Okamoto K., Tsukuba T.;
RT "The Rho-specific guanine nucleotide exchange factor Plekhg5 modulates cell
RT polarity, adhesion, migration, and podosome organization in macrophages and
RT osteoclasts.";
RL Exp. Cell Res. 359:415-430(2017).
RN [12]
RP VARIANT DSMA4 SER-647.
RX PubMed=17564964; DOI=10.1086/518900;
RA Maystadt I., Rezsoehazy R., Barkats M., Duque S., Vannuffel P., Remacle S.,
RA Lambert B., Najimi M., Sokal E., Munnich A., Viollet L.,
RA Verellen-Dumoulin C.;
RT "The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of
RT autosomal recessive lower motor neuron disease with childhood onset.";
RL Am. J. Hum. Genet. 81:67-76(2007).
RN [13]
RP VARIANTS CMTRIC MET-663 AND ARG-820, AND CHARACTERIZATION OF VARIANTS
RP CMTRIC MET-663 AND ARG-820.
RX PubMed=23844677; DOI=10.1186/1750-1172-8-104;
RA Kim H.J., Hong Y.B., Park J.M., Choi Y.R., Kim Y.J., Yoon B.R., Koo H.,
RA Yoo J.H., Kim S.B., Park M., Chung K.W., Choi B.O.;
RT "Mutations in the PLEKHG5 gene is relevant with autosomal recessive
RT intermediate Charcot-Marie-Tooth disease.";
RL Orphanet J. Rare Dis. 8:104-104(2013).
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 (By similarity). Involved in the control of neuronal cell
CC differentiation (PubMed:11704860). Plays a role in angiogenesis through
CC regulation of endothelial cells chemotaxis. Affects also the migration,
CC adhesion, and matrix/bone degradation in macrophages and osteoclasts
CC (PubMed:23777631). {ECO:0000250|UniProtKB:Q66T02,
CC ECO:0000269|PubMed:11704860, ECO:0000269|PubMed:23777631}.
CC -!- SUBUNIT: Interacts with GIPC1/synectin and RHOA. {ECO:0000250}.
CC -!- INTERACTION:
CC O94827-4; O43865: AHCYL1; NbExp=3; IntAct=EBI-11980215, EBI-2371423;
CC O94827-4; Q15669: RHOH; NbExp=3; IntAct=EBI-11980215, EBI-1244971;
CC O94827-4; P61587: RND3; NbExp=3; IntAct=EBI-11980215, EBI-1111534;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q66T02}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q66T02}. Cell
CC membrane {ECO:0000250|UniProtKB:Q66T02}. Cell junction
CC {ECO:0000250|UniProtKB:Q66T02}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q66T02}. 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 Localizes at cell-cell junctions in quiescent endothelial cells, and
CC relocalizes to cytoplasmic vesicle and the leading edge of lamellipodia
CC in migrating endothelial cells. {ECO:0000250|UniProtKB:Q66T02}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O94827-5; Sequence=Displayed;
CC Name=2;
CC IsoId=O94827-3; Sequence=VSP_060959;
CC Name=3;
CC IsoId=O94827-4; Sequence=VSP_060961, VSP_060962;
CC Name=4;
CC IsoId=O94827-7; Sequence=VSP_060960;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the peripheral nervous
CC system and brain. Highest expression is observed in heart, lung,
CC kidney, testis and moderate expression is present in spleen, pancreas,
CC skeletal muscle, ovary and liver. Weakly expressed in glioblastoma
CC (GBM) cell lines. {ECO:0000269|PubMed:11704860,
CC ECO:0000269|PubMed:16467373, ECO:0000269|PubMed:9872452}.
CC -!- DISEASE: Distal spinal muscular atrophy, autosomal recessive, 4 (DSMA4)
CC [MIM:611067]: A neuromuscular disorder. Distal spinal muscular atrophy,
CC also known as distal hereditary motor neuronopathy, represents a
CC heterogeneous group of neuromuscular disorders caused by selective
CC degeneration of motor neurons in the anterior horn of the spinal cord,
CC without sensory deficit in the posterior horn. The overall clinical
CC picture consists of a classical distal muscular atrophy syndrome in the
CC legs without clinical sensory loss. The disease starts with weakness
CC and wasting of distal muscles of the anterior tibial and peroneal
CC compartments of the legs. Later on, weakness and atrophy may expand to
CC the proximal muscles of the lower limbs and/or to the distal upper
CC limbs. DSMA4 is characterized by childhood onset, generalized muscle
CC weakness and atrophy with denervation and normal sensation. Bulbar
CC symptoms and pyramidal signs are absent. {ECO:0000269|PubMed:17564964}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease, recessive, intermediate type, C
CC (CMTRIC) [MIM:615376]: A form of Charcot-Marie-Tooth disease, a
CC disorder of the peripheral nervous system, characterized by progressive
CC weakness and atrophy, initially of the peroneal muscles and later of
CC the distal muscles of the arms. Recessive intermediate forms of
CC Charcot-Marie-Tooth disease are characterized by clinical and
CC pathologic features intermediate between demyelinating and axonal
CC peripheral neuropathies, and motor median nerve conduction velocities
CC ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:23777631,
CC ECO:0000269|PubMed:23844677}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA34440.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC77354.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=BAC85124.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=BAG53269.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAH11909.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB018263; BAA34440.2; ALT_INIT; mRNA.
DR EMBL; AK096347; BAG53269.1; ALT_INIT; mRNA.
DR EMBL; AK294875; BAH11909.1; ALT_INIT; mRNA.
DR EMBL; AK299523; BAH13058.1; -; mRNA.
DR EMBL; AL591866; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL158217; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71539.1; -; Genomic_DNA.
DR EMBL; CH471130; EAW71547.1; -; Genomic_DNA.
DR EMBL; BC015231; AAH15231.1; -; mRNA.
DR EMBL; BC042606; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AB097001; BAC77354.1; ALT_SEQ; mRNA.
DR EMBL; AK131074; BAC85124.1; ALT_SEQ; mRNA.
DR CCDS; CCDS41240.1; -. [O94827-5]
DR CCDS; CCDS41241.1; -. [O94827-3]
DR CCDS; CCDS57967.1; -. [O94827-4]
DR CCDS; CCDS57968.1; -. [O94827-7]
DR CCDS; CCDS57969.1; -. [O94827-3]
DR CCDS; CCDS79.1; -. [O94827-5]
DR RefSeq; NP_001036128.1; NM_001042663.1. [O94827-3]
DR RefSeq; NP_001036129.1; NM_001042664.1. [O94827-5]
DR RefSeq; NP_001036130.1; NM_001042665.1. [O94827-5]
DR RefSeq; NP_001252521.1; NM_001265592.1. [O94827-3]
DR RefSeq; NP_001252522.1; NM_001265593.1. [O94827-7]
DR RefSeq; NP_001252523.1; NM_001265594.1. [O94827-4]
DR RefSeq; NP_065682.2; NM_020631.4. [O94827-5]
DR RefSeq; NP_941374.2; NM_198681.3. [O94827-5]
DR AlphaFoldDB; O94827; -.
DR SMR; O94827; -.
DR BioGRID; 121522; 28.
DR IntAct; O94827; 18.
DR STRING; 9606.ENSP00000439625; -.
DR iPTMnet; O94827; -.
DR PhosphoSitePlus; O94827; -.
DR BioMuta; PLEKHG5; -.
DR EPD; O94827; -.
DR jPOST; O94827; -.
DR MassIVE; O94827; -.
DR PaxDb; O94827; -.
DR PeptideAtlas; O94827; -.
DR PRIDE; O94827; -.
DR ProteomicsDB; 24913; -.
DR ProteomicsDB; 25662; -.
DR ProteomicsDB; 50471; -. [O94827-3]
DR ProteomicsDB; 50472; -. [O94827-4]
DR ProteomicsDB; 50473; -. [O94827-5]
DR Antibodypedia; 27380; 153 antibodies from 25 providers.
DR DNASU; 57449; -.
DR Ensembl; ENST00000340850.10; ENSP00000344570.5; ENSG00000171680.23. [O94827-5]
DR Ensembl; ENST00000377725.5; ENSP00000366954.1; ENSG00000171680.23. [O94827-4]
DR Ensembl; ENST00000377728.8; ENSP00000366957.3; ENSG00000171680.23. [O94827-5]
DR Ensembl; ENST00000377732.5; ENSP00000366961.1; ENSG00000171680.23. [O94827-3]
DR Ensembl; ENST00000377740.5; ENSP00000366969.4; ENSG00000171680.23. [O94827-5]
DR Ensembl; ENST00000400913.6; ENSP00000383704.1; ENSG00000171680.23. [O94827-5]
DR Ensembl; ENST00000400915.8; ENSP00000383706.4; ENSG00000171680.23. [O94827-3]
DR Ensembl; ENST00000537245.6; ENSP00000439625.2; ENSG00000171680.23. [O94827-3]
DR Ensembl; ENST00000675694.1; ENSP00000501925.1; ENSG00000171680.23. [O94827-5]
DR GeneID; 57449; -.
DR KEGG; hsa:57449; -.
DR MANE-Select; ENST00000377728.8; ENSP00000366957.3; NM_020631.6; NP_065682.2.
DR UCSC; uc001ank.1; human. [O94827-5]
DR CTD; 57449; -.
DR DisGeNET; 57449; -.
DR GeneCards; PLEKHG5; -.
DR GeneReviews; PLEKHG5; -.
DR HGNC; HGNC:29105; PLEKHG5.
DR HPA; ENSG00000171680; Tissue enhanced (skin).
DR MalaCards; PLEKHG5; -.
DR MIM; 611067; phenotype.
DR MIM; 611101; gene.
DR MIM; 615376; phenotype.
DR neXtProt; NX_O94827; -.
DR OpenTargets; ENSG00000171680; -.
DR Orphanet; 369867; Autosomal recessive intermediate Charcot-Marie-Tooth disease type C.
DR Orphanet; 206580; Autosomal recessive lower motor neuron disease with childhood onset.
DR PharmGKB; PA142671164; -.
DR VEuPathDB; HostDB:ENSG00000171680; -.
DR eggNOG; KOG3521; Eukaryota.
DR GeneTree; ENSGT00510000046843; -.
DR HOGENOM; CLU_005851_0_0_1; -.
DR InParanoid; O94827; -.
DR OrthoDB; 556467at2759; -.
DR PhylomeDB; O94827; -.
DR TreeFam; TF316755; -.
DR PathwayCommons; O94827; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; O94827; -.
DR SIGNOR; O94827; -.
DR BioGRID-ORCS; 57449; 22 hits in 1070 CRISPR screens.
DR ChiTaRS; PLEKHG5; human.
DR GeneWiki; PLEKHG5; -.
DR GenomeRNAi; 57449; -.
DR Pharos; O94827; Tbio.
DR PRO; PR:O94827; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O94827; protein.
DR Bgee; ENSG00000171680; Expressed in sural nerve and 107 other tissues.
DR ExpressionAtlas; O94827; baseline and differential.
DR Genevisible; O94827; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome.
DR GO; GO:0035767; P:endothelial cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
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 Charcot-Marie-Tooth disease; Cytoplasm; Disease variant; Membrane;
KW Neurodegeneration; Neuropathy; Phosphoprotein; Reference proteome.
FT CHAIN 1..1006
FT /note="Pleckstrin homology domain-containing family G
FT member 5"
FT /id="PRO_0000307134"
FT DOMAIN 336..528
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 584..684
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 148..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 212..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 690..754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 768..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 837..863
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 950..979
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..242
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..727
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 728..754
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..801
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 845..859
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 729
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q66T02"
FT MOD_RES 734
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66T02"
FT MOD_RES 851
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66T02"
FT MOD_RES 876
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66T02"
FT MOD_RES 881
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66T02"
FT VAR_SEQ 1
FT /note="M -> MDKGRAAKVCHHADCQQLHRRGPLNLCEACDSKFHSTM (in
FT isoform 2)"
FT /id="VSP_060959"
FT VAR_SEQ 1
FT /note="M -> MGTGPGVSGRLAASRPGPGLPLRDSEPSWAGGRARDGESQVCHHADC
FT QQLHRRGPLNLCEACDSKFHSTM (in isoform 4)"
FT /id="VSP_060960"
FT VAR_SEQ 913..930
FT /note="GIRTQGSPQEAGPSWDCR -> AQEADPGPALPNQDHPAA (in isoform
FT 3)"
FT /id="VSP_060961"
FT VAR_SEQ 931..1006
FT /note="Missing (in isoform 3)"
FT /id="VSP_060962"
FT VARIANT 647
FT /note="F -> S (in DSMA4; stability and intracellular
FT location affected severely impairing the NF-kappa-B
FT transduction pathway; dbSNP:rs63750315)"
FT /evidence="ECO:0000269|PubMed:17564964"
FT /id="VAR_035357"
FT VARIANT 663
FT /note="T -> M (in CMTRIC; in vitro assay suggests a defect
FT in activating the NF-kappa-B signaling pathway;
FT dbSNP:rs397515456)"
FT /evidence="ECO:0000269|PubMed:23844677"
FT /id="VAR_070217"
FT VARIANT 820
FT /note="G -> R (in CMTRIC; in vitro assay suggests a defect
FT in activating the NF-kappa-B signaling pathway;
FT dbSNP:rs202191898)"
FT /evidence="ECO:0000269|PubMed:23844677"
FT /id="VAR_070218"
FT CONFLICT 106
FT /note="P -> L (in Ref. 2; BAH11909)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="T -> S (in Ref. 1; BAA34440)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="M -> T (in Ref. 2; BAG53269)"
FT /evidence="ECO:0000305"
FT CONFLICT 904
FT /note="E -> G (in Ref. 2; BAG53269)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1006 AA; 111231 MW; 2260D175D3C27D76 CRC64;
MHYDGHVRFD LPPQGSVLAR NVSTRSCPPR TSPAVDLEEE EEESSVDGKG DRKSTGLKLS
KKKARRRHTD DPSKECFTLK FDLNVDIETE IVPAMKKKSL GEVLLPVFER KGIALGKVDI
YLDQSNTPLS LTFEAYRFGG HYLRVKAPAK PGDEGKVEQG MKDSKSLSLP ILRPAGTGPP
ALERVDAQSR RESLDILAPG RRRKNMSEFL GEASIPGQEP PTPSSCSLPS GSSGSTNTGD
SWKNRAASRF SGFFSSGPST SAFGREVDKM EQLEGKLHTY SLFGLPRLPR GLRFDHDSWE
EEYDEDEDED NACLRLEDSW RELIDGHEKL TRRQCHQQEA VWELLHTEAS YIRKLRVIIN
LFLCCLLNLQ ESGLLCEVEA ERLFSNIPEI AQLHRRLWAS VMAPVLEKAR RTRALLQPGD
FLKGFKMFGS LFKPYIRYCM EEEGCMEYMR GLLRDNDLFR AYITWAEKHP QCQRLKLSDM
LAKPHQRLTK YPLLLKSVLR KTEEPRAKEA VVAMIGSVER FIHHVNACMR QRQERQRLAA
VVSRIDAYEV VESSSDEVDK LLKEFLHLDL TAPIPGASPE ETRQLLLEGS LRMKEGKDSK
MDVYCFLFTD LLLVTKAVKK AERTRVIRPP LLVDKIVCRE LRDPGSFLLI YLNEFHSAVG
AYTFQASGQA LCRGWVDTIY NAQNQLQQLR AQEPPGSQQP LQSLEEEEDE QEEEEEEEEE
EEEGEDSGTS AASSPTIMRK SSGSPDSQHC ASDGSTETLA MVVVEPGDTL SSPEFDSGPF
SSQSDETSLS TTASSATPTS ELLPLGPVDG RSCSMDSAYG TLSPTSLQDF VAPGPMAELV
PRAPESPRVP SPPPSPRLRR RTPVQLLSCP PHLLKSKSEA SLLQLLAGAG THGTPSAPSR
SLSELCLAVP APGIRTQGSP QEAGPSWDCR GAPSPGSGPG LVGCLAGEPA GSHRKRCGDL
PSGASPRVQP EPPPGVSAQH RKLTLAQLYR IRTTLLLNST LTASEV
