ARHG6_HUMAN
ID ARHG6_HUMAN Reviewed; 776 AA.
AC Q15052; A6NMW9; A8K6S7; B1AL37; Q15396; Q5JQ66; Q7Z3W1; Q86XH0;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 2.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Rho guanine nucleotide exchange factor 6;
DE AltName: Full=Alpha-Pix;
DE AltName: Full=COOL-2;
DE AltName: Full=PAK-interacting exchange factor alpha;
DE AltName: Full=Rac/Cdc42 guanine nucleotide exchange factor 6;
GN Name=ARHGEF6; Synonyms=COOL2, KIAA0006, PIXA;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Placenta;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adipose tissue;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
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 [MRNA] OF 1-3 (ISOFORM 1).
RX PubMed=11017088; DOI=10.1038/80002;
RA Kutsche K., Yntema H., Brandt A., Jantke I., Nothwang H.G., Orth U.,
RA Boavida M.G., David D., Chelly J., Fryns J.-P., Moraine C., Ropers H.-H.,
RA Hamel B.C.J., van Bokhoven H., Gal A.;
RT "Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for
RT Rho GTPases, in patients with X-linked mental retardation.";
RL Nat. Genet. 26:247-250(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-776 (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S.,
RA Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I. The
RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of
RT randomly sampled cDNA clones from human immature myeloid cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [8]
RP CHARACTERIZATION.
RX PubMed=11337747; DOI=10.1002/ajmg.1189;
RA Lower K.M., Gecz J.;
RT "Characterization of ARHGEF6, a guanine nucleotide exchange factor for Rho
RT GTPases and a candidate gene for X-linked mental retardation: mutation
RT screening in Borjeson-Forssman-Lehmann syndrome and MRX27.";
RL Am. J. Med. Genet. 100:43-48(2001).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [10]
RP INTERACTION WITH PARVB.
RX PubMed=15005707; DOI=10.1111/j.1356-9597.2004.00717.x;
RA Mishima W., Suzuki A., Yamaji S., Yoshimi R., Ueda A., Kaneko T.,
RA Tanaka J., Miwa Y., Ohno S., Ishigatsubo Y.;
RT "The first CH domain of affixin activates Cdc42 and Rac1 through alphaPIX,
RT a Cdc42/Rac1-specific guanine nucleotide exchanging factor.";
RL Genes Cells 9:193-204(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126; SER-144; SER-150;
RP SER-640 AND SER-684, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP INTERACTION WITH BIN2, AND IDENTIFICATION IN A COMPLEX WITH BIN2 AND GIT2.
RX PubMed=23285027; DOI=10.1371/journal.pone.0052401;
RA Sanchez-Barrena M.J., Vallis Y., Clatworthy M.R., Doherty G.J.,
RA Veprintsev D.B., Evans P.R., McMahon H.T.;
RT "Bin2 is a membrane sculpting N-BAR protein that influences leucocyte
RT podosomes, motility and phagocytosis.";
RL PLoS ONE 7:E52401-E52401(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-684, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-133; SER-225 AND SER-684, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP STRUCTURE BY NMR OF 4-222.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the CH domain and the SH3 domain in RAC/CDC42
RT guanine nucleotide exchange factor (GEF) 6.";
RL Submitted (FEB-2004) to the PDB data bank.
CC -!- FUNCTION: Acts as a RAC1 guanine nucleotide exchange factor (GEF).
CC -!- SUBUNIT: Interacts with PAK kinases through the SH3 domain. Interacts
CC with GIT1. Component of cytoplasmic complexes, which also contain PXN,
CC GIT1 and PAK1 (By similarity). Interacts with PARVB. Interacts with
CC BIN2. Identified in a complex with BIN2 and GIT2. {ECO:0000250,
CC ECO:0000269|PubMed:15005707, ECO:0000269|PubMed:23285027}.
CC -!- INTERACTION:
CC Q15052; Q14161-11: GIT2; NbExp=9; IntAct=EBI-1642523, EBI-12028686;
CC Q15052; Q08379: GOLGA2; NbExp=3; IntAct=EBI-1642523, EBI-618309;
CC Q15052; O75031: HSF2BP; NbExp=3; IntAct=EBI-1642523, EBI-7116203;
CC Q15052; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-1642523, EBI-747204;
CC Q15052; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-1642523, EBI-3044087;
CC Q15052; P41227: NAA10; NbExp=3; IntAct=EBI-1642523, EBI-747693;
CC Q15052; Q13153: PAK1; NbExp=4; IntAct=EBI-1642523, EBI-1307;
CC Q15052; Q13177: PAK2; NbExp=5; IntAct=EBI-1642523, EBI-1045887;
CC Q15052; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-1642523, EBI-302345;
CC Q15052; P78424: POU6F2; NbExp=3; IntAct=EBI-1642523, EBI-12029004;
CC Q15052; Q9UIY3: RWDD2A; NbExp=3; IntAct=EBI-1642523, EBI-17677006;
CC Q15052; O60880-1: SH2D1A; NbExp=3; IntAct=EBI-1642523, EBI-15552052;
CC Q15052; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-1642523, EBI-11952721;
CC Q15052; Q12933: TRAF2; NbExp=3; IntAct=EBI-1642523, EBI-355744;
CC Q15052; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-1642523, EBI-2130429;
CC -!- SUBCELLULAR LOCATION: Cell projection, lamellipodium {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15052-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15052-2; Sequence=VSP_015782;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA02796.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK291742; BAF84431.1; -; mRNA.
DR EMBL; AK294929; BAH11929.1; -; mRNA.
DR EMBL; BX537390; CAD97632.1; -; mRNA.
DR EMBL; AL683813; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL135783; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471150; EAW88460.1; -; Genomic_DNA.
DR EMBL; CH471150; EAW88461.1; -; Genomic_DNA.
DR EMBL; BC039856; AAH39856.1; -; mRNA.
DR EMBL; BC043505; AAH43505.1; ALT_TERM; mRNA.
DR EMBL; AF207831; AAG27169.1; -; mRNA.
DR EMBL; D13631; BAA02796.1; ALT_INIT; mRNA.
DR EMBL; D25304; BAA04985.1; -; mRNA.
DR CCDS; CCDS14660.1; -. [Q15052-1]
DR CCDS; CCDS78509.1; -. [Q15052-2]
DR RefSeq; NP_001293106.1; NM_001306177.1. [Q15052-2]
DR RefSeq; NP_004831.1; NM_004840.2. [Q15052-1]
DR PDB; 1UJY; NMR; -; A=160-222.
DR PDB; 1WYR; NMR; -; A=4-111.
DR PDBsum; 1UJY; -.
DR PDBsum; 1WYR; -.
DR AlphaFoldDB; Q15052; -.
DR BMRB; Q15052; -.
DR SMR; Q15052; -.
DR BioGRID; 114847; 83.
DR CORUM; Q15052; -.
DR DIP; DIP-42694N; -.
DR IntAct; Q15052; 55.
DR MINT; Q15052; -.
DR STRING; 9606.ENSP00000250617; -.
DR GlyGen; Q15052; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q15052; -.
DR PhosphoSitePlus; Q15052; -.
DR BioMuta; ARHGEF6; -.
DR DMDM; 17371603; -.
DR CPTAC; CPTAC-1735; -.
DR CPTAC; CPTAC-1736; -.
DR EPD; Q15052; -.
DR jPOST; Q15052; -.
DR MassIVE; Q15052; -.
DR MaxQB; Q15052; -.
DR PaxDb; Q15052; -.
DR PeptideAtlas; Q15052; -.
DR PRIDE; Q15052; -.
DR ProteomicsDB; 60406; -. [Q15052-1]
DR ProteomicsDB; 60407; -. [Q15052-2]
DR Antibodypedia; 515; 154 antibodies from 27 providers.
DR DNASU; 9459; -.
DR Ensembl; ENST00000250617.7; ENSP00000250617.6; ENSG00000129675.16. [Q15052-1]
DR Ensembl; ENST00000370620.5; ENSP00000359654.1; ENSG00000129675.16. [Q15052-2]
DR Ensembl; ENST00000370622.5; ENSP00000359656.1; ENSG00000129675.16. [Q15052-2]
DR GeneID; 9459; -.
DR KEGG; hsa:9459; -.
DR MANE-Select; ENST00000250617.7; ENSP00000250617.6; NM_004840.3; NP_004831.1.
DR UCSC; uc004fab.5; human. [Q15052-1]
DR CTD; 9459; -.
DR DisGeNET; 9459; -.
DR GeneCards; ARHGEF6; -.
DR HGNC; HGNC:685; ARHGEF6.
DR HPA; ENSG00000129675; Low tissue specificity.
DR MalaCards; ARHGEF6; -.
DR MIM; 300267; gene.
DR neXtProt; NX_Q15052; -.
DR OpenTargets; ENSG00000129675; -.
DR Orphanet; 777; X-linked non-syndromic intellectual disability.
DR PharmGKB; PA24976; -.
DR VEuPathDB; HostDB:ENSG00000129675; -.
DR eggNOG; KOG2070; Eukaryota.
DR GeneTree; ENSGT00940000158723; -.
DR HOGENOM; CLU_017010_1_1_1; -.
DR InParanoid; Q15052; -.
DR OMA; ECMRAES; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q15052; -.
DR TreeFam; TF316105; -.
DR PathwayCommons; Q15052; -.
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-446388; Regulation of cytoskeletal remodeling and cell spreading by IPP complex components.
DR Reactome; R-HSA-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR SignaLink; Q15052; -.
DR BioGRID-ORCS; 9459; 16 hits in 707 CRISPR screens.
DR ChiTaRS; ARHGEF6; human.
DR EvolutionaryTrace; Q15052; -.
DR GeneWiki; ARHGEF6; -.
DR GenomeRNAi; 9459; -.
DR Pharos; Q15052; Tbio.
DR PRO; PR:Q15052; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q15052; protein.
DR Bgee; ENSG00000129675; Expressed in biceps brachii and 206 other tissues.
DR Genevisible; Q15052; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; NAS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; NAS:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB.
DR CDD; cd00014; CH; 1.
DR CDD; cd01225; PH_Cool_Pix; 1.
DR CDD; cd00160; RhoGEF; 1.
DR CDD; cd12060; SH3_alphaPIX; 1.
DR Gene3D; 1.10.418.10; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR035788; AlphaPIX_SH3.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR032409; GEF6/7_CC.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR046376; PH_Cool_Pix.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR003096; SM22_calponin.
DR Pfam; PF16523; betaPIX_CC; 1.
DR Pfam; PF00307; CH; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00888; SM22CALPONIN.
DR SMART; SM00033; CH; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47576; SSF47576; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50021; CH; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection;
KW Guanine-nucleotide releasing factor; Phosphoprotein; Reference proteome;
KW SH3 domain.
FT CHAIN 1..776
FT /note="Rho guanine nucleotide exchange factor 6"
FT /id="PRO_0000080917"
FT DOMAIN 1..111
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 160..219
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 241..421
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 443..548
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 115..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 560..581
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 560..578
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 133
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4I3"
FT MOD_RES 640
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..154
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015782"
FT VARIANT 297
FT /note="Q -> H (in dbSNP:rs5974620)"
FT /id="VAR_051981"
FT CONFLICT 199
FT /note="E -> G (in Ref. 2; CAD97632)"
FT /evidence="ECO:0000305"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:1WYR"
FT HELIX 27..37
FT /evidence="ECO:0007829|PDB:1WYR"
FT HELIX 39..48
FT /evidence="ECO:0007829|PDB:1WYR"
FT HELIX 63..80
FT /evidence="ECO:0007829|PDB:1WYR"
FT HELIX 87..91
FT /evidence="ECO:0007829|PDB:1WYR"
FT HELIX 96..110
FT /evidence="ECO:0007829|PDB:1WYR"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:1UJY"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:1UJY"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:1UJY"
FT STRAND 198..202
FT /evidence="ECO:0007829|PDB:1UJY"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:1UJY"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:1UJY"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:1UJY"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:1UJY"
SQ SEQUENCE 776 AA; 87499 MW; 5D2622314E46341B CRC64;
MNPEEQIVTW LISLGVLESP KKTICDPEEF LKSSLKNGVV LCKLINRLMP GSVEKFCLDP
QTEADCINNI NDFLKGCATL QVEIFDPDDL YSGVNFSKVL STLLAVNKAT EDQLSERPCG
RSSSLSAANT SQTNPQGAVS STVSGLQRQS KTVEMTENGS HQLIVKARFN FKQTNEDELS
VCKGDIIYVT RVEEGGWWEG TLNGRTGWFP SNYVREIKSS ERPLSPKAVK GFETAPLTKN
YYTVVLQNIL DTEKEYAKEL QSLLVTYLRP LQSNNNLSTV EVTSLLGNFE EVCTFQQTLC
QALEECSKFP ENQHKVGGCL LSLMPHFKSM YLAYCANHPS AVNVLTQHSD ELEQFMENQG
ASSPGILILT TNLSKPFMRL EKYVTLLQEL ERHMEDTHPD HQDILKAIVA FKTLMGQCQD
LRKRKQLELQ ILSEPIQAWE GEDIKNLGNV IFMSQVMVQY GACEEKEERY LMLFSNVLIM
LSASPRMSGF IYQGKIPIAG TVVTRLDEIE GNDCTFEITG NTVERIVVHC NNNQDFQEWL
EQLNRLIRGP ASCSSLSKTS SSSCSAHSSF SSTGQPRGPL EPPQIIKPWS LSCLRPAPPL
RPSAALGYKE RMSYILKESS KSPKTMKKFL HKRKTERKPS EEEYVIRKST AALEEDAQIL
KVIEAYCTSA NFQQGHGSST RKDSIPQVLL PEEEKLIIEE TRSNGQTIME EKSLVDTVYA
LKDEVRELKQ ENKRMKQCLE EELKSRRDLE KLVRRLLKQT DECIRGESSS KTSILP
