ID ARHG6_MOUSE Reviewed; 771 AA.
AC Q8K4I3; Q8C9V4;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 24-JAN-2024, entry version 153.
DE RecName: Full=Rho guanine nucleotide exchange factor 6;
DE AltName: Full=Alpha-PIX;
DE AltName: Full=Rac/Cdc42 guanine nucleotide exchange factor 6;
GN Name=Arhgef6;
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], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=12063400; DOI=10.1159/000059346;
RA Kutsche K., Gal A.;
RT "The mouse Arhgef6 gene: cDNA sequence, expression analysis, and chromosome
RT assignment.";
RL Cytogenet. Cell Genet. 95:196-201(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-622.
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487 AND SER-679, AND
RP IDENTIFICATION BY 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 [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PARVB.
RX PubMed=18325335; DOI=10.1016/j.febslet.2008.01.064;
RA Matsuda C., Kameyama K., Suzuki A., Mishima W., Yamaji S., Okamoto H.,
RA Nishino I., Hayashi Y.K.;
RT "Affixin activates Rac1 via betaPIX in C2C12 myoblast.";
RL FEBS Lett. 582:1189-1196(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-679, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487; SER-639 AND SER-679, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC 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 [8]
RP STRUCTURE BY NMR OF 429-547.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the pleckstrin homology domain of alpha-PIX.";
RL Submitted (MAY-2004) to the PDB data bank.
CC -!- FUNCTION: Acts as a RAC1 guanine nucleotide exchange factor (GEF).
CC {ECO:0000250}.
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. Interacts with BIN2. Identified in a complex with BIN2
CC and GIT2 (By similarity). Interacts with PARVB. {ECO:0000250,
CC ECO:0000269|PubMed:18325335}.
CC -!- INTERACTION:
CC Q8K4I3; Q9HBI1: PARVB; Xeno; NbExp=3; IntAct=EBI-6272809, EBI-1047679;
CC -!- SUBCELLULAR LOCATION: Cell projection, lamellipodium
CC {ECO:0000269|PubMed:18325335}.
CC -!- TISSUE SPECIFICITY: Detected in adult heart, spleen, lung, skeletal
CC muscle, kidney and testis. Detected throughout embryogenesis.
CC {ECO:0000269|PubMed:12063400}.
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DR EMBL; AF393831; AAM94903.1; -; mRNA.
DR EMBL; AK040468; BAC30599.1; -; mRNA.
DR CCDS; CCDS40984.2; -.
DR RefSeq; NP_690014.2; NM_152801.2.
DR PDB; 1V61; NMR; -; A=429-547.
DR PDBsum; 1V61; -.
DR AlphaFoldDB; Q8K4I3; -.
DR BMRB; Q8K4I3; -.
DR SMR; Q8K4I3; -.
DR BioGRID; 215941; 11.
DR IntAct; Q8K4I3; 5.
DR MINT; Q8K4I3; -.
DR STRING; 10090.ENSMUSP00000033468; -.
DR GlyGen; Q8K4I3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8K4I3; -.
DR PhosphoSitePlus; Q8K4I3; -.
DR EPD; Q8K4I3; -.
DR jPOST; Q8K4I3; -.
DR MaxQB; Q8K4I3; -.
DR PaxDb; 10090-ENSMUSP00000033468; -.
DR ProteomicsDB; 265082; -.
DR DNASU; 73341; -.
DR Ensembl; ENSMUST00000033468.11; ENSMUSP00000033468.6; ENSMUSG00000031133.13.
DR GeneID; 73341; -.
DR KEGG; mmu:73341; -.
DR AGR; MGI:1920591; -.
DR CTD; 9459; -.
DR MGI; MGI:1920591; Arhgef6.
DR eggNOG; KOG2070; Eukaryota.
DR GeneTree; ENSGT00940000158723; -.
DR InParanoid; Q8K4I3; -.
DR OrthoDB; 2879064at2759; -.
DR PhylomeDB; Q8K4I3; -.
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-446388; Regulation of cytoskeletal remodeling and cell spreading by IPP complex components.
DR Reactome; R-MMU-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR BioGRID-ORCS; 73341; 3 hits in 78 CRISPR screens.
DR ChiTaRS; Arhgef6; mouse.
DR EvolutionaryTrace; Q8K4I3; -.
DR PRO; PR:Q8K4I3; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q8K4I3; Protein.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0030032; P:lamellipodium assembly; IMP:UniProtKB.
DR CDD; cd21265; CH_alphaPIX; 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; Calponin-like domain; 1.
DR Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1.
DR Gene3D; 1.20.5.390; L1 transposable element, trimerization domain; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 1.
DR InterPro; IPR035788; AlphaPIX_SH3.
DR InterPro; IPR001715; CH_dom.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR001331; GDS_CDC24_CS.
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 PANTHER; PTHR46026:SF2; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 6; 1.
DR PANTHER; PTHR46026; RHO-TYPE GUANINE NUCLEOTIDE EXCHANGE FACTOR, ISOFORM F; 1.
DR Pfam; PF16523; betaPIX_CC; 1.
DR Pfam; PF00307; CH; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF16615; RhoGEF67_u1; 1.
DR Pfam; PF16614; RhoGEF67_u2; 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; Calponin-homology domain, CH-domain; 1.
DR SUPFAM; SSF48065; DBL homology domain (DH-domain); 1.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF50044; SH3-domain; 1.
DR PROSITE; PS50021; CH; 1.
DR PROSITE; PS00741; DH_1; 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; Cell projection; Guanine-nucleotide releasing factor;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..771
FT /note="Rho guanine nucleotide exchange factor 6"
FT /id="PRO_0000080918"
FT DOMAIN 1..111
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 159..218
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 240..420
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 442..547
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 115..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 556..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..143
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..577
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15052"
FT MOD_RES 133
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q15052"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15052"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 639
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 679
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT TURN 430..432
FT /evidence="ECO:0007829|PDB:1V61"
FT TURN 444..446
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 452..457
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 460..463
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 467..472
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 477..481
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 483..487
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 490..495
FT /evidence="ECO:0007829|PDB:1V61"
FT TURN 497..499
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 507..511
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 515..518
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:1V61"
FT STRAND 524..527
FT /evidence="ECO:0007829|PDB:1V61"
FT HELIX 533..546
FT /evidence="ECO:0007829|PDB:1V61"
SQ SEQUENCE 771 AA; 87051 MW; 3A408B7D0D6FCEAE CRC64;
MNPEERLVTW LISLGVLESP KKTVCDPEEF LKSSLKNGVV LCKLINRLLP GSVEKYCLEP
QTEADCIDNI NDFLKGCATL QVEVFEPDDL YSGANFSKVL NTLLAVNKAT EDQLSERPCG
RSSSLSAATS SQTNPQVAVP STAPEQHSEE KAEMTENGSH QLIVKARFNF KQTNEDELSV
CKGDIIYVTR VEEGGWWEGT LNGRTGWFPS NYVREIKPSE RPLSPKAIKG FDTAPLTKNY
YTVVLQNILD TEKEYAKELQ SLLVTYLRPL QSNNNLSTVE FTCLLGNFEE VCTFQQTLCQ
ALEECSKFPE NQHKVGGCLL NLMPHFKSMY LAYCANHPSA VNVLTQHSDD LERFMENQGA
SSPGILILTT SLSKPFMRLE KYVTLLQELE RHMEDTHPDH QDILKAIIAF KTLMGQCQDL
RKRKQLELQI LSEPIQAWEG DDIKTLGNVI FMSQVVMQHG ACEEKEERYF LLFSSVLIML
SASPRMSGFM YQGKIPIAGM VVNRLDEIEG SDCMFEITGS TVERIVVHCN NNQDFQEWME
QLNRLTKGPT SCGSLSKTSS SSCSTHSSFS STGQPRGPLE PPQIIKPWSL SCLRPAPPLR
PSAALGYKER MSYILKESSK SPKTMKKFLH KRKTERKASE EEYVIRKSTA ALEEDAQILK
VIEAYCTSAS FQQGTRKDSV PQVLLPEEEK LIIEETRSNG QTIIEEKSLV DTVYALKDEV
KELKQENKKM KQCLEEELKS RKDLEKLVRK LLKQTDECIR SESSSKTSIL Q
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