ID   ARHG9_HUMAN             Reviewed;         516 AA.
AC   O43307; Q5JSL6;
DT   17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 3.
DT   25-JAN-2012, entry version 88.
DE   RecName: Full=Rho guanine nucleotide exchange factor 9;
DE   AltName: Full=Collybistin;
DE   AltName: Full=PEM-2 homolog;
DE   AltName: Full=Rac/Cdc42 guanine nucleotide exchange factor 9;
GN   Name=ARHGEF9; Synonyms=KIAA0424;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   MEDLINE=98116655; PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA   Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA   Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. VIII.
RT   78 new cDNA clones from brain which code for large proteins in
RT   vitro.";
RL   DNA Res. 4:307-313(1997).
RN   [2]
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.,
RA   Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA   Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA   Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA   Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA   Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA   Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA   Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA   Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA   Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA   Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA   Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA   Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA   Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA   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.,
RA   Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA   Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA   Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA   Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA   Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA   Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA   Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA   Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA   Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA   de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA   Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA   Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA   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.,
RA   Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA   Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA   Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA   Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA   Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA   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.,
RA   Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA   Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA   Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA   Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA   Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA   Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA   Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA   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.,
RA   Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA   Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=10559246; DOI=10.1074/jbc.274.47.33587;
RA   Reid T., Bathoorn A., Ahmadian M.R., Collard J.G.;
RT   "Identification and characterization of hPEM-2, a guanine nucleotide
RT   exchange factor specific for Cdc42.";
RL   J. Biol. Chem. 274:33587-33593(1999).
RN   [5]
RP   STRUCTURE BY NMR OF 7-75.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the SH3 domain from Rho guanine nucleotide
RT   exchange factor 9.";
RL   Submitted (FEB-2009) to the PDB data bank.
RN   [6]
RP   VARIANT STHEE ALA-55, CHARACTERIZATION OF VARIANT STHEE ALA-55, AND
RP   ALTERNATIVE SPLICING.
RX   PubMed=15215304; DOI=10.1523/JNEUROSCI.1184-04.2004;
RA   Harvey K., Duguid I.C., Alldred M.J., Beatty S.E., Ward H., Keep N.H.,
RA   Lingenfelter S.E., Pearce B.R., Lundgren J., Owen M.J., Smart T.G.,
RA   Luescher B., Rees M.I., Harvey R.J.;
RT   "The GDP-GTP exchange factor collybistin: an essential determinant of
RT   neuronal gephyrin clustering.";
RL   J. Neurosci. 24:5816-5826(2004).
CC   -!- FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for
CC       CDC42. Promotes formation of GPHN clusters.
CC   -!- SUBUNIT: Interacts with GPHN.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- TISSUE SPECIFICITY: Detected in brain. Detected at low levels in
CC       heart.
CC   -!- DISEASE: Defects in ARHGEF9 are a cause of startle disease with
CC       epilepsy (STHEE) [MIM:300607]; also known as hyperekplexia with
CC       epilepsy. Startle disease is a genetically heterogeneous
CC       neurologic disorder. STHE is characterized by muscular rigidity of
CC       central nervous system origin, particularly in the neonatal
CC       period, and by an exaggerated startle response to unexpected
CC       acoustic or tactile stimuli.
CC   -!- SIMILARITY: Contains 1 DH (DBL-homology) domain.
CC   -!- SIMILARITY: Contains 1 PH domain.
CC   -!- SIMILARITY: Contains 1 SH3 domain.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA24854.2; Type=Erroneous initiation;
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ARHGEF9";
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DR   EMBL; AB007884; BAA24854.2; ALT_INIT; mRNA.
DR   EMBL; AL451106; CAI39550.1; -; Genomic_DNA.
DR   EMBL; AL355142; CAI39550.1; JOINED; Genomic_DNA.
DR   EMBL; AL391277; CAI39550.1; JOINED; Genomic_DNA.
DR   EMBL; AL391277; CAI40401.1; -; Genomic_DNA.
DR   EMBL; AL355142; CAI40401.1; JOINED; Genomic_DNA.
DR   EMBL; AL451106; CAI40401.1; JOINED; Genomic_DNA.
DR   EMBL; AL355142; CAI41195.1; -; Genomic_DNA.
DR   EMBL; AL391277; CAI41195.1; JOINED; Genomic_DNA.
DR   EMBL; AL451106; CAI41195.1; JOINED; Genomic_DNA.
DR   EMBL; BC117406; AAI17407.1; -; mRNA.
DR   IPI; IPI00552489; -.
DR   RefSeq; NP_001166950.1; NM_001173479.1.
DR   RefSeq; NP_001166951.1; NM_001173480.1.
DR   RefSeq; NP_056000.1; NM_015185.2.
DR   UniGene; Hs.54697; -.
DR   PDB; 2YSQ; NMR; -; A=7-75.
DR   PDBsum; 2YSQ; -.
DR   ProteinModelPortal; O43307; -.
DR   SMR; O43307; 4-450.
DR   IntAct; O43307; 1.
DR   STRING; O43307; -.
DR   PhosphoSite; O43307; -.
DR   PRIDE; O43307; -.
DR   Ensembl; ENST00000253401; ENSP00000253401; ENSG00000131089.
DR   GeneID; 23229; -.
DR   KEGG; hsa:23229; -.
DR   UCSC; uc004dvl.2; human.
DR   CTD; 23229; -.
DR   GeneCards; GC0XM062771; -.
DR   H-InvDB; HIX0016835; -.
DR   HGNC; HGNC:14561; ARHGEF9.
DR   HPA; HPA035419; -.
DR   MIM; 300429; gene.
DR   MIM; 300607; phenotype.
DR   neXtProt; NX_O43307; -.
DR   Orphanet; 163985; Hyperekplexia - epilepsy.
DR   eggNOG; prNOG07760; -.
DR   GeneTree; ENSGT00600000084023; -.
DR   HOGENOM; HBG402888; -.
DR   HOVERGEN; HBG050568; -.
DR   OrthoDB; EOG4ZPDV0; -.
DR   PhylomeDB; O43307; -.
DR   Reactome; REACT_111102; Signal Transduction.
DR   Reactome; REACT_13685; Neuronal System.
DR   Reactome; REACT_15518; Transmembrane transport of small molecules.
DR   NextBio; 44841; -.
DR   ArrayExpress; O43307; -.
DR   Bgee; O43307; -.
DR   CleanEx; HS_ARHGEF9; -.
DR   Genevestigator; O43307; -.
DR   GermOnline; ENSG00000131089; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005089; F:Rho guanyl-nucleotide exchange factor activity; IEA:InterPro.
DR   GO; GO:0006915; P:apoptotic process; TAS:Reactome.
DR   GO; GO:0008624; P:induction of apoptosis by extracellular signals; TAS:Reactome.
DR   GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR   GO; GO:0048011; P:nerve growth factor receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
DR   GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
DR   GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR   InterPro; IPR000219; DH-domain.
DR   InterPro; IPR011993; PH_type.
DR   InterPro; IPR001849; Pleckstrin_homology.
DR   InterPro; IPR011511; SH3_2.
DR   InterPro; IPR001452; SH3_domain.
DR   Gene3D; G3DSA:2.30.29.30; PH_type; 1.
DR   Gene3D; G3DSA:1.20.900.10; RhoGEF; 1.
DR   Pfam; PF00169; PH; 1.
DR   Pfam; PF00621; RhoGEF; 1.
DR   Pfam; PF07653; SH3_2; 1.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00325; RhoGEF; 1.
DR   SMART; SM00326; SH3; 1.
DR   SUPFAM; SSF48065; DH-domain; 1.
DR   SUPFAM; SSF50044; SH3; 1.
DR   PROSITE; PS00741; DH_1; FALSE_NEG.
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; Complete proteome; Cytoplasm; Disease mutation;
KW   Epilepsy; Guanine-nucleotide releasing factor; Reference proteome;
KW   SH3 domain.
FT   CHAIN         1    516       Rho guanine nucleotide exchange factor 9.
FT                                /FTId=PRO_0000253895.
FT   DOMAIN        8     67       SH3.
FT   DOMAIN      103    287       DH.
FT   DOMAIN      318    425       PH.
FT   REGION      100    110       Interaction with GPHN (By similarity).
FT   VARIANT      55     55       G -> A (in STHEE; affects dendritic
FT                                gephrin clustering and trafficking of
FT                                GABA-A receptors to synapses).
FT                                /FTId=VAR_028752.
FT   STRAND       11     17
FT   STRAND       22     26
FT   STRAND       34     37
FT   STRAND       42     47
FT   HELIX        59     61
FT   STRAND       62     66
SQ   SEQUENCE   516 AA;  60982 MW;  AAEE17366B46B707 CRC64;
     MTLLITGDSI VSAEAVWDHV TMANRELAFK AGDVIKVLDA SNKDWWWGQI DDEEGWFPAS
     FVRLWVNQED EVEEGPSDVQ NGHLDPNSDC LCLGRPLQNR DQMRANVINE IMSTERHYIK
     HLKDICEGYL KQCRKRRDMF SDEQLKVIFG NIEDIYRFQM GFVRDLEKQY NNDDPHLSEI
     GPCFLEHQDG FWIYSEYCNN HLDACMELSK LMKDSRYQHF FEACRLLQQM IDIAIDGFLL
     TPVQKICKYP LQLAELLKYT AQDHSDYRYV AAALAVMRNV TQQINERKRR LENIDKIAQW
     QASVLDWEGE DILDRSSELI YTGEMAWIYQ PYGRNQQRVF FLFDHQMVLC KKDLIRRDIL
     YYKGRIDMDK YEVVDIEDGR DDDFNVSMKN AFKLHNKETE EIHLFFAKKL EEKIRWLRAF
     REERKMVQED EKIGFEISEN QKRQAAMTVR KVPKQKGVNS ARSVPPSYPP PQDPLNHGQY
     LVPDGIAQSQ VFEFTEPKRS QSPFWQNFSR LTPFKK
//