Reviewed, UniProtKB/Swiss-Prot O43307 (ARHG9_HUMAN)

Names and origin

Protein names

Recommended name:
    Rho guanine nucleotide exchange factor 9
Alternative name(s):
    Rac/Cdc42 guanine nucleotide exchange factor 9
    Collybistin
    PEM-2 homolog

Gene names

Name:	ARHGEF9
Synonyms:	KIAA0424

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	516 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters. Ref.4
Subunit structure	Interacts with GPHN.
Subcellular location	Cytoplasm. Ref.4
Tissue specificity	Detected in brain. Detected at low levels in heart. Ref.4
Involvement in disease	Defects in ARHGEF9 are a cause of startle disease with epilepsy (STHEE) [MIM:300607]; also known as hyperekplexia with epilepsy. Startle disease is a genetically heterogeneous neurologic disorder. STHE is characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli. Ref.5
Sequence similarities	Contains 1 DH (DBL-homology) domain. Contains 1 PH domain. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Disease	Disease mutation Epilepsy
Domain	SH3 domain
Molecular function	Guanine-nucleotide releasing factor
Technical term	3D-structure
Gene Ontology (GO)
Biological process	regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 516	516	Rho guanine nucleotide exchange factor 9		PRO_0000253895
Regions
	Domain	8 – 67	60	SH3
	Domain	103 – 287	185	DH
	Domain	318 – 425	108	PH
	Region	100 – 110	11	Interaction with GPHN By similarity
Natural variations
	Natural variant	55	1	G → A in STHEE; affects dendritic gephrin clustering and trafficking of GABA-A receptors to synapses. Ref.5		VAR_028752

Sequences

	Sequence		Length	Mass (Da)
	O43307-1 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: AAEE17366B46B707	FASTA	516	60,982
	10 20 30 40 50 60 MTLLITGDSI VSAEAVWDHV TMANRELAFK AGDVIKVLDA SNKDWWWGQI DDEEGWFPAS 70 80 90 100 110 120 FVRLWVNQED EVEEGPSDVQ NGHLDPNSDC LCLGRPLQNR DQMRANVINE IMSTERHYIK 130 140 150 160 170 180 HLKDICEGYL KQCRKRRDMF SDEQLKVIFG NIEDIYRFQM GFVRDLEKQY NNDDPHLSEI 190 200 210 220 230 240 GPCFLEHQDG FWIYSEYCNN HLDACMELSK LMKDSRYQHF FEACRLLQQM IDIAIDGFLL 250 260 270 280 290 300 TPVQKICKYP LQLAELLKYT AQDHSDYRYV AAALAVMRNV TQQINERKRR LENIDKIAQW 310 320 330 340 350 360 QASVLDWEGE DILDRSSELI YTGEMAWIYQ PYGRNQQRVF FLFDHQMVLC KKDLIRRDIL 370 380 390 400 410 420 YYKGRIDMDK YEVVDIEDGR DDDFNVSMKN AFKLHNKETE EIHLFFAKKL EEKIRWLRAF 430 440 450 460 470 480 REERKMVQED EKIGFEISEN QKRQAAMTVR KVPKQKGVNS ARSVPPSYPP PQDPLNHGQY 490 500 510 LVPDGIAQSQ VFEFTEPKRS QSPFWQNFSR LTPFKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed: 9455477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Identification and characterization of hPEM-2, a guanine nucleotide exchange factor specific for Cdc42." Reid T., Bathoorn A., Ahmadian M.R., Collard J.G. J. Biol. Chem. 274:33587-33593(1999) [PubMed: 10559246] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]	"The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering." Harvey K., Duguid I.C., Alldred M.J., Beatty S.E., Ward H., Keep N.H., Lingenfelter S.E., Pearce B.R., Lundgren J., Owen M.J., Smart T.G., Luescher B., Rees M.I., Harvey R.J. J. Neurosci. 24:5816-5826(2004) [PubMed: 15215304] [Abstract] Cited for: VARIANT STHEE ALA-55, CHARACTERIZATION OF VARIANT STHEE ALA-55, ALTERNATIVE SPLICING.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB007884 mRNA. Translation: BAA24854.2. Different initiation.
AL451106, AL355142, AL391277 Genomic DNA. Translation: CAI39550.1.
AL391277, AL355142, AL451106 Genomic DNA. Translation: CAI40401.1.
AL355142, AL391277, AL451106 Genomic DNA. Translation: CAI41195.1.
BC117406 mRNA. Translation: AAI17407.1.

IPI

IPI00552489.

RefSeq

NP_056000.1.

UniGene

Hs.54697

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YSQ	NMR	-	A	7-75	[»]

SMR

O43307. Positions 90-454.

ModBase

Search...

Proteomic databases

PRIDE

O43307.

Genome annotation databases

Ensembl

ENSG00000131089. Homo sapiens. [Contig view]

GeneID

23229.

KEGG

hsa:23229.

Organism-specific databases

GeneCards

GC0XM062771.

HGNC

HGNC:14561. ARHGEF9.

MIM

300429. gene.
300607. phenotype.

Orphanet

163985. Hyperekplexia - epilepsy.
98465. X-linked neuromuscular intellectual deficit.

PharmGKB

PA24978.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O43307.

Enzyme and pathway databases

Reactome

REACT_11044. Signaling by Rho GTPases.

Gene expression databases

ArrayExpress

O43307.

Bgee

O43307.

CleanEx

HS_ARHGEF9.

GermOnline

ENSG00000131089. Homo sapiens.

Family and domain databases

InterPro

IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001849. Pleckstrin_homology.
IPR001452. SH3_domain.
[Graphical view]

Gene3D

G3DSA:1.20.900.10. RhoGEF. 1 hit.

Pfam

PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

ProDom

PD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

PROSITE

PS00741. DH_1. False negative.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

44841.

SOURCE

Search...

Entry information

Entry name

ARHG9_HUMAN

Accession

Primary (citable) accession number: O43307
Secondary accession number(s): Q5JSL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	October 17, 2006
Last modified:	June 16, 2009
This is version 63 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)