O43307 (ARHG9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rho guanine nucleotide exchange factor 9

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

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.
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.6
Sequence similarities	Contains 1 DH (DBL-homology) domain. Contains 1 PH domain. Contains 1 SH3 domain.
Sequence caution	The sequence BAA24854.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Disease	Disease mutation Epilepsy
Domain	SH3 domain
Molecular function	Guanine-nucleotide releasing factor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Traceable author statement. Source: Reactome induction of apoptosis by extracellular signals Traceable author statement. Source: Reactome ion transmembrane transport Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro small GTPase mediated signal transduction Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
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.6

VAR_028752

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

516

Helix Strand Turn

Details...

Beta strand

11 – 17

7

Beta strand

22 – 26

5

Beta strand

34 – 37

4

Beta strand

42 – 47

6

Helix

59 – 61

3

Beta strand

62 – 66

5

Sequences

	Sequence		Length	Mass (Da)
	O43307 [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]	"Solution structure of the SH3 domain from Rho guanine nucleotide exchange factor 9." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2009) to the PDB data bank Cited for: STRUCTURE BY NMR OF 7-75.
[6]	"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

EMBL
GenBank
DDBJ

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_001166950.1. NM_001173479.1.
NP_001166951.1. NM_001173480.1.
NP_056000.1. NM_015185.2.

UniGene

Hs.54697.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

O43307.

SMR

O43307. Positions 4-450.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43307. 1 interaction.

STRING

O43307.

PTM databases

PhosphoSite

O43307.

Proteomic databases

PRIDE

O43307.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000253401; ENSP00000253401; ENSG00000131089.

GeneID

23229.

KEGG

hsa:23229.

UCSC

uc004dvl.2. human.

Organism-specific databases

CTD

23229.

GeneCards

GC0XM062771.

H-InvDB

HIX0016835.

HGNC

HGNC:14561. ARHGEF9.

HPA

HPA035419.

MIM

300429. gene.
300607. phenotype.

neXtProt

NX_O43307.

Orphanet

163985. Hyperekplexia - epilepsy.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07760.

GeneTree

ENSGT00600000084023.

HOGENOM

HBG402888.

HOVERGEN

HBG050568.

OrthoDB

EOG4ZPDV0.

PhylomeDB

O43307.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpress

O43307.

Bgee

O43307.

CleanEx

HS_ARHGEF9.

Genevestigator

O43307.

GermOnline

ENSG00000131089. Homo sapiens.

Family and domain databases

InterPro

IPR000219. DH-domain.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:1.20.900.10. RhoGEF. 1 hit.

Pfam

PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]

SMART

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

SUPFAM

SSF48065. DH-domain. 1 hit.
SSF50044. SH3. 1 hit.

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

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:	January 25, 2012
This is version 88 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.