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:	ARHDH9, KIAA0424

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.5
Subunit structure	Interacts with GPHN.
Subcellular location	Cytoplasm Ref.5.
Tissue specificity	Detected in brain. Detected at low levels in heart. Ref.5
Involvement in disease	Epileptic encephalopathy, early infantile, 8 (EIEE8) [MIM:300607]: A disorder characterized by hyperekplexia and early infantile epileptic encephalopathy. Neurologic features include exaggerated startle response, seizures, impaired psychomotor development, and mental retardation. Seizures can be provoked by tactile stimulation or extreme emotion. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
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
Coding sequence diversity	Alternative splicing
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 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 regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome 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 phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43307-1)

Also known as: CB3(SH3+);

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O43307-2)

Also known as: CB3(SH3-);

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MTLLITGDSI → MQWIRGGSGM
     11-63: Missing.

Isoform 3 (identifier: O43307-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: Missing.

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

Alternative sequence

1 – 102

102

Missing in isoform 3.

VSP_044555

Alternative sequence

1 – 10

10

MTLLITGDSI → MQWIRGGSGM in isoform 2.

VSP_042920

Alternative sequence

11 – 63

53

Missing in isoform 2.

VSP_042921

Natural variant

55

1

G → A in EIEE8; affects dendritic gephrin clustering and trafficking of GABA-A receptors to synapses. Ref.7

VAR_028752

Experimental info

Sequence conflict

109

1

N → D in BAF82682. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

516

Helix Strand Turn

Details...

Beta strand

11 – 17

7

Beta strand

22 – 26

5

Beta strand

34 – 39

6

Beta strand

42 – 49

8

Beta strand

54 – 58

5

Helix

59 – 61

3

Beta strand

62 – 66

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CB3(SH3+)) [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
	Isoform 2 (CB3(SH3-)) [UniParc]. Checksum: 046F5EC27274EC71	FASTA	463	54,965
	10 20 30 40 50 60 MQWIRGGSGM LWVNQEDEVE EGPSDVQNGH LDPNSDCLCL GRPLQNRDQM RANVINEIMS 70 80 90 100 110 120 TERHYIKHLK DICEGYLKQC RKRRDMFSDE QLKVIFGNIE DIYRFQMGFV RDLEKQYNND 130 140 150 160 170 180 DPHLSEIGPC FLEHQDGFWI YSEYCNNHLD ACMELSKLMK DSRYQHFFEA CRLLQQMIDI 190 200 210 220 230 240 AIDGFLLTPV QKICKYPLQL AELLKYTAQD HSDYRYVAAA LAVMRNVTQQ INERKRRLEN 250 260 270 280 290 300 IDKIAQWQAS VLDWEGEDIL DRSSELIYTG EMAWIYQPYG RNQQRVFFLF DHQMVLCKKD 310 320 330 340 350 360 LIRRDILYYK GRIDMDKYEV VDIEDGRDDD FNVSMKNAFK LHNKETEEIH LFFAKKLEEK 370 380 390 400 410 420 IRWLRAFREE RKMVQEDEKI GFEISENQKR QAAMTVRKVP KQKGVNSARS VPPSYPPPQD 430 440 450 460 PLNHGQYLVP DGIAQSQVFE FTEPKRSQSP FWQNFSRLTP FKK
	Isoform 3 [UniParc]. Checksum: 65A0F069D8E0A009	FASTA	414	49,458
	10 20 30 40 50 60 MRANVINEIM STERHYIKHL KDICEGYLKQ CRKRRDMFSD EQLKVIFGNI EDIYRFQMGF 70 80 90 100 110 120 VRDLEKQYNN DDPHLSEIGP CFLEHQDGFW IYSEYCNNHL DACMELSKLM KDSRYQHFFE 130 140 150 160 170 180 ACRLLQQMID IAIDGFLLTP VQKICKYPLQ LAELLKYTAQ DHSDYRYVAA ALAVMRNVTQ 190 200 210 220 230 240 QINERKRRLE NIDKIAQWQA SVLDWEGEDI LDRSSELIYT GEMAWIYQPY GRNQQRVFFL 250 260 270 280 290 300 FDHQMVLCKK DLIRRDILYY KGRIDMDKYE VVDIEDGRDD DFNVSMKNAF KLHNKETEEI 310 320 330 340 350 360 HLFFAKKLEE KIRWLRAFRE ERKMVQEDEK IGFEISENQK RQAAMTVRKV PKQKGVNSAR 370 380 390 400 410 SVPPSYPPPQ DPLNHGQYLV PDGIAQSQVF EFTEPKRSQS PFWQNFSRLT PFKK

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Hippocampus.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Brain and Uterus.
[5]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"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.
[7]	"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] [Europe PMC] [Abstract] Cited for: VARIANT EIEE8 ALA-55, CHARACTERIZATION OF VARIANT EIEE8 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.
AK289993 mRNA. Translation: BAF82682.1.
AK295033 mRNA. Translation: BAG58088.1.
AL451106, AL355142, AL391277 Genomic DNA. Translation: CAI39550.1.
AL391277, AL355142, AL451106 Genomic DNA. Translation: CAI40401.1.
AL355142, AL391277, AL451106 Genomic DNA. Translation: CAI41195.1.
BC056892 mRNA. No translation available.
BC117406 mRNA. Translation: AAI17407.1.

IPI

IPI00552489.
IPI00642855.
IPI00956432.

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.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43307. 1 interaction.

STRING

9606.ENSP00000253401.

PTM databases

PhosphoSite

O43307.

Proteomic databases

PaxDb

O43307.

PRIDE

O43307.

Protocols and materials databases

DNASU

23229.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000253401; ENSP00000253401; ENSG00000131089.
ENST00000374870; ENSP00000364004; ENSG00000131089.
ENST00000437457; ENSP00000399994; ENSG00000131089.
ENST00000601443; ENSP00000469587; ENSG00000268229.
ENST00000601864; ENSP00000471377; ENSG00000268229.
ENST00000602267; ENSP00000469767; ENSG00000268229.

GeneID

23229.

KEGG

hsa:23229.

UCSC

uc004dvj.2. human.

Organism-specific databases

CTD

23229.

GeneCards

GC0XM062771.

HGNC

HGNC:14561. ARHGEF9.

HPA

HPA035419.

MIM

300429. gene.
300607. phenotype.

neXtProt

NX_O43307.

Orphanet

163985. Hyperekplexia - epilepsy.

PharmGKB

PA24978.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5422.

HOGENOM

HOG000237363.

HOVERGEN

HBG050568.

OMA

VHLFFAK.

OrthoDB

EOG4ZPDV0.

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

Gene3D

1.20.900.10. 1 hit.
2.30.29.30. 1 hit.

InterPro

IPR000219. DH-domain.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00018. SH3_1. 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

EvolutionaryTrace

O43307.

GenomeRNAi

23229.

NextBio

44841.

SOURCE

Search...

Entry information

Entry name

ARHG9_HUMAN

Accession

Primary (citable) accession number: O43307
Secondary accession number(s): A8K1S8 , B4DHC7, F8W7P8, Q5JSL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 101 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.