Rho guanine nucleotide exchange factor 6

Names and origin

Protein names

Recommended name:
    Rho guanine nucleotide exchange factor 6
Alternative name(s):
    Rac/Cdc42 guanine nucleotide exchange factor 6
    PAK-interacting exchange factor alpha
    Alpha-Pix
    COOL-2

Gene names

Name:	ARHGEF6
Synonyms:	COOL2, KIAA0006, PIXA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Hide | Top

Protein attributes

Sequence length	776 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

Hide | Top

General annotation (Comments)

Function	Acts as a RAC1 guanine nucleotide exchange factor (GEF).
Subunit structure	Interacts with PAK kinases through the SH3 domain. Interacts with GIT1. Component of cytoplasmic complexes, which also contain PXN, GIT1 and PAK1 By similarity.
Tissue specificity	Ubiquitous.
Involvement in disease	Defects in ARHGEF6 are the cause of non-syndromic mental retardation X-linked type 46 (MRX46) [MIM:300436]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs.
Sequence similarities	Contains 1 CH (calponin-homology) domain. Contains 1 DH (DBL-homology) domain. Contains 1 PH domain. Contains 1 SH3 domain.

Hide | Top

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Disease	Mental retardation
Domain	SH3 domain
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	JNK cascade Non-traceable author statement. Source: UniProtKB apoptosis Non-traceable author statement. Source: UniProtKB
Cellular component	intracellular Ref.2 Inferred by curator. Source: UniProtKB
Molecular function	GTPase activator activity Non-traceable author statement. Source: UniProtKB Rho guanyl-nucleotide exchange factor activity Ref.2 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Hide | Top

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15052-1) 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: Q15052-2) The sequence of this isoform differs from the canonical sequence as follows: 1-154: Missing.
Notes: No experimental confirmation available.

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 776

776

Rho guanine nucleotide exchange factor 6

Regions

Domain

1 – 110

110

CH

Domain

160 – 219

60

SH3

Domain

241 – 421

181

DH

Domain

443 – 548

106

PH

Amino acid modifications

Modified residue

122

1

Phosphoserine By similarity

Modified residue

225

1

Phosphoserine

Modified residue

488

1

Phosphoserine

Modified residue

640

1

Phosphoserine By similarity

Modified residue

650

1

Phosphothreonine By similarity

Modified residue

684

1

Phosphoserine

Natural variations

Alternative sequence

1 – 154

154

Missing in isoform 2.

Secondary structure

1

.

776

Helix Strand Turn

Details...

Hide | Top

Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified September 26, 2001. Version 2. Checksum: 5D2622314E46341B Show »	FASTA	776	87,499
10 20 30 40 50 60 MNPEEQIVTW LISLGVLESP KKTICDPEEF LKSSLKNGVV LCKLINRLMP GSVEKFCLDP 70 80 90 100 110 120 QTEADCINNI NDFLKGCATL QVEIFDPDDL YSGVNFSKVL STLLAVNKAT EDQLSERPCG 130 140 150 160 170 180 RSSSLSAANT SQTNPQGAVS STVSGLQRQS KTVEMTENGS HQLIVKARFN FKQTNEDELS 190 200 210 220 230 240 VCKGDIIYVT RVEEGGWWEG TLNGRTGWFP SNYVREIKSS ERPLSPKAVK GFETAPLTKN 250 260 270 280 290 300 YYTVVLQNIL DTEKEYAKEL QSLLVTYLRP LQSNNNLSTV EVTSLLGNFE EVCTFQQTLC 310 320 330 340 350 360 QALEECSKFP ENQHKVGGCL LSLMPHFKSM YLAYCANHPS AVNVLTQHSD ELEQFMENQG 370 380 390 400 410 420 ASSPGILILT TNLSKPFMRL EKYVTLLQEL ERHMEDTHPD HQDILKAIVA FKTLMGQCQD 430 440 450 460 470 480 LRKRKQLELQ ILSEPIQAWE GEDIKNLGNV IFMSQVMVQY GACEEKEERY LMLFSNVLIM 490 500 510 520 530 540 LSASPRMSGF IYQGKIPIAG TVVTRLDEIE GNDCTFEITG NTVERIVVHC NNNQDFQEWL 550 560 570 580 590 600 EQLNRLIRGP ASCSSLSKTS SSSCSAHSSF SSTGQPRGPL EPPQIIKPWS LSCLRPAPPL 610 620 630 640 650 660 RPSAALGYKE RMSYILKESS KSPKTMKKFL HKRKTERKPS EEEYVIRKST AALEEDAQIL 670 680 690 700 710 720 KVIEAYCTSA NFQQGHGSST RKDSIPQVLL PEEEKLIIEE TRSNGQTIME EKSLVDTVYA 730 740 750 760 770 LKDEVRELKQ ENKRMKQCLE EELKSRRDLE KLVRRLLKQT DECIRGESSS KTSILP « Hide
Isoform 2 [UniParc]. Checksum: B336793DC9A235ED Show »		622	70,791
10 20 30 40 50 60 MTENGSHQLI VKARFNFKQT NEDELSVCKG DIIYVTRVEE GGWWEGTLNG RTGWFPSNYV 70 80 90 100 110 120 REIKSSERPL SPKAVKGFET APLTKNYYTV VLQNILDTEK EYAKELQSLL VTYLRPLQSN 130 140 150 160 170 180 NNLSTVEVTS LLGNFEEVCT FQQTLCQALE ECSKFPENQH KVGGCLLSLM PHFKSMYLAY 190 200 210 220 230 240 CANHPSAVNV LTQHSDELEQ FMENQGASSP GILILTTNLS KPFMRLEKYV TLLQELERHM 250 260 270 280 290 300 EDTHPDHQDI LKAIVAFKTL MGQCQDLRKR KQLELQILSE PIQAWEGEDI KNLGNVIFMS 310 320 330 340 350 360 QVMVQYGACE EKEERYLMLF SNVLIMLSAS PRMSGFIYQG KIPIAGTVVT RLDEIEGNDC 370 380 390 400 410 420 TFEITGNTVE RIVVHCNNNQ DFQEWLEQLN RLIRGPASCS SLSKTSSSSC SAHSSFSSTG 430 440 450 460 470 480 QPRGPLEPPQ IIKPWSLSCL RPAPPLRPSA ALGYKERMSY ILKESSKSPK TMKKFLHKRK 490 500 510 520 530 540 TERKPSEEEY VIRKSTAALE EDAQILKVIE AYCTSANFQQ GHGSSTRKDS IPQVLLPEEE 550 560 570 580 590 600 KLIIEETRSN GQTIMEEKSL VDTVYALKDE VRELKQENKR MKQCLEEELK SRRDLEKLVR 610 620 RLLKQTDECI RGESSSKTSI LP « Hide

Hide | Top

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1." Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S. DNA Res. 1:27-35(1994) [PubMed: 7584026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-776 (ISOFORM 1). Tissue: Bone marrow.
[2]	"Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation." Kutsche K., Yntema H., Brandt A., Jantke I., Nothwang H.G., Orth U., Boavida M.G., David D., Chelly J., Fryns J.-P., Moraine C., Ropers H.-H., Hamel B.C.J., van Bokhoven H., Gal A. Nat. Genet. 26:247-250(2000) [PubMed: 11017088] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-3 (ISOFORM 1), DISEASE.
[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. Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Testis.
[5]	"Characterization of ARHGEF6, a guanine nucleotide exchange factor for Rho GTPases and a candidate gene for X-linked mental retardation: mutation screening in Borjeson-Forssman-Lehmann syndrome and MRX27." Lower K.M., Gecz J. Am. J. Med. Genet. 100:43-48(2001) [PubMed: 11337747] [Abstract] Cited for: CHARACTERIZATION.
[6]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225 AND SER-684, MASS SPECTROMETRY. Tissue: T-cell.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, MASS SPECTROMETRY.
[11]	"Solution structure of SH3 domain in RAC/CDC42 guanine nucleotide exchange factor(GEF) 6." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 159-222.