Reviewed, UniProtKB/Swiss-Prot Q12774 (ARHG5_HUMAN)

Names and origin

Protein names

Recommended name:
    Rho guanine nucleotide exchange factor 5
Alternative name(s):
    Guanine nucleotide regulatory protein TIM
    Oncogene TIM
    p60 TIM
    Transforming immortalized mammary oncogene

Gene names

Name:	ARHGEF5
Synonyms:	TIM

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1597 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Tissue specificity	Mainly expressed in kidney, liver, pancreas, lung and placenta.
Sequence similarities	Contains 1 DH (DBL-homology) domain. Contains 1 PH domain. Contains 1 SH3 domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	SH3 domain
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular function	GTP binding Ref.1 Traceable author statement. Source: ProtInc Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RHOA	P61586	1	EBI-602199,EBI-446668

Alternative products

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

Isoform 1 (identifier: Q12774-1)

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: Q12774-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1078: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1597	1597	Rho guanine nucleotide exchange factor 5		PRO_0000080916
Regions
	Domain	1174 – 1358	185	DH
	Domain	1390 – 1502	113	PH
	Domain	1513 – 1569	57	SH3
Amino acid modifications
	Modified residue	11	1	Phosphoserine Ref.9
	Modified residue	184	1	Phosphoserine Ref.9
	Modified residue	445	1	Phosphoserine Ref.9
	Modified residue	450	1	Phosphoserine Ref.9
	Modified residue	641	1	Phosphotyrosine Ref.10
	Modified residue	656	1	Phosphotyrosine Ref.10
	Modified residue	1097	1	Phosphotyrosine Ref.10 Ref.6
	Modified residue	1100	1	Phosphotyrosine Ref.10 Ref.6
	Modified residue	1126	1	Phosphoserine Ref.9 Ref.8
	Modified residue	1140	1	Phosphotyrosine Ref.10
	Modified residue	1370	1	Phosphotyrosine Ref.10 Ref.7
Natural variations
	Alternative sequence	1 – 1078	1078	Missing in isoform 2.		VSP_035175

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: 65C95087FC91BA4C	FASTA	1,597	176,758
	10 20 30 40 50 60 MEAEEAQRGA SPPISAIEEF SIIPEAPMRS SQVSALGLEA QEDEDPSYKW REEHRLSATQ 70 80 90 100 110 120 QSELRDVCDY AIETMPSFPK EGSADVEPNQ ESLVAEACDT PEHWEAVPQS LAGRQARTLA 130 140 150 160 170 180 PPELWACPIQ SEHLDMAPFS SDLGSEEEEV EFWPGLTSLT LGSGQAEEEE ETSSDNSGQT 190 200 210 220 230 240 RYYSPCEEHP AETNQNEGSE SGTIRQGEEL PPEELQESQG LLHPQEVQVL EEQGQQEAGF 250 260 270 280 290 300 RGEGTLREDV CADGLLGEEQ MIEQVNDEKG EQKQKQEQVQ DVMLGRQGER MGLTGEPEGL 310 320 330 340 350 360 NDGEWEQEDM ERKAQGQGGP EQGEERKREL QVPEENRADS QDEKSQTFLG KSEEVTGKQE 370 380 390 400 410 420 DHGIKEKGVP VSGQEAKEPE SWDGGRLGAV GRARSREEEN EHHGPSMPAL IAPEDSPHCD 430 440 450 460 470 480 LFPGASYLMT QIPGTQTESR AEELSPAALS PSLEPIRCSH QPISLLGSFL TEESPDKEID 490 500 510 520 530 540 QNSQQEGSRL RKGTVSSQGT EVVFASASVT PPRTPDSAPP SPAEAYPITP ASVSARPPVA 550 560 570 580 590 600 FPRRETSCAA RAPETASAPL SMDDPSPCGT SEMCQAALYG FPSTGTSPPR PPANSTGTVQ 610 620 630 640 650 660 HLRSDSFPGS HRTEQTPDLV GMLLSYSHSE LPQRPPKPAI YSSVTPRRDR RSGRDYSTVS 670 680 690 700 710 720 ASPTALSTLK QDSQESISNL ERPSSPPSIQ PWVSPHNPAF ATESPAYGSS PSFVSMEDVR 730 740 750 760 770 780 IHEPLPPPPP QRRDTHPSVV ETDGHARVVV PTLKQHSHPP PLALGSGLHA PHKGPLPQAS 790 800 810 820 830 840 DPAVARQHRP LPSTPDSSHH AQATPRWRYN KPLPPTPDLP QPHLPPISAP GSSRIYRPLP 850 860 870 880 890 900 PLPIIDPPTE PPPLPPKSRG RSRSTRGGHM NSGGHAKTRP ACQDWTVPLP ASAGRTSWPP 910 920 930 940 950 960 ATARSTESFT STSRSKSEVS PGMAFSNMTN FLCPSSPTTP WTPELQGPTS KDEAGVSEHP 970 980 990 1000 1010 1020 EAPAREPLRR TTPQQGASGP GRSPVGQARQ PEKPSHLHLE KASSWPHRRD SGRPPGDSSG 1030 1040 1050 1060 1070 1080 QAVAPSEGAN KHKGWSRQGL RRPSILPEGS SDSRGPAVEK HPGPSDTVVF REKKPKEVMG 1090 1100 1110 1120 1130 1140 GFSRRCSKLI NSSQLLYQEY SDVVLNKEIQ SQQRLESLSE TPGPSSPRQP RKALVSSESY 1150 1160 1170 1180 1190 1200 LQRLSMASSG SLWQEIPVVR NSTVLLSMTH EDQKLQEVKF ELIVSEASYL RSLNIAVDHF 1210 1220 1230 1240 1250 1260 QLSTSLRATL SNQEHQWLFS RLQDVRDVSA TFLSDLEENF ENNIFSFQVC DVVLNHAPDF 1270 1280 1290 1300 1310 1320 RRVYLPYVTN QTYQERTFQS LMNSNSNFRE VLEKLESDPV CQRLSLKSFL ILPFQRITRL 1330 1340 1350 1360 1370 1380 KLLLQNILKR TQPGSSEEAE ATKAHHALEQ LIRDCNNNVQ SMRRTEELIY LSQKIEFECK 1390 1400 1410 1420 1430 1440 IFPLISQSRW LVKSGELTAL EFSASPGLRR KLNTRPVHLH LFNDCLLLSR PREGSRFLVF 1450 1460 1470 1480 1490 1500 DHAPFSSIRG EKCEMKLHGP HKNLFRLFLR QNTQGAQAEF LFRTETQSEK LRWISALAMP 1510 1520 1530 1540 1550 1560 REELDLLECY NSPQVQCLRA YKPRENDELA LEKADVVMVT QQSSDGWLEG VRLSDGERGW 1570 1580 1590 FPVQQVEFIS NPEVRAQNLK EAHRVKTAKL QLVEQQA
	Isoform 2. Checksum: 2EE2C16B3F42C053	FASTA	519	60,056
	10 20 30 40 50 60 MGGFSRRCSK LINSSQLLYQ EYSDVVLNKE IQSQQRLESL SETPGPSSPR QPRKALVSSE 70 80 90 100 110 120 SYLQRLSMAS SGSLWQEIPV VRNSTVLLSM THEDQKLQEV KFELIVSEAS YLRSLNIAVD 130 140 150 160 170 180 HFQLSTSLRA TLSNQEHQWL FSRLQDVRDV SATFLSDLEE NFENNIFSFQ VCDVVLNHAP 190 200 210 220 230 240 DFRRVYLPYV TNQTYQERTF QSLMNSNSNF REVLEKLESD PVCQRLSLKS FLILPFQRIT 250 260 270 280 290 300 RLKLLLQNIL KRTQPGSSEE AEATKAHHAL EQLIRDCNNN VQSMRRTEEL IYLSQKIEFE 310 320 330 340 350 360 CKIFPLISQS RWLVKSGELT ALEFSASPGL RRKLNTRPVH LHLFNDCLLL SRPREGSRFL 370 380 390 400 410 420 VFDHAPFSSI RGEKCEMKLH GPHKNLFRLF LRQNTQGAQA EFLFRTETQS EKLRWISALA 430 440 450 460 470 480 MPREELDLLE CYNSPQVQCL RAYKPRENDE LALEKADVVM VTQQSSDGWL EGVRLSDGER 490 500 510 GWFPVQQVEF ISNPEVRAQN LKEAHRVKTA KLQLVEQQA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression cDNA cloning of a novel oncogene with sequence similarity to regulators of small GTP-binding proteins." Chan A.M.-L., McGovern E.S., Catalano G., Fleming T.P., Miki T. Oncogene 9:1057-1063(1994) [PubMed: 8134109] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Epithelium.
[2]	"The nucleotide sequence of a long cDNA clone isolated from human spleen." Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O. Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Spleen.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 2). Tissue: Placenta and Skin.
[6]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1097 AND TYR-1100, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1370, MASS SPECTROMETRY.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1126, MASS SPECTROMETRY.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-184; SER-445; SER-450 AND SER-1126, MASS SPECTROMETRY.
[10]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-641; TYR-656; TYR-1097; TYR-1100; TYR-1140 AND TYR-1370, MASS SPECTROMETRY. Tissue: Mammary epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U02082 mRNA. Translation: AAA18010.1. AK160365 mRNA. Translation: BAD18708.1. Different initiation. AC004534 Genomic DNA. Translation: AAC12958.1. CH471146 Genomic DNA. Translation: EAW80096.1. BC010046 mRNA. Translation: AAH10046.1. BC011839 mRNA. Translation: AAH11839.1. BC014555 mRNA. Translation: AAH14555.1.
IPI	IPI00418545. IPI00457243.
PIR	I38402.
RefSeq	NP_005426.2.
UniGene	Hs.334 Hs.591829
3D structure databases
HSSP	HSSP built from PDB template 1BB9 based on UniProtKB O08839.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q12774. 1 interaction.
STRING	Q12774.
Genome annotation databases
Ensembl	ENST00000056217; ENSP00000056217; ENSG00000050327; Homo sapiens. [Genome view] ENST00000344879; ENSP00000343699; ENSG00000050327; Homo sapiens. [Genome view]
GeneID	7984.
KEGG	hsa:7984.
UCSC	uc003wel.1. human. uc003wem.1. human.
Organism-specific databases
CTD	7984.
GeneCards	GC07P143683.
H-InvDB	HIX0007176. HIX0034082.
HGNC	HGNC:13209. ARHGEF5.
HPA	HPA020980.
MIM	600888. gene.
PharmGKB	PA24975.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q12774.
Gene expression databases
ArrayExpress	Q12774.
Bgee	Q12774.
CleanEx	HS_ARHGEF5.
Genevestigator	Q12774.
GermOnline	ENSG00000050327. Homo sapiens.
Family and domain databases
InterPro	IPR000219. DH-domain. IPR001331. GDS_CDC24_CS. IPR001849. Pleckstrin_homology. IPR011511. SH3_2. IPR001452. SH3_domain. [Graphical view]
Gene3D	G3DSA:1.20.900.10. RhoGEF. 1 hit.
Pfam	PF00169. PH. 1 hit. PF00621. RhoGEF. 1 hit. PF07653. SH3_2. 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. 1 hit. PS50010. DH_2. 1 hit. PS50003. PH_DOMAIN. 1 hit. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

ARHG5_HUMAN

Accession

Primary (citable) accession number: Q12774
Secondary accession number(s): A6NNJ2, Q6ZML7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	September 2, 2008
Last modified:	November 3, 2009
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.