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Protein

Rho guanine nucleotide exchange factor 5

Gene

ARHGEF5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Guanine nucleotide exchange factor which activates Rho GTPases (PubMed:15601624). Strongly activates RHOA (PubMed:15601624). Also strongly activates RHOB, weakly activates RHOC and RHOG and shows no effect on RHOD, RHOV, RHOQ or RAC1 (By similarity). Involved in regulation of cell shape and actin cytoskeletal organization (PubMed:15601624). Plays a role in actin organization by generating a loss of actin stress fibers and the formation of membrane ruffles and filopodia (PubMed:14662653). Required for SRC-induced podosome formation (By similarity). Involved in positive regulation of immature dendritic cell migration (By similarity).By similarity2 Publications

GO - Molecular functioni

  • GTP binding Source: ProtInc
  • guanyl-nucleotide exchange factor activity Source: UniProtKB
  • lipid binding Source: UniProtKB-KW
  • Rho guanyl-nucleotide exchange factor activity Source: Reactome

GO - Biological processi

  • actin cytoskeleton organization Source: Ensembl
  • G-protein coupled receptor signaling pathway Source: Reactome
  • intracellular signal transduction Source: InterPro
  • myeloid dendritic cell chemotaxis Source: Ensembl
  • positive regulation of apoptotic process Source: Reactome
  • positive regulation of DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of GTPase activity Source: Ensembl
  • positive regulation of JUN kinase activity Source: UniProtKB
  • positive regulation of podosome assembly Source: Ensembl
  • positive regulation of protein import Source: UniProtKB
  • positive regulation of stress fiber assembly Source: UniProtKB
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of cytoskeleton organization Source: UniProtKB
  • regulation of GTPase activity Source: MGI
  • regulation of Rho protein signal transduction Source: InterPro
  • regulation of small GTPase mediated signal transduction Source: Reactome

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-193648 NRAGE signals death through JNK
R-HSA-194840 Rho GTPase cycle
R-HSA-416482 G alpha (12/13) signalling events

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 5
Alternative name(s):
Ephexin-3
Guanine nucleotide regulatory protein TIM
Oncogene TIM
Transforming immortalized mammary oncogene
p60 TIM
Gene namesi
Name:ARHGEF5
Synonyms:TIM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000050327.14
HGNCiHGNC:13209 ARHGEF5
MIMi600888 gene
neXtProtiNX_Q12774

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi7984
OpenTargetsiENSG00000050327
PharmGKBiPA24975

Polymorphism and mutation databases

BioMutaiARHGEF5
DMDMi290457679

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809161 – 1597Rho guanine nucleotide exchange factor 5Add BLAST1597

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei184PhosphoserineCombined sources1
Modified residuei445PhosphoserineCombined sources1
Modified residuei450PhosphoserineCombined sources1
Modified residuei866Asymmetric dimethylarginineCombined sources1
Modified residuei983PhosphoserineCombined sources1
Modified residuei1011PhosphoserineCombined sources1
Modified residuei1044PhosphoserineCombined sources1
Modified residuei1126PhosphoserineCombined sources1

Post-translational modificationi

Activation of SRC induces tyrosine phosphorylation of ARHGEF5.By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ12774
MaxQBiQ12774
PaxDbiQ12774
PeptideAtlasiQ12774
PRIDEiQ12774

PTM databases

iPTMnetiQ12774
PhosphoSitePlusiQ12774

Expressioni

Tissue specificityi

Ubiquitously expressed with highest levels in placenta. High levels are also found in colon, kidney, trachea, prostate, liver, pancreas, pituitary gland, thyroid gland and mammary gland. In fetal tissues, expressed at high levels in kidney, lung and liver (PubMed:15601624). Expressed at low levels in lung and heart (PubMed:14662653).2 Publications

Gene expression databases

BgeeiENSG00000050327
CleanExiHS_ARHGEF5
ExpressionAtlasiQ12774 baseline and differential
GenevisibleiQ12774 HS

Organism-specific databases

HPAiHPA020980
HPA029504
HPA044188
HPA045619
HPA045699

Interactioni

Subunit structurei

Interacts with SRC (By similarity). Forms a ternary complex with SRC and the PI3K 85 kDa subunit (By similarity). Interacts with and is activated by the heterodimer formed by GNB1 and GNG2 (By similarity). Interacts with ODAM (via C-terminus) (PubMed:25911094). Interacts with RHOA (By similarity).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113696, 21 interactors
IntActiQ12774, 31 interactors
MINTiQ12774
STRINGi9606.ENSP00000056217

Structurei

3D structure databases

ProteinModelPortaliQ12774
SMRiQ12774
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1174 – 1358DHPROSITE-ProRule annotationAdd BLAST185
Domaini1390 – 1502PHPROSITE-ProRule annotationAdd BLAST113
Domaini1510 – 1571SH3PROSITE-ProRule annotationAdd BLAST62

Domaini

The PH domain binds to phosphoinositides and is essential for podosome formation.By similarity

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG3523 Eukaryota
COG5422 LUCA
GeneTreeiENSGT00550000074493
HOGENOMiHOG000170375
HOVERGENiHBG060842
InParanoidiQ12774
KOiK20684
OMAiWPHRRDS
OrthoDBiEOG091G00P4
PhylomeDBiQ12774
TreeFamiTF342609

Family and domain databases

CDDicd00160 RhoGEF, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR029212 ARHGEF5/35_N
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR001331 GDS_CDC24_CS
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF15441 ARHGEF5_35, 1 hit
PF00621 RhoGEF, 1 hit
PF14604 SH3_9, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00325 RhoGEF, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
SSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS00741 DH_1, 1 hit
PS50010 DH_2, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS50002 SH3, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: A number of additional isoforms are detected in primary breast tumors but not in normal tissues.1 Publication
Isoform 1 (identifier: Q12774-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEAEEAQRGA SPPISAIEEF SIIPEAPMRS SQVSALGLEA QEDEDPSYKW
60 70 80 90 100
REEHRLSATQ QSELRDVCDY AIETMPSFPK EGSADVEPNQ ESLVAEACDT
110 120 130 140 150
PEHWEAVPQS LAGRQARTLA PPELWACPIQ SEHLDMAPFS SDLGSEEEEV
160 170 180 190 200
EFWPGLTSLT LGSGQAEEEE ETSSDNSGQT RYYSPCEEHP AETNQNEGSE
210 220 230 240 250
SGTIRQGEEL PPEELQESQG LLHPQEVQVL EEQGQQEAGF RGEGTLREDV
260 270 280 290 300
CADGLLGEEQ MIEQVNDEKG EQKQKQEQVQ DVMLGRQGER MGLTGEPEGL
310 320 330 340 350
NDGEWEQEDM ERKAQGQGGP EQGEERKREL QVPEENRADS QDEKSQTFLG
360 370 380 390 400
KSEEVTGKQE DHGIKEKGVP VSGQEAKEPE SWDGGRLGAV GRARSREEEN
410 420 430 440 450
EHHGPSMPAL IAPEDSPHCD LFPGASYLMT QIPGTQTESR AEELSPAALS
460 470 480 490 500
PSLEPIRCSH QPISLLGSFL TEESPDKEID QNSQQEESRL RKGTVSSQGT
510 520 530 540 550
EVVFASASVT PPRTPDSAPP SPAEAYPITP ASVSARPPVA FPRRETSCAA
560 570 580 590 600
RAPETASAPL SMDDPSPCGT SEMCPAALYG FPSTGTSPPR PPANSTGTVQ
610 620 630 640 650
HLRSDSFPGS HRTEQTPDLV GMLLSYSHSE LPQRPPKPAI YSSVTPRRDR
660 670 680 690 700
RSGRDYSTVS ASPTALSTLK QDSQESISNL ERPSSPPSIQ PWVSPHNPAF
710 720 730 740 750
ATESPAYGSS PSFVSMEDVR IHEPLPPPPP QRRDTHPSVV ETDGHARVVV
760 770 780 790 800
PTLKQHSHPP PLALGSGLHA PHKGPLPQAS DPAVARQHRP LPSTPDSSHH
810 820 830 840 850
AQATPRWRYN KPLPPTPDLP QPHLPPISAP GSSRIYRPLP PLPIIDPPTE
860 870 880 890 900
PPPLPPKSRG RSRSTRGGHM NSGGHAKTRP ACQDWTVPLP ASAGRTSWPP
910 920 930 940 950
ATARSTESFT STSRSKSEVS PGMAFSNMTN FLCPSSPTTP WTPELQGPTS
960 970 980 990 1000
KDEAGVSEHP EAPAREPLRR TTPQQGASGP GRSPVGQARQ PEKPSHLHLE
1010 1020 1030 1040 1050
KASSWPHRRD SGRPPGDSSG QAVAPSEGAN KHKGWSRQGL RRPSILPEGS
1060 1070 1080 1090 1100
SDSRGPAVEK HPGPSDTVVF REKKPKEVMG GFSRRCSKLI NSSQLLYQEY
1110 1120 1130 1140 1150
SDVVLNKEIQ SQQRLESLSE TPGPSSPRQP RKALVSSESY LQRLSMASSG
1160 1170 1180 1190 1200
SLWQEIPVVR NSTVLLSMTH EDQKLQEVKF ELIVSEASYL RSLNIAVDHF
1210 1220 1230 1240 1250
QLSTSLRATL SNQEHQWLFS RLQDVRDVSA TFLSDLEENF ENNIFSFQVC
1260 1270 1280 1290 1300
DVVLNHAPDF RRVYLPYVTN QTYQERTFQS LMNSNSNFRE VLEKLESDPV
1310 1320 1330 1340 1350
CQRLSLKSFL ILPFQRITRL KLLLQNILKR TQPGSSEEAE ATKAHHALEQ
1360 1370 1380 1390 1400
LIRDCNNNVQ SMRRTEELIY LSQKIEFECK IFPLISQSRW LVKSGELTAL
1410 1420 1430 1440 1450
EFSASPGLRR KLNTRPVHLH LFNDCLLLSR PREGSRFLVF DHAPFSSIRG
1460 1470 1480 1490 1500
EKCEMKLHGP HKNLFRLFLR QNTQGAQAEF LFRTETQSEK LRWISALAMP
1510 1520 1530 1540 1550
REELDLLECY NSPQVQCLRA YKPRENDELA LEKADVVMVT QQSSDGWLEG
1560 1570 1580 1590
VRLSDGERGW FPVQQVEFIS NPEVRAQNLK EAHRVKTAKL QLVEQQA
Length:1,597
Mass (Da):176,799
Last modified:March 2, 2010 - v3
Checksum:i93EC1B1D7E1198C5
GO
Isoform 2 (identifier: Q12774-2) [UniParc]FASTAAdd to basket

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

Show »
Length:519
Mass (Da):60,056
Checksum:i2EE2C16B3F42C053
GO

Sequence cautioni

The sequence BAD18708 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti487E → G in BAD18708 (Ref. 2) Curated1
Sequence conflicti575P → Q in BAD18708 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0351751 – 1078Missing in isoform 2. 2 PublicationsAdd BLAST1078

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34771.1 [Q12774-1]
PIRiI38402
RefSeqiNP_005426.2, NM_005435.3 [Q12774-1]
UniGeneiHs.334
Hs.534621

Genome annotation databases

EnsembliENST00000056217; ENSP00000056217; ENSG00000050327 [Q12774-1]
ENST00000471847; ENSP00000418227; ENSG00000050327 [Q12774-2]
GeneIDi7984
KEGGihsa:7984
UCSCiuc003wel.4 human [Q12774-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiARHG5_HUMAN
AccessioniPrimary (citable) accession number: Q12774
Secondary accession number(s): A6NNJ2, Q6ZML7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: March 2, 2010
Last modified: March 28, 2018
This is version 163 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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