UniProtKB - Q12774 (ARHG5_HUMAN)
Rho guanine nucleotide exchange factor 5
ARHGEF5
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 PublicationsGO - Molecular functioni
- GTP binding Source: ProtInc
- guanyl-nucleotide exchange factor activity Source: UniProtKB
- lipid binding Source: UniProtKB-KW
GO - Biological processi
- actin cytoskeleton organization Source: Ensembl
- activation of GTPase activity Source: GO_Central
- hematopoietic stem cell homeostasis Source: Ensembl
- intracellular signal transduction Source: InterPro
- myeloid dendritic cell chemotaxis Source: Ensembl
- positive regulation of DNA-binding transcription factor activity Source: UniProtKB
- 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 small GTPase mediated signal transduction Source: Reactome
Keywordsi
Molecular function | Guanine-nucleotide releasing factor |
Ligand | Lipid-binding |
Enzyme and pathway databases
PathwayCommonsi | Q12774 |
Reactomei | R-HSA-193648, NRAGE signals death through JNK R-HSA-416482, G alpha (12/13) signalling events R-HSA-8980692, RHOA GTPase cycle R-HSA-9013026, RHOB GTPase cycle R-HSA-9013106, RHOC GTPase cycle R-HSA-9013148, CDC42 GTPase cycle R-HSA-9013149, RAC1 GTPase cycle R-HSA-9013408, RHOG GTPase cycle |
SignaLinki | Q12774 |
SIGNORi | Q12774 |
Names & Taxonomyi
Protein namesi | Recommended name: Rho guanine nucleotide exchange factor 5Alternative name(s): Ephexin-3 Guanine nucleotide regulatory protein TIM Oncogene TIM Transforming immortalized mammary oncogene p60 TIM |
Gene namesi | Name:ARHGEF5 Synonyms:TIM |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:13209, ARHGEF5 |
MIMi | 600888, gene |
neXtProti | NX_Q12774 |
VEuPathDBi | HostDB:ENSG00000050327 |
Subcellular locationi
Cytoskeleton
- podosome Source: UniProtKB-SubCell
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- cell junction Source: UniProtKB-KW
- cell periphery Source: UniProtKB
- cell projection Source: UniProtKB-KW
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cell junction, Cell projection, Cytoplasm, NucleusPathology & Biotechi
Keywords - Diseasei
Proto-oncogeneOrganism-specific databases
DisGeNETi | 7984 |
OpenTargetsi | ENSG00000050327 |
PharmGKBi | PA24975 |
Miscellaneous databases
Pharosi | Q12774, Tbio |
Genetic variation databases
BioMutai | ARHGEF5 |
DMDMi | 290457679 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080916 | 1 – 1597 | Rho guanine nucleotide exchange factor 5Add BLAST | 1597 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 184 | PhosphoserineCombined sources | 1 | |
Modified residuei | 445 | PhosphoserineCombined sources | 1 | |
Modified residuei | 450 | PhosphoserineCombined sources | 1 | |
Modified residuei | 866 | Asymmetric dimethylarginineCombined sources | 1 | |
Modified residuei | 983 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1011 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1044 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1126 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
EPDi | Q12774 |
jPOSTi | Q12774 |
MassIVEi | Q12774 |
MaxQBi | Q12774 |
PaxDbi | Q12774 |
PeptideAtlasi | Q12774 |
PRIDEi | Q12774 |
ProteomicsDBi | 58920 [Q12774-1] 58921 [Q12774-2] |
PTM databases
iPTMneti | Q12774 |
PhosphoSitePlusi | Q12774 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000050327, Expressed in thoracic mammary gland and 176 other tissues |
ExpressionAtlasi | Q12774, baseline and differential |
Genevisiblei | Q12774, HS |
Organism-specific databases
HPAi | ENSG00000050327, Tissue enhanced (skin) |
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 PublicationBinary interactionsi
Q12774
Protein-protein interaction databases
BioGRIDi | 113696, 80 interactors |
IntActi | Q12774, 39 interactors |
MINTi | Q12774 |
STRINGi | 9606.ENSP00000056217 |
Miscellaneous databases
RNActi | Q12774, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1174 – 1358 | DHPROSITE-ProRule annotationAdd BLAST | 185 | |
Domaini | 1390 – 1502 | PHPROSITE-ProRule annotationAdd BLAST | 113 | |
Domaini | 1510 – 1571 | SH3PROSITE-ProRule annotationAdd BLAST | 62 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 138 – 246 | DisorderedSequence analysisAdd BLAST | 109 | |
Regioni | 258 – 455 | DisorderedSequence analysisAdd BLAST | 198 | |
Regioni | 467 – 1072 | DisorderedSequence analysisAdd BLAST | 606 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 176 – 203 | Polar residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 262 – 276 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 306 – 373 | Basic and acidic residuesSequence analysisAdd BLAST | 68 | |
Compositional biasi | 390 – 404 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 429 – 443 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 473 – 487 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 488 – 512 | Polar residuesSequence analysisAdd BLAST | 25 | |
Compositional biasi | 590 – 613 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 656 – 687 | Polar residuesSequence analysisAdd BLAST | 32 | |
Compositional biasi | 810 – 827 | Pro residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 836 – 858 | Pro residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 898 – 946 | Polar residuesSequence analysisAdd BLAST | 49 | |
Compositional biasi | 993 – 1014 | Basic and acidic residuesSequence analysisAdd BLAST | 22 |
Domaini
Keywords - Domaini
SH3 domainPhylogenomic databases
eggNOGi | KOG3523, Eukaryota |
GeneTreei | ENSGT01030000234571 |
HOGENOMi | CLU_003633_0_0_1 |
InParanoidi | Q12774 |
OMAi | QDDVMLG |
OrthoDBi | 1176939at2759 |
PhylomeDBi | Q12774 |
TreeFami | TF342609 |
Family and domain databases
CDDi | cd00160, RhoGEF, 1 hit |
Gene3Di | 1.20.900.10, 1 hit 2.30.29.30, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF15441, ARHGEF5_35, 1 hit PF00621, RhoGEF, 1 hit PF14604, SH3_9, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00325, RhoGEF, 1 hit SM00326, SH3, 1 hit |
SUPFAMi | SSF48065, SSF48065, 1 hit SSF50044, SSF50044, 1 hit |
PROSITEi | View protein in PROSITE PS00741, DH_1, 1 hit PS50010, DH_2, 1 hit PS50003, PH_DOMAIN, 1 hit PS50002, SH3, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0Y895 | H0Y895_HUMAN | Rho guanine nucleotide exchange fac... | ARHGEF5 | 797 | Annotation score: | ||
A0A2R8YF49 | A0A2R8YF49_HUMAN | Rho guanine nucleotide exchange fac... | ARHGEF5 | 1,597 | Annotation score: | ||
C9J591 | C9J591_HUMAN | Rho guanine nucleotide exchange fac... | ARHGEF5 | 181 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 487 | E → G in BAD18708 (Ref. 2) Curated | 1 | |
Sequence conflicti | 575 | P → Q in BAD18708 (Ref. 2) Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_035175 | 1 – 1078 | Missing in isoform 2. 2 PublicationsAdd BLAST | 1078 |
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 |
CCDSi | CCDS34771.1 [Q12774-1] |
PIRi | I38402 |
RefSeqi | NP_005426.2, NM_005435.3 [Q12774-1] |
Genome annotation databases
Ensembli | ENST00000056217.10; ENSP00000056217.5; ENSG00000050327.15 ENST00000471847.2; ENSP00000418227.1; ENSG00000050327.15 [Q12774-2] |
GeneIDi | 7984 |
KEGGi | hsa:7984 |
MANE-Selecti | ENST00000056217.10; ENSP00000056217.5; NM_005435.4; NP_005426.2 |
UCSCi | uc003wel.4, human [Q12774-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS34771.1 [Q12774-1] |
PIRi | I38402 |
RefSeqi | NP_005426.2, NM_005435.3 [Q12774-1] |
3D structure databases
AlphaFoldDBi | Q12774 |
SMRi | Q12774 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 113696, 80 interactors |
IntActi | Q12774, 39 interactors |
MINTi | Q12774 |
STRINGi | 9606.ENSP00000056217 |
PTM databases
iPTMneti | Q12774 |
PhosphoSitePlusi | Q12774 |
Genetic variation databases
BioMutai | ARHGEF5 |
DMDMi | 290457679 |
Proteomic databases
EPDi | Q12774 |
jPOSTi | Q12774 |
MassIVEi | Q12774 |
MaxQBi | Q12774 |
PaxDbi | Q12774 |
PeptideAtlasi | Q12774 |
PRIDEi | Q12774 |
ProteomicsDBi | 58920 [Q12774-1] 58921 [Q12774-2] |
Protocols and materials databases
Antibodypediai | 18513, 334 antibodies from 36 providers |
DNASUi | 7984 |
Genome annotation databases
Ensembli | ENST00000056217.10; ENSP00000056217.5; ENSG00000050327.15 ENST00000471847.2; ENSP00000418227.1; ENSG00000050327.15 [Q12774-2] |
GeneIDi | 7984 |
KEGGi | hsa:7984 |
MANE-Selecti | ENST00000056217.10; ENSP00000056217.5; NM_005435.4; NP_005426.2 |
UCSCi | uc003wel.4, human [Q12774-1] |
Organism-specific databases
CTDi | 7984 |
DisGeNETi | 7984 |
GeneCardsi | ARHGEF5 |
HGNCi | HGNC:13209, ARHGEF5 |
HPAi | ENSG00000050327, Tissue enhanced (skin) |
MIMi | 600888, gene |
neXtProti | NX_Q12774 |
OpenTargetsi | ENSG00000050327 |
PharmGKBi | PA24975 |
VEuPathDBi | HostDB:ENSG00000050327 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3523, Eukaryota |
GeneTreei | ENSGT01030000234571 |
HOGENOMi | CLU_003633_0_0_1 |
InParanoidi | Q12774 |
OMAi | QDDVMLG |
OrthoDBi | 1176939at2759 |
PhylomeDBi | Q12774 |
TreeFami | TF342609 |
Enzyme and pathway databases
PathwayCommonsi | Q12774 |
Reactomei | R-HSA-193648, NRAGE signals death through JNK R-HSA-416482, G alpha (12/13) signalling events R-HSA-8980692, RHOA GTPase cycle R-HSA-9013026, RHOB GTPase cycle R-HSA-9013106, RHOC GTPase cycle R-HSA-9013148, CDC42 GTPase cycle R-HSA-9013149, RAC1 GTPase cycle R-HSA-9013408, RHOG GTPase cycle |
SignaLinki | Q12774 |
SIGNORi | Q12774 |
Miscellaneous databases
BioGRID-ORCSi | 7984, 53 hits in 1063 CRISPR screens |
ChiTaRSi | ARHGEF5, human |
GeneWikii | ARHGEF5 |
GenomeRNAii | 7984 |
Pharosi | Q12774, Tbio |
PROi | PR:Q12774 |
RNActi | Q12774, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000050327, Expressed in thoracic mammary gland and 176 other tissues |
ExpressionAtlasi | Q12774, baseline and differential |
Genevisiblei | Q12774, HS |
Family and domain databases
CDDi | cd00160, RhoGEF, 1 hit |
Gene3Di | 1.20.900.10, 1 hit 2.30.29.30, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF15441, ARHGEF5_35, 1 hit PF00621, RhoGEF, 1 hit PF14604, SH3_9, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00325, RhoGEF, 1 hit SM00326, SH3, 1 hit |
SUPFAMi | SSF48065, SSF48065, 1 hit SSF50044, SSF50044, 1 hit |
PROSITEi | View protein in PROSITE PS00741, DH_1, 1 hit PS50010, DH_2, 1 hit PS50003, PH_DOMAIN, 1 hit PS50002, SH3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ARHG5_HUMAN | |
Accessioni | Q12774Primary (citable) accession number: Q12774 Secondary accession number(s): A6NNJ2, Q6ZML7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | March 2, 2010 | |
Last modified: | May 25, 2022 | |
This is version 189 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot