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Protein

Rho guanine nucleotide exchange factor 12

Gene

ARHGEF12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Guanine-nucleotide releasing factor

Enzyme and pathway databases

BioCyciZFISH:G66-30983-MONOMER.
ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-416572. Sema4D induced cell migration and growth-cone collapse.
SIGNORiQ9NZN5.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 12
Alternative name(s):
Leukemia-associated RhoGEF
Gene namesi
Name:ARHGEF12
Synonyms:KIAA0382, LARG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:14193. ARHGEF12.

Subcellular locationi

  • Cytoplasm Curated
  • Membrane Curated

  • Note: Translocated to the membrane upon stimulation.Curated

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving ARHGEF12 may be a cause of acute leukemia. Translocation t(11;11)(q23;23) with KMT2A/MLL1.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei308 – 309Breakpoint for translocation to form KMT2A/MLL1-ARHGEF12 oncogene2

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi23365.
MalaCardsiARHGEF12.
OpenTargetsiENSG00000196914.
PharmGKBiPA24969.

Polymorphism and mutation databases

BioMutaiARHGEF12.
DMDMi34395525.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000809302 – 1544Rho guanine nucleotide exchange factor 12Add BLAST1543

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei41PhosphoserineCombined sources1
Modified residuei309PhosphoserineCombined sources1
Modified residuei341PhosphoserineCombined sources1
Modified residuei637PhosphoserineCombined sources1
Modified residuei736PhosphothreonineCombined sources1
Modified residuei1288PhosphoserineCombined sources1
Modified residuei1327PhosphoserineCombined sources1
Modified residuei1377PhosphoserineCombined sources1
Modified residuei1457PhosphoserineCombined sources1
Modified residuei1541PhosphoserineCombined sources1
Isoform 2 (identifier: Q9NZN5-2)
Modified residuei41PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9NZN5.
MaxQBiQ9NZN5.
PaxDbiQ9NZN5.
PeptideAtlasiQ9NZN5.
PRIDEiQ9NZN5.

PTM databases

iPTMnetiQ9NZN5.
PhosphoSitePlusiQ9NZN5.

Expressioni

Tissue specificityi

Ubiquitously expressed. Isoform 2 is found in jejunum and testis.

Gene expression databases

BgeeiENSG00000196914.
CleanExiHS_ARHGEF12.
ExpressionAtlasiQ9NZN5. baseline and differential.
GenevisibleiQ9NZN5. HS.

Organism-specific databases

HPAiCAB025581.
HPA018911.

Interactioni

Subunit structurei

Interacts with GNA12 and GNA13, probably through the RGS-like domain. Interacts with RHOA, PLXNB1 and PLXNB2. Interacts through its PDZ domain with IGF1R beta subunit. Interacts with GCSAM.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
IGF1RP080697EBI-821440,EBI-475981
Lpar1P617933EBI-821440,EBI-7512335From a different organism.
RHOAP615862EBI-821440,EBI-446668

GO - Molecular functioni

  • G-protein coupled receptor binding Source: MGI

Protein-protein interaction databases

BioGridi116945. 27 interactors.
DIPiDIP-37887N.
IntActiQ9NZN5. 16 interactors.
MINTiMINT-1774807.
STRINGi9606.ENSP00000380942.

Structurei

Secondary structure

11544
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi70 – 76Combined sources7
Beta strandi85 – 87Combined sources3
Beta strandi89 – 91Combined sources3
Beta strandi93 – 96Combined sources4
Helixi102 – 106Combined sources5
Beta strandi112 – 119Combined sources8
Turni122 – 124Combined sources3
Helixi127 – 135Combined sources9
Beta strandi137 – 145Combined sources9
Helixi769 – 772Combined sources4
Helixi775 – 778Combined sources4
Helixi783 – 812Combined sources30
Helixi814 – 820Combined sources7
Helixi825 – 832Combined sources8
Helixi835 – 853Combined sources19
Beta strandi857 – 860Combined sources4
Helixi865 – 872Combined sources8
Helixi875 – 889Combined sources15
Helixi891 – 904Combined sources14
Helixi906 – 917Combined sources12
Helixi919 – 921Combined sources3
Helixi926 – 929Combined sources4
Helixi932 – 949Combined sources18
Helixi954 – 993Combined sources40
Beta strandi1001 – 1003Combined sources3
Helixi1005 – 1007Combined sources3
Helixi1008 – 1011Combined sources4
Helixi1015 – 1017Combined sources3
Beta strandi1020 – 1033Combined sources14
Beta strandi1038 – 1053Combined sources16
Beta strandi1056 – 1058Combined sources3
Beta strandi1078 – 1081Combined sources4
Helixi1082 – 1084Combined sources3
Beta strandi1085 – 1089Combined sources5
Beta strandi1091 – 1093Combined sources3
Beta strandi1096 – 1102Combined sources7
Beta strandi1107 – 1113Combined sources7
Helixi1117 – 1137Combined sources21

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TXDX-ray2.13A766-1138[»]
1X86X-ray3.22A/C/E/G766-1138[»]
2OMJNMR-A67-151[»]
2OS6NMR-A67-151[»]
ProteinModelPortaliQ9NZN5.
SMRiQ9NZN5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NZN5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini72 – 151PDZPROSITE-ProRule annotationAdd BLAST80
Domaini367 – 558RGSLAdd BLAST192
Domaini787 – 977DHPROSITE-ProRule annotationAdd BLAST191
Domaini1019 – 1132PHPROSITE-ProRule annotationAdd BLAST114

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili194 – 262Sequence analysisAdd BLAST69

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 RGSL (RGS-like) domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG3520. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00760000119193.
HOGENOMiHOG000034046.
HOVERGENiHBG050571.
InParanoidiQ9NZN5.
KOiK07532.
OMAiRSTSHDF.
OrthoDBiEOG091G0CZH.
PhylomeDBiQ9NZN5.
TreeFamiTF106495.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001478. PDZ.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR016137. RGS.
IPR015212. RGS-like_dom.
[Graphical view]
PfamiPF00595. PDZ. 1 hit.
PF09128. RGS-like. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF48097. SSF48097. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q9NZN5-1) [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
MSGTQSTITD RFPLKKPIRH GSILNRESPT DKKQKVERIA SHDFDPTDSS
60 70 80 90 100
SKKTKSSSEE SRSEIYGLVQ RCVIIQKDDN GFGLTVSGDN PVFVQSVKED
110 120 130 140 150
GAAMRAGVQT GDRIIKVNGT LVTHSNHLEV VKLIKSGSYV ALTVQGRPPG
160 170 180 190 200
SPQIPLADSE VEPSVIGHMS PIMTSPHSPG ASGNMERITS PVLMGEENNV
210 220 230 240 250
VHNQKVEILR KMLQKEQERL QLLQEDYNRT PAQRLLKEIQ EAKKHIPQLQ
260 270 280 290 300
EQLSKATGSA QDGAVVTPSR PLGDTLTVSE AETDPGDVLG RTDCSSGDAS
310 320 330 340 350
RPSSDNADSP KSGPKERIYL EENPEKSETI QDTDTQSLVG SPSTRIAPHI
360 370 380 390 400
IGAEDDDFGT EHEQINGQCS CFQSIELLKS RPAHLAVFLH HVVSQFDPAT
410 420 430 440 450
LLCYLYSDLY KHTNSKETRR IFLEFHQFFL DRSAHLKVSV PDEMSADLEK
460 470 480 490 500
RRPELIPEDL HRHYIQTMQE RVHPEVQRHL EDFRQKRSMG LTLAESELTK
510 520 530 540 550
LDAERDKDRL TLEKERTCAE QIVAKIEEVL MTAQAVEEDK SSTMQYVILM
560 570 580 590 600
YMKHLGVKVK EPRNLEHKRG RIGFLPKIKQ SMKKDKEGEE KGKRRGFPSI
610 620 630 640 650
LGPPRRPSRH DNSAIGRAME LQKARHPKHL STPSSVSPEP QDSAKLRQSG
660 670 680 690 700
LANEGTDAGY LPANSMSSVA SGASFSQEGG KENDTGSKQV GETSAPGDTL
710 720 730 740 750
DGTPRTLNTV FDFPPPPLDQ VQEEECEVER VTEHGTPKPF RKFDSVAFGE
760 770 780 790 800
SQSEDEQFEN DLETDPPNWQ QLVSREVLLG LKPCEIKRQE VINELFYTER
810 820 830 840 850
AHVRTLKVLD QVFYQRVSRE GILSPSELRK IFSNLEDILQ LHIGLNEQMK
860 870 880 890 900
AVRKRNETSV IDQIGEDLLT WFSGPGEEKL KHAAATFCSN QPFALEMIKS
910 920 930 940 950
RQKKDSRFQT FVQDAESNPL CRRLQLKDII PTQMQRLTKY PLLLDNIAKY
960 970 980 990 1000
TEWPTEREKV KKAADHCRQI LNYVNQAVKE AENKQRLEDY QRRLDTSSLK
1010 1020 1030 1040 1050
LSEYPNVEEL RNLDLTKRKM IHEGPLVWKV NRDKTIDLYT LLLEDILVLL
1060 1070 1080 1090 1100
QKQDDRLVLR CHSKILASTA DSKHTFSPVI KLSTVLVRQV ATDNKALFVI
1110 1120 1130 1140 1150
SMSDNGAQIY ELVAQTVSEK TVWQDLICRM AASVKEQSTK PIPLPQSTPG
1160 1170 1180 1190 1200
EGDNDEEDPS KLKEEQHGIS VTGLQSPDRD LGLESTLISS KPQSHSLSTS
1210 1220 1230 1240 1250
GKSEVRDLFV AERQFAKEQH TDGTLKEVGE DYQIAIPDSH LPVSEERWAL
1260 1270 1280 1290 1300
DALRNLGLLK QLLVQQLGLT EKSVQEDWQH FPRYRTASQG PQTDSVIQNS
1310 1320 1330 1340 1350
ENIKAYHSGE GHMPFRTGTG DIATCYSPRT STESFAPRDS VGLAPQDSQA
1360 1370 1380 1390 1400
SNILVMDHMI MTPEMPTMEP EGGLDDSGEH FFDAREAHSD ENPSEGDGAV
1410 1420 1430 1440 1450
NKEEKDVNLR ISGNYLILDG YDPVQESSTD EEVASSLTLQ PMTGIPAVES
1460 1470 1480 1490 1500
THQQQHSPQN THSDGAISPF TPEFLVQQRW GAMEYSCFEI QSPSSCADSQ
1510 1520 1530 1540
SQIMEYIHKI EADLEHLKKV EESYTILCQR LAGSALTDKH SDKS
Length:1,544
Mass (Da):173,232
Last modified:October 1, 2000 - v1
Checksum:i0B7E319CF7C7A224
GO
Isoform 2 (identifier: Q9NZN5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     48-66: Missing.

Show »
Length:1,525
Mass (Da):171,115
Checksum:i47FF1323DE2DFF55
GO

Sequence cautioni

The sequence AAH63117 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020191973Y → F.1 PublicationCorresponds to variant rs2305013dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00813148 – 66Missing in isoform 2. 2 PublicationsAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF180681 mRNA. Translation: AAF36817.1.
AB002380 mRNA. Translation: BAA20836.2.
BC063117 mRNA. Translation: AAH63117.1. Sequence problems.
CCDSiCCDS41727.1. [Q9NZN5-1]
CCDS55794.1. [Q9NZN5-2]
RefSeqiNP_001185594.1. NM_001198665.1. [Q9NZN5-2]
NP_001288013.1. NM_001301084.1.
NP_056128.1. NM_015313.2. [Q9NZN5-1]
XP_011541022.1. XM_011542720.2.
XP_016872910.1. XM_017017421.1.
UniGeneiHs.24598.

Genome annotation databases

EnsembliENST00000356641; ENSP00000349056; ENSG00000196914. [Q9NZN5-2]
ENST00000397843; ENSP00000380942; ENSG00000196914. [Q9NZN5-1]
GeneIDi23365.
KEGGihsa:23365.
UCSCiuc001pxl.3. human. [Q9NZN5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF180681 mRNA. Translation: AAF36817.1.
AB002380 mRNA. Translation: BAA20836.2.
BC063117 mRNA. Translation: AAH63117.1. Sequence problems.
CCDSiCCDS41727.1. [Q9NZN5-1]
CCDS55794.1. [Q9NZN5-2]
RefSeqiNP_001185594.1. NM_001198665.1. [Q9NZN5-2]
NP_001288013.1. NM_001301084.1.
NP_056128.1. NM_015313.2. [Q9NZN5-1]
XP_011541022.1. XM_011542720.2.
XP_016872910.1. XM_017017421.1.
UniGeneiHs.24598.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TXDX-ray2.13A766-1138[»]
1X86X-ray3.22A/C/E/G766-1138[»]
2OMJNMR-A67-151[»]
2OS6NMR-A67-151[»]
ProteinModelPortaliQ9NZN5.
SMRiQ9NZN5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116945. 27 interactors.
DIPiDIP-37887N.
IntActiQ9NZN5. 16 interactors.
MINTiMINT-1774807.
STRINGi9606.ENSP00000380942.

PTM databases

iPTMnetiQ9NZN5.
PhosphoSitePlusiQ9NZN5.

Polymorphism and mutation databases

BioMutaiARHGEF12.
DMDMi34395525.

Proteomic databases

EPDiQ9NZN5.
MaxQBiQ9NZN5.
PaxDbiQ9NZN5.
PeptideAtlasiQ9NZN5.
PRIDEiQ9NZN5.

Protocols and materials databases

DNASUi23365.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356641; ENSP00000349056; ENSG00000196914. [Q9NZN5-2]
ENST00000397843; ENSP00000380942; ENSG00000196914. [Q9NZN5-1]
GeneIDi23365.
KEGGihsa:23365.
UCSCiuc001pxl.3. human. [Q9NZN5-1]

Organism-specific databases

CTDi23365.
DisGeNETi23365.
GeneCardsiARHGEF12.
H-InvDBHIX0010202.
HIX0036240.
HGNCiHGNC:14193. ARHGEF12.
HPAiCAB025581.
HPA018911.
MalaCardsiARHGEF12.
MIMi604763. gene.
neXtProtiNX_Q9NZN5.
OpenTargetsiENSG00000196914.
PharmGKBiPA24969.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3520. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00760000119193.
HOGENOMiHOG000034046.
HOVERGENiHBG050571.
InParanoidiQ9NZN5.
KOiK07532.
OMAiRSTSHDF.
OrthoDBiEOG091G0CZH.
PhylomeDBiQ9NZN5.
TreeFamiTF106495.

Enzyme and pathway databases

BioCyciZFISH:G66-30983-MONOMER.
ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-416572. Sema4D induced cell migration and growth-cone collapse.
SIGNORiQ9NZN5.

Miscellaneous databases

ChiTaRSiARHGEF12. human.
EvolutionaryTraceiQ9NZN5.
GeneWikiiARHGEF12.
GenomeRNAii23365.
PROiQ9NZN5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196914.
CleanExiHS_ARHGEF12.
ExpressionAtlasiQ9NZN5. baseline and differential.
GenevisibleiQ9NZN5. HS.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001478. PDZ.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR016137. RGS.
IPR015212. RGS-like_dom.
[Graphical view]
PfamiPF00595. PDZ. 1 hit.
PF09128. RGS-like. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF48097. SSF48097. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARHGC_HUMAN
AccessioniPrimary (citable) accession number: Q9NZN5
Secondary accession number(s): O15086, Q6P526
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 151 of the entry and version 1 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.