Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Rho guanine nucleotide exchange factor 12

Gene

ARHGEF12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionGTPase activation, Guanine-nucleotide releasing factor

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
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

EuPathDBiHostDB:ENSG00000196914.8
HGNCiHGNC:14193 ARHGEF12
MIMi604763 gene
neXtProtiNX_Q9NZN5

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

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/MLL1.1 Publication

Sites

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

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi23365
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
ProteomicsDBi83460
83461 [Q9NZN5-2]

PTM databases

iPTMnetiQ9NZN5
PhosphoSitePlusiQ9NZN5

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000196914 Expressed in 235 organ(s), highest expression level in visceral pleura
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116945, 32 interactors
DIPiDIP-37887N
IntActiQ9NZN5, 16 interactors
MINTiQ9NZN5
STRINGi9606.ENSP00000380942

Structurei

Secondary structure

11544
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

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

Family and domain databases

CDDicd13390 PH_LARG, 1 hit
cd08754 RGS_LARG, 1 hit
cd00160 RhoGEF, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR037801 ARHGEF12_PH
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR001331 GDS_CDC24_CS
IPR037884 LARG_RGS
IPR001478 PDZ
IPR036034 PDZ_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR015212 RGS-like_dom
IPR036305 RGS_sf
PfamiView protein in Pfam
PF00595 PDZ, 1 hit
PF09128 RGS-like, 1 hit
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00228 PDZ, 1 hit
SM00233 PH, 1 hit
SM00325 RhoGEF, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
SSF48097 SSF48097, 1 hit
SSF50156 SSF50156, 1 hit
PROSITEiView protein in PROSITE
PS00741 DH_1, 1 hit
PS50010 DH_2, 1 hit
PS50106 PDZ, 1 hit
PS50003 PH_DOMAIN, 1 hit

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PMR6E9PMR6_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF12
1,441Annotation score:

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 → F1 PublicationCorresponds to variant dbSNP:rs2305013Ensembl.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

Similar proteinsi

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, 32 interactors
DIPiDIP-37887N
IntActiQ9NZN5, 16 interactors
MINTiQ9NZN5
STRINGi9606.ENSP00000380942

PTM databases

iPTMnetiQ9NZN5
PhosphoSitePlusiQ9NZN5

Polymorphism and mutation databases

BioMutaiARHGEF12
DMDMi34395525

Proteomic databases

EPDiQ9NZN5
MaxQBiQ9NZN5
PaxDbiQ9NZN5
PeptideAtlasiQ9NZN5
PRIDEiQ9NZN5
ProteomicsDBi83460
83461 [Q9NZN5-2]

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
EuPathDBiHostDB:ENSG00000196914.8
GeneCardsiARHGEF12
H-InvDBiHIX0010202
HIX0036240
HGNCiHGNC:14193 ARHGEF12
HPAiCAB025581
HPA018911
MIMi604763 gene
neXtProtiNX_Q9NZN5
OpenTargetsiENSG00000196914
PharmGKBiPA24969
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

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
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse
SIGNORiQ9NZN5

Miscellaneous databases

ChiTaRSiARHGEF12 human
EvolutionaryTraceiQ9NZN5
GeneWikiiARHGEF12
GenomeRNAii23365
PROiPR:Q9NZN5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196914 Expressed in 235 organ(s), highest expression level in visceral pleura
CleanExiHS_ARHGEF12
ExpressionAtlasiQ9NZN5 baseline and differential
GenevisibleiQ9NZN5 HS

Family and domain databases

CDDicd13390 PH_LARG, 1 hit
cd08754 RGS_LARG, 1 hit
cd00160 RhoGEF, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR037801 ARHGEF12_PH
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR001331 GDS_CDC24_CS
IPR037884 LARG_RGS
IPR001478 PDZ
IPR036034 PDZ_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR015212 RGS-like_dom
IPR036305 RGS_sf
PfamiView protein in Pfam
PF00595 PDZ, 1 hit
PF09128 RGS-like, 1 hit
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00228 PDZ, 1 hit
SM00233 PH, 1 hit
SM00325 RhoGEF, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
SSF48097 SSF48097, 1 hit
SSF50156 SSF50156, 1 hit
PROSITEiView protein in PROSITE
PS00741 DH_1, 1 hit
PS50010 DH_2, 1 hit
PS50106 PDZ, 1 hit
PS50003 PH_DOMAIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiARHGC_HUMAN
AccessioniPrimary (citable) accession number: Q9NZN5
Secondary accession number(s): O15086, Q6P526
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 166 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again