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Protein

Rho guanine nucleotide exchange factor 12

Gene

Arhgef12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Guanine-nucleotide releasing factor

Enzyme and pathway databases

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

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1916882. Arhgef12.

Subcellular locationi

  • Cytoplasm Curated
  • Membrane Curated

  • Note: Translocated to the membrane upon stimulation.Curated

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 15431542Rho guanine nucleotide exchange factor 12PRO_0000080931Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei309 – 3091PhosphoserineCombined sources
Modified residuei341 – 3411PhosphoserineBy similarity
Modified residuei637 – 6371PhosphoserineBy similarity
Modified residuei736 – 7361PhosphothreonineBy similarity
Modified residuei1327 – 13271PhosphoserineCombined sources
Modified residuei1377 – 13771PhosphoserineBy similarity
Modified residuei1457 – 14571PhosphoserineBy similarity
Modified residuei1540 – 15401PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8R4H2.
MaxQBiQ8R4H2.
PaxDbiQ8R4H2.
PRIDEiQ8R4H2.

PTM databases

iPTMnetiQ8R4H2.
PhosphoSiteiQ8R4H2.

Expressioni

Tissue specificityi

Expressed in brain, predominantly in neuronal cell bodies.1 Publication

Gene expression databases

BgeeiQ8R4H2.
CleanExiMM_ARHGEF12.
ExpressionAtlasiQ8R4H2. baseline and differential.
GenevisibleiQ8R4H2. MM.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
Plxnb1Q8CJH32EBI-8046267,EBI-2637650

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ8R4H2. 4 interactions.
MINTiMINT-1774761.
STRINGi10090.ENSMUSP00000126598.

Structurei

3D structure databases

ProteinModelPortaliQ8R4H2.
SMRiQ8R4H2. Positions 67-151, 766-1138.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini72 – 15180PDZPROSITE-ProRule annotationAdd
BLAST
Domaini367 – 558192RGSLAdd
BLAST
Domaini787 – 977191DHPROSITE-ProRule annotationAdd
BLAST
Domaini1019 – 1132114PHPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili194 – 26269Sequence analysisAdd
BLAST
Coiled coili981 – 100424Sequence analysisAdd
BLAST

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.
InParanoidiQ8R4H2.

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]

Sequencei

Sequence statusi: Complete.

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

Q8R4H2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGTQSTITD RFPLKKPIRH GSILNRESPT DKKQKVERSS SHDFDPTDSS
60 70 80 90 100
SKKTKSSSEE SRSEIYGLVQ RCVIIQKDDN GFGLTVSGDN PVFVQSVKED
110 120 130 140 150
GAAMRAGVQT GDRIIKVNGT LVTHSNHLEV VKLIRSGSYV ALTVQGRPPG
160 170 180 190 200
SPQIPLADSE VEPSVTGHMS PIMTSPHSPG AAGNMERITS PVLVGEENNV
210 220 230 240 250
VHNQKVEILR KMLQKEQERL QLLQEDYNRT ATQRLLKEIQ EAKKHIPQLQ
260 270 280 290 300
EQLSKATGSA QDGAVIAPSR PLGDALTLSE AEADPGDGLC RTDWSSGDAS
310 320 330 340 350
RPSSDSADSP KSSLRERSYL EEAPERSEGV QDAEPQSLVG SPSTRGAPHI
360 370 380 390 400
IGAEDDDFGT EHEQINGQCS CFQSIELLKS RPAHLAVFLH HVVSQFDPAT
410 420 430 440 450
LLCYLYSDLY KQTNSKETRR VFLEFHQFFL DRSAHLKVPV PEEISVDLEK
460 470 480 490 500
RRPELIPEDL HRLYIQTMQE RVHPEVQRHL EDFRQKRSMG LTLAESELTK
510 520 530 540 550
LDAERDKDRG TLEKERACAE QIVTKIEEVL MTAQAVEEER SSTMQYVILM
560 570 580 590 600
YMKYLGVKVK EPRNLEHKRG RIGFLPKIKQ SMKKDREGEE KGKRRGFPSI
610 620 630 640 650
LGPPRRPSRH DNSAIGRAME IQKSRHPKHL STPSSVSPEP QDPAKLRQSG
660 670 680 690 700
VANEGTDTGY LPASSMSSAT SGTALSQEGG RENDTGTKQV GEASAPGDCL
710 720 730 740 750
DSTPRVPTTV FDFPPPLLDQ VQEEECEVER VAEHGTPKPF RKFDSIAFGE
760 770 780 790 800
SQSEDEQFEN DLETDPPNWQ QLVSREVLLG LKPSEIKRQE VINELFYTER
810 820 830 840 850
AHVRTLKVLD QVFYQRVSRE GILSPSELRK IFSNLEDILQ LHVGLNEQMK
860 870 880 890 900
AVRKRNETSV IDHIGEDLLI WFSGPGEEKL KHAAATFCSN QPFALEMIKS
910 920 930 940 950
RQKKDSRFHT FVQDAESNPL CRRLQLKDII PTQMQRLTKY PLLLDNIAKY
960 970 980 990 1000
TEWPPEREKV KKAADHCRQI LNYVNQAVRE AENKQRLEDY QRRLDTSNLK
1010 1020 1030 1040 1050
LSEYPNVDEL RNLDLTKRKM IHEGPLVWKV NRDKSIDLYT LLLEDILVLL
1060 1070 1080 1090 1100
QKQDDRLVLR CHSKILASTA DSKHTFSPVI KLSTVLVRQV ATDNKALFVI
1110 1120 1130 1140 1150
SMSDNGAQIY ELVAQTVSEK TVWQDLICRM AASVKEQSTK PIPLPQPPPC
1160 1170 1180 1190 1200
EGDNDEEEPA KLKVEHHDLS VAGLQSPDRV LGLESPLISS KPQSHSLNTP
1210 1220 1230 1240 1250
GKSAAEHLFV TATQFAKEQH ANGALKEGDG GYPVTIPGPH LPVSEERWAL
1260 1270 1280 1290 1300
DALRNLGLLK QLLVQQLGLT EKSTQEDWQS FSRYGPASEE VQADSGIRDL
1310 1320 1330 1340 1350
ENVKACHARE GQMSFKTGTG DIATCDSPRT STESCAAQDS VILASQDSQA
1360 1370 1380 1390 1400
SNVLVMDHMI LTPEMPPAEP EGGLDESGEH FFDAREAHSD DNPSEGDGAV
1410 1420 1430 1440 1450
KKEEKDVNLR ISGNCLILDG YDAVQESSTD EEVASSFPLQ PVTGIPAVDS
1460 1470 1480 1490 1500
SHQQQHSPQN VHPEGPVSPF TPEFLVQRHW RAMEDTCFEI QSPSCTDSQS
1510 1520 1530 1540
QILEYIHKIE ADLEHLKKVE ESYALLCQRL AGSALPDKLS DKS
Length:1,543
Mass (Da):172,349
Last modified:July 27, 2011 - v2
Checksum:i9A3D0B3BB8E40A86
GO

Sequence cautioni

The sequence BAC65549.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti307 – 3071A → V in BAC65549 (PubMed:12693553).Curated
Sequence conflicti320 – 3201L → S in AAL87100 (Ref. 1) Curated
Sequence conflicti334 – 3341E → QE in BAC65549 (PubMed:12693553).Curated
Sequence conflicti1447 – 14471A → T in BAC65549 (PubMed:12693553).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF467766 mRNA. Translation: AAL87100.1.
AK122267 mRNA. Translation: BAC65549.1. Different initiation.
AC110169 Genomic DNA. No translation available.
AC160123 Genomic DNA. No translation available.
RefSeqiXP_006510649.1. XM_006510586.2.
UniGeneiMm.275266.

Genome annotation databases

EnsembliENSMUST00000072767; ENSMUSP00000072547; ENSMUSG00000059495.
GeneIDi69632.
UCSCiuc009pbb.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF467766 mRNA. Translation: AAL87100.1.
AK122267 mRNA. Translation: BAC65549.1. Different initiation.
AC110169 Genomic DNA. No translation available.
AC160123 Genomic DNA. No translation available.
RefSeqiXP_006510649.1. XM_006510586.2.
UniGeneiMm.275266.

3D structure databases

ProteinModelPortaliQ8R4H2.
SMRiQ8R4H2. Positions 67-151, 766-1138.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8R4H2. 4 interactions.
MINTiMINT-1774761.
STRINGi10090.ENSMUSP00000126598.

PTM databases

iPTMnetiQ8R4H2.
PhosphoSiteiQ8R4H2.

Proteomic databases

EPDiQ8R4H2.
MaxQBiQ8R4H2.
PaxDbiQ8R4H2.
PRIDEiQ8R4H2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000072767; ENSMUSP00000072547; ENSMUSG00000059495.
GeneIDi69632.
UCSCiuc009pbb.1. mouse.

Organism-specific databases

CTDi23365.
MGIiMGI:1916882. Arhgef12.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG3520. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00760000119193.
HOGENOMiHOG000034046.
HOVERGENiHBG050571.
InParanoidiQ8R4H2.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiArhgef12. mouse.
PROiQ8R4H2.
SOURCEiSearch...

Gene expression databases

BgeeiQ8R4H2.
CleanExiMM_ARHGEF12.
ExpressionAtlasiQ8R4H2. baseline and differential.
GenevisibleiQ8R4H2. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "A novel murine gene encoding guanine nucleotide exchange factor and expressed in non-differentiated hematopoietic cells."
    Zinovyeva M.V., Sveshnikova E.V., Visser J.M., Belyavsky A.V.
    Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
    DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "Characterization of the expression of PDZ-RhoGEF, LARG and G(alpha)12/G(alpha)13 proteins in the murine nervous system."
    Kuner R., Swiercz J.M., Zywietz A., Tappe A., Offermanns S.
    Eur. J. Neurosci. 16:2333-2341(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1327, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309 AND SER-1327, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiARHGC_MOUSE
AccessioniPrimary (citable) accession number: Q8R4H2
Secondary accession number(s): E9QPW9, Q80U18
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: July 27, 2011
Last modified: May 11, 2016
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.