Q8R4H2

SS
Gene name
Arhgef12 (Kiaa0382, Larg)
Protein name
Rho guanine nucleotide exchange factor 12
Names
Leukemia-associated RhoGEF
Species
Mus musculus (Mouse)
KEGG Pathway
EC number
Protein Class

Descriptions

ARHGEF12 plays a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). It acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Its linker region connecting the N-terminal RGS-homology (RH) domain and the DH domain inhibits the intrinsic guanine nucleotide exchange (GEF) activity of ARHGEF12. Deletion of this region (residues 765-782) or mutations of a conserved tryptophan residue within this region, produced 80% declines in GEF activity of the LARG DH/PH domains toward RhoA.

Autoinhibitory domains (AIDs)

765-782 (Autoinhibitory region) SS

Target domain

413-766 (DH-PH domains)

Relief mechanism

Partner binding

Assay

240-394 (RGS-DH linker) SS

Target domain

413-766 (DH-PH domains)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q8R4H2

Entry ID Method Resolution Chain Position Source
AF-Q8R4H2-F1 Predicted AlphaFoldDB

84 variants for Q8R4H2

Variant ID(s) Position Change Description Diseaes Association Provenance
rs224684642 18 I>L No EVA
rs3389045145 27 E>* No EVA
rs3400052230 57 S>R No EVA
rs37844418 74 I>S No EVA
rs3389035030 81 G>V No EVA
rs3388985993 115 I>F No EVA
rs3389025668 129 E>K No EVA
rs238258906 151 S>L No EVA
rs3400077249 152 P>H No EVA
rs215564486 194 V>M No EVA
rs3389045196 230 T>M No EVA
rs3389032618 260 A>V No EVA
rs1132179521 273 G>C No EVA
rs586906045 335 P>T No EVA
rs212776529 339 V>L No EVA
rs3389038958 387 V>F No EVA
rs3389032628 398 P>H No EVA
rs3400139159 407 S>C No EVA
rs3400139159 407 S>CLLIQV* No EVA
rs3400111679 410 Y>S No EVA
rs3399983987 413 T>KKN* No EVA
rs3389025701 433 S>Y No EVA
rs3389045146 435 H>Y No EVA
rs219680544 503 A>S No EVA
rs3389035290 511 T>S No EVA
rs3389039030 520 E>D No EVA
rs3547290300 523 V>I No EVA
rs3389045189 529 V>M No EVA
rs3389030491 581 S>G No EVA
rs3389013030 617 R>K No EVA
rs3389045209 661 L>M No EVA
rs243638481 663 A>T No EVA
rs3389039032 680 G>W No EVA
rs232258381 694 S>L No EVA
rs3399523746 717 L>P No EVA
rs3400157829 717 L>V No EVA
rs3400066831 739 P>H No EVA
rs3389030552 750 E>V No EVA
rs3389005213 765 D>G No EVA
rs3389035032 781 L>Q No EVA
rs3389005277 851 A>T No EVA
rs3389035024 922 R>S No EVA
rs3389025677 941 P>S No EVA
rs3389013006 944 L>W No EVA
rs3389042776 972 N>D No EVA
rs3389037223 1007 V>A No EVA
rs3389017188 1012 N>D No EVA
rs3400051557 1023 E>L No EVA
rs3389039033 1029 K>N No EVA
rs3389038990 1033 D>N No EVA
rs3389037207 1036 I>N No EVA
rs3400176542 1044 E>* No EVA
rs261771400 1046 I>V No EVA
rs3389042775 1070 A>P No EVA
rs3389035336 1087 V>F No EVA
rs3389017134 1090 V>A No EVA
rs3389035313 1120 K>R No EVA
rs243265991 1186 P>R No EVA
rs36449735 1204 A>E No EVA
rs36449735 1204 A>V No EVA
rs36332333 1212 A>T No EVA
rs36562004 1224 A>T No EVA
rs3389005276 1250 L>F No EVA
rs37977986 1257 G>D No EVA
rs3389038754 1277 D>Y No EVA
rs3547207214 1283 R>Q No EVA
rs3399737555 1330 T>A No EVA
rs3399500460 1335 C>W No EVA
rs3400066881 1336 A>D No EVA
rs3389038802 1336 A>T No EVA
rs3400156815 1341 V>L No EVA
rs3412613819 1377 S>N No EVA
rs3389040029 1398 G>A No EVA
rs262410493 1400 V>I No EVA
rs3389017183 1443 T>K No EVA
rs29892489 1447 A>P No EVA
rs29892489 1447 A>T No EVA
rs258132010 1449 D>N No EVA
rs3389035088 1454 Q>* No EVA
rs3400156845 1460 N>D No EVA
rs3399872201 1463 P>S No EVA
rs3389012938 1494 S>L No EVA
rs3389035339 1498 S>P No EVA
rs3389042720 1519 V>* No EVA

No associated diseases with Q8R4H2

8 regional properties for Q8R4H2

Type Name Position InterPro Accession
domain Dbl homology (DH) domain 787 - 977 IPR000219
conserved_site Guanine-nucleotide dissociation stimulator, CDC24, conserved site 926 - 951 IPR001331
domain PDZ domain 71 - 148 IPR001478
domain Pleckstrin homology domain 1019 - 1134 IPR001849
domain Regulator of G protein signalling-like domain 368 - 558 IPR015212
domain ARHGEF12, PH domain 995 - 1132 IPR037801
domain LARG, RGS domain 349 - 570 IPR037884
domain ARHGEF1-like, PH domain 1006 - 1129 IPR041020

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Membrane
  • Translocated to the membrane upon stimulation
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.

3 GO annotations of molecular function

Name Definition
G protein-coupled receptor binding Binding to a G protein-coupled receptor.
GTPase activator activity Binds to and increases the activity of a GTPase, an enzyme that catalyzes the hydrolysis of GTP.
guanyl-nucleotide exchange factor activity Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions.

3 GO annotations of biological process

Name Definition
G protein-coupled receptor signaling pathway The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
regulation of blood pressure Any process that modulates the force with which blood travels through the circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure.
Rho protein signal transduction The series of molecular signals within the cell that are mediated by a member of the Rho family of proteins switching to a GTP-bound active state.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q92974 ARHGEF2 Rho guanine nucleotide exchange factor 2 Homo sapiens (Human) PR
O15085 ARHGEF11 Rho guanine nucleotide exchange factor 11 Homo sapiens (Human) EV
Q9NZN5 ARHGEF12 Rho guanine nucleotide exchange factor 12 Homo sapiens (Human) EV
Q60875 Arhgef2 Rho guanine nucleotide exchange factor 2 Mus musculus (Mouse) PR
Q9ES67 Arhgef11 Rho guanine nucleotide exchange factor 11 Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MSGTQSTITD RFPLKKPIRH GSILNRESPT DKKQKVERSS SHDFDPTDSS SKKTKSSSEE
70 80 90 100 110 120
SRSEIYGLVQ RCVIIQKDDN GFGLTVSGDN PVFVQSVKED GAAMRAGVQT GDRIIKVNGT
130 140 150 160 170 180
LVTHSNHLEV VKLIRSGSYV ALTVQGRPPG SPQIPLADSE VEPSVTGHMS PIMTSPHSPG
190 200 210 220 230 240
AAGNMERITS PVLVGEENNV VHNQKVEILR KMLQKEQERL QLLQEDYNRT ATQRLLKEIQ
250 260 270 280 290 300
EAKKHIPQLQ EQLSKATGSA QDGAVIAPSR PLGDALTLSE AEADPGDGLC RTDWSSGDAS
310 320 330 340 350 360
RPSSDSADSP KSSLRERSYL EEAPERSEGV QDAEPQSLVG SPSTRGAPHI IGAEDDDFGT
370 380 390 400 410 420
EHEQINGQCS CFQSIELLKS RPAHLAVFLH HVVSQFDPAT LLCYLYSDLY KQTNSKETRR
430 440 450 460 470 480
VFLEFHQFFL DRSAHLKVPV PEEISVDLEK RRPELIPEDL HRLYIQTMQE RVHPEVQRHL
490 500 510 520 530 540
EDFRQKRSMG LTLAESELTK LDAERDKDRG TLEKERACAE QIVTKIEEVL MTAQAVEEER
550 560 570 580 590 600
SSTMQYVILM YMKYLGVKVK EPRNLEHKRG RIGFLPKIKQ SMKKDREGEE KGKRRGFPSI
610 620 630 640 650 660
LGPPRRPSRH DNSAIGRAME IQKSRHPKHL STPSSVSPEP QDPAKLRQSG VANEGTDTGY
670 680 690 700 710 720
LPASSMSSAT SGTALSQEGG RENDTGTKQV GEASAPGDCL DSTPRVPTTV FDFPPPLLDQ
730 740 750 760 770 780
VQEEECEVER VAEHGTPKPF RKFDSIAFGE SQSEDEQFEN DLETDPPNWQ QLVSREVLLG
790 800 810 820 830 840
LKPSEIKRQE VINELFYTER AHVRTLKVLD QVFYQRVSRE GILSPSELRK IFSNLEDILQ
850 860 870 880 890 900
LHVGLNEQMK AVRKRNETSV IDHIGEDLLI WFSGPGEEKL KHAAATFCSN QPFALEMIKS
910 920 930 940 950 960
RQKKDSRFHT FVQDAESNPL CRRLQLKDII PTQMQRLTKY PLLLDNIAKY TEWPPEREKV
970 980 990 1000 1010 1020
KKAADHCRQI LNYVNQAVRE AENKQRLEDY QRRLDTSNLK LSEYPNVDEL RNLDLTKRKM
1030 1040 1050 1060 1070 1080
IHEGPLVWKV NRDKSIDLYT LLLEDILVLL QKQDDRLVLR CHSKILASTA DSKHTFSPVI
1090 1100 1110 1120 1130 1140
KLSTVLVRQV ATDNKALFVI SMSDNGAQIY ELVAQTVSEK TVWQDLICRM AASVKEQSTK
1150 1160 1170 1180 1190 1200
PIPLPQPPPC EGDNDEEEPA KLKVEHHDLS VAGLQSPDRV LGLESPLISS KPQSHSLNTP
1210 1220 1230 1240 1250 1260
GKSAAEHLFV TATQFAKEQH ANGALKEGDG GYPVTIPGPH LPVSEERWAL DALRNLGLLK
1270 1280 1290 1300 1310 1320
QLLVQQLGLT EKSTQEDWQS FSRYGPASEE VQADSGIRDL ENVKACHARE GQMSFKTGTG
1330 1340 1350 1360 1370 1380
DIATCDSPRT STESCAAQDS VILASQDSQA SNVLVMDHMI LTPEMPPAEP EGGLDESGEH
1390 1400 1410 1420 1430 1440
FFDAREAHSD DNPSEGDGAV KKEEKDVNLR ISGNCLILDG YDAVQESSTD EEVASSFPLQ
1450 1460 1470 1480 1490 1500
PVTGIPAVDS SHQQQHSPQN VHPEGPVSPF TPEFLVQRHW RAMEDTCFEI QSPSCTDSQS
1510 1520 1530 1540
QILEYIHKIE ADLEHLKKVE ESYALLCQRL AGSALPDKLS DKS