Q9ES67

SS
Gene name
Arhgef11
Protein name
Rho guanine nucleotide exchange factor 11
Names
RhoGEF glutamate transport modulator GTRAP48
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:78966
EC number
Protein Class

Descriptions

ARHGEF11 belongs to a small family of RhoA-specific nucleotide exchange factors that mediates signaling through select G-protein-coupled receptors via Gα12/13 and activates RhoA by catalyzing the exchange of GDP to GTP. ARHGEF11 is a multidomain protein composed of PDZ, regulators of G-protein signaling-like (RGSL), Dbl-homology (DH), and pleckstrin-homology (PH) domains. The autoinhibitory activity resides in the 672-712 fragment in such a way that it disturbs the catalytically competent conformation of the GEF switch. The intrinsically disordered L2 linker located between RGSL domain and DH domain occupied the RhoA-binding site on DH domain, thereby suppressing the DH domain. In addition, ARHGEF12 removed RGSL domain showed partial relief of autoinhibition, suggesting that RGSL domain supports autoinhibition indirectly.

Autoinhibitory domains (AIDs)

680-720 (Autoinhibitory region) SS

Target domain

742-1087 (DH-PH tandem)

Relief mechanism

Partner binding

Assay

508-679 (L2 linker) SS

Target domain

742-1087 (DH-PH tandem)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

4 structures for Q9ES67

Entry ID Method Resolution Chain Position Source
3CX6 X-ray 250 A B 307-508 PDB
3CX7 X-ray 225 A B 307-508 PDB
3CX8 X-ray 200 A B 307-508 PDB
AF-Q9ES67-F1 Predicted AlphaFoldDB

No variants for Q9ES67

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9ES67

1 associated diseases with Q9ES67

[MIM: 610725]: Nephrotic syndrome 3 (NPHS3)

A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen. . Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID
  • A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen. . Note=The disease is caused by variants affecting the gene represented in this entry.

9 regional properties for Q9ES67

Type Name Position InterPro Accession
domain C2 domain 1851 - 1976 IPR000008
domain Ras-associating domain 2135 - 2238 IPR000159
domain Phosphatidylinositol-specific phospholipase C, X domain 1392 - 1541 IPR000909
domain Phospholipase C, phosphatidylinositol-specific, Y domain 1729 - 1846 IPR001711
domain Ras guanine-nucleotide exchange factors catalytic domain 528 - 831 IPR001895
domain Phosphoinositide-specific phospholipase C, EF-hand-like domain 1327 - 1378 IPR015359
domain 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, RA domain 2 2134 - 2236 IPR028398
domain 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, catalytic domain 1391 - 1833 IPR046973
domain 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, EF-hand domain 1198 - 1378 IPR046974

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.

4 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.
positive regulation of DNA-templated transcription Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of L-glutamate import across plasma membrane Any process that activates or increases the frequency, rate or extent of L-glutamate import into a cell.
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
Q9NZN5 ARHGEF12 Rho guanine nucleotide exchange factor 12 Homo sapiens (Human) EV
O15085 ARHGEF11 Rho guanine nucleotide exchange factor 11 Homo sapiens (Human) EV
Q60875 Arhgef2 Rho guanine nucleotide exchange factor 2 Mus musculus (Mouse) PR
Q8R4H2 Arhgef12 Rho guanine nucleotide exchange factor 12 Mus musculus (Mouse) SS
10 20 30 40 50 60
MSIRLPHSID RSASKKQSHL SSPIASWLSS LSSLGDSTPE RTSPSHHRQP SDTSETTAGL
70 80 90 100 110 120
VQRCVIIQKD QHGFGFTVSG DRIVLVQSVR PGGAAMKAGV KEGDRIIKVN GTMVTNSSHL
130 140 150 160 170 180
EVVKLIKSGA YAALTLLGSS PPSVGVSGLQ QNPSVAGVLR VNPIIPPPPP PPPLPPPQHI
190 200 210 220 230 240
TGPKPLQDPE VQKHATQILW NMLRQEEEEL QDILPPCGET SQRTCEGRLS VDSQEADSGL
250 260 270 280 290 300
DSGTERFPSI SESLMNRNSV LSDPGLDSPQ TSPVILARVA QHHRRQGSDA ALLPLNHQGI
310 320 330 340 350 360
DQSPKPLIIG PEEDYDPGYF NNESDIIFQD LEKLKSHPAY LVVFLRYILS QADPGPLLFY
370 380 390 400 410 420
LCSEVYQQTN PKDSRSLGKD IWNIFLEKNA PLRVKIPEML QAEIDLRLRN NEDPRNVLCE
430 440 450 460 470 480
AQEAVMLEIQ EQINDYRSKR TLGLGSLYGE NDLLGLDGDP LRERQMAEKQ LAALGDILSK
490 500 510 520 530 540
YEEDRSAPMD FAVNTFMSHA GIRLRESRSS CTAEKTQSAP DKDKWLPFFP KTKKQSSNSK
550 560 570 580 590 600
KEKDALEDKK RNPILRYIGK PKSSSQSIKP GNVRNIIQHF ENSHQYDVPE PGTQRLSTGS
610 620 630 640 650 660
FPEDLLESDS SRSEIRLGRS GSLKGREEMK RSRKAENVPR PRSDVDMDAA AEAARLHQSA
670 680 690 700 710 720
SSSASSLSTR SLENPTPPFT PKMGRRSIES PNLGFCTDVI LPHLLEDDLG QLSDLEPEPE
730 740 750 760 770 780
VQNWQHTVGK DVVANLTQRE IDRQEVINEL FVTEASHLRT LRVLDLIFYQ RMRKENLMPR
790 800 810 820 830 840
EELARLFPNL PELIEIHNSW CEAMKKLREE GPIIRDISDP MLARFDGPAR EELQQVAAQF
850 860 870 880 890 900
CSYQSVALEL IRTKQRKESR FQLFMQEAES HPQCRRLQLR DLIVSEMQRL TKYPLLLENI
910 920 930 940 950 960
IKHTEGGTSE HEKLCRARDQ CREILKFVNE AVKQTENRHR LEGYQKRLDA TALERASNPL
970 980 990 1000 1010 1020
AAEFKSLDLT TRKMIHEGPL TWRISKDKTL DLQVLLLEDL VVLLQRQEER LLLKCHSKTA
1030 1040 1050 1060 1070 1080
VGSSDSKQTF SPVLKLNAVL IRSVATDKRA FFIICTSELG PPQIYELVAL TSSDKNIWME
1090 1100 1110 1120 1130 1140
LLEEAVQNAT KHPGAAPIPI HPSPPGSQEP AYQGSTSSRV EINDSEVYHT EKEPKKLPEG
1150 1160 1170 1180 1190 1200
PGPEQRVQDK QLIAQGEPVQ EEDEEELRTL PRAPPSLDGE NRGIRTRDPV LLALTGPLLM
1210 1220 1230 1240 1250 1260
EGLADAALED VENLRHLILW SLLPGHTVKT QAAGEPEDDL TPTPSVVSIT SHPWDPGSPG
1270 1280 1290 1300 1310 1320
QAPTISDSTR LARPEGSQPE GEDVAVSSLA HLPPRTRSSG VWDSPELDRN PAAEAASTEP
1330 1340 1350 1360 1370 1380
AASYKVVRKV SLLPGGGVGA AKVAGSNAIP DSGQSESELS EVEGGAQATG NCFYVSMPAG
1390 1400 1410 1420 1430 1440
PLDSSTEPTG TPPSPSQCHS LPAWPTEPQP YRGVRGGQCS SLVRRDVDVI FHTIEQLTIK
1450 1460 1470 1480 1490 1500
LHRLKDMELA HRELLKSLGG ESSGGTTPVG SFHTEAARWT DYSLSPPAKE ALASDSQNGQ
1510 1520
EQGSCPEEGS DIALEDSATD TAVSPGP