Descriptions

The translocation of Son of Sevenless 1 (SOS1) protein to the plasma membrane enables activation of membrane-bound Ras, which is a vital regulator of cell proliferation and differentiation. The autoinhibitory conformation of SOS1 consists of the histone domain, the Dbl homology (DH), the Pleckstrin homology (PH) domain, and PH-Rem helical linker. SOS is inactive by the DH-PH unit, which blocks allosteric Ras binding. In addition, the histone domain plays a dual role in occluding the allosteric site and in stabilizing the autoinhibitory conformation of the DH-PH unit. Autoinhibition of the catalytic domain of SOS is released by enhancing the density of PIP2 and the local concentration of Ras-GTP, consequently increasing the activity of SOS at the membrane.

Autoinhibitory domains (AIDs)

Target domain

825-1067 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Partner binding

Assay

Target domain

825-1067 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

2 structures for P26675

Entry ID Method Resolution Chain Position Source
1AZE NMR - B 1342-1350 PDB
AF-P26675-F1 Predicted AlphaFoldDB

3 variants for P26675

Variant ID(s) Position Change Description Diseaes Association Provenance
1256 P>L strain: St_L028 and St_L033 [UniProt] No
1322 A>S strain: In_L019 [UniProt] No
1503 S>N strain: In_L019 [UniProt] No

No associated diseases with P26675

5 regional properties for P26675

Type Name Position InterPro Accession
domain Dbl homology (DH) domain 248 - 434 IPR000219
domain Ras-like guanine nucleotide exchange factor, N-terminal 636 - 792 IPR000651
domain Pleckstrin homology domain 480 - 590 IPR001849
domain Ras guanine-nucleotide exchange factors catalytic domain 825 - 1067 IPR001895
conserved_site Ras guanine-nucleotide exchange factor, conserved site 976 - 1007 IPR019804

Functions

Description
EC Number
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extrinsic component of cytoplasmic side of plasma membrane The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
rhabdomere microvillus membrane The portion of the plasma membrane surrounding a microvillus of a rhabdomere.

2 GO annotations of molecular function

Name Definition
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.
protein heterodimerization activity Binding to a nonidentical protein to form a heterodimer.

17 GO annotations of biological process

Name Definition
axon midline choice point recognition The recognition of molecules at the central nervous system midline choice point by an axon growth cone; this choice point determines whether the growth cone will cross the midline.
defense response to virus Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
epidermal growth factor receptor signaling pathway The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
epithelial cell migration, open tracheal system The orderly movement of epithelial cells during development of an open tracheal system. An example of this is found in Drosophila melanogaster.
fibroblast growth factor receptor signaling pathway The series of molecular signals generated as a consequence of a fibroblast growth factor receptor binding to one of its physiological ligands.
imaginal disc-derived leg morphogenesis The process in which the anatomical structures of a leg derived from an imaginal disc are generated and organized. A leg is a limb on which an animal walks and stands. An example of this is found in Drosophila melanogaster.
negative regulation of G1/S transition of mitotic cell cycle Any signalling pathway that decreases or inhibits the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the mitotic cell cycle.
photoreceptor cell fate determination The process in which a cell becomes capable of differentiating autonomously into a photoreceptor cell regardless of its environment; upon determination, the cell fate cannot be reversed.
positive regulation of cell size Any process that increases cell size.
positive regulation of Rac protein signal transduction Any process that activates or increases the frequency, rate or extent of Rac protein signal transduction.
positive regulation of Ras protein signal transduction Any process that activates or increases the frequency, rate or extent of Ras protein signal transduction.
R7 cell fate commitment The process in which the R7 photoreceptor commits to its cell fate. The R7 receptor contributes the central part of the rhabdomere in the apical parts of the ommatidium.
Ras protein signal transduction The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state.
sevenless signaling pathway The series of molecular signals initiated by an extracellular ligand binding to sevenless (sev; a receptor tyrosine kinase) on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
torso signaling pathway The series of molecular signals initiated by an extracellular ligand binding to torso (a receptor tyrosine kinase) on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
tracheal outgrowth, open tracheal system The projection of branches of an open tracheal system towards their target tissues. An example of this is found in Drosophila melanogaster.
vascular endothelial growth factor receptor signaling pathway The series of molecular signals initiated by a ligand binding to a vascular endothelial growth factor receptor (VEGFR) on the surface of the target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.

24 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A6N9I4 RASGRP2 RAS guanyl-releasing protein 2 Bos taurus (Bovine) SS
Q1LZ97 RASGRP4 RAS guanyl-releasing protein 4 Bos taurus (Bovine) SS
A0A3S5ZPR1 RASGRP3 RAS guanyl releasing protein 3 Gallus gallus (Chicken) SS
Q5JS13 RALGPS1 Ras-specific guanine nucleotide-releasing factor RalGPS1 Homo sapiens (Human) PR
O95267 RASGRP1 RAS guanyl-releasing protein 1 Homo sapiens (Human) EV
Q7LDG7 RASGRP2 RAS guanyl-releasing protein 2 Homo sapiens (Human) EV SS
Q86X27 RALGPS2 Ras-specific guanine nucleotide-releasing factor RalGPS2 Homo sapiens (Human) PR
Q8IV61 RASGRP3 Ras guanyl-releasing protein 3 Homo sapiens (Human) SS
Q8TDF6 RASGRP4 RAS guanyl-releasing protein 4 Homo sapiens (Human) SS
Q13905 RAPGEF1 Rap guanine nucleotide exchange factor 1 Homo sapiens (Human) PR
Q07890 SOS2 Son of sevenless homolog 2 Homo sapiens (Human) SS
Q07889 SOS1 Son of sevenless homolog 1 Homo sapiens (Human) EV
A2AR50 Ralgps1 Ras-specific guanine nucleotide-releasing factor RalGPS1 Mus musculus (Mouse) PR
Q8BTM9 Rasgrp4 RAS guanyl-releasing protein 4 Mus musculus (Mouse) SS
Q9Z1S3 Rasgrp1 RAS guanyl-releasing protein 1 Mus musculus (Mouse) SS
Q9QUG9 Rasgrp2 RAS guanyl-releasing protein 2 Mus musculus (Mouse) SS
Q9ERD6 Ralgps2 Ras-specific guanine nucleotide-releasing factor RalGPS2 Mus musculus (Mouse) PR
Q02384 Sos2 Son of sevenless homolog 2 Mus musculus (Mouse) SS
Q62245 Sos1 Son of sevenless homolog 1 Mus musculus (Mouse) SS
Q9R1K8 Rasgrp1 RAS guanyl-releasing protein 1 Rattus norvegicus (Rat) SS
P0C643 Rasgrp2 RAS guanyl-releasing protein 2 Rattus norvegicus (Rat) SS
Q8R5I4 Rasgrp4 RAS guanyl-releasing protein 4 Rattus norvegicus (Rat) SS
Q9N5D3 sos-1 Son of sevenless homolog Caenorhabditis elegans EV
A4IJ06 rasgrp1 RAS guanyl-releasing protein 1 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
10 20 30 40 50 60
MFSGPSGHAH TISYGGGIGL GTGGGGGSGG SGSGSQGGGG GIGIGGGGVA GLQDCDGYDF
70 80 90 100 110 120
TKCENAARWR GLFTPSLKKV LEQVHPRVTA KEDALLYVEK LCLRLLAMLC AKPLPHSVQD
130 140 150 160 170 180
VEEKVNKSFP APIDQWALNE AKEVINSKKR KSVLPTEKVH TLLQKDVLQY KIDSSVSAFL
190 200 210 220 230 240
VAVLEYISAD ILKMAGDYVI KIAHCEITKE DIEVVMNADR VLMDMLNQSE AHILPSPLSL
250 260 270 280 290 300
PAQRASATYE ETVKELIHDE KQYQRDLHMI IRVFREELVK IVSDPRELEP IFSNIMDIYE
310 320 330 340 350 360
VTVTLLGSLE DVIEMSQEQS APCVGSCFEE LAEAEEFDVY KKYAYDVTSQ ASRDALNNLL
370 380 390 400 410 420
SKPGASSLTT AGHGFRDAVK YYLPKLLLVP ICHAFVYFDY IKHLKDLSSS QDDIESFEQV
430 440 450 460 470 480
QGLLHPLHCD LEKVMASLSK ERQVPVSGRV RRQLAIERTR ELQMKVEHWE DKDVGQNCNE
490 500 510 520 530 540
FIREDSLSKL GSGKRIWSER KVFLFDGLMV LCKANTKKQT PSAGATAYDY RLKEKYFMRR
550 560 570 580 590 600
VDINDRPDSD DLKNSFELAP RMQPPIVLTA KNAQHKHDWM ADLLMVITKS MLDRHLDSIL
610 620 630 640 650 660
QDIERKHPLR MPSPEIYKFA VPDSGDNIVL EERESAGVPM IKGATLCKLI ERLTYHIYAD
670 680 690 700 710 720
PTFVRTFLTT YRYFCSPQQL LQLLVERFNI PDPSLVYQDT GTAGAGGMGG VGGDKEHKNS
730 740 750 760 770 780
HREDWKRYRK EYVQPVQFRV LNVLRHWVDH HFYDFEKDPM LLEKLLNFLE HVNGKSMRKW
790 800 810 820 830 840
VDSVLKIVQR KNEQEKSNKK IVYAYGHDPP PIEHHLSVPN DEITLLTLHP LELARQLTLL
850 860 870 880 890 900
EFEMYKNVKP SELVGSPWTK KDKEVKSPNL LKIMKHTTNV TRWIEKSITE AENYEERLAI
910 920 930 940 950 960
MQRAIEVMMV MLELNNFNGI LSIVAAMGTA SVYRLRWTFQ GLPERYRKFL EECRELSDDH
970 980 990 1000 1010 1020
LKKYQERLRS INPPCVPFFG RYLTNILHLE EGNPDLLANT ELINFSKRRK VAEIIGEIQQ
1030 1040 1050 1060 1070 1080
YQNQPYCLNE ESTIRQFFEQ LDPFNGLSDK QMSDYLYNES LRIEPRGCKT VPKFPRKWPH
1090 1100 1110 1120 1130 1140
IPLKSPGIKP RRQNQTNSSS KLSNSTSSVA AAAAASSTAT SIATASAPSL HASSIMDAPT
1150 1160 1170 1180 1190 1200
AAAANAGSGT LAGEQSPQHN PHAFSVFAPV IIPERNTSSW SGTPQHTRTD QNNGEVSVPA
1210 1220 1230 1240 1250 1260
PHLPKKPGAH VWANNNSTLA SASAMDVVFS PALPEHLPPQ SLPDSNPFAS DTEAPPSPLP
1270 1280 1290 1300 1310 1320
KLVVSPRHET GNRSPFHGRM QNSPTHSTAS TVTLTGMSTS GGEEFCAGGF YFNSAHQGQP
1330 1340 1350 1360 1370 1380
GAVPISPHVN VPMATNMEYR AVPPPLPPRR KERTESCADM AQKRQAPDAP TLPPRDGELS
1390 1400 1410 1420 1430 1440
PPPIPPRLNH STGISYLRQS HGKSKEFVGN SSLLLPNTSS IMIRRNSAIE KRAAATSQPN
1450 1460 1470 1480 1490 1500
QAAAGPISTT LVTVSQAVAT DEPLPLPISP AASSSTTTSP LTPAMSPMSP NIPSHPVEST
1510 1520 1530 1540 1550 1560
SSSYAHQLRM RQQQQQQTHP AIYSQHHQHH ATHLPHHPHQ HHSNPTQSRS SPKEFFPIAT
1570 1580 1590
SLEGTPKLPP KPSLSANFYN NPDKGTMFLY PSTNEE