Q9N5D3
Gene name |
sos-1 |
Protein name |
Son of sevenless homolog |
Names |
Guanine nucleotide exchange factor for RAS |
Species |
Caenorhabditis elegans |
KEGG Pathway |
cel:CELE_T28F12.3 |
EC number |
|
Protein Class |
GUANINE NUCLEOTIDE EXCHANGE FACTOR (PTHR23113) |
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. SOS1 consists of the histone domain, the Dbl homology (DH), the Pleckstrin homology (PH) domain, and PH-Rem helical linker, and C-terminal region providing docking sites for adaptor proteins such as Grb2. SOS is inactive by the DH-PH unit, which blocks allosteric Ras binding. In addition, the histone-fold 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. Ras-GTP allosterically regulates the catalytic domain.
Autoinhibitory domains (AIDs)
Target domain |
893-1165 (Ras guanine-nucleotide exchange factors catalytic domain) |
Relief mechanism |
Partner binding |
Assay |
Mutagenesis experiment, Structural analysis |
Target domain |
893-1165 (Ras guanine-nucleotide exchange factors catalytic domain) |
Relief mechanism |
Ligand binding |
Assay |
Mutagenesis experiment, Structural analysis |
Target domain |
893-1165 (Ras guanine-nucleotide exchange factors catalytic domain) |
Relief mechanism |
Partner binding |
Assay |
Deletion assay |
Accessory elements
No accessory elements
References
- Tartaglia M et al. (2010) "Noonan syndrome: clinical aspects and molecular pathogenesis", Molecular syndromology, 1, 2-26
- Sondermann H et al. (2004) "Structural analysis of autoinhibition in the Ras activator Son of sevenless", Cell, 119, 393-405
- Gureasko J et al. (2010) "Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless", Proceedings of the National Academy of Sciences of the United States of America, 107, 3430-5
- Modzelewska K et al. (2007) "An activating mutation in sos-1 identifies its Dbl domain as a critical inhibitor of the epidermal growth factor receptor pathway during Caenorhabditis elegans vulval development", Molecular and cellular biology, 27, 3695-707
Autoinhibited structure
Activated structure
1 structures for Q9N5D3
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q9N5D3-F1 | Predicted | AlphaFoldDB |
No variants for Q9N5D3
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q9N5D3 | |||||
No associated diseases with Q9N5D3
Functions
| Description | ||
|---|---|---|
| EC Number | ||
| Subcellular Localization |
|
|
| PANTHER Family | PTHR23113 | GUANINE NUCLEOTIDE EXCHANGE FACTOR |
| PANTHER Subfamily | PTHR23113:SF373 | PROTEIN SON OF SEVENLESS |
| PANTHER Protein Class |
guanyl-nucleotide exchange factor
G-protein modulator protein-binding activity modulator |
|
| PANTHER Pathway Category |
FGF signaling pathway SOS Angiogenesis SOS-1 Integrin signalling pathway SOS PDGF signaling pathway SOS Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade SOS EGF receptor signaling pathway SOS Ras Pathway SOS |
|
No GO annotations of cellular component
| Name | Definition |
|---|---|
| No GO annotations for cellular component |
3 GO annotations of molecular function
| Name | Definition |
|---|---|
| calmodulin binding | Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states. |
| 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. |
5 GO annotations of biological process
| Name | Definition |
|---|---|
| cell migration | The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms. |
| embryo development ending in birth or egg hatching | The process whose specific outcome is the progression of an embryo over time, from zygote formation until the end of the embryonic life stage. The end of the embryonic life stage is organism-specific and may be somewhat arbitrary; for mammals it is usually considered to be birth, for insects the hatching of the first instar larva from the eggshell. |
| female gamete generation | Generation of the female gamete; specialised haploid cells produced by meiosis and along with a male gamete takes part in sexual reproduction. |
| positive regulation of vulval development | Any process that activates or increases the frequency, rate or extent of development of the vulva. Vulval development is the process whose specific outcome is the progression of the egg-laying organ of female and hermaphrodite nematodes over time, from its formation to the mature structure. In nematodes, the vulva is formed from ventral epidermal cells during larval stages to give rise to a fully formed vulva in the adult. |
| small GTPase mediated signal transduction | The series of molecular signals in which a small monomeric GTPase relays a signal. |
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 |
| P26675 | Sos | Protein son of sevenless | Drosophila melanogaster (Fruit fly) | 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 |
| Q13905 | RAPGEF1 | Rap guanine nucleotide exchange factor 1 | 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 |
| 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 |
| A4IJ06 | rasgrp1 | RAS guanyl-releasing protein 1 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSIMSISLHS | ASSDTVSLTS | RRTISTSKHW | AAIFDERIYQ | ICNIVHPGLP | IDNAAVEHIR |
| 70 | 80 | 90 | 100 | 110 | 120 |
| YFLQSIVFEL | IEARATSVVE | VDKTAKKLFA | FGLQTVCKEA | WDNMHQQLQK | HKYQKALKTV |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LESQHRLAAV | IKETLGPREK | EKKDREKKEI | ERIACYIYYA | CESVTEDVLR | LTGNYVKNIR |
| 190 | 200 | 210 | 220 | 230 | 240 |
| NSEQKITMAN | LDVAMNGDKA | LMELRTKLRN | EEEAESPGGF | GFLSEFEEFV | AEETEEKTLS |
| 250 | 260 | 270 | 280 | 290 | 300 |
| NSQTYESVAV | DFLRDERRFI | RELNRINVFR | RRIESVAATD | VDKQIVCNLF | GNLTEIHDLA |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LKIERTLEDA | IELSDTQCIG | MGIWEHGEAY | EFDTYTFYIR | RDGGEMNETR | HATYVINDNI |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KALLESERFA | SLFQSGEHYL | GSSLDGQSFR | LAVQYVLPQL | LHIPIFHIYQ | YHEYITRLHQ |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LSSSEEDRRD | LNDCRSAFER | VVGCVSDMSP | ELKTKITQFL | DQQAKSEKIY | NVKRLNEIQS |
| 490 | 500 | 510 | 520 | 530 | 540 |
| SIDGFTGSPI | GKTCNELEKD | GDLGMIRPSL | QFSSEITKNK | KWKTERFVYI | FDQMIVLCKR |
| 550 | 560 | 570 | 580 | 590 | 600 |
| HRNTLKFKDR | LAVHSIDVFD | IPDSEVTNCF | KIESHDKSSL | PKIYHFVCKN | PEEKRQWMAV |
| 610 | 620 | 630 | 640 | 650 | 660 |
| LVKVTTKSVL | DRILDNHEKE | EAKRIPLVVP | GPDQYRFSEP | DTEDNISFED | YTSSSGIPVI |
| 670 | 680 | 690 | 700 | 710 | 720 |
| KCGTVLKLIE | RLTYHSYTDS | KYILTFLISY | RSFCTPNDLF | SLLLERFNIP | TPKKLQQPKQ |
| 730 | 740 | 750 | 760 | 770 | 780 |
| GGGPLAGRYD | TVQSHGLSAI | SSSSCINPLC | EQKFRKEFQQ | PIQLRVLSVI | NQWVKLHWYD |
| 790 | 800 | 810 | 820 | 830 | 840 |
| FQCDPVLLDA | LELFLNRCCD | PREGLSKQHK | KFCKTILALI | EKRVKNPPGI | MQQPNENGDK |
| 850 | 860 | 870 | 880 | 890 | 900 |
| GAADEGHVNS | AFVFGDDQQH | PPQHQVYTNE | SPKETNQVLW | HTAQKGDVDH | YDLLTLHPIE |
| 910 | 920 | 930 | 940 | 950 | 960 |
| IGRQLTLLHS | DLYRAIQPIE | LVEAAWTKAE | KWRKSPQLLR | LTDHSTLLTY | WVSRSIVETE |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| SLEERMAMFN | RVLEVMSVFE | ELHNFTGLVA | FYSALNSSCI | FRLKWCWDGL | DNEKKKCFDR |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| FNTLCERRWQ | EMQKRLSSIN | PPCIPFFGHY | LSNIYFLEQG | NSTFVNKSPP | HGAAGAQKQQ |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| KDDLKASDPE | NSNKQFKQLV | SFLKLRKISN | VIREIQIFQD | QRYSLTLEPT | IRQFFESINP |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| KNDFKSNEDL | EEYLYNKSLE | IQPKGLDTPT | AELKPKHNAS | TLRSPGVKPP | KAAGNHYSAN |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| HPIGLHLHSQ | NSHSAPHAMS | SQSSTVPNTP | LSAHETKRSL | SHNQDDAPLQ | QFVDIRFERK |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| GTHPKIPVLQ | PPPLLPRSSR | ANQSNSVSLP | PTTQAPMPPA | PKSSGMMSTA | TSPTTLTTTT |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| TPSSAGGPPP | KLHPRRMTQQ | PMSPLAKSPL | TPSRDNSSPS | AFQFPVVYEA | STAPPLPPRP |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| STSSDVSSSP | STSGSTSSAT | KENQEQLRVI | FDREESHSPT | VRLSVPLPPA | LPPPRGSSVF |
| 1450 | 1460 | 1470 | 1480 | 1490 | |
| RAPPPLPPKS | NRHNSNSPTL | SSEQPFEDPM | SPSIFVNTPP | PPLPPKTYRS | SNK |