Q02384

SS
Gene name
Sos2
Protein name
Son of sevenless homolog 2
Names
SOS-2 , mSOS-2
Species
Mus musculus (Mouse)
KEGG Pathway
EC number
Protein Class

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)

199-389 (DH domain) SS

Target domain

775-1019 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Partner binding

Assay

442-547 (PH domain) SS

Target domain

775-1019 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

2 structures for Q02384

Entry ID Method Resolution Chain Position Source
1GBR NMR - B 1300-1314 PDB
AF-Q02384-F1 Predicted AlphaFoldDB

59 variants for Q02384

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389215955 37 T>A No EVA
rs3389236964 89 D>N No EVA
rs3389173074 144 L>M No EVA
rs3389227673 147 N>K No EVA
rs3389227647 152 I>V No EVA
rs3389255489 168 A>V No EVA
rs3403409901 242 E>Q No EVA
rs3389252132 326 I>T No EVA
rs3389209425 340 R>H No EVA
rs3389227657 344 V>A No EVA
rs3389235103 359 L>M No EVA
rs3403523481 363 S>T No EVA
rs3389237045 374 Q>* No EVA
rs3389235060 415 H>Q No EVA
rs3389215988 425 Q>R No EVA
rs3389235131 433 G>S No EVA
rs3389215968 462 L>P No EVA
rs3389227685 467 M>R No EVA
rs3389243653 469 S>C No EVA
rs3389173048 479 L>E No EVA
rs3389244852 479 L>F No EVA
rs3389243681 486 E>K No EVA
rs3389235061 488 R>K No EVA
rs266162497 498 I>V No EVA
rs3389236962 504 E>D No EVA
rs3402075307 535 N>K No EVA
rs3403009168 544 H>D No EVA
rs3389239860 594 R>SE* No EVA
rs3389239797 595 S>N No EVA
rs3389240835 623 V>L No EVA
rs3389237043 627 L>P No EVA
rs3389202444 688 V>I No EVA
rs3389237046 691 V>I No EVA
rs3389235121 693 R>S No EVA
rs3389215987 847 R>Q No EVA
rs3389227644 848 V>M No EVA
rs3389244845 867 F>V No EVA
rs3389227609 871 L>* No EVA
rs3412830622 873 I>K No EVA
rs3389173060 875 S>G No EVA
rs3389252141 948 K>* No EVA
rs3389227661 952 K>E No EVA
rs3389249800 966 I>L No EVA
rs3403318566 1007 Y>D No EVA
rs3403578347 1009 F>L No EVA
rs3402749201 1028 R>I No EVA
rs3389173095 1032 F>L No EVA
rs3389215947 1033 S>P No EVA
rs3389235111 1035 K>N No EVA
rs3389244848 1039 I>L No EVA
rs3389249812 1079 S>T No EVA
rs13473164 1202 P>S No EVA
rs3389236965 1230 N>T No EVA
rs37505837 1281 S>G No EVA
rs3403404763 1305 K>R No EVA
rs3549524763 1316 S>P No EVA
rs3549500115 1317 H>P No EVA
rs214807057 1323 L>M No EVA
rs3403398483 1330 E>Q No EVA

No associated diseases with Q02384

5 regional properties for Q02384

Type Name Position InterPro Accession
domain Dbl homology (DH) domain 199 - 389 IPR000219
domain Ras-like guanine nucleotide exchange factor, N-terminal 595 - 740 IPR000651
domain Pleckstrin homology domain 442 - 547 IPR001849
domain Ras guanine-nucleotide exchange factors catalytic domain 775 - 1019 IPR001895
conserved_site Ras guanine-nucleotide exchange factor, conserved site 926 - 959 IPR019804

Functions

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

1 GO annotations of cellular component

Name Definition
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

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.

9 GO annotations of biological process

Name Definition
B cell homeostasis The process of regulating the proliferation and elimination of B cells such that the total number of B cells within a whole or part of an organism is stable over time in the absence of an outside stimulus.
insulin receptor signaling pathway The series of molecular signals generated as a consequence of the insulin receptor binding to insulin.
lymphocyte homeostasis The process of regulating the proliferation and elimination of lymphocytes such that the total number of lymphocytes within a whole or part of an organism is stable over time in the absence of an outside stimulus.
positive regulation of small GTPase mediated signal transduction Any process that activates or increases the frequency, rate or extent of small GTPase mediated signal transduction.
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.
regulation of pro-B cell differentiation Any process that modulates the frequency, rate or extent of pro-B cell differentiation.
regulation of T cell differentiation in thymus Any process that modulates the frequency, rate or extent of T cell differentiation in the thymus.
regulation of T cell proliferation Any process that modulates the frequency, rate or extent of T cell proliferation.
small GTPase-mediated signal transduction The series of molecular signals in which a small monomeric GTPase relays a signal.

28 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
Q07889 SOS1 Son of sevenless homolog 1 Homo sapiens (Human) EV
Q8TDF6 RASGRP4 RAS guanyl-releasing protein 4 Homo sapiens (Human) SS
Q07890 SOS2 Son of sevenless homolog 2 Homo sapiens (Human) SS
Q62245 Sos1 Son of sevenless homolog 1 Mus musculus (Mouse) SS
Q9Z1S3 Rasgrp1 RAS guanyl-releasing protein 1 Mus musculus (Mouse) SS
Q8VCC8 Rapgef3 Rap guanine nucleotide exchange factor 3 Mus musculus (Mouse) SS
Q9EQZ6 Rapgef4 Rap guanine nucleotide exchange factor 4 Mus musculus (Mouse) EV
Q9D300 Rasgef1c Ras-GEF domain-containing family member 1C Mus musculus (Mouse) PR
Q03385 Ralgds Ral guanine nucleotide dissociation stimulator Mus musculus (Mouse) PR
Q8BTM9 Rasgrp4 RAS guanyl-releasing protein 4 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
A2AR50 Ralgps1 Ras-specific guanine nucleotide-releasing factor RalGPS1 Mus musculus (Mouse) PR
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
MQQAPQPYEF FSEENSPKWR GLLVPALRKV QEQVHPTLSA NEESLYYIEE LIFQLLNKLC
70 80 90 100 110 120
MAQPRTVQDV EERVQKTFPH PIDKWAIADA QSAIEKRKRR NPLLLPVDKI HPSLKEVLGY
130 140 150 160 170 180
KVDYHVSLYI VAVLEYISAD ILKLAGNYVF NIRHYEISQQ DIKVSMCADK VLMDMFDQDD
190 200 210 220 230 240
DIGLVSLCED EPCSSGELNY YDLVRTEIAE ERQYLRELNM IIKVFREAFL LDRKLFKPSE
250 260 270 280 290 300
IEKIFSNISD IHELTVKLLG LIEDTVEMTD ESSPHPLAGS CFEDLAEEQA FDPYETLSQD
310 320 330 340 350 360
ILAPEFNDHF SKLMARPAVA LHFQSIADGF KEAVRYVLPR LMLVPVYHCW HYFELLKQLK
370 380 390 400 410 420
ACSEEQEDKE CLNQAITALM NLQGSMDRIY KQHSPRRRPG DPVCLFYNRQ LRSKHLAIKK
430 440 450 460 470 480
MNEIQKNIDG WEGKDIGQCC NEFIMEGPLT RIGAKHERHI FLFDGLMISC KPNHGQTRLP
490 500 510 520 530 540
GYSSAEYRLK EKFVMRKIQI CDKEDACEYR HAFELVSKDE NSVIFAAKSA EEKNNWMAAL
550 560 570 580 590 600
ISLHYRSTLD RMLDSVLLKE ENEQPLRLPS PDMYRFVVTD SEENIVFEDN LQSRSGIPII
610 620 630 640 650 660
KGGTVVKLIE RLTYHMYADP NFVRTFLTTY RSFCKPQELL NLLIERFEIP EPEPTEADKL
670 680 690 700 710 720
ALEKGEQPIS ADLKRFRKEY VQPVQLRVLN VFRHWVEHHY YDFERDLELL ERLESFISSV
730 740 750 760 770 780
RGKAMKKWVE SIAKIIKRKK QAQANGISHN ITFESSPPPV EWHISRTGQF ETFDLMTLHP
790 800 810 820 830 840
IEIARQLTLL ESDLYRKVQP SELVGSVWTK EDKEINSPNL LKMIRHTTNL TLWFEKCIVE
850 860 870 880 890 900
AENFEERVAV LSRIVEILQV FQDLNNFNGV LEIVSAVNSV SVYRLDHTFE ALQERKRRIL
910 920 930 940 950 960
DDAVELSQDH FKKYLVKLKS INPPCVPFFG IYLTNILKTE EGNSDFLKRK GKDLINFSKR
970 980 990 1000 1010 1020
RKVAEITGEI QQYQNQPYCL RTEPEMRRFF ENLNPMGILS EKEFTDYLFN KSLEIEPRNC
1030 1040 1050 1060 1070 1080
KQPPRFPRKS TFSLKSPGIR PNAGRHGSTS GTLRGHPTPL EREPYKISFS RIAETELEST
1090 1100 1110 1120 1130 1140
VSAPTSPNTP STPPVSASSD HSVFLDVDLN SSCGSNTIFA PVLLPHSKTF FSSCGSLHKL
1150 1160 1170 1180 1190 1200
SEEPLIPPPL PPRKKFDHDA LNSKGAVKSD DDPPAIPPRQ PPPPKVKPRV PVLMGTFDGP
1210 1220 1230 1240 1250 1260
VPSPPPPPPR DPLPDTPPPV PLRPPEHFIN CPFNLQPPPL GHPHRDPDWL RDVSTCPNSP
1270 1280 1290 1300 1310 1320
STPPTTPSPR IPRSCHLLSS SHSSLAHLPA PPVPPRQNSS PLLPKLPPKT YKRELSHPPL
1330
YRLPLLENAE TPQ