Descriptions

RAS guanyl-releasing protein 1 (RasGRP1) is a nucleotide exchange factor that controls the development of immune cells, and leukemia and lupus can result if RasGRP1 is not regulated correctly. Inactive RasGRP1 is stabilized by the C1-dimer interface, which sequesters the membrane-interacting surface of the C1 domain, and the active-site blocking RasGEF catalytic domain (Cdc25)-EF domain linker. The C-terminal coiled-coil stabilizes the dimer, thereby preventing inappropriate Ras activation. The autoinhibited form is activated by multiple signaling inputs that enhance nucleotide exchange activity. Diacylglycerol binding disrupts C1 dimerization, while Ca2+ binding to EF1 causes a conformational change that contributes to C1 reorientation, and the release of the inhibitory segment from the Ras-binding surface. Phosphorylation of the Cdc25 domain could aid in removal of the inhibitory linker.

Autoinhibitory domains (AIDs)

Target domain

150-388 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Ligand binding, PTM

Assay

Target domain

419-463 (EF domain)

Relief mechanism

Ligand binding, PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q9QUG9

Entry ID Method Resolution Chain Position Source
AF-Q9QUG9-F1 Predicted AlphaFoldDB

40 variants for Q9QUG9

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389514284 26 D>E No EVA
rs3389501202 31 R>L No EVA
rs3389526741 34 Q>H No EVA
rs3389536765 93 N>K No EVA
rs3389531155 95 E>* No EVA
rs3389514952 100 I>V No EVA
rs3389478196 102 E>G No EVA
rs3389514927 109 Q>E No EVA
rs3389514935 154 E>K No EVA
rs3389501188 163 T>I No EVA
rs3389533448 201 N>D No EVA
rs3389521938 231 A>T No EVA
rs3407830269 233 R>K No EVA
rs3389536796 299 F>I No EVA
rs3389514964 312 V>M No EVA
rs3389514244 343 E>D No EVA
rs3389514288 357 N>S No EVA
rs3389514300 359 D>H No EVA
rs3389501275 387 R>C No EVA
rs3389478133 394 S>I No EVA
rs3389533483 395 P>L No EVA
rs3554101415 396 T>A No EVA
rs3389514961 398 C>S No EVA
rs3389521918 399 T>S No EVA
rs3389478164 400 P>L No EVA
rs3389526755 443 D>N No EVA
rs3389536711 447 S>T No EVA
rs3389488071 462 S>N No EVA
rs3389514254 479 E>D No EVA
rs3389501186 518 L>P No EVA
rs3389501205 533 G>R No EVA
rs3389501229 545 S>L No EVA
rs3389521940 554 S>G No EVA
rs387318325 562 P>S No EVA
rs3389517048 569 T>I No EVA
rs3409011441 572 R>Q No EVA
rs3408933005 580 R>G No EVA
rs3408829784 581 P>R No EVA
rs3407830282 584 R>H No EVA
rs260219837 598 S>T No EVA

No associated diseases with Q9QUG9

6 regional properties for Q9QUG9

Type Name Position InterPro Accession
domain Ras-like guanine nucleotide exchange factor, N-terminal 3 - 126 IPR000651
domain Ras guanine-nucleotide exchange factors catalytic domain 150 - 388 IPR001895
domain EF-hand domain 426 - 487 IPR002048
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 498 - 550 IPR002219
binding_site EF-Hand 1, calcium-binding site 439 - 451 IPR018247-1
binding_site EF-Hand 1, calcium-binding site 468 - 480 IPR018247-2

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm, cytosol
  • Cell membrane ; Peripheral membrane protein
  • Synapse, synaptosome
  • Cell projection, ruffle membrane ; Peripheral membrane protein
  • Found both in the cytosol and associated with membranes
  • Enriched at juxtamembrane areas and membrane ruffles
  • Localizes to the cell bodies and axons of striatal neurons
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

5 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.
neuron projection A prolongation or process extending from a nerve cell, e.g. an axon or dendrite.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
ruffle membrane The portion of the plasma membrane surrounding a ruffle.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

2 GO annotations of molecular function

Name Definition
calcium ion binding Binding to a calcium ion (Ca2+).
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.

2 GO annotations of biological process

Name Definition
cellular response to calcium ion Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a calcium ion stimulus.
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.

28 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q1LZ97 RASGRP4 RAS guanyl-releasing protein 4 Bos taurus (Bovine) SS
A6N9I4 RASGRP2 RAS guanyl-releasing protein 2 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
Q07890 SOS2 Son of sevenless homolog 2 Homo sapiens (Human) SS
Q5JS13 RALGPS1 Ras-specific guanine nucleotide-releasing factor RalGPS1 Homo sapiens (Human) PR
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
Q07889 SOS1 Son of sevenless homolog 1 Homo sapiens (Human) EV
Q8TDF6 RASGRP4 RAS guanyl-releasing protein 4 Homo sapiens (Human) SS
O95267 RASGRP1 RAS guanyl-releasing protein 1 Homo sapiens (Human) EV
Q8IV61 RASGRP3 Ras guanyl-releasing protein 3 Homo sapiens (Human) SS
Q7LDG7 RASGRP2 RAS guanyl-releasing protein 2 Homo sapiens (Human) EV SS
Q02384 Sos2 Son of sevenless homolog 2 Mus musculus (Mouse) SS
Q62245 Sos1 Son of sevenless homolog 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
Q9Z1S3 Rasgrp1 RAS guanyl-releasing protein 1 Mus musculus (Mouse) SS
Q8BTM9 Rasgrp4 RAS guanyl-releasing protein 4 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
Q8R5I4 Rasgrp4 RAS guanyl-releasing protein 4 Rattus norvegicus (Rat) SS
Q9R1K8 Rasgrp1 RAS guanyl-releasing protein 1 Rattus norvegicus (Rat) SS
P0C643 Rasgrp2 RAS guanyl-releasing protein 2 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
MTSTLDLDKG CTVEELLRGC IEAFDDSGKV RDPQLVRMFL MMHPWYIPSS QLASKLLHFY
70 80 90 100 110 120
QQSRKDNSNS LQMKTCHLVR YWISAFPAEF DLNPELAEQI KELKALLDQE GNRRHSSLID
130 140 150 160 170 180
IESVPTYKWK RQVTQRNPVE QKKRKMSLLF DHLEPMELAE HLTYLEYRSF CKILFQDYHS
190 200 210 220 230 240
FVTHGCTVDN PVLERFISLF NSVSQWVQLM ILSKPTATQR ALVITHFVHV AERLLQLQNF
250 260 270 280 290 300
NTLMAVVGGL SHSSISRLKE THSHVSPDTI KLWEGLTELV TATGNYSNYR RRLAACVGFR
310 320 330 340 350 360
FPILGVHLKD LVALQLALPD WLDPGRTRLN GAKMRQLFCI LEELAMVTSL RPPVQANPDL
370 380 390 400 410 420
LSLLTVSLDQ YQTEDELYQL SLQREPRSKS SPTSPTSCTP PPRPPVLEEW TSVAKPKLDQ
430 440 450 460 470 480
ALVAEHIEKM VESVFRNFDV DGDGHISQEE FQIIRGNFPY LSAFGDLDQN QDGCISREEM
490 500 510 520 530 540
ISYFLRSSSV LGGRMGFVHN FQESNSLRPV ACRHCKALIL GIYKQGLKCR ACGVNCHKQC
550 560 570 580 590 600
KERLSVECRR RAQSVSLEGS APSPSPTHTH HRAFSFSLPR PGRRSSRPPE IREEEVQSVE
DGVFDIHL