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

197-433 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Ligand binding, PTM

Assay

Target domain

459-501 (EF domain)

Relief mechanism

Ligand binding, PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q8BTM9

Entry ID Method Resolution Chain Position Source
AF-Q8BTM9-F1 Predicted AlphaFoldDB

38 variants for Q8BTM9

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388887175 5 D>Y No EVA
rs32155624 24 S>P No EVA
rs3388883616 25 R>C No EVA
rs3388889172 26 Q>R No EVA
rs3397308548 33 C>* No EVA
rs3388855548 46 M>T No EVA
rs3388891970 57 S>C No EVA
rs32107664 72 A>S No EVA
rs46375256 92 V>G No EVA
rs3388883618 96 S>L No EVA
rs3388855534 128 W>R No EVA
rs45673726 182 M>I No EVA
rs3545426092 235 R>K No EVA
rs248946222 276 R>H No EVA
rs3412865575 299 H>Q No EVA
rs31372739 342 G>S No EVA
rs3397317067 346 F>C No EVA
rs3396934574 346 F>I No EVA
rs3397317078 348 L>M No EVA
rs3397773208 348 L>Q No EVA
rs46371097 362 Y>H No EVA
rs240065004 390 M>T No EVA
rs32365817 443 K>R No EVA
rs3388898366 444 A>S No EVA
rs3388869733 450 W>R No EVA
rs3388896486 458 P>S No EVA
rs48706891 468 E>G No EVA
rs3388877376 508 P>H No EVA
rs3388875297 536 G>D No EVA
rs3388869783 590 C>R No EVA
rs243429647 596 T>I No EVA
rs3388900363 608 P>S No EVA
rs3388883652 626 T>I No EVA
rs3388889099 628 S>F No EVA
rs3388855554 645 E>K No EVA
rs3388875254 657 P>T No EVA
rs3388889097 664 P>Q No EVA
rs48237048 669 S>L No EVA

No associated diseases with Q8BTM9

7 regional properties for Q8BTM9

Type Name Position InterPro Accession
domain Ras-like guanine nucleotide exchange factor, N-terminal 49 - 175 IPR000651
domain Ras guanine-nucleotide exchange factors catalytic domain 197 - 433 IPR001895
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 540 - 592 IPR002219
domain Diacylglycerol/phorbol-ester binding 538 - 552 IPR020454-1
domain Diacylglycerol/phorbol-ester binding 554 - 563 IPR020454-2
domain Diacylglycerol/phorbol-ester binding 567 - 578 IPR020454-3
domain Diacylglycerol/phorbol-ester binding 579 - 591 IPR020454-4

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Cell membrane
  • Recruited to membranes upon activation by DAG
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 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.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
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.
metal ion binding Binding to a metal ion.

5 GO annotations of biological process

Name Definition
cell differentiation The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
cell population proliferation The multiplication or reproduction of cells, resulting in the expansion of a cell population.
positive regulation of Ras protein signal transduction Any process that activates or increases the frequency, rate or extent of Ras protein 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.
response to extracellular stimulus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an extracellular stimulus.

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
Q07890 SOS2 Son of sevenless homolog 2 Homo sapiens (Human) 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
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
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
MNRKDIKRKS HQECSGKAGG RGRSRQARRH KTCPTPREIS KVMASMNLGV LSESSCSEDE
70 80 90 100 110 120
LLEECIRCFD SAGSLRRGDH ILKMVLTMHS WVLPSSELAA RLLTSYQKAA KDAQELRQLQ
130 140 150 160 170 180
ICYLVRYWLT HHHEAVHQEP QLEAVISRFW TTVAQEGNMA QRSLGDASSL LSPGGPGPPP
190 200 210 220 230 240
PMSSPGLGKK RKVSLLFDHL ETEELAQHLT YLEFRSFQAI TPQDLRGYVL QGSVRGCPAL
250 260 270 280 290 300
EGSVGLSNSV SRWVQVMVLS RPGPAQRAQV LDKFIRVAQR LHQLQNFNTL MAVTGGLCHS
310 320 330 340 350 360
AISRLKDSHV HLSPDSTKAL LELTELLSSH NNYAHYRRTW AGCTGFRLPV LGVHLKDLVS
370 380 390 400 410 420
LYEAHPDRLP DGRLHLPKLN SLYLRLQELM ALQGQHPPCS ANEDLLHLLT LSLDLFYTED
430 440 450 460 470 480
EIYELSYARE PRCPKSLPPS PFKAPVVVEW AQGVTPKPDS VTLGQHVEQL VESVFKNYDP
490 500 510 520 530 540
EGRGSISLED FERLSGNFPF ACHGLHPPPR HGSGSFSREE LTKYLLHASA ICSKLGLAFL
550 560 570 580 590 600
HAFQEVTFRK PTFCHSCSGF LWGVTKQGYR CRDCGLCCHR HCRDQVRVEC KKRPETKGDP
610 620 630 640 650 660
GPPGAPVPAT SLPPANCGSE ESLSYTLSPD PESGCHLRHA WTQTESSHSS WEPEVVPCPA
670
RVLPSRASSK PSV