Q8R5I4

SS
Gene name
Rasgrp4
Protein name
RAS guanyl-releasing protein 4
Names
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:170668
EC number
Protein Class

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)

432-458 (RasGEF catalytic domain-EF domain linker) SS

Target domain

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

Relief mechanism

Ligand binding, PTM

Assay

540-595 (C1 domain) SS

Target domain

459-501 (EF domain)

Relief mechanism

Ligand binding, PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q8R5I4

Entry ID Method Resolution Chain Position Source
AF-Q8R5I4-F1 Predicted AlphaFoldDB

No variants for Q8R5I4

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q8R5I4

No associated diseases with Q8R5I4

4 regional properties for Q8R5I4

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 EF-hand domain 466 - 501 IPR002048
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 540 - 597 IPR002219

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
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.
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
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.

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.

26 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
Q62245 Sos1 Son of sevenless homolog 1 Mus musculus (Mouse) SS
A2AR50 Ralgps1 Ras-specific guanine nucleotide-releasing factor RalGPS1 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
Q02384 Sos2 Son of sevenless homolog 2 Mus musculus (Mouse) SS
Q8BTM9 Rasgrp4 RAS guanyl-releasing protein 4 Mus musculus (Mouse) SS
Q9Z1C8 Rapgef3 Rap guanine nucleotide exchange factor 3 Rattus norvegicus (Rat) SS
Q03386 Ralgds Ral guanine nucleotide dissociation stimulator Rattus norvegicus (Rat) PR
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
MNRKDIKRKS HQECSGKAGG HGRPRQARRH KTCPTPREIS KVMASLNLGV LSESSCSVDE
70 80 90 100 110 120
LLEECIRCFD SAGSLHRGDH ILKMVLTMHS WVLPSSDLAA RLLTSYQKAA KDARELRQLQ
130 140 150 160 170 180
ICYLVRYWLT HHPEVVHQEP QLEAIINRFW TTVAQEGNMA QRSLGDASNL LSPGGPGPPP
190 200 210 220 230 240
LMSSPGLGKK RKVSLLFDHL ETEELAQHLT YLEFRSFQAI TPQDLRGYVL QGSVRGCPAL
250 260 270 280 290 300
EGSVGLSNSV SRWVQVMVLS RPGPAQRAQV LDKFIRVAQR LRQMQNFNTL MAVTGGLCHS
310 320 330 340 350 360
AISRLKDSHV HLSPDSTKAL LELTELLSSH NNYAYYRRTW ASCTDFRLPV LGVHLKDLVS
370 380 390 400 410 420
LYEAHPDRLP DGRLHLPKLN SLYLRLQELA ALQRQHPPCS ANEDLLHLLT LSLDLFYTED
430 440 450 460 470 480
EIYELSYARE PRCPKSLPLS PFKAPVVVEW AHGVTPKPDS ATLGQHVEQL VESVFKNYDP
490 500 510 520 530 540
EGHGSISLED FEKLSANFPF ACHGLHPPPR HGSGSFSREE LTKYLLHASA ICSKLGLAFL
550 560 570 580 590 600
HAFQEVTFRK PTFCHSCNGF VSTGPLWGVT KRGYRCQDCG LCCHRHCRDQ VRVECKKRPE
610 620 630 640 650 660
TKGDPGPPGA PGPATPLPPT GCGSEEGLSY TLSPHLESGC HLHHAWTQTE SSHSSWEPEM
670
VPCPAPVLPS KASSKSSV