P0C643

SS
Gene name
Rasgrp2
Protein name
RAS guanyl-releasing protein 2
Names
Calcium and DAG-regulated guanine nucleotide exchange factor I , CalDAG-GEFI
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:361714
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)

387-418 (RasGEF catalytic domain-EF domain linker) SS

Target domain

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

Relief mechanism

Ligand binding, PTM

Assay

498-548 (C1 domain) SS

Target domain

419-463 (EF domain)

Relief mechanism

Ligand binding, PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for P0C643

Entry ID Method Resolution Chain Position Source
AF-P0C643-F1 Predicted AlphaFoldDB

No variants for P0C643

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P0C643

No associated diseases with P0C643

6 regional properties for P0C643

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 (By similarity)
  • Enriched at juxtamembrane areas and membrane ruffles (By similarity)
  • 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.

26 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
O95267 RASGRP1 RAS guanyl-releasing protein 1 Homo sapiens (Human) EV
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
Q7LDG7 RASGRP2 RAS guanyl-releasing protein 2 Homo sapiens (Human) EV 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
Q8BTM9 Rasgrp4 RAS guanyl-releasing protein 4 Mus musculus (Mouse) SS
Q9Z1S3 Rasgrp1 RAS guanyl-releasing protein 1 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
Q9QUG9 Rasgrp2 RAS guanyl-releasing protein 2 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
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
MASTLDLDKG CTVEELLRGC IEAFDDSGKV RDPQLVRMFL MMHPWYIPSS QLASKLLHFY
70 80 90 100 110 120
QQSRKDNSNS LQVKTCHLVR YWVSAFPAEF 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 AEKLLQLQNF
250 260 270 280 290 300
NTLMAVVGGL SHSSISRLKE THSHVSPDTI KLWEGLTELV TATGNYSNYR RRLAACVGFR
310 320 330 340 350 360
FPILGVHLKD LVALQLALPD WLDPGRTRLN GAKMRQLFSI 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 LQESNSLRPV ACRHCKALIL GIYKQGLKCR ACGVNCHKQC
550 560 570 580 590 600
KDRLSVECRR RAQSVSLEGS APSPSPTHTH HRAFSFSLPR PGRRSSRPPE IREEEVQTVE
DGVFDIHL