Q9R1K8

SS
Gene name
Rasgrp1 (Rasgrp)
Protein name
RAS guanyl-releasing protein 1
Names
Calcium and DAG-regulated guanine nucleotide exchange factor II , CalDAG-GEFII , Ras guanyl-releasing protein
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:29434
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)

436-462 (RasGEF catalytic domain-EF domain linker) SS

Target domain

201-437 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Ligand binding, PTM

Assay

541-591 (C1 domain) SS

Target domain

463-505 (EF domain)

Relief mechanism

Ligand binding, PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q9R1K8

Entry ID Method Resolution Chain Position Source
AF-Q9R1K8-F1 Predicted AlphaFoldDB

No variants for Q9R1K8

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9R1K8

No associated diseases with Q9R1K8

10 regional properties for Q9R1K8

Type Name Position InterPro Accession
domain Ras-like guanine nucleotide exchange factor, N-terminal 52 - 177 IPR000651
domain Ras guanine-nucleotide exchange factors catalytic domain 201 - 437 IPR001895
domain EF-hand domain 470 - 521 IPR002048
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 541 - 593 IPR002219
binding_site EF-Hand 1, calcium-binding site 483 - 495 IPR018247-1
binding_site EF-Hand 1, calcium-binding site 510 - 522 IPR018247-2
domain Diacylglycerol/phorbol-ester binding 539 - 553 IPR020454-1
domain Diacylglycerol/phorbol-ester binding 555 - 564 IPR020454-2
domain Diacylglycerol/phorbol-ester binding 568 - 579 IPR020454-3
domain Diacylglycerol/phorbol-ester binding 580 - 592 IPR020454-4

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm, cytosol
  • Cell membrane; Peripheral membrane protein
  • Golgi apparatus membrane ; Peripheral membrane protein
  • Endoplasmic reticulum membrane ; Peripheral membrane protein
  • Found both in the cytosol and associated with membranes
  • Relocalization to the cell membrane upon activation is F-actin-dependent (By similarity)
  • Translocates to the Golgi in response to phorbol ester or nerve growth factor (By similarity)
  • Localizes to somata and dendrites but not to axons of hippocampal pyramidal cells
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.
endoplasmic reticulum membrane The lipid bilayer surrounding the endoplasmic reticulum.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
Golgi membrane The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

6 GO annotations of molecular function

Name Definition
calcium ion binding Binding to a calcium ion (Ca2+).
diacylglycerol binding Binding to a diacylglycerol, a diester of glycerol and two fatty acids.
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.
identical protein binding Binding to an identical protein or proteins.
phosphatidylcholine binding Binding to a phosphatidylcholine, a glycophospholipid in which a phosphatidyl group is esterified to the hydroxyl group of choline.
zinc ion binding Binding to a zinc ion (Zn).

24 GO annotations of biological process

Name Definition
B cell activation The change in morphology and behavior of a mature or immature B cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
B cell proliferation The expansion of a B cell population by cell division. Follows B cell activation.
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.
inflammatory response to antigenic stimulus An inflammatory response to an antigenic stimulus, which can be include any number of T cell or B cell epitopes.
mast cell degranulation The regulated exocytosis of secretory granules containing preformed mediators such as histamine, serotonin, and neutral proteases by a mast cell.
natural killer cell activation The change in morphology and behavior of a natural killer cell in response to a cytokine, chemokine, cellular ligand, or soluble factor.
positive regulation of ERK1 and ERK2 cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of granulocyte macrophage colony-stimulating factor production Any process that activates or increases the frequency, rate, or extent of granulocyte macrophage colony-stimulating factor production.
positive regulation of JNK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade.
positive regulation of natural killer cell activation Any process that activates or increases the frequency, rate or extent of natural killer cell activation.
positive regulation of natural killer cell differentiation Any process that activates or increases the frequency, rate or extent of natural killer cell differentiation.
positive regulation of natural killer cell mediated cytotoxicity Any process that activates or increases the frequency, rate or extent of natural killer cell mediated cytotoxicity.
positive regulation of protein phosphorylation Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of Ras protein signal transduction Any process that activates or increases the frequency, rate or extent of Ras protein signal transduction.
positive regulation of T cell differentiation in thymus Any process that activates or increases the frequency, rate or extent of T cell differentiation in the thymus.
positive regulation of tumor necrosis factor production Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production.
positive regulation of type II interferon production Any process that activates or increases the frequency, rate, or extent of interferon-gamma production. Interferon-gamma is also known as type II interferon.
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 ERK1 and ERK2 cascade Any process that modulates the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction Any process that modulates the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
secretory granule localization Any process in which a secretory granule is transported to, and/or maintained in, a specific location within the cell.
T cell activation The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
T cell proliferation The expansion of a T cell population by cell division. Follows T cell activation.
vesicle transport along microtubule The directed movement of a vesicle along a microtubule, mediated by motor proteins. This process begins with the attachment of a vesicle to a microtubule, and ends when the vesicle reaches its final destination.

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
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
Q7LDG7 RASGRP2 RAS guanyl-releasing protein 2 Homo sapiens (Human) EV SS
Q8IV61 RASGRP3 Ras guanyl-releasing protein 3 Homo sapiens (Human) SS
O95267 RASGRP1 RAS guanyl-releasing protein 1 Homo sapiens (Human) EV
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
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
Q9Z1S3 Rasgrp1 RAS guanyl-releasing protein 1 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
Q8R5I4 Rasgrp4 RAS guanyl-releasing protein 4 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
MGTLGKAREA PRKPCHGSRA GPKGRLEAKS TNSPLPAQPS LAQITQFRMM VSLGHLAKGA
70 80 90 100 110 120
SLDDLIDSCI QSFDADGNLC RSNQLLQVML TMHRIIISSA ELLQKLMNLY KDALEKNSPG
130 140 150 160 170 180
ICLKICYFVR YWITEFWIMF KMDASLTSTM EEFQDLVKAN GEESHCHLID TTQINSRDWS
190 200 210 220 230 240
RKLTQRIKSN TSKKRKVSLL FDHLEPEELS EHLTYLEFKS FRRISFSDYQ NYLVNSCVKE
250 260 270 280 290 300
NPTMERSIAL CNGISQWVQL MVLSRPTPQL RAEVFIKFIH VAQKLHQLQN FNTLMAVIGG
310 320 330 340 350 360
LCHSSISRLK ETSSHVPHEI NKVLGEMTEL LSSCRNYDNY RRAYGECTHF KIPILGVHLK
370 380 390 400 410 420
DLISLYEAMP DYLEDGKVNV QKLLALYNHI NELVQLQDVA PPLDANKDLV HLLTLSLDLY
430 440 450 460 470 480
YTEDEIYELS YAREPRNHRA PPLTPSKPPV VVDWASGVSP KPDPKTISKH VQRMVDSVFK
490 500 510 520 530 540
NYDLDQDGYI SQEEFEKIAA SFPFSFCVMD KDREGLISRD EITAYFMRAS SIYSKLGLGF
550 560 570 580 590 600
PHNFQETTYL KPTFCDNCAG FLWGVIKQGY RCKDCGMNCH KQCKDLVVFE CKKRSKSPAV
610 620 630 640 650 660
STENISSVVP MSTLCPLGTK DLLHAPEEGS FIFQNGEVVD HSEESKDRTI MLLGVSSQKI
670 680 690 700 710 720
SVRLKRTVAH KTTQTESFPW VGGEMPPGHF VLTSPRKSAQ GALYVHSPAS PCPSPALVRK
730 740 750 760 770 780
RAFVKWENKE SLIKPKPELH LRLRTYQELE QEVNTLRADN DALKIQLKYA QKQIESLQLG
790
KSNHVLAQMD HGDGT