Q9Z1S3

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
Mus musculus (Mouse)
KEGG Pathway
mmu:19419
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 Q9Z1S3

Entry ID Method Resolution Chain Position Source
AF-Q9Z1S3-F1 Predicted AlphaFoldDB

49 variants for Q9Z1S3

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3392084572 16 H>L No EVA
rs3392112566 16 H>Y No EVA
rs3391934371 18 S>A No EVA
rs3392112585 19 R>S No EVA
rs3392112614 20 A>S No EVA
rs3392000432 22 P>A No EVA
rs3392098425 23 K>I No EVA
rs3388577301 55 H>N No EVA
rs3388577549 57 A>V No EVA
rs3388575042 68 S>R No EVA
rs3388570416 139 M>I No EVA
rs3388565805 203 H>R No EVA
rs3388577332 240 E>D No EVA
rs3388576110 242 P>L No EVA
rs3388572290 298 I>F No EVA
rs3388577307 300 G>E No EVA
rs3388580945 302 C>S No EVA
rs3388576047 323 V>* No EVA
rs3388577319 353 P>T No EVA
rs3388565818 358 H>Q No EVA
rs3388572306 361 D>N No EVA
rs3388583099 364 S>P No EVA
rs3388577620 371 D>N No EVA
rs3388583106 393 L>S No EVA
rs3388575058 420 Y>F No EVA
rs3388565795 424 D>N No EVA
rs3392084535 433 R>P No EVA
rs3388579481 437 N>I No EVA
rs3388570498 465 K>Q No EVA
rs3388576447 490 I>M No EVA
rs3388577629 508 V>M No EVA
rs3388576425 534 S>Y No EVA
rs3388580888 539 G>D No EVA
rs3388572253 548 T>N No EVA
rs3388576095 566 I>F No EVA
rs3388572250 574 D>N No EVA
rs3388573412 576 G>W No EVA
rs3388577311 589 F>L No EVA
rs3388579430 603 E>* No EVA
rs3388573410 604 N>I No EVA
rs3388579441 611 M>I No EVA
rs3388577589 634 Q>L No EVA
rs243390638 638 I>V No EVA
rs222296530 686 T>A No EVA
rs222296530 686 T>P No EVA
rs3388576478 716 A>S No EVA
rs3388575419 718 V>I No EVA
rs3388579431 741 L>F No EVA
rs3388576416 782 S>G No EVA

No associated diseases with Q9Z1S3

3 regional properties for Q9Z1S3

Type Name Position InterPro Accession
domain Protein kinase domain 102 - 367 IPR000719
active_site Serine/threonine-protein kinase, active site 225 - 237 IPR008271
binding_site Protein kinase, ATP binding site 108 - 131 IPR017441

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
  • Localizes to somata and dendrites but not to axons of hippocampal pyramidal cells (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 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 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).

22 GO annotations of biological process

Name Definition
activation of GTPase activity Any process that initiates the activity of an inactive GTPase through the replacement of GDP by GTP.
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 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 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.

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
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
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
Q8BTM9 Rasgrp4 RAS guanyl-releasing protein 4 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
P0C643 Rasgrp2 RAS guanyl-releasing protein 2 Rattus norvegicus (Rat) SS
Q8R5I4 Rasgrp4 RAS guanyl-releasing protein 4 Rattus norvegicus (Rat) SS
Q9R1K8 Rasgrp1 RAS guanyl-releasing protein 1 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 GPKARLEAKS TNSPLPAQPS LAQITQFRMM VSLGHLAKGA
70 80 90 100 110 120
SLDDLIDSCI QSFDADGNLC RNNQLLQVML TMHRIIISSA ELLQKVMNLY KDALEKNSPG
130 140 150 160 170 180
VCLKICYFVR YWITEFWIMF KMDASLTSTM EEFQDLVKAN GEETHCHLID 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 NELVQLQEMA 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 CKKRIKSPAI
610 620 630 640 650 660
STENISSVVP MSTLCPLGTK DLLHAPEEGS FIFQNGEIVD HSEESKDRTI MLLGVSSQKI
670 680 690 700 710 720
SVRLKRTVAH KSTQTESFPW VGGETTPGHF VLSSPRKSAQ GALYVHSPAS PCPSPALVRK
730 740 750 760 770 780
RAFVKWENKE SLIKPKPELH LRLRTYQELE QEINTLKADN DALKIQLKYA QKKIESLQLG
790
KSNHVLAQMD HGDSA