A4IJ06

SS
Gene name
rasgrp1
Protein name
RAS guanyl-releasing protein 1
Names
Species
Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)
KEGG Pathway
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

537-587 (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 A4IJ06

Entry ID Method Resolution Chain Position Source
AF-A4IJ06-F1 Predicted AlphaFoldDB

No variants for A4IJ06

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for A4IJ06

No associated diseases with A4IJ06

10 regional properties for A4IJ06

Type Name Position InterPro Accession
domain Ras-like guanine nucleotide exchange factor, N-terminal 48 - 173 IPR000651
domain Ras guanine-nucleotide exchange factors catalytic domain 197 - 433 IPR001895
domain EF-hand domain 466 - 517 IPR002048
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 537 - 589 IPR002219
binding_site EF-Hand 1, calcium-binding site 479 - 491 IPR018247-1
binding_site EF-Hand 1, calcium-binding site 506 - 518 IPR018247-2
domain Diacylglycerol/phorbol-ester binding 535 - 549 IPR020454-1
domain Diacylglycerol/phorbol-ester binding 551 - 560 IPR020454-2
domain Diacylglycerol/phorbol-ester binding 564 - 575 IPR020454-3
domain Diacylglycerol/phorbol-ester binding 576 - 588 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
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.

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
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.
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
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
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
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
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
Q9Z1S3 Rasgrp1 RAS guanyl-releasing protein 1 Mus musculus (Mouse) SS
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
A0JM95 rasgef1a Ras-GEF domain-containing family member 1A Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) PR
Q28EC1 rasgef1b Ras-GEF domain-containing family member 1B Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) PR
10 20 30 40 50 60
MGTVGKKKDR PTHGCSTIPK LALELKQIIH STTHPKVPPV TPLRVMMPLG KLSKGASLDD
70 80 90 100 110 120
LIQMCIQAFD LDGNMGQNSE LLQIMLTMHG FLLPSTELLM KLRTLYQDAL QNRSFSFCLR
130 140 150 160 170 180
ICYFIRYWVT ELWVMFKMDA KLTQAMEEFQ ELVRSKGEEL HWRLIDTAQI NSRDWSRKLT
190 200 210 220 230 240
QRIKPNCSKK RKVSLLFDHL EPQELAEHLT YLEFKAFRRI SFSDYQNYIV SGCVKENPTM
250 260 270 280 290 300
ERSIALCNGI SQWVQFMVLS RPTPQLRAEV LTKFIHVAQK LHQLQNFNTL MAVIGGLCHS
310 320 330 340 350 360
SISRLKDTSA HVSHDVNKVL NEMTELLSSC RNYDNYRRVY NECTNFKIPI LGVHLKDLIA
370 380 390 400 410 420
LHEAMPDFLE DSKINVPKLH SLYNHINELI QLQNIAPPLE ANMDLVHLLT LSLDLYYTED
430 440 450 460 470 480
EMYELSYARE PRNHRAPPVT PSKPPVVADW ASGVSPKPDP KTISKHVQRM VDSVFKNYDL
490 500 510 520 530 540
DQDGYISQEE FEKIAASFPF SFCVMDKDRE GLISRQEITA YFMRASSICS KLGLGFLHNF
550 560 570 580 590 600
QETTYLRPTF CDNCAGFLWG VIKQGYRCKD CGMNCHKQCK ELVVFECKKR SKLSVGENSS
610 620 630 640 650 660
MFDSGQLEVI PAGGKGQTND CLGAEEGPYS YPNGDGDIHT EVSKDRTIML MGSSAQKISV
670 680 690 700 710 720
RLQPAVKHRA TQTENEPQSL CLQVPSPQRS RTPGLTSHLP ISPMPSPCPS PVPTRKKAYA
730 740 750 760 770 780
KWENKDSIRK ARAELRGGKA GIQELEKEKA LLKEENTTLK IQLKDAQRRV ETLRAELRKY
790
VLDSDVHQTG S