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Protein

RAS guanyl-releasing protein 1

Gene

Rasgrp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. Activates the Erk/MAP kinase cascade. Regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. Regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways (By similarity). Functions in mast cell degranulation and cytokine secretion, regulating FcERI-evoked allergic responses (PubMed:17190838). May also function in differentiation of other cell types. Proto-oncogene, which promotes T-cell lymphomagenesis when its expression is deregulated (PubMed:15829980, PubMed:17210708).By similarity13 Publications

Activity regulationi

Autoinhibited. Activated by diacylglycerol and calcium binding, which induces a conformational change releasing the autoinhibitory state. Regulated by DGKA. Regulated by DGKZ. Regulated by PLC gamma and F-actin polymerization (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi483 – 494PROSITE-ProRule annotationAdd BLAST12
Zinc fingeri541 – 591Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
Biological processDifferentiation
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1169092 Activation of RAS in B cells
R-MMU-354192 Integrin alphaIIb beta3 signaling
R-MMU-392517 Rap1 signalling
R-MMU-5673001 RAF/MAP kinase cascade

Names & Taxonomyi

Protein namesi
Recommended name:
RAS guanyl-releasing protein 1
Alternative name(s):
Calcium and DAG-regulated guanine nucleotide exchange factor II
Short name:
CalDAG-GEFII
Ras guanyl-releasing protein
Gene namesi
Name:Rasgrp1
Synonyms:Rasgrp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1314635 Rasgrp1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice fail to mount anaphylactic allergic reactions and display chronic T-cell immunodeficiencies. Lag (lymphoproliferation-autoimmunity-glomerulonephritis) mice do not express Rasgrp1 and display a systemic lupus erythematosus-like phenotype.3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi271R → E: Loss of function and transforming activity. 2 Publications1

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003169791 – 795RAS guanyl-releasing protein 1Add BLAST795

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei184Phosphothreonine; by PKCBy similarity1
Modified residuei597PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Z1S3
MaxQBiQ9Z1S3
PaxDbiQ9Z1S3
PRIDEiQ9Z1S3

PTM databases

iPTMnetiQ9Z1S3
PhosphoSitePlusiQ9Z1S3

Expressioni

Tissue specificityi

Detected in spleen and thymus. Expressed by mature thymocytes and to a lower extent by bone marrow-derived mast cells (at protein level). Detected in B-cells and keratinocytes (at protein level).6 Publications

Inductioni

Up-regulated at the double-negative to double-positive transition during thymocyte development. Down-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA).2 Publications

Gene expression databases

BgeeiENSMUSG00000027347 Expressed in 174 organ(s), highest expression level in CA1 field of hippocampus
CleanExiMM_RASGRP1
ExpressionAtlasiQ9Z1S3 baseline and differential
GenevisibleiQ9Z1S3 MM

Interactioni

Subunit structurei

Homodimer. Forms a signaling complex with DGKZ and HRAS. Interacts with F-actin. Interacts with SKAP1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000099593

Structurei

3D structure databases

ProteinModelPortaliQ9Z1S3
SMRiQ9Z1S3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 176N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST124
Domaini205 – 436Ras-GEFPROSITE-ProRule annotationAdd BLAST232
Domaini470 – 505EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini497 – 532EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni57 – 110Ras exchanger motif region; required for transforming activityAdd BLAST54
Regioni686 – 694Suppress the PT region-mediated translocation to plasma membrane9
Regioni717 – 795PT region; mediates the BCR-dependent translocation to plasma membraneAdd BLAST79

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili738 – 779Sequence analysisAdd BLAST42

Domaini

The phorbol-ester/DAG-type zinc finger is the principal mediator of the targeting to membranes and is required for functional activation through DAG-binding.
Two EF-hand domains are present. However, only EF-hand 1 (and not EF-hand 2) binds calcium.By similarity

Sequence similaritiesi

Belongs to the RASGRP family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri541 – 591Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IQ6J Eukaryota
ENOG410ZKZ2 LUCA
GeneTreeiENSGT00880000137870
HOGENOMiHOG000293171
HOVERGENiHBG007513
InParanoidiQ9Z1S3
KOiK04350
OMAiEGPFTFP
OrthoDBiEOG091G03RN
PhylomeDBiQ9Z1S3
TreeFamiTF312918

Family and domain databases

CDDicd00029 C1, 1 hit
cd00051 EFh, 1 hit
cd00155 RasGEF, 1 hit
cd06224 REM, 1 hit
Gene3Di1.10.840.10, 1 hit
InterProiView protein in InterPro
IPR020454 DAG/PE-bd
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR002219 PE/DAG-bd
IPR000651 Ras-like_Gua-exchang_fac_N
IPR023578 Ras_GEF_dom_sf
IPR001895 RASGEF_cat_dom
IPR036964 RASGEF_cat_dom_sf
IPR029645 RASGRP1/RASGRP3
PANTHERiPTHR23113:SF178 PTHR23113:SF178, 1 hit
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF13202 EF-hand_5, 1 hit
PF00617 RasGEF, 1 hit
PF00618 RasGEF_N, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00054 EFh, 1 hit
SM00147 RasGEF, 1 hit
SM00229 RasGEFN, 1 hit
SUPFAMiSSF47473 SSF47473, 2 hits
SSF48366 SSF48366, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 3 hits
PS50009 RASGEF_CAT, 1 hit
PS50212 RASGEF_NTER, 1 hit
PS00479 ZF_DAG_PE_1, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

Q9Z1S3-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGTLGKAREA PRKPCHGSRA GPKARLEAKS TNSPLPAQPS LAQITQFRMM
60 70 80 90 100
VSLGHLAKGA SLDDLIDSCI QSFDADGNLC RNNQLLQVML TMHRIIISSA
110 120 130 140 150
ELLQKVMNLY KDALEKNSPG VCLKICYFVR YWITEFWIMF KMDASLTSTM
160 170 180 190 200
EEFQDLVKAN GEETHCHLID TTQINSRDWS RKLTQRIKSN TSKKRKVSLL
210 220 230 240 250
FDHLEPEELS EHLTYLEFKS FRRISFSDYQ NYLVNSCVKE NPTMERSIAL
260 270 280 290 300
CNGISQWVQL MVLSRPTPQL RAEVFIKFIH VAQKLHQLQN FNTLMAVIGG
310 320 330 340 350
LCHSSISRLK ETSSHVPHEI NKVLGEMTEL LSSCRNYDNY RRAYGECTHF
360 370 380 390 400
KIPILGVHLK DLISLYEAMP DYLEDGKVNV QKLLALYNHI NELVQLQEMA
410 420 430 440 450
PPLDANKDLV HLLTLSLDLY YTEDEIYELS YAREPRNHRA PPLTPSKPPV
460 470 480 490 500
VVDWASGVSP KPDPKTISKH VQRMVDSVFK NYDLDQDGYI SQEEFEKIAA
510 520 530 540 550
SFPFSFCVMD KDREGLISRD EITAYFMRAS SIYSKLGLGF PHNFQETTYL
560 570 580 590 600
KPTFCDNCAG FLWGVIKQGY RCKDCGMNCH KQCKDLVVFE CKKRIKSPAI
610 620 630 640 650
STENISSVVP MSTLCPLGTK DLLHAPEEGS FIFQNGEIVD HSEESKDRTI
660 670 680 690 700
MLLGVSSQKI SVRLKRTVAH KSTQTESFPW VGGETTPGHF VLSSPRKSAQ
710 720 730 740 750
GALYVHSPAS PCPSPALVRK RAFVKWENKE SLIKPKPELH LRLRTYQELE
760 770 780 790
QEINTLKADN DALKIQLKYA QKKIESLQLG KSNHVLAQMD HGDSA
Length:795
Mass (Da):90,304
Last modified:May 1, 1999 - v1
Checksum:iE2096D985DFB79A0
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3UYC3G3UYC3_MOUSE
RAS guanyl-releasing protein 1
Rasgrp1
760Annotation score:
G3UWW4G3UWW4_MOUSE
RAS guanyl-releasing protein 1
Rasgrp1
597Annotation score:
G3UYP5G3UYP5_MOUSE
RAS guanyl-releasing protein 1
Rasgrp1
481Annotation score:
G3UZQ7G3UZQ7_MOUSE
RAS guanyl-releasing protein 1
Rasgrp1
546Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti171T → R in BAE24718 (PubMed:16141072).Curated1
Sequence conflicti472Q → K in BAE20439 (PubMed:16141072).Curated1
Sequence conflicti485D → E in BAE20439 (PubMed:16141072).Curated1
Sequence conflicti501S → T in BAE20439 (PubMed:16141072).Curated1
Sequence conflicti520D → H in BAE20439 (PubMed:16141072).Curated1
Sequence conflicti768K → R in BAC33100 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF106070 mRNA Translation: AAC97348.1
AK028308 mRNA Translation: BAE20439.1
AK047613 mRNA Translation: BAC33100.1
AK141524 mRNA Translation: BAE24718.1
AL844579, AL928959 Genomic DNA Translation: CAM17832.1
AL928959, AL844579 Genomic DNA Translation: CAM26780.1
BC057120 mRNA Translation: AAH57120.1
BC057341 mRNA Translation: AAH57341.1
CCDSiCCDS16572.1
RefSeqiNP_035376.1, NM_011246.2
UniGeneiMm.42150

Genome annotation databases

EnsembliENSMUST00000102534; ENSMUSP00000099593; ENSMUSG00000027347
ENSMUST00000178884; ENSMUSP00000136423; ENSMUSG00000027347
GeneIDi19419
KEGGimmu:19419
UCSCiuc033hpk.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF106070 mRNA Translation: AAC97348.1
AK028308 mRNA Translation: BAE20439.1
AK047613 mRNA Translation: BAC33100.1
AK141524 mRNA Translation: BAE24718.1
AL844579, AL928959 Genomic DNA Translation: CAM17832.1
AL928959, AL844579 Genomic DNA Translation: CAM26780.1
BC057120 mRNA Translation: AAH57120.1
BC057341 mRNA Translation: AAH57341.1
CCDSiCCDS16572.1
RefSeqiNP_035376.1, NM_011246.2
UniGeneiMm.42150

3D structure databases

ProteinModelPortaliQ9Z1S3
SMRiQ9Z1S3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000099593

PTM databases

iPTMnetiQ9Z1S3
PhosphoSitePlusiQ9Z1S3

Proteomic databases

EPDiQ9Z1S3
MaxQBiQ9Z1S3
PaxDbiQ9Z1S3
PRIDEiQ9Z1S3

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000102534; ENSMUSP00000099593; ENSMUSG00000027347
ENSMUST00000178884; ENSMUSP00000136423; ENSMUSG00000027347
GeneIDi19419
KEGGimmu:19419
UCSCiuc033hpk.1 mouse

Organism-specific databases

CTDi10125
MGIiMGI:1314635 Rasgrp1

Phylogenomic databases

eggNOGiENOG410IQ6J Eukaryota
ENOG410ZKZ2 LUCA
GeneTreeiENSGT00880000137870
HOGENOMiHOG000293171
HOVERGENiHBG007513
InParanoidiQ9Z1S3
KOiK04350
OMAiEGPFTFP
OrthoDBiEOG091G03RN
PhylomeDBiQ9Z1S3
TreeFamiTF312918

Enzyme and pathway databases

ReactomeiR-MMU-1169092 Activation of RAS in B cells
R-MMU-354192 Integrin alphaIIb beta3 signaling
R-MMU-392517 Rap1 signalling
R-MMU-5673001 RAF/MAP kinase cascade

Miscellaneous databases

PROiPR:Q9Z1S3
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027347 Expressed in 174 organ(s), highest expression level in CA1 field of hippocampus
CleanExiMM_RASGRP1
ExpressionAtlasiQ9Z1S3 baseline and differential
GenevisibleiQ9Z1S3 MM

Family and domain databases

CDDicd00029 C1, 1 hit
cd00051 EFh, 1 hit
cd00155 RasGEF, 1 hit
cd06224 REM, 1 hit
Gene3Di1.10.840.10, 1 hit
InterProiView protein in InterPro
IPR020454 DAG/PE-bd
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR002219 PE/DAG-bd
IPR000651 Ras-like_Gua-exchang_fac_N
IPR023578 Ras_GEF_dom_sf
IPR001895 RASGEF_cat_dom
IPR036964 RASGEF_cat_dom_sf
IPR029645 RASGRP1/RASGRP3
PANTHERiPTHR23113:SF178 PTHR23113:SF178, 1 hit
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF13202 EF-hand_5, 1 hit
PF00617 RasGEF, 1 hit
PF00618 RasGEF_N, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00054 EFh, 1 hit
SM00147 RasGEF, 1 hit
SM00229 RasGEFN, 1 hit
SUPFAMiSSF47473 SSF47473, 2 hits
SSF48366 SSF48366, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 3 hits
PS50009 RASGEF_CAT, 1 hit
PS50212 RASGEF_NTER, 1 hit
PS00479 ZF_DAG_PE_1, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGRP1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1S3
Secondary accession number(s): Q3URH0, Q3V401, Q8BQP6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: May 1, 1999
Last modified: September 12, 2018
This is version 155 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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