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Protein

RAS guanyl-releasing protein 1

Gene

Rasgrp1

Organism
Rattus norvegicus (Rat)
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 (PubMed:9789079, PubMed:9582122). 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. May also function in differentiation of other cell types. Proto-oncogene, which promotes T-cell lymphomagenesis when its expression is deregulated (By similarity).By similarity2 Publications

Activity regulationi

Autoinhibited (By similarity). Activated by diacylglycerol and calcium binding, which induces a conformational change releasing the autoinhibitory state (PubMed:9582122). Regulated by DGKA. Regulated by DGKZ. Regulated by PLC gamma and F-actin polymerization (By similarity).By similarity1 Publication

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-RNO-1169092 Activation of RAS in B cells
R-RNO-354192 Integrin alphaIIb beta3 signaling
R-RNO-392517 Rap1 signalling
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi3539 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi510 – 521DKDRE…ISRDE → AKARAGLISRDA: Loss of calcium-binding. 1 PublicationAdd BLAST12

Chemistry databases

ChEMBLiCHEMBL3109

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003169801 – 795RAS guanyl-releasing protein 1Add BLAST795

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei184Phosphothreonine; by PKCBy similarity1
Modified residuei597PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9R1K8
PRIDEiQ9R1K8

PTM databases

iPTMnetiQ9R1K8
PhosphoSitePlusiQ9R1K8

Expressioni

Tissue specificityi

Specifically expressed in brain with higher density in hippocampal CA1 and CA3 fields. Detected in interneurons and projection neurons with no restriction to any neuronal type or neurotransmitter phenotype but not detected in glial cells. Expressed in the hematopoietic system. Expressed in several neuronal types of the hippocampus and entorhinal cortex (at protein level).3 Publications

Developmental stagei

Expression appears in neurons of the hippocampus during the first 2 weeks after birth (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000005404 Expressed in 10 organ(s), highest expression level in brain
GenevisibleiQ9R1K8 RN

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

STRINGi10116.ENSRNOP00000007687

Chemistry databases

BindingDBiQ9R1K8

Structurei

3D structure databases

ProteinModelPortaliQ9R1K8
SMRiQ9R1K8
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 activityBy similarityAdd BLAST54
Regioni686 – 694Suppress the PT region-mediated translocation to plasma membraneBy similarity9
Regioni717 – 795PT region; mediates the BCR-dependent translocation to plasma membraneBy similarityAdd 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
InParanoidiQ9R1K8
KOiK04350
OMAiEGPFTFP
OrthoDBiEOG091G03RN
PhylomeDBiQ9R1K8
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

Sequencei

Sequence statusi: Complete.

Q9R1K8-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGTLGKAREA PRKPCHGSRA GPKGRLEAKS TNSPLPAQPS LAQITQFRMM
60 70 80 90 100
VSLGHLAKGA SLDDLIDSCI QSFDADGNLC RSNQLLQVML TMHRIIISSA
110 120 130 140 150
ELLQKLMNLY KDALEKNSPG ICLKICYFVR YWITEFWIMF KMDASLTSTM
160 170 180 190 200
EEFQDLVKAN GEESHCHLID 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 NELVQLQDVA
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 CKKRSKSPAV
610 620 630 640 650
STENISSVVP MSTLCPLGTK DLLHAPEEGS FIFQNGEVVD HSEESKDRTI
660 670 680 690 700
MLLGVSSQKI SVRLKRTVAH KTTQTESFPW VGGEMPPGHF VLTSPRKSAQ
710 720 730 740 750
GALYVHSPAS PCPSPALVRK RAFVKWENKE SLIKPKPELH LRLRTYQELE
760 770 780 790
QEVNTLRADN DALKIQLKYA QKQIESLQLG KSNHVLAQMD HGDGT
Length:795
Mass (Da):90,245
Last modified:May 1, 2000 - v1
Checksum:i14CC12EBBC967C39
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24G → A in AAC40137 (PubMed:9582122).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF081196 mRNA Translation: AAC79700.1
AF060819 mRNA Translation: AAC40137.1
RefSeqiNP_062084.2, NM_019211.2
UniGeneiRn.162685

Genome annotation databases

EnsembliENSRNOT00000007687; ENSRNOP00000007687; ENSRNOG00000005404
GeneIDi29434
KEGGirno:29434
UCSCiRGD:3539 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF081196 mRNA Translation: AAC79700.1
AF060819 mRNA Translation: AAC40137.1
RefSeqiNP_062084.2, NM_019211.2
UniGeneiRn.162685

3D structure databases

ProteinModelPortaliQ9R1K8
SMRiQ9R1K8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000007687

Chemistry databases

BindingDBiQ9R1K8
ChEMBLiCHEMBL3109

PTM databases

iPTMnetiQ9R1K8
PhosphoSitePlusiQ9R1K8

Proteomic databases

PaxDbiQ9R1K8
PRIDEiQ9R1K8

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000007687; ENSRNOP00000007687; ENSRNOG00000005404
GeneIDi29434
KEGGirno:29434
UCSCiRGD:3539 rat

Organism-specific databases

CTDi10125
RGDi3539 Rasgrp1

Phylogenomic databases

eggNOGiENOG410IQ6J Eukaryota
ENOG410ZKZ2 LUCA
GeneTreeiENSGT00880000137870
HOGENOMiHOG000293171
HOVERGENiHBG007513
InParanoidiQ9R1K8
KOiK04350
OMAiEGPFTFP
OrthoDBiEOG091G03RN
PhylomeDBiQ9R1K8
TreeFamiTF312918

Enzyme and pathway databases

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

Miscellaneous databases

PROiPR:Q9R1K8

Gene expression databases

BgeeiENSRNOG00000005404 Expressed in 10 organ(s), highest expression level in brain
GenevisibleiQ9R1K8 RN

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_RAT
AccessioniPrimary (citable) accession number: Q9R1K8
Secondary accession number(s): O88469
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: May 1, 2000
Last modified: September 12, 2018
This is version 133 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
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Main funding by: National Institutes of Health

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