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Protein

RAS guanyl-releasing protein 1

Gene

Rasgrp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi483 – 49412PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri541 – 59151Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Differentiation

Keywords - Ligandi

Calcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi3539. Rasgrp1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi510 – 52112DKDRE…ISRDE → AKARAGLISRDA: Loss of calcium-binding. 1 PublicationAdd
BLAST

Chemistry

ChEMBLiCHEMBL3109.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 795795RAS guanyl-releasing protein 1PRO_0000316980Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei184 – 1841Phosphothreonine; by PKCBy similarity
Modified residuei597 – 5971PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9R1K8.

PTM databases

iPTMnetiQ9R1K8.
PhosphoSiteiQ9R1K8.

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

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000007687.

Chemistry

BindingDBiQ9R1K8.

Structurei

3D structure databases

ProteinModelPortaliQ9R1K8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini53 – 176124N-terminal Ras-GEFPROSITE-ProRule annotationAdd
BLAST
Domaini205 – 436232Ras-GEFPROSITE-ProRule annotationAdd
BLAST
Domaini470 – 50536EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini497 – 53236EF-hand 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni57 – 11054Ras exchanger motif region; required for transforming activityBy similarityAdd
BLAST
Regioni686 – 6949Suppress the PT region-mediated translocation to plasma membraneBy similarity
Regioni717 – 79579PT region; mediates the BCR-dependent translocation to plasma membraneBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili738 – 77942Sequence analysisAdd
BLAST

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
Contains 2 EF-hand domains.PROSITE-ProRule annotation
Contains 1 N-terminal Ras-GEF domain.PROSITE-ProRule annotation
Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 Ras-GEF domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri541 – 59151Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IQ6J. Eukaryota.
ENOG410ZKZ2. LUCA.
GeneTreeiENSGT00810000125357.
HOGENOMiHOG000293171.
HOVERGENiHBG007513.
InParanoidiQ9R1K8.
KOiK04350.
OMAiEGPFTFP.
OrthoDBiEOG72G16V.
PhylomeDBiQ9R1K8.
TreeFamiTF312918.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
1.10.840.10. 1 hit.
InterProiIPR020454. 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.
IPR001895. RASGEF_cat_dom.
IPR029647. RasGRP1.
[Graphical view]
PANTHERiPTHR23113:SF174. PTHR23113:SF174. 1 hit.
PfamiPF00130. C1_1. 1 hit.
PF13202. EF-hand_5. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00054. EFh. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 2 hits.
SSF48366. SSF48366. 1 hit.
PROSITEiPS00018. 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.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti24 – 241G → A in AAC40137 (PubMed:9582122).Curated

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.

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000007687.

Chemistry

BindingDBiQ9R1K8.
ChEMBLiCHEMBL3109.

PTM databases

iPTMnetiQ9R1K8.
PhosphoSiteiQ9R1K8.

Proteomic databases

PaxDbiQ9R1K8.

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.
GeneTreeiENSGT00810000125357.
HOGENOMiHOG000293171.
HOVERGENiHBG007513.
InParanoidiQ9R1K8.
KOiK04350.
OMAiEGPFTFP.
OrthoDBiEOG72G16V.
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

PROiQ9R1K8.

Gene expression databases

GenevisibleiQ9R1K8. RN.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
1.10.840.10. 1 hit.
InterProiIPR020454. 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.
IPR001895. RASGEF_cat_dom.
IPR029647. RasGRP1.
[Graphical view]
PANTHERiPTHR23113:SF174. PTHR23113:SF174. 1 hit.
PfamiPF00130. C1_1. 1 hit.
PF13202. EF-hand_5. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00054. EFh. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 2 hits.
SSF48366. SSF48366. 1 hit.
PROSITEiPS00018. 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.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS RAS ACTIVATOR, TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "RasGRP, a Ras guanyl nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs."
    Ebinu J.O., Bottorff D.A., Chan E.Y.W., Stang S.L., Dunn R.J., Stone J.C.
    Science 280:1082-1086(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS RAS ACTIVATOR, ENZYME REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH RAS, CALCIUM-BINDING, MUTAGENESIS OF 510-ASP--GLU-521.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  3. "Distribution of ras guanyl releasing protein (RasGRP) mRNA in the adult rat central nervous system."
    Pierret P., Dunn R.J., Djordjevic B., Stone J.C., Richardson P.M.
    J. Neurocytol. 29:485-497(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "The guanine nucleotide exchange factor RasGRP is a high -affinity target for diacylglycerol and phorbol esters."
    Lorenzo P.S., Beheshti M., Pettit G.R., Stone J.C., Blumberg P.M.
    Mol. Pharmacol. 57:840-846(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: DIACYLGLYCEROL-BINDING.
  5. "Cellular and subcellular localization of Ras guanyl nucleotide-releasing protein in the rat hippocampus."
    Pierret P., Vallee A., Mechawar N., Dower N.A., Stone J.C., Richardson P.M., Dunn R.J.
    Neuroscience 108:381-390(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  6. "T cell activation in vivo targets diacylglycerol kinase alpha to the membrane: a novel mechanism for Ras attenuation."
    Sanjuan M.A., Pradet-Balade B., Jones D.R., Martinez-A C., Stone J.C., Garcia-Sanz J.A., Merida I.
    J. Immunol. 170:2877-2883(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "Diacylglycerol-dependent binding recruits PKCtheta and RasGRP1 C1 domains to specific subcellular localizations in living T lymphocytes."
    Carrasco S., Merida I.
    Mol. Biol. Cell 15:2932-2942(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TOPOLOGY.
  8. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-597, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiGRP1_RAT
AccessioniPrimary (citable) accession number: Q9R1K8
Secondary accession number(s): O88469
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 119 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.