RAS guanyl-releasing protein 1 - Rattus norvegicus (Rat)

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Reviewed, UniProtKB/Swiss-Prot Q9R1K8 (GRP1_RAT)

Last modified October 13, 2009. Version 65. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    RAS guanyl-releasing protein 1
Alternative name(s):
    Ras guanyl-releasing protein
    Calcium and DAG-regulated guanine nucleotide exchange factor II
      Short name=CalDAG-GEFII

Gene names

Name:	Rasgrp1
Synonyms:	Rasgrp

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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Protein attributes

Sequence length	795 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. Activates the Erk/MAP kinase cascade. Couples T-lymphocytes and B-lymphocytes antigen receptors to the activation of Ras. Hence, regulates T-cells and B-cells development, homeostasis and differentiation. Functions also in FcERI-evoked degranulation and cytokine secretion by mast cells, regulating allergic responses. May also function in other cell types differentiation. Ref.1 Ref.2
Enzyme regulation	Regulated by PLC gamma, DGKA, DGKZ and by F-actin polymerization By similarity. Probably regulated by calcium.
Subunit structure	Forms a signaling complex with DGKZ and HRAS. Interacts with F-actin. Interacts with SKAP1 By similarity.
Subcellular location	Cytoplasm › cytosol. Cell membrane; Peripheral membrane protein. Golgi apparatus membrane; Peripheral membrane protein By similarity. Endoplasmic reticulum membrane; Peripheral membrane protein By similarity. Note: 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 By similarity. Localizes to somata and dendrites but not to axons of hippocampal pyramidal cells.
Tissue specificity	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). Ref.1 Ref.3 Ref.5
Developmental stage	Expression appears in neurons of the hippocampus during the first 2 weeks after birth (at protein level). Ref.5
Domain	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.
Sequence similarities	Belongs to the RASGRP family. Contains 2 EF-hand domains. Contains 1 N-terminal Ras-GEF domain. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 Ras-GEF domain.

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Ontologies

Keywords
Biological process	Differentiation
Cellular component	Cell membrane Cytoplasm Endoplasmic reticulum Golgi apparatus Membrane
Domain	Coiled coil Phorbol-ester binding Repeat Zinc-finger
Ligand	Calcium Metal-binding Zinc
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW regulation of small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-KW cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	Rap guanyl-nucleotide exchange factor activity Ref.1 Traceable author statement. Source: RGD calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 795

795

RAS guanyl-releasing protein 1

PRO_0000316980

Regions

Domain

53 – 176

124

N-terminal Ras-GEF

Domain

205 – 436

232

Ras-GEF

Domain

470 – 505

EF-hand 1

Domain

497 – 532

EF-hand 2

Calcium binding

483 – 494

1 Potential

Calcium binding

510 – 521

2 Potential

Zinc finger

541 – 591

Phorbol-ester/DAG-type

Region

57 – 110

Ras exchanger motif region; required for transforming activity By similarity

Region

686 – 694

Suppress the PT region-mediated translocation to plasma membrane By similarity

Region

717 – 795

PT region; mediates the BCR-dependent translocation to plasma membrane By similarity

Coiled coil

738 – 779

Potential

Amino acid modifications

Modified residue

184

Phosphothreonine; by PKC By similarity

Experimental info

Mutagenesis

510 – 521

DKDRE…ISRDE → AKARAGLISRDA: Loss of calcium-binding. Ref.2

Sequence conflict

G → A in AAC40137. Ref.2

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9R1K8-1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 14CC12EBBC967C39
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FASTA

795

90,245

        10         20         30         40         50         60 
MGTLGKAREA PRKPCHGSRA GPKGRLEAKS TNSPLPAQPS LAQITQFRMM VSLGHLAKGA 

        70         80         90        100        110        120 
SLDDLIDSCI QSFDADGNLC RSNQLLQVML TMHRIIISSA ELLQKLMNLY KDALEKNSPG 

       130        140        150        160        170        180 
ICLKICYFVR YWITEFWIMF KMDASLTSTM EEFQDLVKAN GEESHCHLID 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 NELVQLQDVA 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 CKKRSKSPAV 

       610        620        630        640        650        660 
STENISSVVP MSTLCPLGTK DLLHAPEEGS FIFQNGEVVD HSEESKDRTI MLLGVSSQKI 

       670        680        690        700        710        720 
SVRLKRTVAH KTTQTESFPW VGGEMPPGHF VLTSPRKSAQ GALYVHSPAS PCPSPALVRK 

       730        740        750        760        770        780 
RAFVKWENKE SLIKPKPELH LRLRTYQELE QEVNTLRADN DALKIQLKYA QKQIESLQLG 

       790 
KSNHVLAQMD HGDGT

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References

[1]	"A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia." Kawasaki H., Springett G.M., Toki S., Canales J.J., Harlan P., Blumenstiel J.P., Chen E.J., Bany I.A., Mochizuki N., Ashbacher A., Matsuda M., Housman D.E., Graybiel A.M. Proc. Natl. Acad. Sci. U.S.A. 95:13278-13283(1998) [PubMed: 9789079] [Abstract] 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: 9582122] [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: 11279364] [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: 10779365] [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: 11738253] [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: 12626538] [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: 15064353] [Abstract] Cited for: SUBCELLULAR LOCATION, TOPOLOGY.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	AF081196 mRNA. Translation: AAC79700.1. AF060819 mRNA. Translation: AAC40137.1.
IPI	IPI00214389.
RefSeq	NP_062084.2.
UniGene	Rn.162685
3D structure databases
HSSP	HSSP built from PDB template 1PTQ based on UniProtKB P28867.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9R1K8.
PTM databases
PhosphoSite	Q9R1K8.
Genome annotation databases
Ensembl	ENSRNOT00000007687; ENSRNOP00000007687; ENSRNOG00000005404; Rattus norvegicus. [Genome view]
GeneID	29434.
KEGG	rno:29434.
UCSC	NM_019211. rat.
Organism-specific databases
CTD	29434.
RGD	3539. Rasgrp1.
Phylogenomic databases
HOVERGEN	Q9R1K8.
Gene expression databases
ArrayExpress	Q9R1K8.
Genevestigator	Q9R1K8.
Family and domain databases
InterPro	IPR020454. DAG/PE_bd. IPR011992. EF-Hand_type. IPR018248. EF_hand. IPR018247. EF_HAND_1_Ca_BS. IPR018249. EF_HAND_2. IPR002219. Prot_Kinase_C-like_PE/DAG_bd. IPR000651. Ras-like_Gua-exchang_fac_N. IPR019804. Ras_G-nucl-exch_fac_CS. IPR008937. Ras_GEF. IPR001895. RasGRF_CDC25. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 1 hit. G3DSA:1.10.840.10. RasGRF_CDC25. 1 hit.
PANTHER	PTHR23113. Ras_GEF. 1 hit.
Pfam	PF00130. C1_1. 1 hit. PF00036. efhand. 1 hit. PF00617. RasGEF. 1 hit. PF00618. RasGEF_N. 1 hit. [Graphical view]
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 1 hit. SM00147. RasGEF. 1 hit. SM00229. RasGEFN. 1 hit. [Graphical view]
PROSITE	PS00018. EF_HAND_1. 2 hits. PS50222. EF_HAND_2. 3 hits. PS00720. RASGEF. False negative. 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]
ProtoNet	Search...
Other Resources
NextBio	609166.

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Entry information

Entry name

GRP1_RAT

Accession

Primary (citable) accession number: Q9R1K8
Secondary accession number(s): O88469

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	May 1, 2000
Last modified:	October 13, 2009
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents