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Protein

RAS guanyl-releasing protein 2

Gene

Rasgrp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.9 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi439 – 4501PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi468 – 4792PROSITE-ProRule annotationAdd BLAST12
Zinc fingeri498 – 548Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-114508. Effects of PIP2 hydrolysis.
R-MMU-354192. Integrin alphaIIb beta3 signaling.
R-MMU-392517. Rap1 signalling.

Names & Taxonomyi

Protein namesi
Recommended name:
RAS guanyl-releasing protein 2
Alternative name(s):
Calcium and DAG-regulated guanine nucleotide exchange factor I
Short name:
CalDAG-GEFI
F25B3.3 kinase-like protein
Gene namesi
Name:Rasgrp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1333849. Rasgrp2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Disruption phenotypei

Mice have a combination of defects in leukocytes and platelet functions which are reminiscent of the human leukocyte adhesion deficiency type III syndrome (LAD3). They display bleeding diathesis due to a defect in platelet aggregation and are resistant to collagen-induced thrombosis. In parallel, they also display impaired response to acute inflammation associated with defects in beta-1 and beta-2 integrin-mediated adhesion of neutrophils.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003156091 – 608RAS guanyl-releasing protein 2Add BLAST608

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei116PhosphoserineCombined sources1
Modified residuei117PhosphoserineCombined sources1
Modified residuei147PhosphoserineCombined sources1
Modified residuei554PhosphoserineCombined sources1
Modified residuei575PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9QUG9.
PaxDbiQ9QUG9.
PeptideAtlasiQ9QUG9.
PRIDEiQ9QUG9.

PTM databases

iPTMnetiQ9QUG9.
PhosphoSitePlusiQ9QUG9.

Expressioni

Tissue specificityi

Detected in megakaryocytes, platelet and neutrophils but not in lymphocytes (at protein level). Isoform 1 and isoform 3 are detected in brain basal glanglia, heart, lung, spleen, liver and kidney interstitial cells.3 Publications

Developmental stagei

Expressed in embryo with higher expression between E15 and E17.1 Publication

Gene expression databases

BgeeiENSMUSG00000032946.
CleanExiMM_RASGRP2.
ExpressionAtlasiQ9QUG9. baseline and differential.
GenevisibleiQ9QUG9. MM.

Interactioni

Subunit structurei

Forms a signaling complex with RAP1 and BRAF. Interacts with F-actin (By similarity). Interacts with RAP1.By similarity1 Publication

Protein-protein interaction databases

IntActiQ9QUG9. 1 interactor.
MINTiMINT-4130449.
STRINGi10090.ENSMUSP00000041135.

Structurei

3D structure databases

ProteinModelPortaliQ9QUG9.
SMRiQ9QUG9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 126N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST123
Domaini154 – 387Ras-GEFPROSITE-ProRule annotationAdd BLAST234
Domaini426 – 461EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini455 – 490EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Domaini

The N-terminal Ras-GEF domain mediates association with F-actin.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)DescriptionActionsGraphical viewLength
Zinc fingeri498 – 548Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG3417. Eukaryota.
ENOG410XR96. LUCA.
GeneTreeiENSGT00850000132267.
HOGENOMiHOG000293171.
HOVERGENiHBG007513.
InParanoidiQ9QUG9.
KOiK12361.
OMAiQWIQLMV.
OrthoDBiEOG091G03RN.
PhylomeDBiQ9QUG9.
TreeFamiTF312918.

Family and domain databases

CDDicd00029. C1. 1 hit.
cd00051. EFh. 1 hit.
cd00155. RasGEF. 1 hit.
cd06224. REM. 1 hit.
Gene3Di1.10.238.10. 1 hit.
1.10.840.10. 1 hit.
InterProiIPR011992. 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.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF13202. EF-hand_5. 2 hits.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00054. EFh. 2 hits.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF48366. SSF48366. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9QUG9-1) [UniParc]FASTAAdd to basket
Also known as: CalDAG-GEF1a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTSTLDLDKG CTVEELLRGC IEAFDDSGKV RDPQLVRMFL MMHPWYIPSS
60 70 80 90 100
QLASKLLHFY QQSRKDNSNS LQMKTCHLVR YWISAFPAEF DLNPELAEQI
110 120 130 140 150
KELKALLDQE GNRRHSSLID IESVPTYKWK RQVTQRNPVE QKKRKMSLLF
160 170 180 190 200
DHLEPMELAE HLTYLEYRSF CKILFQDYHS FVTHGCTVDN PVLERFISLF
210 220 230 240 250
NSVSQWVQLM ILSKPTATQR ALVITHFVHV AERLLQLQNF NTLMAVVGGL
260 270 280 290 300
SHSSISRLKE THSHVSPDTI KLWEGLTELV TATGNYSNYR RRLAACVGFR
310 320 330 340 350
FPILGVHLKD LVALQLALPD WLDPGRTRLN GAKMRQLFCI LEELAMVTSL
360 370 380 390 400
RPPVQANPDL LSLLTVSLDQ YQTEDELYQL SLQREPRSKS SPTSPTSCTP
410 420 430 440 450
PPRPPVLEEW TSVAKPKLDQ ALVAEHIEKM VESVFRNFDV DGDGHISQEE
460 470 480 490 500
FQIIRGNFPY LSAFGDLDQN QDGCISREEM ISYFLRSSSV LGGRMGFVHN
510 520 530 540 550
FQESNSLRPV ACRHCKALIL GIYKQGLKCR ACGVNCHKQC KERLSVECRR
560 570 580 590 600
RAQSVSLEGS APSPSPTHTH HRAFSFSLPR PGRRSSRPPE IREEEVQSVE

DGVFDIHL
Length:608
Mass (Da):69,446
Last modified:January 15, 2008 - v2
Checksum:i1E6F768EF00B0468
GO
Isoform 2 (identifier: Q9QUG9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     472-608: Missing.

Note: No experimental confirmation available.
Show »
Length:471
Mass (Da):54,054
Checksum:i3C2F75238F062E1A
GO
Isoform 3 (identifier: Q9QUG9-3) [UniParc]FASTAAdd to basket
Also known as: CalDAG-GEF1b

The sequence of this isoform differs from the canonical sequence as follows:
     125-141: PTYKWKRQVTQRNPVEQ → CVGAERKGHYACYTICA
     142-608: Missing.

Note: The corresponding protein is not undetectable.
Show »
Length:141
Mass (Da):16,187
Checksum:i242C314B00AD9191
GO

Sequence cautioni

The sequence BAC28797 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2T → A in AAC79697 (PubMed:9789079).Curated1
Sequence conflicti2T → A in AAD12742 (PubMed:9789079).Curated1
Sequence conflicti73M → V in AAC79697 (PubMed:9789079).Curated1
Sequence conflicti73M → V in AAD12742 (PubMed:9789079).Curated1
Sequence conflicti83I → V in AAC79697 (PubMed:9789079).Curated1
Sequence conflicti83I → V in AAD12742 (PubMed:9789079).Curated1
Sequence conflicti99Q → P in AAC79697 (PubMed:9789079).Curated1
Sequence conflicti99Q → P in AAD12742 (PubMed:9789079).Curated1
Sequence conflicti233R → K in AAC79697 (PubMed:9789079).Curated1
Sequence conflicti233R → K in AAD12742 (PubMed:9789079).Curated1
Sequence conflicti339C → S in AAC79697 (PubMed:9789079).Curated1
Sequence conflicti339C → S in AAD12742 (PubMed:9789079).Curated1
Sequence conflicti542E → D in AAC79697 (PubMed:9789079).Curated1
Sequence conflicti542E → D in AAD12742 (PubMed:9789079).Curated1
Sequence conflicti598S → T in AAC79697 (PubMed:9789079).Curated1
Sequence conflicti598S → T in AAD12742 (PubMed:9789079).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030577125 – 141PTYKW…NPVEQ → CVGAERKGHYACYTICA in isoform 3. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_030578142 – 608Missing in isoform 3. 1 PublicationAdd BLAST467
Alternative sequenceiVSP_030579472 – 608Missing in isoform 2. 1 PublicationAdd BLAST137

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF081193 mRNA. Translation: AAC79697.1.
U78171 mRNA. Translation: AAD12742.1.
BC051474 mRNA. Translation: AAH51474.1.
AK034683 mRNA. Translation: BAC28797.1. Different initiation.
Y12339 mRNA. Translation: CAA73008.1.
CCDSiCCDS37898.1. [Q9QUG9-1]
RefSeqiNP_035372.2. NM_011242.2. [Q9QUG9-1]
XP_006531748.1. XM_006531685.3. [Q9QUG9-1]
XP_006531749.1. XM_006531686.3. [Q9QUG9-1]
XP_006531750.1. XM_006531687.2. [Q9QUG9-1]
XP_006531751.1. XM_006531688.3. [Q9QUG9-1]
XP_006531752.1. XM_006531689.3. [Q9QUG9-1]
XP_006531753.1. XM_006531690.3. [Q9QUG9-1]
XP_006531754.1. XM_006531691.3. [Q9QUG9-1]
UniGeneiMm.77017.

Genome annotation databases

EnsembliENSMUST00000035716; ENSMUSP00000041135; ENSMUSG00000032946. [Q9QUG9-1]
ENSMUST00000113471; ENSMUSP00000109099; ENSMUSG00000032946. [Q9QUG9-3]
ENSMUST00000113472; ENSMUSP00000109100; ENSMUSG00000032946. [Q9QUG9-3]
ENSMUST00000113475; ENSMUSP00000109103; ENSMUSG00000032946. [Q9QUG9-3]
ENSMUST00000113476; ENSMUSP00000109104; ENSMUSG00000032946. [Q9QUG9-1]
ENSMUST00000167240; ENSMUSP00000129873; ENSMUSG00000032946. [Q9QUG9-1]
ENSMUST00000200711; ENSMUSP00000144159; ENSMUSG00000106685. [Q9QUG9-1]
ENSMUST00000200777; ENSMUSP00000143871; ENSMUSG00000106685. [Q9QUG9-1]
ENSMUST00000200858; ENSMUSP00000143974; ENSMUSG00000106685. [Q9QUG9-3]
ENSMUST00000201065; ENSMUSP00000143947; ENSMUSG00000106685. [Q9QUG9-1]
ENSMUST00000201395; ENSMUSP00000144508; ENSMUSG00000106685. [Q9QUG9-3]
ENSMUST00000202484; ENSMUSP00000144241; ENSMUSG00000106685. [Q9QUG9-3]
GeneIDi19395.
KEGGimmu:19395.
UCSCiuc008gip.1. mouse. [Q9QUG9-1]
uc008gir.1. mouse. [Q9QUG9-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF081193 mRNA. Translation: AAC79697.1.
U78171 mRNA. Translation: AAD12742.1.
BC051474 mRNA. Translation: AAH51474.1.
AK034683 mRNA. Translation: BAC28797.1. Different initiation.
Y12339 mRNA. Translation: CAA73008.1.
CCDSiCCDS37898.1. [Q9QUG9-1]
RefSeqiNP_035372.2. NM_011242.2. [Q9QUG9-1]
XP_006531748.1. XM_006531685.3. [Q9QUG9-1]
XP_006531749.1. XM_006531686.3. [Q9QUG9-1]
XP_006531750.1. XM_006531687.2. [Q9QUG9-1]
XP_006531751.1. XM_006531688.3. [Q9QUG9-1]
XP_006531752.1. XM_006531689.3. [Q9QUG9-1]
XP_006531753.1. XM_006531690.3. [Q9QUG9-1]
XP_006531754.1. XM_006531691.3. [Q9QUG9-1]
UniGeneiMm.77017.

3D structure databases

ProteinModelPortaliQ9QUG9.
SMRiQ9QUG9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9QUG9. 1 interactor.
MINTiMINT-4130449.
STRINGi10090.ENSMUSP00000041135.

PTM databases

iPTMnetiQ9QUG9.
PhosphoSitePlusiQ9QUG9.

Proteomic databases

EPDiQ9QUG9.
PaxDbiQ9QUG9.
PeptideAtlasiQ9QUG9.
PRIDEiQ9QUG9.

Protocols and materials databases

DNASUi19395.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035716; ENSMUSP00000041135; ENSMUSG00000032946. [Q9QUG9-1]
ENSMUST00000113471; ENSMUSP00000109099; ENSMUSG00000032946. [Q9QUG9-3]
ENSMUST00000113472; ENSMUSP00000109100; ENSMUSG00000032946. [Q9QUG9-3]
ENSMUST00000113475; ENSMUSP00000109103; ENSMUSG00000032946. [Q9QUG9-3]
ENSMUST00000113476; ENSMUSP00000109104; ENSMUSG00000032946. [Q9QUG9-1]
ENSMUST00000167240; ENSMUSP00000129873; ENSMUSG00000032946. [Q9QUG9-1]
ENSMUST00000200711; ENSMUSP00000144159; ENSMUSG00000106685. [Q9QUG9-1]
ENSMUST00000200777; ENSMUSP00000143871; ENSMUSG00000106685. [Q9QUG9-1]
ENSMUST00000200858; ENSMUSP00000143974; ENSMUSG00000106685. [Q9QUG9-3]
ENSMUST00000201065; ENSMUSP00000143947; ENSMUSG00000106685. [Q9QUG9-1]
ENSMUST00000201395; ENSMUSP00000144508; ENSMUSG00000106685. [Q9QUG9-3]
ENSMUST00000202484; ENSMUSP00000144241; ENSMUSG00000106685. [Q9QUG9-3]
GeneIDi19395.
KEGGimmu:19395.
UCSCiuc008gip.1. mouse. [Q9QUG9-1]
uc008gir.1. mouse. [Q9QUG9-2]

Organism-specific databases

CTDi10235.
MGIiMGI:1333849. Rasgrp2.

Phylogenomic databases

eggNOGiKOG3417. Eukaryota.
ENOG410XR96. LUCA.
GeneTreeiENSGT00850000132267.
HOGENOMiHOG000293171.
HOVERGENiHBG007513.
InParanoidiQ9QUG9.
KOiK12361.
OMAiQWIQLMV.
OrthoDBiEOG091G03RN.
PhylomeDBiQ9QUG9.
TreeFamiTF312918.

Enzyme and pathway databases

ReactomeiR-MMU-114508. Effects of PIP2 hydrolysis.
R-MMU-354192. Integrin alphaIIb beta3 signaling.
R-MMU-392517. Rap1 signalling.

Miscellaneous databases

PROiQ9QUG9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032946.
CleanExiMM_RASGRP2.
ExpressionAtlasiQ9QUG9. baseline and differential.
GenevisibleiQ9QUG9. MM.

Family and domain databases

CDDicd00029. C1. 1 hit.
cd00051. EFh. 1 hit.
cd00155. RasGEF. 1 hit.
cd06224. REM. 1 hit.
Gene3Di1.10.238.10. 1 hit.
1.10.840.10. 1 hit.
InterProiIPR011992. 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.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF13202. EF-hand_5. 2 hits.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00054. EFh. 2 hits.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF48366. SSF48366. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 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...

Entry informationi

Entry nameiGRP2_MOUSE
AccessioniPrimary (citable) accession number: Q9QUG9
Secondary accession number(s): O09004, Q80WC0, Q8BSC8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: November 30, 2016
This is version 134 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.