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Q9QUG9 (GRP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Rasgrp2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length608 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Subunit structure

Forms a signaling complex with RAP1 and BRAF. Interacts with F-actin By similarity. Interacts with RAP1. Ref.11

Subcellular location

Cytoplasmcytosol By similarity. Cell membrane; Peripheral membrane protein By similarity. Cell junctionsynapsesynaptosome By similarity. Cell projectionruffle membrane; Peripheral membrane protein Potential. Note: Found both in the cytosol and associated with membranes By similarity. Enriched at juxtamembrane areas and membrane ruffles By similarity. Localizes to the cell bodies and axons of striatal neurons By similarity.

Tissue specificity

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. Ref.6 Ref.9 Ref.11

Developmental stage

Expressed in embryo with higher expression between E15 and E17. Ref.9

Domain

The N-terminal Ras-GEF domain mediates association with F-actin By similarity.

Disruption phenotype

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. Ref.11 Ref.13

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.

Sequence caution

The sequence BAC28797.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9QUG9-1)

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.
Isoform 2 (identifier: Q9QUG9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     472-608: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9QUG9-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 608608RAS guanyl-releasing protein 2
PRO_0000315609

Regions

Domain4 – 126123N-terminal Ras-GEF
Domain154 – 387234Ras-GEF
Domain426 – 46136EF-hand 1
Domain455 – 49036EF-hand 2
Calcium binding439 – 450121 Potential
Calcium binding468 – 479122 Potential
Zinc finger498 – 54851Phorbol-ester/DAG-type

Amino acid modifications

Modified residue1161Phosphoserine Ref.14
Modified residue1171Phosphoserine Ref.14

Natural variations

Alternative sequence125 – 14117PTYKW…NPVEQ → CVGAERKGHYACYTICA in isoform 3.
VSP_030577
Alternative sequence142 – 608467Missing in isoform 3.
VSP_030578
Alternative sequence472 – 608137Missing in isoform 2.
VSP_030579

Experimental info

Sequence conflict21T → A in AAC79697. Ref.1
Sequence conflict21T → A in AAD12742. Ref.1
Sequence conflict731M → V in AAC79697. Ref.1
Sequence conflict731M → V in AAD12742. Ref.1
Sequence conflict831I → V in AAC79697. Ref.1
Sequence conflict831I → V in AAD12742. Ref.1
Sequence conflict991Q → P in AAC79697. Ref.1
Sequence conflict991Q → P in AAD12742. Ref.1
Sequence conflict2331R → K in AAC79697. Ref.1
Sequence conflict2331R → K in AAD12742. Ref.1
Sequence conflict3391C → S in AAC79697. Ref.1
Sequence conflict3391C → S in AAD12742. Ref.1
Sequence conflict5421E → D in AAC79697. Ref.1
Sequence conflict5421E → D in AAD12742. Ref.1
Sequence conflict5981S → T in AAC79697. Ref.1
Sequence conflict5981S → T in AAD12742. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CalDAG-GEF1a) [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: 1E6F768EF00B0468

FASTA60869,446
        10         20         30         40         50         60 
MTSTLDLDKG CTVEELLRGC IEAFDDSGKV RDPQLVRMFL MMHPWYIPSS QLASKLLHFY 

        70         80         90        100        110        120 
QQSRKDNSNS LQMKTCHLVR YWISAFPAEF DLNPELAEQI KELKALLDQE GNRRHSSLID 

       130        140        150        160        170        180 
IESVPTYKWK RQVTQRNPVE QKKRKMSLLF DHLEPMELAE HLTYLEYRSF CKILFQDYHS 

       190        200        210        220        230        240 
FVTHGCTVDN PVLERFISLF NSVSQWVQLM ILSKPTATQR ALVITHFVHV AERLLQLQNF 

       250        260        270        280        290        300 
NTLMAVVGGL SHSSISRLKE THSHVSPDTI KLWEGLTELV TATGNYSNYR RRLAACVGFR 

       310        320        330        340        350        360 
FPILGVHLKD LVALQLALPD WLDPGRTRLN GAKMRQLFCI LEELAMVTSL RPPVQANPDL 

       370        380        390        400        410        420 
LSLLTVSLDQ YQTEDELYQL SLQREPRSKS SPTSPTSCTP PPRPPVLEEW TSVAKPKLDQ 

       430        440        450        460        470        480 
ALVAEHIEKM VESVFRNFDV DGDGHISQEE FQIIRGNFPY LSAFGDLDQN QDGCISREEM 

       490        500        510        520        530        540 
ISYFLRSSSV LGGRMGFVHN FQESNSLRPV ACRHCKALIL GIYKQGLKCR ACGVNCHKQC 

       550        560        570        580        590        600 
KERLSVECRR RAQSVSLEGS APSPSPTHTH HRAFSFSLPR PGRRSSRPPE IREEEVQSVE 


DGVFDIHL 

« Hide

Isoform 2 [UniParc].

Checksum: 3C2F75238F062E1A
Show »

FASTA47154,054
Isoform 3 (CalDAG-GEF1b) [UniParc].

Checksum: 242C314B00AD9191
Show »

FASTA14116,187

References

« Hide 'large scale' 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION AS A RAP ACTIVATOR.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Strain: C57BL/6J.
Tissue: Mammary gland.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 204-608 (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Embryo.
[4]"The germinal centre kinase gene and a novel CDC25-like gene are located in the vicinity of the PYGM gene on 11q13."
Kedra D., Seroussi E., Fransson I., Trifunovic J., Clark M., Lagercrantz J., Blennow E., Mehlin H., Dumanski J.
Hum. Genet. 100:611-619(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 349-608 (ISOFORM 1).
[5]"Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3."
Ohba Y., Mochizuki N., Yamashita S., Chan A.M., Schrader J.W., Hattori S., Nagashima K., Matsuda M.
J. Biol. Chem. 275:20020-20026(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"CalDAG-GEFIII activation of Ras, R-ras, and Rap1."
Yamashita S., Mochizuki N., Ohba Y., Tobiume M., Okada Y., Sawa H., Nagashima K., Matsuda M.
J. Biol. Chem. 275:25488-25493(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade."
Ohba Y., Mochizuki N., Matsuo K., Yamashita S., Nakaya M., Hashimoto Y., Hamaguchi M., Kurata T., Nagashima K., Matsuda M.
Mol. Cell. Biol. 20:6074-6083(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS RAP2 ACTIVATOR.
[8]"Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis."
Ohba Y., Ikuta K., Ogura A., Matsuda J., Mochizuki N., Nagashima K., Kurokawa K., Mayer B.J., Maki K., Miyazaki J., Matsuda M.
EMBO J. 20:3333-3341(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Activation of the Rap1 guanine nucleotide exchange gene, CalDAG-GEF I, in BXH-2 murine myeloid leukemia."
Dupuy A.J., Morgan K., von Lintig F.C., Shen H., Acar H., Hasz D.E., Jenkins N.A., Copeland N.G., Boss G.R., Largaespada D.A.
J. Biol. Chem. 276:11804-11811(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[10]"Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling."
Eto K., Murphy R., Kerrigan S.W., Bertoni A., Stuhlmann H., Nakano T., Leavitt A.D., Shattil S.J.
Proc. Natl. Acad. Sci. U.S.A. 99:12819-12824(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation."
Crittenden J.R., Bergmeier W., Zhang Y., Piffath C.L., Liang Y., Wagner D.D., Housman D.E., Graybiel A.M.
Nat. Med. 10:982-986(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PLATELET AGGREGATION, DISRUPTION PHENOTYPE, INTERACTION WITH RAP1, TISSUE SPECIFICITY.
[12]"The small GTPase Rap1b regulates the cross talk between platelet integrin alpha2beta1 and integrin alphaIIbbeta3."
Bernardi B., Guidetti G.F., Campus F., Crittenden J.R., Graybiel A.M., Balduini C., Torti M.
Blood 107:2728-2735(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III."
Bergmeier W., Goerge T., Wang H.-W., Crittenden J.R., Baldwin A.C.W., Cifuni S.M., Housman D.E., Graybiel A.M., Wagner D.D.
J. Clin. Invest. 117:1699-1707(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[14]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116 AND SER-117, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS37898.1. [Q9QUG9-1]
RefSeqNP_035372.2. NM_011242.2. [Q9QUG9-1]
XP_006531748.1. XM_006531685.1. [Q9QUG9-1]
XP_006531749.1. XM_006531686.1. [Q9QUG9-1]
XP_006531750.1. XM_006531687.1. [Q9QUG9-1]
XP_006531751.1. XM_006531688.1. [Q9QUG9-1]
XP_006531752.1. XM_006531689.1. [Q9QUG9-1]
XP_006531753.1. XM_006531690.1. [Q9QUG9-1]
XP_006531754.1. XM_006531691.1. [Q9QUG9-1]
UniGeneMm.77017.

3D structure databases

ProteinModelPortalQ9QUG9.
SMRQ9QUG9. Positions 7-550.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9QUG9. 1 interaction.
MINTMINT-4130449.

PTM databases

PhosphoSiteQ9QUG9.

Proteomic databases

MaxQBQ9QUG9.
PaxDbQ9QUG9.
PRIDEQ9QUG9.

Protocols and materials databases

DNASU19395.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035716; 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]
GeneID19395.
KEGGmmu:19395.
UCSCuc008gip.1. mouse. [Q9QUG9-1]
uc008gir.1. mouse. [Q9QUG9-2]

Organism-specific databases

CTD10235.
MGIMGI:1333849. Rasgrp2.

Phylogenomic databases

eggNOGNOG256085.
GeneTreeENSGT00750000117506.
HOGENOMHOG000293171.
HOVERGENHBG007513.
InParanoidQ9QUG9.
KOK12361.
OMAFPYLSAF.
OrthoDBEOG72G16V.
PhylomeDBQ9QUG9.
TreeFamTF312918.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.
REACT_224553. Hemostasis.

Gene expression databases

ArrayExpressQ9QUG9.
BgeeQ9QUG9.
CleanExMM_RASGRP2.
GenevestigatorQ9QUG9.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
1.10.840.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR023578. Ras_GEF_dom.
IPR001895. RasGRF_CDC25.
[Graphical view]
PfamPF00130. C1_1. 1 hit.
PF13202. EF-hand_5. 2 hits.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
SMARTSM00109. C1. 1 hit.
SM00054. EFh. 2 hits.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMSSF48366. SSF48366. 1 hit.
PROSITEPS00018. 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]
ProtoNetSearch...

Other

NextBio296505.
PROQ9QUG9.
SOURCESearch...

Entry information

Entry nameGRP2_MOUSE
AccessionPrimary (citable) accession number: Q9QUG9
Secondary accession number(s): O09004, Q80WC0, Q8BSC8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: July 9, 2014
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot