HUMAN:GRP1

Species (Taxon ID)	Homo sapiens (Human). (9606)
Gene Name(s)	RASGRP1 (synonyms: RASGRP)
Protein Name(s)	RAS guanyl-releasing protein 1 Calcium and DAG-regulated guanine nucleotide exchange factor II CalDAG-GEFII Ras guanyl-releasing protein
External Links
UniProt	O95267
EMBL	AF081195 AF081197 AF106071 AY634315 AY858556 AY954625 AY966005 BC067298 BC109296 BC109297 AB208848
CCDS	CCDS45221.1 CCDS45222.1
RefSeq	NP_001122074.1 NP_005730.2
UniGene	Hs.591127
PDB	4L9M 4L9U
PDBsum	4L9M 4L9U
ProteinModelPortal	O95267
SMR	O95267
BioGrid	115429
IntAct	O95267
MINT	MINT-7970969
ChEMBL	CHEMBL5953
PhosphoSite	O95267
MaxQB	O95267
PaxDb	O95267
PRIDE	O95267
DNASU	10125
Ensembl	ENST00000310803 ENST00000414708 ENST00000450598 ENST00000558164 ENST00000559830
GeneID	10125
KEGG	hsa:10125
UCSC	uc001zkd.4 uc001zke.4 uc010bbf.3 uc010bbg.3
CTD	10125
GeneCards	GC15M038780
H-InvDB	HIX0038076
HGNC	HGNC:9878
MIM	152700 603962
neXtProt	NX_O95267
PharmGKB	PA34240
eggNOG	NOG256085
GeneTree	ENSGT00770000120448
HOVERGEN	HBG007513
InParanoid	O95267
KO	K04350
OrthoDB	EOG72G16V
PhylomeDB	O95267
TreeFam	TF312918
Reactome	REACT_118778 REACT_15523 REACT_163994 REACT_2202 REACT_23898
GeneWiki	RASGRP1
GenomeRNAi	10125
NextBio	38299
PRO	PR:O95267
Proteomes	UP000005640
Bgee	O95267
ExpressionAtlas	O95267
Genevestigator	O95267
GO	GO:0005829 GO:0005789 GO:0000139 GO:0042629 GO:0016020 GO:0005886 GO:0005509 GO:0005085 GO:0008289 GO:0032862 GO:0007596 GO:0030154 GO:0001816 GO:0038095 GO:0002437 GO:0045087 GO:0043303 GO:0030168 GO:0007265 GO:0014066 GO:0032252 GO:0007165 GO:0047496
Gene3D	1.10.238.10 1.10.840.10
InterPro	IPR020454 IPR011992 IPR018247 IPR002048 IPR002219 IPR000651 IPR023578 IPR001895 IPR029647
PANTHER	PTHR23113:SF174
Pfam	PF00130 PF13405 PF00617 PF00618
PRINTS	PR00008
SMART	SM00109 SM00147 SM00229
SUPFAM	SSF48366
PROSITE	PS00018 PS50222 PS50009 PS50212 PS00479 PS50081

Annotations

Qualifier	GO ID	GO term name	Reference	ECO ID	ECO term name	with/from	Aspect	Extension	Notes	Status
	GO:0043406	positive regulation of MAP kinase activity	PMID:15899849^[1]	ECO:0000315			P		Fig 4B. Erk1/Erk2 phosphorylation (via MAPK) was delayed and reduced in RasGRP1- mutants.	complete CACAO 2101
	GO:0010628	positive regulation of gene expression	PMID:21966541^[2]	ECO:0000315			P		Figure 3	complete CACAO 2105
	GO:0005794	Golgi apparatus	PMID:21968647^[3]	ECO:0000314			C		Under the condition of serum starvation, RasGRP1 was predominantly diffusely distributed…with a small portion localized to the Golgi (Figure 5C). when PAQR10 or PAQR11 was coexpressed, the localization of RasGRP1 in the Golgi compartment was profoundly increased under unstimulated condition (Figure 5C).	complete CACAO 2199
	GO:0001934	positive regulation of protein phosphorylation	PMID:21968647^[3]	ECO:0000314			P		We found that the PAQR10/ PAQR11-induced ERK phosphorylation was inhibited by RasGRP1-specific siRNAs (Figure 5D). In Hela cells, RasGRP1-specific siRNA could also abrogate PAQR10/ PAQR11-mediated accumulation of GFP-RBD in the Golgi apparatus (Supplementary information, Figure S12)	complete CACAO 2200
	GO:0090630	activation of GTPase activity	PMID:12845332^[4]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Fig 3e; overexpression of RasGRP1 was induced to determine the protein's normal function	complete CACAO 2538
	GO:0090630	activation of GTPase activity	PMID:10807788^[5]	ECO:0000314	direct assay evidence used in manual assertion		P		Fig 4; overexpression of RasGRP1 -> hypersensitive Jurkat cells. However, we observed that RasGRP can activate Ras in vivo even in the presence of EGTA plus BAPTA/AM, compounds that sequester extracellular and intracellular calcium, respectively (data not shown).	complete CACAO 2548
involved_in	GO:0046579	positive regulation of Ras protein signal transduction	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	causally_upstream_of:(GO:0002370)	Seeded From UniProt	complete
NOT\|involved_in	GO:1900274	regulation of phospholipase C activity	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0032760	positive regulation of tumor necrosis factor production	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	occurs_in:(CL:0000623)	Seeded From UniProt	complete
involved_in	GO:1902715	positive regulation of interferon-gamma secretion	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	occurs_in:(CL:0000623)	Seeded From UniProt	complete
involved_in	GO:0032725	positive regulation of granulocyte macrophage colony-stimulating factor production	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	occurs_in:(CL:0000623)	Seeded From UniProt	complete
involved_in	GO:0051259	protein complex oligomerization	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
enables	GO:0005509	calcium ion binding	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
involved_in	GO:0001934	positive regulation of protein phosphorylation	PMID:21968647^[3]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
part_of	GO:0005794	Golgi apparatus	PMID:21968647^[3]	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
enables	GO:0008270	zinc ion binding	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
involved_in	GO:0043547	positive regulation of GTPase activity	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	causally_upstream_of:(GO:0070372)	Seeded From UniProt	complete
involved_in	GO:0070372	regulation of ERK1 and ERK2 cascade	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
enables	GO:0001786	phosphatidylserine binding	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		F	happens_during:(GO:0090630)	Seeded From UniProt	complete
enables	GO:0019992	diacylglycerol binding	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		F	happens_during:(GO:0090630)	Seeded From UniProt	complete
enables	GO:0031210	phosphatidylcholine binding	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		F	happens_during:(GO:0090630)	Seeded From UniProt	complete
involved_in	GO:0045954	positive regulation of natural killer cell mediated cytotoxicity	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
enables	GO:0005088	Ras guanyl-nucleotide exchange factor activity	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		F	causally_upstream_of:(GO:0070372) causally_upstream_of:(GO:0043547)	Seeded From UniProt	complete
involved_in	GO:0001934	positive regulation of protein phosphorylation	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	part_of:(GO:0070372)	Seeded From UniProt	complete
enables	GO:0042803	protein homodimerization activity	PMID:23908768^[7]	ECO:0000315	mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
NOT\|involved_in	GO:1900744	regulation of p38MAPK cascade	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0046330	positive regulation of JNK cascade	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	occurs_in:(CL:0000623)	Seeded From UniProt	complete
involved_in	GO:0070374	positive regulation of ERK1 and ERK2 cascade	PMID:19933860^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	occurs_in:(CL:0000623)	Seeded From UniProt	complete
involved_in	GO:0090630	activation of GTPase activity	PMID:10807788^[5]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0043406	positive regulation of MAP kinase activity	PMID:15899849^[1]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0090630	activation of GTPase activity	PMID:12845332^[4]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
part_of	GO:0005886	plasma membrane	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005829	cytosol	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0042629	mast cell granule	GO_REF:0000108	ECO:0000366	evidence based on logical inference from automatic annotation used in automatic assertion	GO:0043303	C		Seeded From UniProt	complete
involved_in	GO:0090630	activation of GTPase activity	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0047496	vesicle transport along microtubule	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0043303	mast cell degranulation	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0033089	positive regulation of T cell differentiation in thymus	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0032825	positive regulation of natural killer cell differentiation	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0032816	positive regulation of natural killer cell activation	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0032252	secretory granule localization	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0014066	regulation of phosphatidylinositol 3-kinase signaling	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0002437	inflammatory response to antigenic stimulus	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
involved_in	GO:0001816	cytokine production	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:Q9Z1S3 ensembl:ENSMUSP00000099593	P		Seeded From UniProt	complete
enables	GO:0005085	guanyl-nucleotide exchange factor activity	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR001895 InterPro:IPR008937 InterPro:IPR036964	F		Seeded From UniProt	complete
enables	GO:0005096	GTPase activator activity	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR029645	F		Seeded From UniProt	complete
enables	GO:0005509	calcium ion binding	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR002048	F		Seeded From UniProt	complete
involved_in	GO:0007264	small GTPase mediated signal transduction	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR001895 InterPro:IPR008937 InterPro:IPR036964	P		Seeded From UniProt	complete
involved_in	GO:0007265	Ras protein signal transduction	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR029645	P		Seeded From UniProt	complete
involved_in	GO:0035556	intracellular signal transduction	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR002219	P		Seeded From UniProt	complete
involved_in	GO:0043087	regulation of GTPase activity	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR029645	P		Seeded From UniProt	complete
part_of	GO:0016020	membrane	PMID:9582122^[8]	ECO:0000304	author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
enables	GO:0008289	lipid binding	PMID:9582122^[8]	ECO:0000304	author statement supported by traceable reference used in manual assertion		F		Seeded From UniProt	complete
involved_in	GO:0007265	Ras protein signal transduction	PMID:9582122^[8]	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0007165	signal transduction	PMID:9789079^[9]	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
enables	GO:0005509	calcium ion binding	PMID:9582122^[8]	ECO:0000304	author statement supported by traceable reference used in manual assertion		F		Seeded From UniProt	complete
enables	GO:0005085	guanyl-nucleotide exchange factor activity	PMID:9789079^[9] Reactome:R-HSA-1168636	ECO:0000304	author statement supported by traceable reference used in manual assertion		F		Seeded From UniProt	complete
part_of	GO:0005886	plasma membrane	Reactome:R-HSA-5672965 Reactome:R-HSA-1168636	ECO:0000304	author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005829	cytosol	Reactome:R-HSA-5672965 Reactome:R-HSA-354173	ECO:0000304	author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
involved_in	GO:0000165	MAPK cascade	Reactome:R-HSA-5673001	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0030154	cell differentiation	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0221	P		Seeded From UniProt	complete
part_of	GO:0005737	cytoplasm	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0963	C		Seeded From UniProt	complete
part_of	GO:0005783	endoplasmic reticulum	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0256	C		Seeded From UniProt	complete
enables	GO:0005085	guanyl-nucleotide exchange factor activity	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0344	F		Seeded From UniProt	complete
part_of	GO:0016020	membrane	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0472	C		Seeded From UniProt	complete
part_of	GO:0005886	plasma membrane	GO_REF:0000037 GO_REF:0000039	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-1003 UniProtKB-SubCell:SL-0039	C		Seeded From UniProt	complete
enables	GO:0046872	metal ion binding	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0479	F		Seeded From UniProt	complete
part_of	GO:0005794	Golgi apparatus	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0333	C		Seeded From UniProt	complete
part_of	GO:0005829	cytosol	GO_REF:0000039	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-SubCell:SL-0091	C		Seeded From UniProt	complete
part_of	GO:0005789	endoplasmic reticulum membrane	GO_REF:0000039	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-SubCell:SL-0097	C		Seeded From UniProt	complete
part_of	GO:0000139	Golgi membrane	GO_REF:0000039	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-SubCell:SL-0134	C		Seeded From UniProt	complete
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Notes

References

See Help:References for how to manage references in GONUTS.

↑ ^1.0 ^1.1 Roose, JP et al. (2005) A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol. Cell. Biol. 25 4426-41 PubMed GONUTS page
↑ Markegard, E et al. (2011) Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression. PLoS ONE 6 e25540 PubMed GONUTS page
↑ ^3.0 ^3.1 ^3.2 ^3.3 Jin, T et al. (2012) PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus. Cell Res. 22 661-76 PubMed GONUTS page
↑ ^4.0 ^4.1 Bivona, TG et al. (2003) Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature 424 694-8 PubMed GONUTS page
↑ ^5.0 ^5.1 Ebinu, JO et al. (2000) RasGRP links T-cell receptor signaling to Ras. Blood 95 3199-203 PubMed GONUTS page
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 ^6.6 ^6.7 ^6.8 Lee, SH et al. (2009) RasGRP1 is required for human NK cell function. J. Immunol. 183 7931-8 PubMed GONUTS page
↑ ^7.00 ^7.01 ^7.02 ^7.03 ^7.04 ^7.05 ^7.06 ^7.07 ^7.08 ^7.09 ^7.10 Iwig, JS et al. (2013) Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1. Elife 2 e00813 PubMed GONUTS page
↑ ^8.0 ^8.1 ^8.2 ^8.3 Ebinu, JO et al. (1998) RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs. Science 280 1082-6 PubMed GONUTS page
↑ ^9.0 ^9.1 Kawasaki, H et al. (1998) A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc. Natl. Acad. Sci. U.S.A. 95 13278-83 PubMed GONUTS page

[PMID:15899849-1] 1.0 ^1.1 Roose, JP et al. (2005) A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol. Cell. Biol. 25 4426-41 PubMed GONUTS page

[PMID:21966541-2] Markegard, E et al. (2011) Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression. PLoS ONE 6 e25540 PubMed GONUTS page

[PMID:21968647-3] 3.0 ^3.1 ^3.2 ^3.3 Jin, T et al. (2012) PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus. Cell Res. 22 661-76 PubMed GONUTS page

[PMID:12845332-4] 4.0 ^4.1 Bivona, TG et al. (2003) Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature 424 694-8 PubMed GONUTS page

[PMID:10807788-5] 5.0 ^5.1 Ebinu, JO et al. (2000) RasGRP links T-cell receptor signaling to Ras. Blood 95 3199-203 PubMed GONUTS page

[PMID:19933860-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 ^6.6 ^6.7 ^6.8 Lee, SH et al. (2009) RasGRP1 is required for human NK cell function. J. Immunol. 183 7931-8 PubMed GONUTS page

[PMID:23908768-7] 7.00 ^7.01 ^7.02 ^7.03 ^7.04 ^7.05 ^7.06 ^7.07 ^7.08 ^7.09 ^7.10 Iwig, JS et al. (2013) Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1. Elife 2 e00813 PubMed GONUTS page

[PMID:9582122-8] 8.0 ^8.1 ^8.2 ^8.3 Ebinu, JO et al. (1998) RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs. Science 280 1082-6 PubMed GONUTS page

[PMID:9789079-9] 9.0 ^9.1 Kawasaki, H et al. (1998) A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc. Natl. Acad. Sci. U.S.A. 95 13278-83 PubMed GONUTS page

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HUMAN:GRP1

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