UniProtKB - Q8TDF6 (GRP4_HUMAN)
Protein
RAS guanyl-releasing protein 4
Gene
RASGRP4
Organism
Homo sapiens (Human)
Status
Functioni
Functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. May function in mast cells differentiation.4 Publications
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 540 – 590 | Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST | 51 |
GO - Molecular functioni
- calcium ion binding Source: InterPro
- diacylglycerol binding Source: UniProtKB
- GTP-dependent protein binding Source: UniProtKB
- guanyl-nucleotide exchange factor activity Source: UniProtKB
GO - Biological processi
- activation of phospholipase C activity Source: UniProtKB
- cell population proliferation Source: UniProtKB
- MAPK cascade Source: Reactome
- myeloid cell differentiation Source: UniProtKB
- positive regulation of Ras protein signal transduction Source: UniProtKB
- regulation of G protein-coupled receptor signaling pathway Source: UniProtKB
- response to extracellular stimulus Source: UniProtKB
- small GTPase mediated signal transduction Source: InterPro
- transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Guanine-nucleotide releasing factor |
Biological process | Differentiation |
Ligand | Calcium, Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q8TDF6 |
Reactomei | R-HSA-2871837, FCERI mediated NF-kB activation R-HSA-5673001, RAF/MAP kinase cascade |
Names & Taxonomyi
Protein namesi | Recommended name: RAS guanyl-releasing protein 4 |
Gene namesi | Name:RASGRP4 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18958, RASGRP4 |
MIMi | 607320, gene |
neXtProti | NX_Q8TDF6 |
VEuPathDBi | HostDB:ENSG00000171777.15 |
Subcellular locationi
Plasma membrane
Cytoplasm and Cytosol
Note: Recruited to membranes upon activation by DAG.
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- membrane Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 548 | F → S: Loss of cell membrane targeting. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 115727 |
OpenTargetsi | ENSG00000171777 |
PharmGKBi | PA38770 |
Miscellaneous databases
Pharosi | Q8TDF6, Tbio |
Genetic variation databases
BioMutai | RASGRP4 |
DMDMi | 296434529 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000315213 | 1 – 673 | RAS guanyl-releasing protein 4Add BLAST | 673 |
Proteomic databases
EPDi | Q8TDF6 |
MassIVEi | Q8TDF6 |
PaxDbi | Q8TDF6 |
PeptideAtlasi | Q8TDF6 |
PRIDEi | Q8TDF6 |
ProteomicsDBi | 74276 [Q8TDF6-1] 74277 [Q8TDF6-2] 74278 [Q8TDF6-3] 74279 [Q8TDF6-5] 74280 [Q8TDF6-6] 74281 [Q8TDF6-7] |
PTM databases
iPTMneti | Q8TDF6 |
PhosphoSitePlusi | Q8TDF6 |
Expressioni
Tissue specificityi
Expressed by mast cells and their progenitors (at protein level). Specifically expressed in mononuclear leukocytes. Highly expressed in myeloid cells compared to lymphoid cells. Also detected in heart, skeletal muscle, spleen, liver, placenta and lung. Not detected in brain. Isoform 1 is the major isoform in normal individuals. Isoform 2 is more significantly expressed in a patient with asthma. Isoform 3 is more significantly expressed in a patient with asthma and a mastocytosis patient.2 Publications
Developmental stagei
Expressed early during development. Detected in all fetal tissues tested.1 Publication
Gene expression databases
Bgeei | ENSG00000171777, Expressed in blood and 113 other tissues |
ExpressionAtlasi | Q8TDF6, baseline and differential |
Genevisiblei | Q8TDF6, HS |
Organism-specific databases
HPAi | ENSG00000171777, Tissue enhanced (blood, bone marrow, lymphoid tissue) |
Interactioni
Binary interactionsi
Hide detailsIsoform 2 [Q8TDF6-2]
With | #Exp. | IntAct |
---|---|---|
BNIP2 [Q12982] | 3 | EBI-12816371,EBI-752094 |
DYNLL1 [P63167] | 3 | EBI-12816371,EBI-349105 |
SEC22A [Q96IW7] | 3 | EBI-12816371,EBI-8652744 |
TMPRSS4 [Q9NRS4] | 3 | EBI-12816371,EBI-10313040 |
GO - Molecular functioni
- GTP-dependent protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 125451, 11 interactors |
IntActi | Q8TDF6, 9 interactors |
STRINGi | 9606.ENSP00000479844 |
Miscellaneous databases
RNActi | Q8TDF6, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8TDF6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 49 – 175 | N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST | 127 | |
Domaini | 201 – 432 | Ras-GEFPROSITE-ProRule annotationAdd BLAST | 232 | |
Domaini | 466 – 501 | EF-handPROSITE-ProRule annotationAdd BLAST | 36 |
Domaini
The phorbol-ester/DAG-type zinc finger mediates the binding and the functional activation by DAG.
Sequence similaritiesi
Belongs to the RASGRP family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 540 – 590 | Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST | 51 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG3417, Eukaryota |
GeneTreei | ENSGT00940000159883 |
HOGENOMi | CLU_019261_2_1_1 |
InParanoidi | Q8TDF6 |
OMAi | LHHAWTQ |
OrthoDBi | 355412at2759 |
PhylomeDBi | Q8TDF6 |
Family and domain databases
CDDi | cd00029, C1, 1 hit cd00155, RasGEF, 1 hit cd06224, REM, 1 hit |
Gene3Di | 1.10.840.10, 1 hit |
InterProi | View protein in InterPro IPR020454, DAG/PE-bd IPR002048, EF_hand_dom IPR002219, PE/DAG-bd IPR008937, Ras-like_GEF IPR000651, Ras-like_Gua-exchang_fac_N IPR023578, Ras_GEF_dom_sf IPR001895, RASGEF_cat_dom IPR036964, RASGEF_cat_dom_sf |
PANTHERi | PTHR23113, PTHR23113, 1 hit |
Pfami | View protein in Pfam PF00130, C1_1, 1 hit PF00617, RasGEF, 1 hit |
PRINTSi | PR00008, DAGPEDOMAIN |
SMARTi | View protein in SMART SM00109, C1, 1 hit SM00147, RasGEF, 1 hit |
SUPFAMi | SSF48366, SSF48366, 1 hit |
PROSITEi | View protein in PROSITE PS50222, EF_HAND_2, 1 hit PS50009, RASGEF_CAT, 1 hit PS50212, RASGEF_NTER, 1 hit PS00479, ZF_DAG_PE_1, 1 hit PS50081, ZF_DAG_PE_2, 1 hit |
s (8+)i Sequence
Sequence statusi: Complete.
This entry describes 8 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 8 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8TDF6-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNRKDSKRKS HQECTGKIGG RGRPRQVRRH KTCPSPREIS KVMASMNLGL
60 70 80 90 100
LSEGGCSEDE LLEKCIQSFD SAGSLCHEDH MLNMVLAMHS WVLPSADLAA
110 120 130 140 150
RLLTSYQKAT GDTQELRRLQ ICHLVRYWLM RHPEVMHQDP QLEEVIGRFW
160 170 180 190 200
ATVAREGNSA QRRLGDSSDL LSPGGPGPPL PMSSPGLGKK RKVSLLFDHL
210 220 230 240 250
ETGELAQHLT YLEFRSFQAI TPQDLRSYVL QGSVRGCPAL EGSVGLSNSV
260 270 280 290 300
SRWVQVMVLS RPGPLQRAQV LDKFIHVAQR LHQLQNFNTL MAVTGGLCHS
310 320 330 340 350
AISRLKDSHA HLSPDSTKAL LELTELLASH NNYARYRRTW AGCAGFRLPV
360 370 380 390 400
LGVHLKDLVS LHEAQPDRLP DGRLHLPKLN NLYLRLQELV ALQGQHPPCS
410 420 430 440 450
ANEDLLHLLT LSLDLFYTED EIYELSYARE PRCPKSLPPS PFNAPLVVEW
460 470 480 490 500
APGVTPKPDR VTLGRHVEQL VESVFKNYDP EGRGTISQED FERLSGNFPF
510 520 530 540 550
ACHGLHPPPR QGRGSFSREE LTGYLLRASA ICSKLGLAFL HTFHEVTFRK
560 570 580 590 600
PTFCDSCSGF LWGVTKQGYR CRECGLCCHK HCRDQVKVEC KKRPGAKGDA
610 620 630 640 650
GPPGAPVPST PAPHASCGSE ENHSYTLSLE PETGCQLRHA WTQTESPHPS
660 670
WETDTVPCPV MDPPSTASSK LDS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketC0LTP6 | C0LTP6_HUMAN | RAS guanyl releasing protein 4 vari... | RASGRP4 | 617 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 27 | V → A in AAK85703 (PubMed:11956218).Curated | 1 | |
Sequence conflicti | 73 | G → D in AAK85703 (PubMed:11956218).Curated | 1 | |
Sequence conflicti | 554 | C → R in AAK85703 (PubMed:11956218).Curated | 1 | |
Sequence conflicti | 671 | L → P in AAK85701 (PubMed:11956218).Curated | 1 | |
Sequence conflicti | 671 | L → P in AAK85703 (PubMed:11956218).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_038144 | 18 | I → T3 PublicationsCorresponds to variant dbSNP:rs892055Ensembl. | 1 | |
Natural variantiVAR_038145 | 120 | Q → L1 Publication | 1 | |
Natural variantiVAR_038146 | 145 | V → A1 Publication | 1 | |
Natural variantiVAR_038147 | 261 | R → C1 Publication | 1 | |
Natural variantiVAR_038148 | 335 | R → G1 PublicationCorresponds to variant dbSNP:rs202008979EnsemblClinVar. | 1 | |
Natural variantiVAR_057172 | 620 | E → K. Corresponds to variant dbSNP:rs34377632Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_030479 | 171 – 673 | Missing in isoform 3. 1 PublicationAdd BLAST | 503 | |
Alternative sequenceiVSP_030480 | 171 – 184 | Missing in isoform 2. 2 PublicationsAdd BLAST | 14 | |
Alternative sequenceiVSP_043176 | 221 – 409 | Missing in isoform 5. 1 PublicationAdd BLAST | 189 | |
Alternative sequenceiVSP_043392 | 222 – 318 | Missing in isoform 6. 1 PublicationAdd BLAST | 97 | |
Alternative sequenceiVSP_046907 | 222 – 255 | Missing in isoform 7. 1 PublicationAdd BLAST | 34 | |
Alternative sequenceiVSP_043138 | 319 – 410 | Missing in isoform 4. 1 PublicationAdd BLAST | 92 | |
Alternative sequenceiVSP_046908 | 319 – 387 | Missing in isoform 8. 1 PublicationAdd BLAST | 69 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6AXG | X-ray | 3.30 | A/C/E/G/I/K | 46-460 | [»] | |
SMRi | Q8TDF6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 125451, 11 interactors |
IntActi | Q8TDF6, 9 interactors |
STRINGi | 9606.ENSP00000479844 |
PTM databases
iPTMneti | Q8TDF6 |
PhosphoSitePlusi | Q8TDF6 |
Genetic variation databases
BioMutai | RASGRP4 |
DMDMi | 296434529 |
Proteomic databases
EPDi | Q8TDF6 |
MassIVEi | Q8TDF6 |
PaxDbi | Q8TDF6 |
PeptideAtlasi | Q8TDF6 |
PRIDEi | Q8TDF6 |
ProteomicsDBi | 74276 [Q8TDF6-1] 74277 [Q8TDF6-2] 74278 [Q8TDF6-3] 74279 [Q8TDF6-5] 74280 [Q8TDF6-6] 74281 [Q8TDF6-7] |
Protocols and materials databases
Antibodypediai | 30068, 80 antibodies |
Genome annotation databases
Organism-specific databases
CTDi | 115727 |
DisGeNETi | 115727 |
GeneCardsi | RASGRP4 |
HGNCi | HGNC:18958, RASGRP4 |
HPAi | ENSG00000171777, Tissue enhanced (blood, bone marrow, lymphoid tissue) |
MIMi | 607320, gene |
neXtProti | NX_Q8TDF6 |
OpenTargetsi | ENSG00000171777 |
PharmGKBi | PA38770 |
VEuPathDBi | HostDB:ENSG00000171777.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3417, Eukaryota |
GeneTreei | ENSGT00940000159883 |
HOGENOMi | CLU_019261_2_1_1 |
InParanoidi | Q8TDF6 |
OMAi | LHHAWTQ |
OrthoDBi | 355412at2759 |
PhylomeDBi | Q8TDF6 |
Enzyme and pathway databases
PathwayCommonsi | Q8TDF6 |
Reactomei | R-HSA-2871837, FCERI mediated NF-kB activation R-HSA-5673001, RAF/MAP kinase cascade |
Miscellaneous databases
BioGRID-ORCSi | 115727, 4 hits in 996 CRISPR screens |
ChiTaRSi | RASGRP4, human |
GenomeRNAii | 115727 |
Pharosi | Q8TDF6, Tbio |
PROi | PR:Q8TDF6 |
RNActi | Q8TDF6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000171777, Expressed in blood and 113 other tissues |
ExpressionAtlasi | Q8TDF6, baseline and differential |
Genevisiblei | Q8TDF6, HS |
Family and domain databases
CDDi | cd00029, C1, 1 hit cd00155, RasGEF, 1 hit cd06224, REM, 1 hit |
Gene3Di | 1.10.840.10, 1 hit |
InterProi | View protein in InterPro IPR020454, DAG/PE-bd IPR002048, EF_hand_dom IPR002219, PE/DAG-bd IPR008937, Ras-like_GEF IPR000651, Ras-like_Gua-exchang_fac_N IPR023578, Ras_GEF_dom_sf IPR001895, RASGEF_cat_dom IPR036964, RASGEF_cat_dom_sf |
PANTHERi | PTHR23113, PTHR23113, 1 hit |
Pfami | View protein in Pfam PF00130, C1_1, 1 hit PF00617, RasGEF, 1 hit |
PRINTSi | PR00008, DAGPEDOMAIN |
SMARTi | View protein in SMART SM00109, C1, 1 hit SM00147, RasGEF, 1 hit |
SUPFAMi | SSF48366, SSF48366, 1 hit |
PROSITEi | View protein in PROSITE PS50222, EF_HAND_2, 1 hit PS50009, RASGEF_CAT, 1 hit PS50212, RASGEF_NTER, 1 hit PS00479, ZF_DAG_PE_1, 1 hit PS50081, ZF_DAG_PE_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GRP4_HUMAN | |
Accessioni | Q8TDF6Primary (citable) accession number: Q8TDF6 Secondary accession number(s): A6H8M4 Q96QN7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 15, 2008 |
Last sequence update: | May 18, 2010 | |
Last modified: | April 7, 2021 | |
This is version 160 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families