Free for academic non-profit institutions. Other users need a Commercial license

Aliases for RAPGEF4 Gene

Aliases for RAPGEF4 Gene

  • Rap Guanine Nucleotide Exchange Factor 4 2 3 5
  • CAMP-Regulated Guanine Nucleotide Exchange Factor II 2 3 4
  • Exchange Protein Directly Activated By CAMP 2 2 3 4
  • RAP Guanine-Nucleotide-Exchange Factor (GEF) 4 2 3
  • Rap Guanine Nucleotide Exchange Factor (GEF) 4 2 3
  • Exchange Factor Directly Activated By CAMP 2 3 4
  • CAMP-GEFII 3 4
  • EPAC 2 3 4
  • CGEF2 3 4
  • EPAC2 3 4
  • Putative Protein Product Of Nbla00496 3
  • Nbla00496 3
  • EPAC 3

External Ids for RAPGEF4 Gene

Previous GeneCards Identifiers for RAPGEF4 Gene

  • GC02P173804
  • GC02P173426
  • GC02P173308
  • GC02P173600
  • GC02P165478

Summaries for RAPGEF4 Gene

GeneCards Summary for RAPGEF4 Gene

RAPGEF4 (Rap Guanine Nucleotide Exchange Factor 4) is a Protein Coding gene. Diseases associated with RAPGEF4 include Lesch-Nyhan Syndrome and Hypoglycemic Coma. Among its related pathways are cAMP signaling pathway and Integrin alphaIIb beta3 signaling. GO annotations related to this gene include guanyl-nucleotide exchange factor activity and Ras GTPase binding. An important paralog of this gene is RASGEF1A.

UniProtKB/Swiss-Prot for RAPGEF4 Gene

  • Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2 (By similarity).

Gene Wiki entry for RAPGEF4 Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RAPGEF4 Gene

Genomics for RAPGEF4 Gene

Regulatory Elements for RAPGEF4 Gene

Enhancers for RAPGEF4 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around RAPGEF4 on UCSC Golden Path with GeneCards custom track

Promoters for RAPGEF4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around RAPGEF4 on UCSC Golden Path with GeneCards custom track

Genomic Location for RAPGEF4 Gene

Chromosome:
2
Start:
172,735,274 bp from pter
End:
173,052,893 bp from pter
Size:
317,620 bases
Orientation:
Plus strand

Genomic View for RAPGEF4 Gene

Genes around RAPGEF4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RAPGEF4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RAPGEF4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RAPGEF4 Gene

Proteins for RAPGEF4 Gene

  • Protein details for RAPGEF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WZA2-RPGF4_HUMAN
    Recommended name:
    Rap guanine nucleotide exchange factor 4
    Protein Accession:
    Q8WZA2
    Secondary Accessions:
    • B2R7R3
    • B7Z283
    • B7Z3T6
    • B7Z912
    • O95636
    • Q8IXK6
    • Q8TAA4

    Protein attributes for RAPGEF4 Gene

    Size:
    1011 amino acids
    Molecular mass:
    115522 Da
    Quaternary structure:
    • Interacts with RIMS1 and RIMS2. Probably part of a complex with RIMS2 and GTP-activated RAB3A (By similarity).

    Alternative splice isoforms for RAPGEF4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RAPGEF4 Gene

Proteomics data for RAPGEF4 Gene at MOPED

Post-translational modifications for RAPGEF4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for RAPGEF4 Gene

Domains & Families for RAPGEF4 Gene

Gene Families for RAPGEF4 Gene

IUPHAR :

Graphical View of Domain Structure for InterPro Entry

Q8WZA2

UniProtKB/Swiss-Prot:

RPGF4_HUMAN :
  • The N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2.
Domain:
  • The N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2.
  • The DEP domain is involved in membrane localization independent from regulation by cAMP.
  • Contains 2 cyclic nucleotide-binding domains.
  • Contains 1 DEP domain.
  • Contains 1 N-terminal Ras-GEF domain.
  • Contains 1 Ras-GEF domain.
genes like me logo Genes that share domains with RAPGEF4: view

Function for RAPGEF4 Gene

Molecular function for RAPGEF4 Gene

UniProtKB/Swiss-Prot Function:
Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2 (By similarity).
genes like me logo Genes that share phenotypes with RAPGEF4: view

Animal Models for RAPGEF4 Gene

MGI Knock Outs for RAPGEF4:

Animal Model Products

CRISPR Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RAPGEF4 Gene

Localization for RAPGEF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RAPGEF4 Gene

Cytoplasm. Membrane; Peripheral membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RAPGEF4 Gene COMPARTMENTS Subcellular localization image for RAPGEF4 gene
Compartment Confidence
plasma membrane 5
cytosol 4
nucleus 2
endoplasmic reticulum 1

No data available for Gene Ontology (GO) - Cellular Components for RAPGEF4 Gene

Pathways & Interactions for RAPGEF4 Gene

genes like me logo Genes that share pathways with RAPGEF4: view

Gene Ontology (GO) - Biological Process for RAPGEF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0017157 regulation of exocytosis IEA --
GO:0030073 insulin secretion IEA --
GO:0030168 platelet activation TAS --
GO:0035556 intracellular signal transduction IEA --
GO:0044281 small molecule metabolic process TAS --
genes like me logo Genes that share ontologies with RAPGEF4: view

No data available for SIGNOR curated interactions for RAPGEF4 Gene

Drugs & Compounds for RAPGEF4 Gene

(6) Drugs for RAPGEF4 Gene - From: DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0
HJC 0350 Pharma 0
genes like me logo Genes that share compounds with RAPGEF4: view

Transcripts for RAPGEF4 Gene

Unigene Clusters for RAPGEF4 Gene

Rap guanine nucleotide exchange factor (GEF) 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for RAPGEF4 Gene

No ASD Table

Relevant External Links for RAPGEF4 Gene

GeneLoc Exon Structure for
RAPGEF4
ECgene alternative splicing isoforms for
RAPGEF4

Expression for RAPGEF4 Gene

mRNA expression in normal human tissues for RAPGEF4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RAPGEF4 Gene

This gene is overexpressed in Brain - Hippocampus (x8.8), Brain - Anterior cingulate cortex (BA24) (x7.6), Brain - Amygdala (x7.5), Brain - Cortex (x6.8), and Brain - Frontal Cortex (BA9) (x6.1).

Protein differential expression in normal tissues from HIPED for RAPGEF4 Gene

This gene is overexpressed in Platelet (34.8) and Frontal cortex (19.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for RAPGEF4 Gene



SOURCE GeneReport for Unigene cluster for RAPGEF4 Gene Hs.470646

mRNA Expression by UniProt/SwissProt for RAPGEF4 Gene

Q8WZA2-RPGF4_HUMAN
Tissue specificity: Predominantly expressed in brain and adrenal gland. Isoform 2 is expressed in liver. Isoform 1 is expressed in liver at very low levels.
genes like me logo Genes that share expression patterns with RAPGEF4: view

Protein tissue co-expression partners for RAPGEF4 Gene

- Elite partner

Primer Products

Orthologs for RAPGEF4 Gene

This gene was present in the common ancestor of animals.

Orthologs for RAPGEF4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia RAPGEF4 35
  • 94.66 (n)
  • 98.02 (a)
RAPGEF4 36
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia RAPGEF4 35
  • 94.64 (n)
  • 97.8 (a)
RAPGEF4 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rapgef4 35
  • 91.53 (n)
  • 97.33 (a)
Rapgef4 16
Rapgef4 36
  • 97 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia RAPGEF4 35
  • 99.5 (n)
  • 99.77 (a)
RAPGEF4 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Rapgef4 35
  • 87.84 (n)
  • 92.45 (a)
oppossum
(Monodelphis domestica)
Mammalia RAPGEF4 36
  • 95 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RAPGEF4 36
  • 93 (a)
OneToOne
chicken
(Gallus gallus)
Aves RAPGEF4 35
  • 83.47 (n)
  • 92.08 (a)
lizard
(Anolis carolinensis)
Reptilia RAPGEF4 36
  • 88 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rapgef4 35
  • 77.5 (n)
  • 87.12 (a)
zebrafish
(Danio rerio)
Actinopterygii rapgef4 35
  • 71.95 (n)
  • 79.09 (a)
rapgef4 36
  • 77 (a)
OneToMany
RAPGEF4 (1 of 2) 36
  • 79 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4614 35
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007307 35
  • 54.99 (n)
  • 52.69 (a)
fruit fly
(Drosophila melanogaster)
Insecta Epac 35
  • 53.54 (n)
  • 50.82 (a)
Epac 36
  • 50 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea epac-1 35
  • 47.32 (n)
  • 38.2 (a)
epac-1 36
  • 34 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 40 (a)
OneToMany
Species with no ortholog for RAPGEF4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RAPGEF4 Gene

ENSEMBL:
Gene Tree for RAPGEF4 (if available)
TreeFam:
Gene Tree for RAPGEF4 (if available)

Paralogs for RAPGEF4 Gene

genes like me logo Genes that share paralogs with RAPGEF4: view

Variants for RAPGEF4 Gene

Sequence variations from dbSNP and Humsavar for RAPGEF4 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs717524 -- 172,962,683(+) TTGAC(A/C)GAATT intron-variant
rs718902 -- 172,998,451(-) CAGGC(A/G)TGAGC intron-variant
rs724997 -- 172,843,389(+) ACTTG(A/G)ATAAT intron-variant
rs729486 -- 173,029,437(-) CACAG(C/G)TACTT intron-variant
rs1551248 -- 173,044,549(+) TCCTC(A/G)AGTGC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RAPGEF4 Gene

Variant ID Type Subtype PubMed ID
esv269328 CNV Insertion 20981092
esv2668640 CNV Deletion 23128226
esv2721145 CNV Deletion 23290073
nsv834459 CNV Gain 17160897
nsv483123 CNV Gain 15286789
esv267517 CNV Insertion 20981092
esv5188 CNV Deletion 18987735
esv2678314 CNV Deletion 23128226
esv2721146 CNV Deletion 23290073

Variation tolerance for RAPGEF4 Gene

Residual Variation Intolerance Score: 10.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.74; 46.84% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RAPGEF4 Gene

Human Gene Mutation Database (HGMD)
RAPGEF4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RAPGEF4 Gene

Disorders for RAPGEF4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for RAPGEF4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
lesch-nyhan syndrome
  • complete hypoxanthine-guanine phosphoribosyltransferase deficiency
hypoglycemic coma
  • hypoglycaemic coma
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for RAPGEF4

Genetic Association Database (GAD)
RAPGEF4
Human Genome Epidemiology (HuGE) Navigator
RAPGEF4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RAPGEF4
genes like me logo Genes that share disorders with RAPGEF4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RAPGEF4 Gene

Publications for RAPGEF4 Gene

  1. Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. (PMID: 10777494) de Rooij J. … Bos J.L. (J. Biol. Chem. 2000) 2 3 4 67
  2. Critical role of cAMP-GEFII--Rim2 complex in incretin-potentiated insulin secretion. (PMID: 11598134) Kashima Y. … Seino S. (J. Biol. Chem. 2001) 3 23
  3. Characterization of the gene EPAC2: structure, chromosomal localization, tissue expression, and identification of the liver- specific isoform. (PMID: 11707077) Ueno H. … Seino S. (Genomics 2001) 3 23
  4. A family of cAMP-binding proteins that directly activate rap1. (PMID: 9856955) Kawasaki H. … Graybiel A.M. (Science 1998) 2 3
  5. Structure and functional roles of Epac2 (Rapgef4). (PMID: 26390815) Sugawara K. … Seino S. (Gene 2016) 3

Products for RAPGEF4 Gene

Sources for RAPGEF4 Gene

Content