Human Gene RAPGEF4 (ENST00000397081.8_4) from GENCODE V47lift37

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Description: Rap guanine nucleotide exchange factor 4, transcript variant 21 (from RefSeq NR_164741.1)
Gencode Transcript: ENST00000397081.8_4
Gencode Gene: ENSG00000091428.18_8
Transcript (Including UTRs)
Position: hg19 chr2:173,600,573-173,917,621 Size: 317,049 Total Exon Count: 31 Strand: +
Coding Region
Position: hg19 chr2:173,600,712-173,916,495 Size: 315,784 Coding Exon Count: 31

Page Index	Sequence and Links	UniProtKB Comments	Primers	MalaCards	CTD
Gene Alleles	RNA-Seq Expression	Microarray Expression	RNA Structure	Protein Structure	Other Species
GO Annotations	mRNA Descriptions	Pathways	Other Names	Model Information	Methods

Data last updated at UCSC: 2024-08-22 23:36:26

Sequence and Links to Tools and Databases

Genomic Sequence (chr2:173,600,573-173,917,621)			mRNA (may differ from genome)		Protein (1011 aa)
Gene Sorter	Genome Browser	Other Species FASTA	VisiGene	Gene interactions	Table Schema
AlphaFold	BioGPS	Ensembl	Entrez Gene	ExonPrimer	GeneCards
HGNC	Human Cortex Gene Expression	Malacards	MGI	OMIM	PubMed
Reactome	UniProtKB	Wikipedia	BioGrid CRISPR DB

Comments and Description Text from UniProtKB


	ID: RPGF4_HUMAN DESCRIPTION: RecName: Full=Rap guanine nucleotide exchange factor 4; AltName: Full=Exchange factor directly activated by cAMP 2; AltName: Full=Exchange protein directly activated by cAMP 2; Short=EPAC 2; AltName: Full=cAMP-regulated guanine nucleotide exchange factor II; Short=cAMP-GEFII; 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). SUBUNIT: Interacts with RIMS1 and RIMS2. Probably part of a complex with RIMS2 and GTP-activated RAB3A (By similarity). SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein (By similarity). 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. DOMAIN: The N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2. DOMAIN: The DEP domain is involved in membrane localization independent from regulation by cAMP (By similarity). SIMILARITY: Contains 2 cyclic nucleotide-binding domains. SIMILARITY: Contains 1 DEP domain. SIMILARITY: Contains 1 N-terminal Ras-GEF domain. SIMILARITY: Contains 1 Ras-GEF domain.

Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

MalaCards Disease Associations


	MalaCards Gene Search: RAPGEF4 Diseases sorted by gene-association score: lesch-nyhan syndrome (8), acrodysostosis (4)

Comparative Toxicogenomics Database (CTD)


	The following chemicals interact with this gene D013749 Tetrachlorodibenzodioxin D001564 Benzo(a)pyrene D016572 Cyclosporine D010634 Phenobarbital C006253 pirinixic acid C049325 1,2-dithiol-3-thione C028474 1,4-bis(2-(3,5-dichloropyridyloxy))benzene C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl C518576 2-methylbutyric acid 4-((1,3)dioxan-5-ylmethoxyimino)-8-(2-(4-hydroxy-6-oxo-tetrahydropyran-2-yl)ethyl -7-methyl-6-oxo-1,2,3,4,6,7,8,8a-octahydronaphthyl)heptanoate C473217 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3'-5'-cyclic monophosphate D015127 9,10-Dimethyl-1,2-benzanthracene D016604 Aflatoxin B1 D000535 Aluminum D001554 Benzene D002251 Carbon Tetrachloride D002737 Chloroprene D002922 Ciguatoxins D002994 Clofibrate D002995 Clofibric Acid D003010 Clorgyline D003024 Clozapine D003042 Cocaine D019327 Copper Sulfate D003345 Corticosterone D004052 Diethylnitrosamine D004958 Estradiol D006220 Haloperidol D007545 Isoproterenol D009151 Mustard Gas D010126 Ozone D010656 Phenylephrine D010672 Phenytoin D011189 Potassium Chloride D012402 Rotenone D014028 Tobacco Smoke Pollution D014212 Tretinoin D014635 Valproic Acid C432165 anthra(1,9-cd)pyrazol-6(2H)-one C006632 arsenic trioxide C093628 cyproconazole C109476 epoxiconazole C008493 methylselenic acid C076029 olanzapine C086401 pentabromodiphenyl ether C018637 phorone C045950 propiconazole C009250 sevoflurane C016104 sodium bichromate

Common Gene Haplotype Alleles


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RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)


	Highest median expression: 107.96 RPKM in Brain - Anterior cingulate cortex (BA24) Total median expression: 734.95 RPKM View in GTEx track of Genome Browser View at GTEx portal View GTEx Body Map

Microarray Expression Data


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mRNA Secondary Structure of 3' and 5' UTRs

Region	Fold Energy	Bases	Energy/Base	Display As
5' UTR	-78.20	139	-0.563	Picture	PostScript	Text
3' UTR	-240.20	1126	-0.213	Picture	PostScript	Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

Protein Domain and Structure Information

InterPro Domains: Graphical view of domain structure
IPR002373 - cAMP/cGMP_kin
IPR018490 - cNMP-bd-like
IPR000595 - cNMP-bd_dom
IPR000591 - DEP_dom
IPR000159 - Ras-assoc
IPR000651 - Ras-like_Gua-exchang_fac_N
IPR019804 - Ras_G-nucl-exch_fac_CS
IPR008937 - Ras_GEF
IPR023578 - Ras_GEF_dom
IPR001895 - RasGRF_CDC25
IPR014710 - RmlC-like_jellyroll
IPR011991 - WHTH_trsnscrt_rep_DNA-bd

Pfam Domains:
PF00027 - Cyclic nucleotide-binding domain
PF00610 - Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)
PF00617 - RasGEF domain
PF00618 - RasGEF N-terminal motif

SCOP Domains:
48366 - Ras GEF
46785 - "Winged helix" DNA-binding domain
51206 - cAMP-binding domain-like
54236 - Ubiquitin-like
54277 - CAD & PB1 domains

ModBase Predicted Comparative 3D Structure on Q8WZA2


Front	Top	Side

The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

Orthologous Genes in Other Species

Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.

Mouse	Rat	Zebrafish	D. melanogaster	C. elegans	S. cerevisiae
No ortholog	No ortholog	No ortholog	No ortholog	Genome Browser	No ortholog
Gene Details	Gene Details		Gene Details	Gene Details
Gene Sorter	Gene Sorter		Gene Sorter	Gene Sorter
	RGD	Ensembl		WormBase
				Protein Sequence
				Alignment

Gene Ontology (GO) Annotations with Structured Vocabulary


	Molecular Function: GO:0000166 nucleotide binding GO:0005085 guanyl-nucleotide exchange factor activity GO:0005088 Ras guanyl-nucleotide exchange factor activity GO:0005515 protein binding GO:0017016 Ras GTPase binding GO:0030552 cAMP binding Biological Process: GO:0006887 exocytosis GO:0007186 G-protein coupled receptor signaling pathway GO:0007264 small GTPase mediated signal transduction GO:0017156 calcium ion regulated exocytosis GO:0017157 regulation of exocytosis GO:0019933 cAMP-mediated signaling GO:0030073 insulin secretion GO:0035556 intracellular signal transduction GO:0050796 regulation of insulin secretion Cellular Component: GO:0005737 cytoplasm GO:0005829 cytosol GO:0005886 plasma membrane GO:0016020 membrane

Descriptions from all associated GenBank mRNAs


	AB209681 - Homo sapiens mRNA for RAP guanine-nucleotide-exchange factor 4 variant protein. U78516 - Homo sapiens cAMP-regulated guanine nucleotide exchange factor II (cAMP-GEFII) mRNA, complete cds. AB027471 - Homo sapiens EPAC2 mRNA for cAMP-GEFII, complete cds. AK313084 - Homo sapiens cDNA, FLJ93567, highly similar to Homo sapiens Rap guanine nucleotide exchange factor (GEF) 4 (RAPGEF4), mRNA. BC024004 - Homo sapiens Rap guanine nucleotide exchange factor (GEF) 4, mRNA (cDNA clone MGC:26434 IMAGE:4823935), complete cds. AB590290 - Synthetic construct DNA, clone: pFN21AE1437, Homo sapiens RAPGEF4 gene for Rap guanine nucleotide exchange factor (GEF) 4, without stop codon, in Flexi system. DQ894011 - Synthetic construct Homo sapiens clone IMAGE:100008471; FLH166516.01L; RZPDo839H0985D Rap guanine nucleotide exchange factor (GEF) 4 (RAPGEF4) gene, encodes complete protein. DQ890549 - Synthetic construct clone IMAGE:100003179; FLH166520.01X; RZPDo839H0986D Rap guanine nucleotide exchange factor (GEF) 4 (RAPGEF4) gene, encodes complete protein. KJ534978 - Homo sapiens clone RAPGEF4_iso-A_adult-A14 RAP guanine nucleotide exchange factor 4 isoform A (RAPGEF4) mRNA, partial cds, alternatively spliced. KJ534924 - Homo sapiens clone RAPGEF4_iso-B_adult-A09 RAP guanine nucleotide exchange factor 4 isoform B (RAPGEF4) mRNA, partial cds, alternatively spliced. KJ534925 - Homo sapiens clone RAPGEF4_iso-C_adult-A16 RAP guanine nucleotide exchange factor 4 isoform C (RAPGEF4) mRNA, partial cds, alternatively spliced. AK294997 - Homo sapiens cDNA FLJ57302 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK310373 - Homo sapiens cDNA, FLJ17415. BC040183 - Homo sapiens Rap guanine nucleotide exchange factor (GEF) 4, mRNA (cDNA clone MGC:42189 IMAGE:4801092), complete cds. AK311500 - Homo sapiens cDNA, FLJ18542. AK311697 - Homo sapiens cDNA, FLJ18739. AK304278 - Homo sapiens cDNA FLJ51189 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK296340 - Homo sapiens cDNA FLJ58368 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK316014 - Homo sapiens cDNA, FLJ78913 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK295002 - Homo sapiens cDNA FLJ50959 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK316072 - Homo sapiens cDNA, FLJ78971 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK294445 - Homo sapiens cDNA FLJ57298 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK311165 - Homo sapiens cDNA, FLJ18207. CU691830 - Synthetic construct Homo sapiens gateway clone IMAGE:100020500 5' read RAPGEF4 mRNA. KJ898347 - Synthetic construct Homo sapiens clone ccsbBroadEn_07741 RAPGEF4 gene, encodes complete protein. AK294914 - Homo sapiens cDNA FLJ50956 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK302732 - Homo sapiens cDNA FLJ51706 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AK311575 - Homo sapiens cDNA, FLJ18617. AK294433 - Homo sapiens cDNA FLJ61771 complete cds, highly similar to Rap guanine nucleotide exchange factor 4. AB075513 - Homo sapiens neuroblastoma cDNA, clone:Nbla00496, full insert sequence. JD197058 - Sequence 178082 from Patent EP1572962. JD111720 - Sequence 92744 from Patent EP1572962. JD420754 - Sequence 401778 from Patent EP1572962. JD137140 - Sequence 118164 from Patent EP1572962. JD221187 - Sequence 202211 from Patent EP1572962. JD244801 - Sequence 225825 from Patent EP1572962. JD113199 - Sequence 94223 from Patent EP1572962. JD327808 - Sequence 308832 from Patent EP1572962. JD349686 - Sequence 330710 from Patent EP1572962. JD302576 - Sequence 283600 from Patent EP1572962. JD304340 - Sequence 285364 from Patent EP1572962. JD110815 - Sequence 91839 from Patent EP1572962. JD291107 - Sequence 272131 from Patent EP1572962.

Biochemical and Signaling Pathways


	Reactome (by CSHL, EBI, and GO) Protein Q8WZA2 (Reactome details) participates in the following event(s): R-HSA-381608 cAMP activates EPAC2 R-HSA-392834 Activation of EPACs by cAMP R-HSA-939265 Activation of Rap1 by membrane-associated GEFs R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-HSA-392517 Rap1 signalling R-HSA-422356 Regulation of insulin secretion R-HSA-1280218 Adaptive Immune System R-HSA-354192 Integrin alphaIIb beta3 signaling R-HSA-163685 Energy Metabolism R-HSA-168256 Immune System R-HSA-76009 Platelet Aggregation (Plug Formation) R-HSA-9006921 Integrin signaling R-HSA-1430728 Metabolism R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-162582 Signal Transduction R-HSA-109582 Hemostasis

Other Names for This Gene


	Alternate Gene Symbols: B2R7R3, B7Z283, B7Z3T6, B7Z912, CGEF2, ENST00000397081.1, ENST00000397081.2, ENST00000397081.3, ENST00000397081.4, ENST00000397081.5, ENST00000397081.6, ENST00000397081.7, EPAC2, NR_164741, O95636, Q8IXK6, Q8TAA4, Q8WZA2, RPGF4_HUMAN, uc318ysm.1, uc318ysm.2 UCSC ID: ENST00000397081.8_4 RefSeq Accession: NM_007023.4 Protein: Q8WZA2 (aka RPGF4_HUMAN or RGE4_HUMAN)

Gene Model Information


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Methods, Credits, and Use Restrictions


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