RAPGEF4 (Rap guanine nucleotide exchange factor 4)

Gene

• Entrez ID: 11069
• Gene name: Rap guanine nucleotide exchange factor 4
• Gene symbol: RAPGEF4
• Synonyms: CAMP-GEFII, CGEF2, EPAC, EPAC 2, EPAC2, Nbla00496
• Chromosome: 2
• Chromosome location: 2q31.1

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018141	hsa-miR-335-5p	Microarray	18185580
MIRT027613	hsa-miR-98-5p	Microarray	19088304
MIRT029706	hsa-miR-26b-5p	Microarray	19088304
MIRT156411	hsa-miR-106b-5p	HITS-CLIP	22473208
MIRT156404	hsa-miR-20a-5p	HITS-CLIP	22473208
MIRT156411	hsa-miR-106b-5p	HITS-CLIP	22473208
MIRT156401	hsa-miR-17-5p	HITS-CLIP	22473208
MIRT156417	hsa-miR-20b-5p	HITS-CLIP	22473208
MIRT156406	hsa-miR-93-5p	HITS-CLIP	22473208
MIRT156424	hsa-miR-519d-3p	HITS-CLIP	22473208
MIRT156402	hsa-miR-19a-3p	HITS-CLIP	22473208
MIRT156403	hsa-miR-19b-3p	HITS-CLIP	22473208
MIRT156404	hsa-miR-20a-5p	HITS-CLIP	22473208
MIRT1290845	hsa-miR-106a	CLIP-seq
MIRT1290846	hsa-miR-106b	CLIP-seq
MIRT1290847	hsa-miR-130a	CLIP-seq
MIRT1290848	hsa-miR-130b	CLIP-seq
MIRT1290849	hsa-miR-17	CLIP-seq
MIRT1290850	hsa-miR-19a	CLIP-seq
MIRT1290851	hsa-miR-19b	CLIP-seq
MIRT1290852	hsa-miR-20a	CLIP-seq
MIRT1290853	hsa-miR-20b	CLIP-seq
MIRT1290854	hsa-miR-301a	CLIP-seq
MIRT1290855	hsa-miR-301b	CLIP-seq
MIRT1290856	hsa-miR-3666	CLIP-seq
MIRT1290857	hsa-miR-4295	CLIP-seq
MIRT1290858	hsa-miR-454	CLIP-seq
MIRT1290859	hsa-miR-488	CLIP-seq
MIRT1290860	hsa-miR-519a	CLIP-seq
MIRT1290861	hsa-miR-519b-3p	CLIP-seq
MIRT1290862	hsa-miR-519c-3p	CLIP-seq
MIRT1290863	hsa-miR-519d	CLIP-seq
MIRT1290864	hsa-miR-93	CLIP-seq
MIRT2086496	hsa-miR-1265	CLIP-seq
MIRT2086497	hsa-miR-1266	CLIP-seq
MIRT2086498	hsa-miR-1273e	CLIP-seq
MIRT2086499	hsa-miR-129-5p	CLIP-seq
MIRT2086500	hsa-miR-3664-3p	CLIP-seq
MIRT2086501	hsa-miR-4518	CLIP-seq
MIRT2086502	hsa-miR-4764-5p	CLIP-seq
MIRT2086496	hsa-miR-1265	CLIP-seq
MIRT2086497	hsa-miR-1266	CLIP-seq
MIRT2086498	hsa-miR-1273e	CLIP-seq
MIRT2086499	hsa-miR-129-5p	CLIP-seq
MIRT2086500	hsa-miR-3664-3p	CLIP-seq
MIRT2086501	hsa-miR-4518	CLIP-seq
MIRT2086502	hsa-miR-4764-5p	CLIP-seq
MIRT2607976	hsa-miR-3681	CLIP-seq
MIRT2607977	hsa-miR-3924	CLIP-seq
MIRT2607978	hsa-miR-410	CLIP-seq
MIRT2607979	hsa-miR-4460	CLIP-seq
MIRT2607980	hsa-miR-4727-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	ISS
GO:0005515	Function	Protein binding	IPI	11438518, 24722188, 25416956, 32296183, 32814053
GO:0005829	Component	Cytosol	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	9856955
GO:0007264	Process	Small GTPase mediated signal transduction	IEA
GO:0016020	Component	Membrane	TAS	10777494
GO:0017156	Process	Calcium-ion regulated exocytosis	IEA
GO:0017157	Process	Regulation of exocytosis	IEA
GO:0019933	Process	CAMP-mediated signaling	IEA
GO:0030073	Process	Insulin secretion	IEA
GO:0030552	Function	CAMP binding	ISS
GO:0031267	Function	Small GTPase binding	ISS
GO:0050790	Process	Regulation of catalytic activity	IEA
GO:0050796	Process	Regulation of insulin secretion	TAS
GO:0098686	Component	Hippocampal mossy fiber to CA3 synapse	IEA
GO:0098693	Process	Regulation of synaptic vesicle cycle	IEA

Other IDs

• MIM: 606058
• HGNC: 16626
• e!Ensembl: ENSG00000091428

Protein

• UniProt ID: Q8WZA2
• Protein name: Rap guanine nucleotide exchange factor 4 (Exchange factor directly activated by cAMP 2) (Exchange protein directly activated by cAMP 2) (EPAC 2) (cAMP-regulated guanine nucleotide exchange factor II) (cAMP-GEFII)
• Protein 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 similarit
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00027	cNMP_binding	61 → 150	Cyclic nucleotide-binding domain	Domain
  PF00610	DEP	220 → 289	Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)	Domain
  PF00027	cNMP_binding	375 → 459	Cyclic nucleotide-binding domain	Domain
  PF00618	RasGEF_N	499 → 605	RasGEF N-terminal motif	Domain
  PF00617	RasGEF	775 → 952	RasGEF domain	Family

• Sequence:

  MVAAHAAHSSSSAEWIACLDKRPLERSSEDVDIIFTRLKEVKAFEKFHPNLLHQICLCGY
  YENLEKGITLFRQGDIGTNWYAVLAGSLDVKVSETSSHQDAVTICTLGIGTAFGESILDN
  TPRHATIVTRESSELLRIEQKDFKALWEKYRQYMAGLLAPPYGVMETGSNNDRIPDKENT
  PLIEPHVPLRPANTITKVPSEKILRAGKILRNAILSRAPHMIRDRKYHLKTYRQCCVGTE
  LVDWMMQQTPCVHSRTQAVGMWQVLLEDGVLNHVDQEHHFQDKYLFYRFLDDEHEDAPLP
  TEEEKKECDEELQDTMLLLSQMGPDAHMRMILRKPPGQRTVDDLEIIYEELLHIKALSHL
  STTVKRELAGVLIFESHAKGGTVLFNQGEEGTSWYIILKGSVNVVIYGKGVVCTLHEGDD
  FGKLALVNDAPRAASIVLREDNCHFLRVDKEDFNRILRDVEANTVRLKEHDQDVLVLEKV
  PAGNRASNQGNSQPQQKYTVMSGTPEKILEHFLETIRLEATLNEATDSVLNDFIMMHCVF
  MPNTQLCPALVAHYHAQPSQGTEQEKMDYALNNKRRVIRLVLQWAAMYGDLLQEDDVSMA
  FLEEFYVSVSDDARMIAALKEQLPELEKIVKQISEDAKAPQKKHKVLLQQFNTGDERAQK
  RQPIRGSDEVLFKVYCMDHTYTTIRVPVATSVKEVISAVADKLGSGEGLIIVKMSSGGEK
  VVLKPNDVSVFTTLTINGRLFACPREQFDSLTPLPEQEGPTVGTVGTFELMSSKDLAYQM
  TIYDWELFNCVHELELIYHTFGRHNFKKTTANLDLFLRRFNEIQFWVVTEICLCSQLSKR
  VQLLKKFIKIAAHCKEYKNLNSFFAIVMGLSNVAVSRLALTWEKLPSKFKKFYAEFESLM
  DPSRNHRAYRLTVAKLEPPLIPFMPLLIKDMTFTHEGNKTFIDNLVNFEKMRMIANTART
  VRYYRSQPFNPDAAQANKNHQDVRSYVRQLNVIDNQRTLSQMSHRLEPRRP

• Sequence length: 1011

Pathways

KEGG:

Rap1 signaling pathway
cAMP signaling pathway
Phospholipase D signaling pathway
Hormone signaling
Adrenergic signaling in cardiomyocytes
Leukocyte transendothelial migration
Insulin secretion

Reactome:

Integrin signaling
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
Rap1 signalling
Regulation of insulin secretion

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Moyamoya disease	Moyamoya Disease, Moyamoya disease 1	rs121434527, rs121434528, rs387906592, rs397514563, rs797045187, rs1555675538, rs1568149971, rs1599150380, rs2079443410	29273593
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	31374203