UniProtKB - Q9EQZ6 (RPGF4_MOUSE)
Rap guanine nucleotide exchange factor 4
Rapgef4
Functioni
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.
1 PublicationRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 422 – 425 | 3',5'-cAMPBy similarity | 4 | |
Nucleotide bindingi | 432 – 433 | 3',5'-cAMPBy similarity | 2 |
GO - Molecular functioni
- cAMP binding Source: UniProtKB
- guanyl-nucleotide exchange factor activity Source: UniProtKB
- protein-containing complex binding Source: MGI
- small GTPase binding Source: UniProtKB
GO - Biological processi
- adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: MGI
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway Source: MGI
- calcium-ion regulated exocytosis Source: MGI
- insulin secretion Source: MGI
- negative regulation of synaptic transmission Source: MGI
- positive regulation of neuronal action potential Source: MGI
- positive regulation of protein secretion Source: MGI
- positive regulation of smooth muscle cell migration Source: MGI
- regulation of dendrite development Source: MGI
- regulation of exocytosis Source: MGI
- regulation of neurotransmitter receptor localization to postsynaptic specialization membrane Source: MGI
- regulation of postsynapse organization Source: MGI
- regulation of synaptic vesicle cycle Source: SynGO
- signal transduction Source: MGI
- small GTPase mediated signal transduction Source: InterPro
Keywordsi
Molecular function | Guanine-nucleotide releasing factor |
Biological process | Exocytosis |
Ligand | cAMP, cAMP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-354192, Integrin signaling R-MMU-381676, Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-MMU-392517, Rap1 signalling R-MMU-422356, Regulation of insulin secretion |
Names & Taxonomyi
Protein namesi | Recommended name: Rap guanine nucleotide exchange factor 4Alternative name(s): Exchange factor directly activated by cAMP 2 Exchange protein directly activated by cAMP 2 Short name: EPAC 2 cAMP-dependent Rap1 guanine-nucleotide exchange factor cAMP-regulated guanine nucleotide exchange factor II Short name: cAMP-GEFII |
Gene namesi | Name:Rapgef4 Synonyms:Cgef2, Epac2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1917723, Rapgef4 |
VEuPathDBi | HostDB:ENSMUSG00000049044 |
Subcellular locationi
Cytoplasm and Cytosol
Other locations
- Membrane By similarity; Peripheral membrane protein By similarity
Cytosol
- cytosol Source: MGI
Plasma Membrane
- apical plasma membrane Source: MGI
- basolateral plasma membrane Source: MGI
- plasma membrane Source: MGI
Other locations
- axon Source: MGI
- brush border Source: MGI
- cilium Source: MGI
- cone cell pedicle Source: MGI
- dendrite Source: MGI
- dendritic spine Source: MGI
- excitatory synapse Source: MGI
- glutamatergic synapse Source: MGI
- growth cone Source: MGI
- hippocampal mossy fiber to CA3 synapse Source: SynGO
- neuronal cell body Source: MGI
- photoreceptor inner segment Source: MGI
- photoreceptor outer segment Source: MGI
- postsynaptic density Source: MGI
- protein-containing complex Source: MGI
Keywords - Cellular componenti
Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 467 | L → A: Less than 10% of the wild-type maximal activity. 1 Publication | 1 | |
Mutagenesisi | 498 | Y → F: 2-fold reduction in maximal activity. 1 Publication | 1 | |
Mutagenesisi | 569 | Y → A: 2-fold reduction in maximal activity. 1 Publication | 1 | |
Mutagenesisi | 569 | Y → F: 2-fold reduction in maximal activity. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL3593151 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000068871 | 1 – 1011 | Rap guanine nucleotide exchange factor 4Add BLAST | 1011 |
Proteomic databases
MaxQBi | Q9EQZ6 |
PaxDbi | Q9EQZ6 |
PeptideAtlasi | Q9EQZ6 |
PRIDEi | Q9EQZ6 |
ProteomicsDBi | 299872 [Q9EQZ6-1] 299873 [Q9EQZ6-2] 299874 [Q9EQZ6-3] |
PTM databases
iPTMneti | Q9EQZ6 |
PhosphoSitePlusi | Q9EQZ6 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000049044, Expressed in globus pallidus and 260 other tissues |
ExpressionAtlasi | Q9EQZ6, baseline and differential |
Genevisiblei | Q9EQZ6, MM |
Interactioni
Subunit structurei
Interacts with RAP1B, RIMS1 and RIMS2. Probably part of a complex with RIMS2 and GTP-activated RAB3A.
2 PublicationsBinary interactionsi
Q9EQZ6
With | #Exp. | IntAct |
---|---|---|
HRAS [P01112] from Homo sapiens. | 3 | EBI-772212,EBI-350145 |
Isoform 3 [Q9EQZ6-3]
With | #Exp. | IntAct |
---|---|---|
RAP1B [P61224] from Homo sapiens. | 3 | EBI-15566495,EBI-358143 |
GO - Molecular functioni
- small GTPase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 208026, 24 interactors |
CORUMi | Q9EQZ6 |
DIPi | DIP-32333N |
IntActi | Q9EQZ6, 7 interactors |
STRINGi | 10090.ENSMUSP00000099759 |
Chemistry databases
BindingDBi | Q9EQZ6 |
Miscellaneous databases
RNActi | Q9EQZ6, protein |
Structurei
Secondary structure
3D structure databases
SASBDBi | Q9EQZ6 |
SMRi | Q9EQZ6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9EQZ6 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 216 – 291 | DEPPROSITE-ProRule annotationAdd BLAST | 76 | |
Domaini | 496 – 634 | N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST | 139 | |
Domaini | 772 – 1009 | Ras-GEFPROSITE-ProRule annotationAdd BLAST | 238 |
Domaini
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG2378, Eukaryota |
GeneTreei | ENSGT00940000156075 |
InParanoidi | Q9EQZ6 |
OMAi | HHPDVWT |
OrthoDBi | 143470at2759 |
PhylomeDBi | Q9EQZ6 |
TreeFami | TF313184 |
Family and domain databases
CDDi | cd00038, CAP_ED, 2 hits cd00155, RasGEF, 1 hit cd06224, REM, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 1.10.840.10, 1 hit 2.60.120.10, 2 hits |
InterProi | View protein in InterPro IPR018490, cNMP-bd-like IPR000595, cNMP-bd_dom IPR000591, DEP_dom IPR008937, Ras-like_GEF IPR000651, Ras-like_Gua-exchang_fac_N IPR019804, Ras_G-nucl-exch_fac_CS IPR023578, Ras_GEF_dom_sf IPR001895, RASGEF_cat_dom IPR036964, RASGEF_cat_dom_sf IPR014710, RmlC-like_jellyroll IPR029071, Ubiquitin-like_domsf IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR23113, PTHR23113, 2 hits |
Pfami | View protein in Pfam PF00027, cNMP_binding, 2 hits PF00610, DEP, 1 hit PF00617, RasGEF, 1 hit PF00618, RasGEF_N, 1 hit |
SMARTi | View protein in SMART SM00100, cNMP, 2 hits SM00049, DEP, 1 hit SM00147, RasGEF, 1 hit SM00229, RasGEFN, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF48366, SSF48366, 1 hit SSF51206, SSF51206, 2 hits SSF54236, SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS50042, CNMP_BINDING_3, 2 hits PS50186, DEP, 1 hit PS00720, RASGEF, 1 hit PS50009, RASGEF_CAT, 1 hit PS50212, RASGEF_NTER, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative promoter usage and alternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
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
MVAAHAAHSQ SSAEWIACLD KRPLERSSED VDIIFTRLKG VKAFEKFHPN
60 70 80 90 100
LLRQICLCGY YENLEKGITL FRQGDIGTNW YAVLAGSLDV KVSETSSHQD
110 120 130 140 150
AVTICTLGIG TAFGESILDN TPRHATIVTR ESSELLRIEQ EDFKALWEKY
160 170 180 190 200
RQYMAGLLAP PYGVMETGSN NDRIPDKENT PLIEPHVPLR PAHTITKVPS
210 220 230 240 250
EKILRAGKIL RIAILSRAPH MIRDRKYHLK TYRQCCVGTE LVDWMIQQTS
260 270 280 290 300
CVHSRTQAVG MWQVLLEDGV LNHVDQERHF QDKYLFYRFL DDEREDAPLP
310 320 330 340 350
TEEEKKECDE ELQDTMLLLS QMGPDAHMRM ILRKPPGQRT VDDLEIIYDE
360 370 380 390 400
LLHIKALSHL STTVKRELAG VLIFESHAKG GTVLFNQGEE GTSWYIILKG
410 420 430 440 450
SVNVVIYGKG VVCTLHEGDD FGKLALVNDA PRAASIVLRE DNCHFLRVDK
460 470 480 490 500
EDFNRILRDV EANTVRLKEH DQDVLVLEKV PAGNRAANQG NSQPQQKYTV
510 520 530 540 550
MSGTPEKILE HFLETIRLEP SLNEATDSVL NDFVMMHCVF MPNTQLCPAL
560 570 580 590 600
VAHYHAQPSQ GTEQERMDYA LNNKRRVIRL VLQWAAMYGD LLQEDDVAMA
610 620 630 640 650
FLEEFYVSVS DDARMMAAFK EQLPELEKIV KQISEDAKAP QKKHKVLLQQ
660 670 680 690 700
FNTGDERAQK RQPIRGSDEV LFKVYCIDHT YTTIRVPVAA SVKEVISAVA
710 720 730 740 750
DKLGSGEGLI IVKMNSGGEK VVLKSNDVSV FTTLTINGRL FACPREQFDS
760 770 780 790 800
LTPLPEQEGP TTGTVGTFEL MSSKDLAYQM TTYDWELFNC VHELELIYHT
810 820 830 840 850
FGRHNFKKTT ANLDLFLRRF NEIQFWVVTE VCLCSQLSKR VQLLKKFIKI
860 870 880 890 900
AAHCKEYKNL NSFFAIVMGL SNVAVSRLAL TWEKLPSKFK KFYAEFESLM
910 920 930 940 950
DPSRNHRAYR LTAAKLEPPL IPFMPLLIKD MTFTHEGNKT FIDNLVNFEK
960 970 980 990 1000
MRMIANTART VRYYRSQPFN PDAAQANKNH QDVRSYVRQL NVIDNQRTLS
1010
QMSHRLEPRR P
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA2ASW8 | A2ASW8_MOUSE | Rap guanine nucleotide exchange fac... | Rapgef4 cAMP-GEFII | 867 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 313 | Q → E in BAB23633 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 452 | D → E in BAB23633 (PubMed:16141072).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_007614 | 1 – 315 | Missing in isoform 2. 2 PublicationsAdd BLAST | 315 | |
Alternative sequenceiVSP_007615 | 180 – 197 | Missing in isoform 3. 1 PublicationAdd BLAST | 18 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF115480 mRNA Translation: AAD09132.1 AB021132 mRNA Translation: BAB18976.1 AB037668 mRNA Translation: BAB72180.1 AK004874 mRNA Translation: BAB23633.1 |
CCDSi | CCDS16120.1 [Q9EQZ6-3] CCDS57176.1 [Q9EQZ6-1] |
RefSeqi | NP_001191094.1, NM_001204165.1 [Q9EQZ6-1] NP_001191095.1, NM_001204166.1 NP_062662.1, NM_019688.2 [Q9EQZ6-3] |
Genome annotation databases
Ensembli | ENSMUST00000090826; ENSMUSP00000088336; ENSMUSG00000049044 [Q9EQZ6-1] ENSMUST00000102698; ENSMUSP00000099759; ENSMUSG00000049044 [Q9EQZ6-3] |
GeneIDi | 56508 |
KEGGi | mmu:56508 |
UCSCi | uc008kbn.2, mouse [Q9EQZ6-1] uc008kbo.2, mouse [Q9EQZ6-3] |
Keywords - Coding sequence diversityi
Alternative promoter usage, Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF115480 mRNA Translation: AAD09132.1 AB021132 mRNA Translation: BAB18976.1 AB037668 mRNA Translation: BAB72180.1 AK004874 mRNA Translation: BAB23633.1 |
CCDSi | CCDS16120.1 [Q9EQZ6-3] CCDS57176.1 [Q9EQZ6-1] |
RefSeqi | NP_001191094.1, NM_001204165.1 [Q9EQZ6-1] NP_001191095.1, NM_001204166.1 NP_062662.1, NM_019688.2 [Q9EQZ6-3] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1O7F | X-ray | 2.50 | A | 1-481 | [»] | |
2BYV | X-ray | 2.70 | E | 1-1011 | [»] | |
3CF6 | X-ray | 2.20 | E | 324-1011 | [»] | |
4F7Z | X-ray | 2.60 | A | 1-1011 | [»] | |
4MGI | X-ray | 2.80 | E | 324-1011 | [»] | |
4MGK | X-ray | 2.70 | E | 324-1011 | [»] | |
4MGY | X-ray | 2.60 | E | 324-1011 | [»] | |
4MGZ | X-ray | 3.00 | E | 324-1011 | [»] | |
4MH0 | X-ray | 2.40 | E | 324-1011 | [»] | |
SASBDBi | Q9EQZ6 | |||||
SMRi | Q9EQZ6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 208026, 24 interactors |
CORUMi | Q9EQZ6 |
DIPi | DIP-32333N |
IntActi | Q9EQZ6, 7 interactors |
STRINGi | 10090.ENSMUSP00000099759 |
Chemistry databases
BindingDBi | Q9EQZ6 |
ChEMBLi | CHEMBL3593151 |
PTM databases
iPTMneti | Q9EQZ6 |
PhosphoSitePlusi | Q9EQZ6 |
Proteomic databases
MaxQBi | Q9EQZ6 |
PaxDbi | Q9EQZ6 |
PeptideAtlasi | Q9EQZ6 |
PRIDEi | Q9EQZ6 |
ProteomicsDBi | 299872 [Q9EQZ6-1] 299873 [Q9EQZ6-2] 299874 [Q9EQZ6-3] |
Protocols and materials databases
Antibodypediai | 3825, 172 antibodies from 33 providers |
DNASUi | 56508 |
Genome annotation databases
Ensembli | ENSMUST00000090826; ENSMUSP00000088336; ENSMUSG00000049044 [Q9EQZ6-1] ENSMUST00000102698; ENSMUSP00000099759; ENSMUSG00000049044 [Q9EQZ6-3] |
GeneIDi | 56508 |
KEGGi | mmu:56508 |
UCSCi | uc008kbn.2, mouse [Q9EQZ6-1] uc008kbo.2, mouse [Q9EQZ6-3] |
Organism-specific databases
CTDi | 11069 |
MGIi | MGI:1917723, Rapgef4 |
VEuPathDBi | HostDB:ENSMUSG00000049044 |
Phylogenomic databases
eggNOGi | KOG2378, Eukaryota |
GeneTreei | ENSGT00940000156075 |
InParanoidi | Q9EQZ6 |
OMAi | HHPDVWT |
OrthoDBi | 143470at2759 |
PhylomeDBi | Q9EQZ6 |
TreeFami | TF313184 |
Enzyme and pathway databases
Reactomei | R-MMU-354192, Integrin signaling R-MMU-381676, Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-MMU-392517, Rap1 signalling R-MMU-422356, Regulation of insulin secretion |
Miscellaneous databases
BioGRID-ORCSi | 56508, 2 hits in 65 CRISPR screens |
ChiTaRSi | Rapgef4, mouse |
EvolutionaryTracei | Q9EQZ6 |
PROi | PR:Q9EQZ6 |
RNActi | Q9EQZ6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000049044, Expressed in globus pallidus and 260 other tissues |
ExpressionAtlasi | Q9EQZ6, baseline and differential |
Genevisiblei | Q9EQZ6, MM |
Family and domain databases
CDDi | cd00038, CAP_ED, 2 hits cd00155, RasGEF, 1 hit cd06224, REM, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 1.10.840.10, 1 hit 2.60.120.10, 2 hits |
InterProi | View protein in InterPro IPR018490, cNMP-bd-like IPR000595, cNMP-bd_dom IPR000591, DEP_dom IPR008937, Ras-like_GEF IPR000651, Ras-like_Gua-exchang_fac_N IPR019804, Ras_G-nucl-exch_fac_CS IPR023578, Ras_GEF_dom_sf IPR001895, RASGEF_cat_dom IPR036964, RASGEF_cat_dom_sf IPR014710, RmlC-like_jellyroll IPR029071, Ubiquitin-like_domsf IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR23113, PTHR23113, 2 hits |
Pfami | View protein in Pfam PF00027, cNMP_binding, 2 hits PF00610, DEP, 1 hit PF00617, RasGEF, 1 hit PF00618, RasGEF_N, 1 hit |
SMARTi | View protein in SMART SM00100, cNMP, 2 hits SM00049, DEP, 1 hit SM00147, RasGEF, 1 hit SM00229, RasGEFN, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF48366, SSF48366, 1 hit SSF51206, SSF51206, 2 hits SSF54236, SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS50042, CNMP_BINDING_3, 2 hits PS50186, DEP, 1 hit PS00720, RASGEF, 1 hit PS50009, RASGEF_CAT, 1 hit PS50212, RASGEF_NTER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RPGF4_MOUSE | |
Accessioni | Q9EQZ6Primary (citable) accession number: Q9EQZ6 Secondary accession number(s): Q8VIP9, Q9CW52, Q9Z1P0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 20, 2003 |
Last sequence update: | March 1, 2001 | |
Last modified: | February 23, 2022 | |
This is version 180 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references