CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-018387
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Rap guanine nucleotide exchange factor 4 
Protein Synonyms/Alias
 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 
Gene Name
 RAPGEF4 
Gene Synonyms/Alias
 CGEF2; EPAC2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
497GNSQPQQKYTVMSGTubiquitination[1]
645KAPQKKHKVLLQQFNacetylation[2]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 
Functional Description
 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). 
Sequence Annotation
 DOMAIN 216 291 DEP.
 DOMAIN 496 634 N-terminal Ras-GEF.
 DOMAIN 772 1009 Ras-GEF.
 NP_BIND 43 166 cAMP 1.
 NP_BIND 356 476 cAMP 2.
 MOD_RES 681 681 Phosphotyrosine (By similarity).  
Keyword
 Alternative promoter usage; Alternative splicing; cAMP; cAMP-binding; Complete proteome; Cytoplasm; Exocytosis; Guanine-nucleotide releasing factor; Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1011 AA 
Protein Sequence
MVAAHAAHSS SSAEWIACLD KRPLERSSED VDIIFTRLKE VKAFEKFHPN LLHQICLCGY 60
YENLEKGITL FRQGDIGTNW YAVLAGSLDV KVSETSSHQD AVTICTLGIG TAFGESILDN 120
TPRHATIVTR ESSELLRIEQ KDFKALWEKY RQYMAGLLAP PYGVMETGSN NDRIPDKENT 180
PLIEPHVPLR PANTITKVPS EKILRAGKIL RNAILSRAPH MIRDRKYHLK TYRQCCVGTE 240
LVDWMMQQTP CVHSRTQAVG MWQVLLEDGV LNHVDQEHHF QDKYLFYRFL DDEHEDAPLP 300
TEEEKKECDE ELQDTMLLLS QMGPDAHMRM ILRKPPGQRT VDDLEIIYEE LLHIKALSHL 360
STTVKRELAG VLIFESHAKG GTVLFNQGEE GTSWYIILKG SVNVVIYGKG VVCTLHEGDD 420
FGKLALVNDA PRAASIVLRE DNCHFLRVDK EDFNRILRDV EANTVRLKEH DQDVLVLEKV 480
PAGNRASNQG NSQPQQKYTV MSGTPEKILE HFLETIRLEA TLNEATDSVL NDFIMMHCVF 540
MPNTQLCPAL VAHYHAQPSQ GTEQEKMDYA LNNKRRVIRL VLQWAAMYGD LLQEDDVSMA 600
FLEEFYVSVS DDARMIAALK EQLPELEKIV KQISEDAKAP QKKHKVLLQQ FNTGDERAQK 660
RQPIRGSDEV LFKVYCMDHT YTTIRVPVAT SVKEVISAVA DKLGSGEGLI IVKMSSGGEK 720
VVLKPNDVSV FTTLTINGRL FACPREQFDS LTPLPEQEGP TVGTVGTFEL MSSKDLAYQM 780
TIYDWELFNC VHELELIYHT FGRHNFKKTT ANLDLFLRRF NEIQFWVVTE ICLCSQLSKR 840
VQLLKKFIKI AAHCKEYKNL NSFFAIVMGL SNVAVSRLAL TWEKLPSKFK KFYAEFESLM 900
DPSRNHRAYR LTVAKLEPPL IPFMPLLIKD MTFTHEGNKT FIDNLVNFEK MRMIANTART 960
VRYYRSQPFN PDAAQANKNH QDVRSYVRQL NVIDNQRTLS QMSHRLEPRR P 1011 
Gene Ontology
 GO:0005952; C:cAMP-dependent protein kinase complex; IEA:InterPro.
 GO:0005829; C:cytosol; IEA:Compara.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0030552; F:cAMP binding; ISS:UniProtKB.
 GO:0008603; F:cAMP-dependent protein kinase regulator activity; IEA:InterPro.
 GO:0017016; F:Ras GTPase binding; ISS:UniProtKB.
 GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
 GO:0017156; P:calcium ion-dependent exocytosis; IEA:Compara.
 GO:0019933; P:cAMP-mediated signaling; IEA:Compara.
 GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
 GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:ProtInc.
 GO:0030073; P:insulin secretion; IEA:Compara.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0017157; P:regulation of exocytosis; IEA:Compara.
 GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
 GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
 GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome. 
Interpro
 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_DNA-bd_dom. 
Pfam
 PF00027; cNMP_binding
 PF00610; DEP
 PF00788; RA
 PF00617; RasGEF
 PF00618; RasGEF_N 
SMART
 SM00100; cNMP
 SM00049; DEP
 SM00147; RasGEF
 SM00229; RasGEFN 
PROSITE
 PS00888; CNMP_BINDING_1
 PS00889; CNMP_BINDING_2
 PS50042; CNMP_BINDING_3
 PS50186; DEP
 PS00720; RASGEF
 PS50009; RASGEF_CAT
 PS50212; RASGEF_NTER 
PRINTS
 PR00103; CAMPKINASE.