Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (CNrasGEF) (Neural RAP guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) (RA-GEF-1) (Ras/Rap1-associating GEF-1)
1_MKPLA 6_ IPANH 11_ GVMGQ 16_ QEKHS 21_ LPADF 26_ TKLHL 31_ TDSLH 36_ PQVTH 41_ VSSSH 46_ SGCSI 51_ TSDSG 56_ SSSLS 61_ DIYQA 66_ TESEA 71_ GDMDL 76_ SGLPE 81_ TAVDS 86_ EDDDD 91_ EEDIE 96_ RASDP 101_ LMSRD 106_ IVRDC 111_ LEKDP 116_ IDRTD 121_ DDIEQ 126_ LLEFM 131_ HQLPA 136_ FANMT 141_ MSVRR 146_ ELCAV 151_ MVFAV 156_ VERAG 161_ TIVLN 166_ DGEEL 171_ DSWSV 176_ ILNGS 181_ VEVTY 186_ PDGKA 191_ EILCM 196_ GNSFG 201_ VSPTM 206_ DKEYM 211_ KGVMR 216_ TKVDD 221_ CQFVC 226_ IAQQD 231_ YCRIL 236_ NQVEK 241_ NMQKV 246_ EEEGE 251_ IVMVK 256_ EHREL 261_ DRTGT 266_ RKGHI 271_ VIKGT 276_ SERLT 281_ MHLVE 286_ EHSVV 291_ DPTFI 296_ EDFLL 301_ TYRTF 306_ LSSPM 311_ EVGKK 316_ LLEWF 321_ NDPSL 326_ RDKVT 331_ RVVLL 336_ WVNNH 341_ FNDFE 346_ GDPAM 351_ TRFLE 356_ EFENN 361_ LEREK 366_ MGGHL 371_ RLLNI 376_ ACAAK 381_ AKRRL 386_ MTLTK 391_ PSREA 396_ PLPFI 401_ LLGGS 406_ EKGFG 411_ IFVDS 416_ VDSGS 421_ KATEA 426_ GLKRG 431_ DQILE 436_ VNGQN 441_ FENIQ 446_ LSKAM 451_ EILRN 456_ NTHLS 461_ ITVKT 466_ NLFVF 471_ KELLT 476_ RLSEE 481_ KRNGA 486_ PHLPK 491_ IGDIK 496_ KASRY 501_ SIPDL 506_ AVDVE 511_ QVIGL 516_ EKVNK 521_ KSKAN 526_ TVGGR 531_ NKLKK 536_ ILDKT 541_ RISIL 546_ PQKPY 551_ NDIGI 556_ GQSQD 561_ DSIVG 566_ LRQTK 571_ HIPTA 576_ LPVSG 581_ TLSSS 586_ NPDLL 591_ QSHHR 596_ ILDFS 601_ ATPDL 606_ PDQVL 611_ RVFKA 616_ DQQSR 621_ YIMIS 626_ KDTTA 631_ KEVVI 636_ QAIRE 641_ FAVTA 646_ TPDQY 651_ SLCEV 656_ SVTPE 661_ GVIKQ 666_ RRLPD 671_ QLSKL 676_ ADRIQ 681_ LSGRY 686_ YLKNN 691_ METET 696_ LCSDE 701_ DAQEL 706_ LRESQ 711_ ISLLQ 716_ LSTVE 721_ VATQL 726_ SMRNF 731_ ELFRN 736_ IEPTE 741_ YIDDL 746_ FKLRS 751_ KTSCA 756_ NLKRF 761_ EEVIN 766_ QETFW 771_ VASEI 776_ LRETN 781_ QLKRM 786_ KIIKH 791_ FIKIA 796_ LHCRE 801_ CKNFN 806_ SMFAI 811_ ISGLN 816_ LAPVA 821_ RLRTT 826_ WEKLP 831_ NKYEK 836_ LFQDL 841_ QDLFD 846_ PSRNM 851_ AKYRN 856_ VLNSQ 861_ NLQPP 866_ IIPLF 871_ PVIKK 876_ DLTFL 881_ HEGND 886_ SKVDG 891_ LVNFE 896_ KLRMI 901_ AKEIR 906_ HVGRM 911_ ASVNM 916_ DPALM 921_ FRTRK 926_ KKWRS 931_ LGSLS 936_ QGSTN 941_ ATVLD 946_ VAQTG 951_ GHKKR 956_ VRRSS 961_ FLNAK 966_ KLYED 971_ AQMAR 976_ KVKQY 981_ LSNLE 986_ LEMDE 991_ ESLQT 996_ LSLQC 1001_ EPATN 1006_ TLPKN 1011_ PGDKK 1016_ PVKSE 1021_ TSPVA 1026_ PRAGS 1031_ QQKAQ 1036_ SLPQP 1041_ QQQPP 1046_ PAHKI 1051_ NQGLQ 1056_ VPAVS 1061_ LYPSR 1066_ KKVPV 1071_ KDLPP 1076_ FGINS 1081_ PQALK 1086_ KILSL 1091_ SEEGS 1096_ LERHK 1101_ KQAED 1106_ TISNA 1111_ SSQLS 1116_ SPPTS 1121_ PQSSP 1126_ RKGYT 1131_ LAPSG 1136_ TVDNF 1141_ SDSGH 1146_ SEISS 1151_ RSSIV 1156_ SNSSF 1161_ DSVPV 1166_ SLHDE 1171_ RRQRH 1176_ SVSIV 1181_ ETNLG 1186_ MGRME 1191_ RRTMI 1196_ EPDQY 1201_ SLGSY 1206_ APMSE 1211_ GRGLY 1216_ ATATV 1221_ ISSPS 1226_ TEELS 1231_ QDQGD 1236_ RASLD 1241_ AADSG 1246_ RGSWT 1251_ SCSSG 1256_ SHDNI 1261_ QTIQH 1266_ QRSWE 1271_ TLPFG 1276_ HTHFD 1281_ YSGDP 1286_ AGLWA 1291_ SSSHM 1296_ DQIMF 1301_ SDHST 1306_ KYNRQ 1311_ NQSRE 1316_ SLEQA 1321_ QSRAS 1326_ WASST 1331_ GYWGE 1336_ DSEGD 1341_ TGTIK 1346_ RRGGK 1351_ DVSIE 1356_ AESSS 1361_ LTSVT 1366_ TEETK 1371_ PVPMP 1376_ AHIAV 1381_ ASSTT 1386_ KGLIA 1391_ RKEGR 1396_ YREPP 1401_ PTPPG 1406_ YIGIP 1411_ ITDFP 1416_ EGHSH 1421_ PARKP 1426_ PDYNV 1431_ ALQRS 1436_ RMVAR 1441_ SSDTA 1446_ GPSSV 1451_ QQPHG 1456_ HPTSS 1461_ RPVNK 1466_ PQWHK 1471_ PNESD 1476_ PRLAP 1481_ YQSQG 1486_ FSTEE 1491_DEDEQ
1: Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Also acts as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10548487, PubMed:10608844, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Also provides inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions