Q9Y4G8

PTMD Annotation Information

※ Protein Information

Tag	Content
UniProt Accession	RPGF2_HUMAN; Q9Y4G8;
Entrez ID	9693
GenBank Protein ID
GenBank Nucleotide ID
Protein Name	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)
Gene Name	RAPGEF2; KIAA0313; NRAPGEP; PDZGEF1
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	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. Acts also 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:1(view all) Functional Description 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. Acts also 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:10608844, PubMed:10548487, 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. Provides also 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.
Sequence (Fasta)	MKPLAIPANH GVMGQQEKHS LPADFTKLHL TDSLHPQVTH VSSSHSGCSI TSDSGSSSLS 60 DIYQATESEA GDMDLSGLPE TAVDSEDDDD EEDIERASDP LMSRDIVRDC LEKDPIDRTD 120 DDIEQLLEFM HQLPAFANMT MSVRRELCAV MVFAVVERAG TIVLNDGEEL DSWSVILNGS 180 VEVTYPDGKA EILCMGNSFG VSPTMDKEYM KGVMRTKVDD CQFVCIAQQD YCRILNQVEK 240 NMQKVEEEGE IVMVKEHREL DRTGTRKGHI VIKGTSERLT MHLVEEHSVV DPTFIEDFLL 300 TYRTFLSSPM EVGKKLLEWF NDPSLRDKVT RVVLLWVNNH FNDFEGDPAM TRFLEEFENN 360 LEREKMGGHL RLLNIACAAK AKRRLMTLTK PSREAPLPFI LLGGSEKGFG IFVDSVDSGS 420 KATEAGLKRG DQILEVNGQN FENIQLSKAM EILRNNTHLS ITVKTNLFVF KELLTRLSEE 480 KRNGAPHLPK IGDIKKASRY SIPDLAVDVE QVIGLEKVNK KSKANTVGGR NKLKKILDKT 540 RISILPQKPY NDIGIGQSQD DSIVGLRQTK HIPTALPVSG TLSSSNPDLL QSHHRILDFS 600 ATPDLPDQVL RVFKADQQSR YIMISKDTTA KEVVIQAIRE FAVTATPDQY SLCEVSVTPE 660 GVIKQRRLPD QLSKLADRIQ LSGRYYLKNN METETLCSDE DAQELLRESQ ISLLQLSTVE 720 VATQLSMRNF ELFRNIEPTE YIDDLFKLRS KTSCANLKRF EEVINQETFW VASEILRETN 780 QLKRMKIIKH FIKIALHCRE CKNFNSMFAI ISGLNLAPVA RLRTTWEKLP NKYEKLFQDL 840 QDLFDPSRNM AKYRNVLNSQ NLQPPIIPLF PVIKKDLTFL HEGNDSKVDG LVNFEKLRMI 900 AKEIRHVGRM ASVNMDPALM FRTRKKKWRS LGSLSQGSTN ATVLDVAQTG GHKKRVRRSS 960 FLNAKKLYED AQMARKVKQY LSNLELEMDE ESLQTLSLQC EPATNTLPKN PGDKKPVKSE 1020 TSPVAPRAGS QQKAQSLPQP QQQPPPAHKI NQGLQVPAVS LYPSRKKVPV KDLPPFGINS 1080 PQALKKILSL SEEGSLERHK KQAEDTISNA SSQLSSPPTS PQSSPRKGYT LAPSGTVDNF 1140 SDSGHSEISS RSSIVSNSSF DSVPVSLHDE RRQRHSVSIV ETNLGMGRME RRTMIEPDQY 1200 SLGSYAPMSE GRGLYATATV ISSPSTEELS QDQGDRASLD AADSGRGSWT SCSSGSHDNI 1260 QTIQHQRSWE TLPFGHTHFD YSGDPAGLWA SSSHMDQIMF SDHSTKYNRQ NQSRESLEQA 1320 QSRASWASST GYWGEDSEGD TGTIKRRGGK DVSIEAESSS LTSVTTEETK PVPMPAHIAV 1380 ASSTTKGLIA RKEGRYREPP PTPPGYIGIP ITDFPEGHSH PARKPPDYNV ALQRSRMVAR 1440 SSDTAGPSSV QQPHGHPTSS RPVNKPQWHK PNESDPRLAP YQSQGFSTEE DEDEQVSAV 1500 Fasta Sequence >Q9Y4G8\|RAPGEF2; KIAA0313; NRAPGEP; PDZGEF1\|Homo sapiens (Human) MKPLAIPANHGVMGQQEKHSLPADFTKLHLTDSLHPQVTHVSSSHSGCSITSDSGSSSLSDIYQATESEAGDMDLSGLPETAVDSEDDDDEEDIERASDPLMSRDIVRDCLEKDPIDRTDDDIEQLLEFMHQLPAFANMTMSVRRELCAVMVFAVVERAGTIVLNDGEELDSWSVILNGSVEVTYPDGKAEILCMGNSFGVSPTMDKEYMKGVMRTKVDDCQFVCIAQQDYCRILNQVEKNMQKVEEEGEIVMVKEHRELDRTGTRKGHIVIKGTSERLTMHLVEEHSVVDPTFIEDFLLTYRTFLSSPMEVGKKLLEWFNDPSLRDKVTRVVLLWVNNHFNDFEGDPAMTRFLEEFENNLEREKMGGHLRLLNIACAAKAKRRLMTLTKPSREAPLPFILLGGSEKGFGIFVDSVDSGSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTHLSITVKTNLFVFKELLTRLSEEKRNGAPHLPKIGDIKKASRYSIPDLAVDVEQVIGLEKVNKKSKANTVGGRNKLKKILDKTRISILPQKPYNDIGIGQSQDDSIVGLRQTKHIPTALPVSGTLSSSNPDLLQSHHRILDFSATPDLPDQVLRVFKADQQSRYIMISKDTTAKEVVIQAIREFAVTATPDQYSLCEVSVTPEGVIKQRRLPDQLSKLADRIQLSGRYYLKNNMETETLCSDEDAQELLRESQISLLQLSTVEVATQLSMRNFELFRNIEPTEYIDDLFKLRSKTSCANLKRFEEVINQETFWVASEILRETNQLKRMKIIKHFIKIALHCRECKNFNSMFAIISGLNLAPVARLRTTWEKLPNKYEKLFQDLQDLFDPSRNMAKYRNVLNSQNLQPPIIPLFPVIKKDLTFLHEGNDSKVDGLVNFEKLRMIAKEIRHVGRMASVNMDPALMFRTRKKKWRSLGSLSQGSTNATVLDVAQTGGHKKRVRRSSFLNAKKLYEDAQMARKVKQYLSNLELEMDEESLQTLSLQCEPATNTLPKNPGDKKPVKSETSPVAPRAGSQQKAQSLPQPQQQPPPAHKINQGLQVPAVSLYPSRKKVPVKDLPPFGINSPQALKKILSLSEEGSLERHKKQAEDTISNASSQLSSPPTSPQSSPRKGYTLAPSGTVDNFSDSGHSEISSRSSIVSNSSFDSVPVSLHDERRQRHSVSIVETNLGMGRMERRTMIEPDQYSLGSYAPMSEGRGLYATATVISSPSTEELSQDQGDRASLDAADSGRGSWTSCSSGSHDNIQTIQHQRSWETLPFGHTHFDYSGDPAGLWASSSHMDQIMFSDHSTKYNRQNQSRESLEQAQSRASWASSTGYWGEDSEGDTGTIKRRGGKDVSIEAESSSLTSVTTEETKPVPMPAHIAVASSTTKGLIARKEGRYREPPPTPPGYIGIPITDFPEGHSHPARKPPDYNVALQRSRMVARSSDTAGPSSVQQPHGHPTSSRPVNKPQWHKPNESDPRLAPYQSQGFSTEEDEDEQVSAV

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Ubiquitination	Glioma/Adult gliomas	cell line	P		24340059
1	[Reference]: NEDD4-1 regulates migration and invasion of glioma cells through CNrasGEF ubiquitination in vitro

※ Disease Cross-ref Annotation

Database	Annotation
GWASdb (count: 4)	rs4396948; Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis rs11723634; Urinary metabolites; kidney disease rs11723634; Asthma; asthma rs11727094; Urinary metabolites; kidney disease

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 62) (view all)	1006 QCEPATNTLPKNPGD dbPAF 1021 KKPVKSETSPVAPRA dbPAF 1022 KPVKSETSPVAPRAG dbPAF 1080 LPPFGINSPQALKKI dbPAF 1089 QALKKILSLSEEGSL dbPAF 1091 LKKILSLSEEGSLER dbPAF 1095 LSLSEEGSLERHKKQ dbPAF 1108 KQAEDTISNASSQLS dbPAF 1112 DTISNASSQLSSPPT dbPAF 1115 SNASSQLSSPPTSPQ dbPAF 1116 NASSQLSSPPTSPQS dbPAF 1119 SQLSSPPTSPQSSPR dbPAF 1120 QLSSPPTSPQSSPRK dbPAF 1123 SPPTSPQSSPRKGYT dbPAF 1124 PPTSPQSSPRKGYTL dbPAF 1156 SSRSSIVSNSSFDSV dbPAF 1159 SSIVSNSSFDSVPVS dbPAF 1176 DERRQRHSVSIVETN dbPAF 1178 RRQRHSVSIVETNLG dbPAF 1193 MGRMERRTMIEPDQY dbPAF 1200 TMIEPDQYSLGSYAP dbPAF 1223 ATATVISSPSTEELS dbPAF 1244 ASLDAADSGRGSWTS dbPAF 1248 AADSGRGSWTSCSSG dbPAF 1254 GSWTSCSSGSHDNIQ dbPAF 1256 WTSCSSGSHDNIQTI dbPAF 1316 RQNQSRESLEQAQSR dbPAF 1322 ESLEQAQSRASWASS dbPAF 1325 EQAQSRASWASSTGY dbPAF 1337 TGYWGEDSEGDTGTI dbPAF 1341 GEDSEGDTGTIKRRG dbPAF 1343 DSEGDTGTIKRRGGK dbPAF 1487 PYQSQGFSTEEDEDE dbPAF 1488 YQSQGFSTEEDEDEQ dbPAF 275 GHIVIKGTSERLTMH dbPAF 276 HIVIKGTSERLTMHL dbPAF 288 MHLVEEHSVVDPTFI dbPAF 293 EHSVVDPTFIEDFLL dbPAF 301 FIEDFLLTYRTFLSS dbPAF 302 IEDFLLTYRTFLSSP dbPAF 387 KAKRRLMTLTKPSRE dbPAF 460 LRNNTHLSITVKTNL dbPAF 462 NNTHLSITVKTNLFV dbPAF 498 IGDIKKASRYSIPDL dbPAF 500 DIKKASRYSIPDLAV dbPAF 501 IKKASRYSIPDLAVD dbPAF 583 LPVSGTLSSSNPDLL dbPAF 584 PVSGTLSSSNPDLLQ dbPAF 585 VSGTLSSSNPDLLQS dbPAF 592 SNPDLLQSHHRILDF dbPAF 602 RILDFSATPDLPDQV dbPAF 644 AIREFAVTATPDQYS dbPAF 682 LADRIQLSGRYYLKN dbPAF 85 LPETAVDSEDDDDEE dbPAF 853 PSRNMAKYRNVLNSQ dbPAF 859 KYRNVLNSQNLQPPI dbPAF 930 TRKKKWRSLGSLSQG dbPAF 933 KKWRSLGSLSQGSTN dbPAF 935 WRSLGSLSQGSTNAT dbPAF 959 HKKRVRRSSFLNAKK dbPAF 960 KKRVRRSSFLNAKKL dbPAF 968 FLNAKKLYEDAQMAR dbPAF
Ubiquitination (count: 4)	382 IACAAKAKRRLMTLT PLMD 548 RISILPQKPYNDIGI PLMD 688 LSGRYYLKNNMETET PLMD 747 EYIDDLFKLRSKTSC PLMD
Glycation (count: 1)	244 QVEKNMQKVEEEGEI PLMD

※ Protein-Protein Interaction

Network

Interaction

A

B

Source

H0YG33	Q9Y4G8	IntAct
P03928	Q9Y4G8	IntAct
P33176	Q9Y4G8	IntAct
P35222	Q9Y4G8	HPRD
P41743	Q9Y4G8	IntAct
P46934	Q9Y4G8	MINT
P61225	Q9Y4G8	HPRD
P62834	Q9Y4G8	HPRD
P63104	Q9Y4G8	MINT
P78352	Q9Y4G8	MINT
Q12840	Q9Y4G8	IntAct
Q86UL8	Q9Y4G8	HPRD; MINT
Q96PU5	Q9Y4G8	MINT
Q99623	Q9Y4G8	IntAct
Q9Y3A3	Q9Y4G8	IntAct