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Protein

Rap guanine nucleotide exchange factor 4

Gene

RAPGEF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 (By similarity).By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi43 – 166cAMP 1Add BLAST124
Nucleotide bindingi356 – 476cAMP 2Add BLAST121

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
Biological processExocytosis
LigandcAMP, cAMP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-354192 Integrin alphaIIb beta3 signaling
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-392517 Rap1 signalling
R-HSA-422356 Regulation of insulin secretion

Names & Taxonomyi

Protein namesi
Recommended name:
Rap guanine nucleotide exchange factor 4
Alternative name(s):
Exchange factor directly activated by cAMP 2
Exchange protein directly activated by cAMP 2
Short name:
EPAC 2
cAMP-regulated guanine nucleotide exchange factor II
Short name:
cAMP-GEFII
Gene namesi
Name:RAPGEF4
Synonyms:CGEF2, EPAC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000091428.17
HGNCiHGNC:16626 RAPGEF4
MIMi606058 gene
neXtProtiNX_Q8WZA2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi11069
OpenTargetsiENSG00000091428
PharmGKBiPA134861108

Chemistry databases

ChEMBLiCHEMBL2029198
GuidetoPHARMACOLOGYi1293

Polymorphism and mutation databases

BioMutaiRAPGEF4
DMDMi32171491

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000688701 – 1011Rap guanine nucleotide exchange factor 4Add BLAST1011

Proteomic databases

PaxDbiQ8WZA2
PeptideAtlasiQ8WZA2
PRIDEiQ8WZA2
ProteomicsDBi75243
75244 [Q8WZA2-2]
75245 [Q8WZA2-3]

PTM databases

iPTMnetiQ8WZA2
PhosphoSitePlusiQ8WZA2

Expressioni

Tissue specificityi

Predominantly expressed in brain and adrenal gland. Isoform 2 is expressed in liver. Isoform 1 is expressed in liver at very low levels.

Gene expression databases

BgeeiENSG00000091428
CleanExiHS_RAPGEF4
ExpressionAtlasiQ8WZA2 baseline and differential
GenevisibleiQ8WZA2 HS

Organism-specific databases

HPAiCAB004388
HPA028968

Interactioni

Subunit structurei

Interacts with RIMS1 and RIMS2. Probably part of a complex with RIMS2 and GTP-activated RAB3A (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
C16orf45Q96MC53EBI-948476,EBI-718468

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116253, 11 interactors
IntActiQ8WZA2, 3 interactors
STRINGi9606.ENSP00000380271

Chemistry databases

BindingDBiQ8WZA2

Structurei

3D structure databases

ProteinModelPortaliQ8WZA2
SMRiQ8WZA2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini216 – 291DEPPROSITE-ProRule annotationAdd BLAST76
Domaini496 – 634N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST139
Domaini772 – 1009Ras-GEFPROSITE-ProRule annotationAdd BLAST238

Domaini

The N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2.
The DEP domain is involved in membrane localization independent from regulation by cAMP.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2378 Eukaryota
ENOG410XPX9 LUCA
GeneTreeiENSGT00880000137870
HOGENOMiHOG000230545
HOVERGENiHBG056985
InParanoidiQ8WZA2
KOiK04351
OMAiCKEYKNL
OrthoDBiEOG091G0HKG
PhylomeDBiQ8WZA2
TreeFamiTF313184

Family and domain databases

CDDicd00038 CAP_ED, 2 hits
cd00155 RasGEF, 1 hit
cd06224 REM, 1 hit
Gene3Di1.10.10.10, 1 hit
1.10.840.10, 1 hit
2.60.120.10, 2 hits
InterProiView protein in InterPro
IPR018490 cNMP-bd-like
IPR000595 cNMP-bd_dom
IPR000591 DEP_dom
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
PfamiView protein in Pfam
PF00027 cNMP_binding, 2 hits
PF00610 DEP, 1 hit
PF00617 RasGEF, 1 hit
PF00618 RasGEF_N, 1 hit
SMARTiView protein in SMART
SM00100 cNMP, 2 hits
SM00049 DEP, 1 hit
SM00147 RasGEF, 1 hit
SM00229 RasGEFN, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF48366 SSF48366, 2 hits
SSF51206 SSF51206, 2 hits
SSF54236 SSF54236, 1 hit
PROSITEiView 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

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WZA2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVAAHAAHSS SSAEWIACLD KRPLERSSED VDIIFTRLKE VKAFEKFHPN
60 70 80 90 100
LLHQICLCGY YENLEKGITL FRQGDIGTNW YAVLAGSLDV KVSETSSHQD
110 120 130 140 150
AVTICTLGIG TAFGESILDN TPRHATIVTR ESSELLRIEQ KDFKALWEKY
160 170 180 190 200
RQYMAGLLAP PYGVMETGSN NDRIPDKENT PLIEPHVPLR PANTITKVPS
210 220 230 240 250
EKILRAGKIL RNAILSRAPH MIRDRKYHLK TYRQCCVGTE LVDWMMQQTP
260 270 280 290 300
CVHSRTQAVG MWQVLLEDGV LNHVDQEHHF QDKYLFYRFL DDEHEDAPLP
310 320 330 340 350
TEEEKKECDE ELQDTMLLLS QMGPDAHMRM ILRKPPGQRT VDDLEIIYEE
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 PAGNRASNQG NSQPQQKYTV
510 520 530 540 550
MSGTPEKILE HFLETIRLEA TLNEATDSVL NDFIMMHCVF MPNTQLCPAL
560 570 580 590 600
VAHYHAQPSQ GTEQEKMDYA LNNKRRVIRL VLQWAAMYGD LLQEDDVSMA
610 620 630 640 650
FLEEFYVSVS DDARMIAALK EQLPELEKIV KQISEDAKAP QKKHKVLLQQ
660 670 680 690 700
FNTGDERAQK RQPIRGSDEV LFKVYCMDHT YTTIRVPVAT SVKEVISAVA
710 720 730 740 750
DKLGSGEGLI IVKMSSGGEK VVLKPNDVSV FTTLTINGRL FACPREQFDS
760 770 780 790 800
LTPLPEQEGP TVGTVGTFEL MSSKDLAYQM TIYDWELFNC VHELELIYHT
810 820 830 840 850
FGRHNFKKTT ANLDLFLRRF NEIQFWVVTE ICLCSQLSKR VQLLKKFIKI
860 870 880 890 900
AAHCKEYKNL NSFFAIVMGL SNVAVSRLAL TWEKLPSKFK KFYAEFESLM
910 920 930 940 950
DPSRNHRAYR LTVAKLEPPL IPFMPLLIKD MTFTHEGNKT FIDNLVNFEK
960 970 980 990 1000
MRMIANTART VRYYRSQPFN PDAAQANKNH QDVRSYVRQL NVIDNQRTLS
1010
QMSHRLEPRR P
Note: Produced by alternative promoter usage. Promoter analysis was carried out in mouse.
Length:1,011
Mass (Da):115,522
Last modified:March 1, 2002 - v1
Checksum:i9427C5F92F2FFAD1
GO
Isoform 2 (identifier: Q8WZA2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-315: Missing.

Note: Produced by alternative promoter usage. Promoter analysis was carried out in mouse.
Show »
Length:696
Mass (Da):79,492
Checksum:i936C1CEC6FA169C8
GO
Isoform 3 (identifier: Q8WZA2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-144: Missing.
     145-148: ALWE → MLYK

Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.
Show »
Length:867
Mass (Da):99,523
Checksum:i5CA711EAD3DBEE66
GO
Isoform 4 (identifier: Q8WZA2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-153: Missing.

Note: No experimental confirmation available.
Show »
Length:858
Mass (Da):98,248
Checksum:iAD52D5D0637CF299
GO
Isoform 5 (identifier: Q8WZA2-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-153: Missing.
     180-197: Missing.

Note: No experimental confirmation available.
Show »
Length:840
Mass (Da):96,269
Checksum:i6FF8498DB079C13C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti324P → R in AAH40183 (PubMed:15489334).Curated1
Sequence conflicti511H → R in AAH40183 (PubMed:15489334).Curated1
Sequence conflicti647L → I in AAH40183 (PubMed:15489334).Curated1
Sequence conflicti679H → P in AAH24004 (PubMed:15489334).Curated1
Sequence conflicti732T → M in AAH24004 (PubMed:15489334).Curated1
Sequence conflicti873V → I in AAD03422 (PubMed:9856955).Curated1
Sequence conflicti902P → T in AAH40183 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0076111 – 315Missing in isoform 2. 1 PublicationAdd BLAST315
Alternative sequenceiVSP_0544231 – 153Missing in isoform 4 and isoform 5. 1 PublicationAdd BLAST153
Alternative sequenceiVSP_0076121 – 144Missing in isoform 3. 2 PublicationsAdd BLAST144
Alternative sequenceiVSP_007613145 – 148ALWE → MLYK in isoform 3. 2 Publications4
Alternative sequenceiVSP_054424180 – 197Missing in isoform 5. 1 PublicationAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78516 mRNA Translation: AAD03422.1
AB027471 mRNA Translation: BAB72179.1
AK294445 mRNA Translation: BAH11769.1
AK296340 mRNA Translation: BAH12322.1
AK304278 mRNA Translation: BAH14148.1
AK313084 mRNA Translation: BAG35910.1
AK316072 mRNA Translation: BAH14443.1
AC009484 Genomic DNA No translation available.
AC018712 Genomic DNA No translation available.
AC019046 Genomic DNA No translation available.
AC104086 Genomic DNA No translation available.
BC024004 mRNA Translation: AAH24004.1
BC040183 mRNA Translation: AAH40183.1
CCDSiCCDS42775.1 [Q8WZA2-1]
CCDS42776.1 [Q8WZA2-3]
CCDS63060.1 [Q8WZA2-4]
CCDS63061.1 [Q8WZA2-5]
RefSeqiNP_001093867.1, NM_001100397.1 [Q8WZA2-3]
NP_001269828.1, NM_001282899.1 [Q8WZA2-4]
NP_001269829.1, NM_001282900.1 [Q8WZA2-5]
NP_001269830.1, NM_001282901.1
NP_008954.2, NM_007023.3 [Q8WZA2-1]
XP_006712268.1, XM_006712205.3 [Q8WZA2-5]
UniGeneiHs.470646

Genome annotation databases

EnsembliENST00000397081; ENSP00000380271; ENSG00000091428 [Q8WZA2-1]
ENST00000397087; ENSP00000380276; ENSG00000091428 [Q8WZA2-3]
ENST00000538974; ENSP00000440135; ENSG00000091428 [Q8WZA2-5]
ENST00000540783; ENSP00000440250; ENSG00000091428 [Q8WZA2-4]
GeneIDi11069
KEGGihsa:11069
UCSCiuc002uhv.5 human [Q8WZA2-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiRPGF4_HUMAN
AccessioniPrimary (citable) accession number: Q8WZA2
Secondary accession number(s): B2R7R3
, B7Z283, B7Z3T6, B7Z912, O95636, Q8IXK6, Q8TAA4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: March 1, 2002
Last modified: June 20, 2018
This is version 148 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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