Q92565 (RPGF5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rap guanine nucleotide exchange factor 5

Alternative name(s):
Guanine nucleotide exchange factor for Rap1
M-Ras-regulated Rap GEF
Short name=MR-GEF
Related to Epac
Short name=Repac

Gene names

Name:	RAPGEF5
Synonyms:	GFR, KIAA0277, MRGEF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	580 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation. Ref.5 Ref.6
Subcellular location	Nucleus.
Tissue specificity	Widely expressed with highest levels in brain.
Sequence similarities	Contains 1 N-terminal Ras-GEF domain. Contains 1 Ras-GEF domain.
Sequence caution	The sequence BAA13406.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Guanine-nucleotide releasing factor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	nervous system development Non-traceable author statement Ref.4. Source: UniProtKB regulation of small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro small GTPase mediated signal transduction Non-traceable author statement Ref.4. Source: UniProtKB
Cellular component	nucleus Inferred from direct assay Ref.4. Source: UniProtKB
Molecular function	GTP-dependent protein binding Inferred from physical interaction Ref.6. Source: UniProtKB Rap guanyl-nucleotide exchange factor activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q92565-1)

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.

Isoform 2 (identifier: Q92565-2)

The sequence of this isoform differs from the canonical sequence as follows:
     270-405: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 580

580

Rap guanine nucleotide exchange factor 5

PRO_0000068873

Regions

Domain

68 – 201

134

N-terminal Ras-GEF

Domain

345 – 579

235

Ras-GEF

Natural variations

Alternative sequence

270 – 405

136

Missing in isoform 2.

VSP_007616

Experimental info

Sequence conflict

497

1

M → V in AAH39203. Ref.3

Secondary structure

1

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580

Helix Strand Turn

Details...

Beta strand

245 – 248

4

Beta strand

250 – 252

3

Beta strand

254 – 257

4

Helix

266 – 276

11

Helix

280 – 282

3

Beta strand

283 – 288

6

Beta strand

301 – 304

4

Beta strand

313 – 318

6

Beta strand

321 – 323

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 732FB7AA11DFDA1C	FASTA	580	67,733
	10 20 30 40 50 60 MGSSRLRVFD PHLERKDSAA ALSDRELPLP TFDVPYFKYI DEEDEDDEWS SRSQSSTEDD 70 80 90 100 110 120 SVDSLLSDRY VVVSGTPEKI LEHLLNDLHL EEVQDKETET LLDDFLLTYT VFMTTDDLCQ 130 140 150 160 170 180 ALLRHYSAKK YQGKEENSDV PRRKRKVLHL VSQWIALYKD WLPEDEHSKM FLKTIYRNVL 190 200 210 220 230 240 DDVYEYPILE KELKEFQKIL GMHRRHTVDE YSPQKKNKAL FHQFSLKENW LQHRGTVTET 250 260 270 280 290 300 EEIFCHVYIT EHSYVSVKAK VSSIAQEILK VVAEKIQYAE EDLALVAITF SGEKHELQPN 310 320 330 340 350 360 DLVISKSLEA SGRIYVYRKD LADTLNPFAE NEESQQRSMR ILGMNTWDLA LELMNFDWSL 370 380 390 400 410 420 FNSIHEQELI YFTFSRQGSG EHTANLSLLL QRCNEVQLWV ATEILLCSQL GKRVQLVKKF 430 440 450 460 470 480 IKIAAHCKAQ RNLNSFFAIV MGLNTASVSR LSQTWEKIPG KFKKLFSELE SLTDPSLNHK 490 500 510 520 530 540 AYRDAFKKMK PPKIPFMPLL LKDVTFIHEG NKTFLDNLVN FEKLHMIADT VRTLRHCRTN 550 560 570 580 QFGDLSPKEH QELKSYVNHL YVIDSQQALF ELSHRIEPRV
	Isoform 2 [UniParc]. Checksum: F615DF931DCEF02B	FASTA	444	52,083
	10 20 30 40 50 60 MGSSRLRVFD PHLERKDSAA ALSDRELPLP TFDVPYFKYI DEEDEDDEWS SRSQSSTEDD 70 80 90 100 110 120 SVDSLLSDRY VVVSGTPEKI LEHLLNDLHL EEVQDKETET LLDDFLLTYT VFMTTDDLCQ 130 140 150 160 170 180 ALLRHYSAKK YQGKEENSDV PRRKRKVLHL VSQWIALYKD WLPEDEHSKM FLKTIYRNVL 190 200 210 220 230 240 DDVYEYPILE KELKEFQKIL GMHRRHTVDE YSPQKKNKAL FHQFSLKENW LQHRGTVTET 250 260 270 280 290 300 EEIFCHVYIT EHSYVSVKAK VSSIAQEILL CSQLGKRVQL VKKFIKIAAH CKAQRNLNSF 310 320 330 340 350 360 FAIVMGLNTA SVSRLSQTWE KIPGKFKKLF SELESLTDPS LNHKAYRDAF KKMKPPKIPF 370 380 390 400 410 420 MPLLLKDVTF IHEGNKTFLD NLVNFEKLHM IADTVRTLRH CRTNQFGDLS PKEHQELKSY 430 440 VNHLYVIDSQ QALFELSHRI EPRV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed: 9039502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Characterization of GFR, a novel guanine nucleotide exchange factor for Rap1." Ichiba T., Hoshi Y., Eto Y., Tajima N., Kuraishi Y. FEBS Lett. 457:85-89(1999) [PubMed: 10486569] [Abstract] Cited for: CHARACTERIZATION.
[5]	"Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs." de Rooij J., Rehmann H., van Triest M., Cool R.H., Wittinghofer A., Bos J.L. J. Biol. Chem. 275:20829-20836(2000) [PubMed: 10777494] [Abstract] Cited for: FUNCTION.
[6]	"Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction." Rebhun J.F., Castro A.F., Quilliam L.A. J. Biol. Chem. 275:34901-34908(2000) [PubMed: 10934204] [Abstract] Cited for: FUNCTION AS A MRAS EFFECTOR.
[7]	"RA domain of guanine nucleotide exchange factor for RAP1." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 241-331.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D87467 mRNA. Translation: BAA13406.2. Different initiation.
CH236948 Genomic DNA. Translation: EAL24270.1.
BC039203 mRNA. Translation: AAH39203.1.

IPI

IPI00293938.
IPI00939482.

RefSeq

NP_036426.3. NM_012294.3.

UniGene

Hs.174768.
Hs.713217.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WGY	NMR	-	A	241-331	[»]

ProteinModelPortal

Q92565.

SMR

Q92565. Positions 65-579.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q92565. 3 interactions.

STRING

Q92565.

PTM databases

PhosphoSite

Q92565.

Polymorphism databases

DMDM

32171396.

Proteomic databases

PRIDE

Q92565.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000401957; ENSP00000384044; ENSG00000136237.

GeneID

9771.

KEGG

hsa:9771.

Organism-specific databases

CTD

9771.

GeneCards

GC07M022128.

H-InvDB

HIX0006511.

HGNC

HGNC:16862. RAPGEF5.

MIM

609527. gene.

neXtProt

NX_Q92565.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09265.

GeneTree

ENSGT00560000077091.

HOVERGEN

HBG056985.

OrthoDB

EOG40GCQB.

Gene expression databases

ArrayExpress

Q92565.

Bgee

Q92565.

CleanEx

HS_RAPGEF5.

Genevestigator

Q92565.

GermOnline

ENSG00000136237. Homo sapiens.

Family and domain databases

InterPro

IPR000651. Ras-like_Gua-exchang_fac_N.
IPR019804. Ras_G-nucl-exch_fac_CS.
IPR008937. Ras_GEF.
IPR023578. Ras_GEF_dom.
IPR001895. RasGRF_CDC25.
[Graphical view]

Gene3D

G3DSA:1.10.840.10. RasGRF_CDC25. 1 hit.

KO

K08019.

PANTHER

PTHR23113. Ras_GEF. 1 hit.

Pfam

PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]

SMART

SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]

SUPFAM

SSF48366. Ras_GEF. 1 hit.

PROSITE

PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

SOURCE

Search...

Entry information

Entry name

RPGF5_HUMAN

Accession

Primary (citable) accession number: Q92565
Secondary accession number(s): A4D140, Q8IXU5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2003
Last sequence update:	February 1, 1997
Last modified:	December 14, 2011
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.