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Q8TEU7 (RPGF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rap guanine nucleotide exchange factor 6
Alternative name(s):
PDZ domain-containing guanine nucleotide exchange factor 2
Short name=PDZ-GEF2
RA-GEF-2
Gene names
Name:RAPGEF6
Synonyms:PDZGEF2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length1601 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Guanine nucleotide exchange factor (GEF) for Rap1A, Rap2A and M-Ras GTPases. Does not interact with cAMP. Ref.1 Ref.3

Subunit structure

Interacts with the second PDZ domain of human PTP1e. Ref.2

Subcellular location

Cytoplasm. Cell membrane. Note: Upon binding to M-Ras, it translocates to the plasma membrane. Ref.3

Tissue specificity

Isoform 3 has highest expression levels in the brain, heart, liver, lung and placenta and is barely detectable in skeletal muscle, kidney and pancreas. Ref.3

Post-translational modification

Phosphorylated upon DNA damage, probably by ATM or ATR.

Sequence similarities

Contains 1 cyclic nucleotide-binding domain.

Contains 1 N-terminal Ras-GEF domain. Ref.3

Contains 1 PDZ (DHR) domain.

Contains 1 Ras-associating domain.

Contains 1 Ras-GEF domain. Ref.3

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8TEU7-1)

Also known as: PDZ-GEF2A;

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: Q8TEU7-2)

Also known as: PDZ-GEF2B;

The sequence of this isoform differs from the canonical sequence as follows:
     1249-1391: GYTLIPSAKS...PKSWDFLNSY → VGSIISDHSS...RFKSKRRKTL
     1392-1601: Missing.
Isoform 3 (identifier: Q8TEU7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     747-747: D → AVGFYY
     1067-1067: R → RKKRWRSLG
     1489-1593: Missing.
Isoform 4 (identifier: Q8TEU7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1067-1067: R → RKKRWRSLG
Note: No experimental confirmation available.
Isoform 5 (identifier: Q8TEU7-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1067-1067: R → RKKRWRSLG
     1489-1593: Missing.
Isoform 6 (identifier: Q8TEU7-6)

The sequence of this isoform differs from the canonical sequence as follows:
     828-1601: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 16011601Rap guanine nucleotide exchange factor 6
PRO_0000068876

Regions

Domain412 – 526115N-terminal Ras-GEF Ref.3
Domain530 – 61586PDZ Ref.3
Domain749 – 83587Ras-associating Ref.3
Domain860 – 1088229Ras-GEF Ref.3
Nucleotide binding280 – 399120cNMP Ref.3
Compositional bias1229 – 1440212Ser-rich

Natural variations

Alternative sequence7471D → AVGFYY in isoform 3. Ref.3
VSP_050607
Alternative sequence828 – 1601774Missing in isoform 6.
VSP_045027
Alternative sequence10671R → RKKRWRSLG in isoform 3, isoform 4 and isoform 5. Ref.3
VSP_050608
Alternative sequence1249 – 1391143GYTLI…FLNSY → VGSIISDHSSKISGQSCPGI GGAYLQKKILQITRSTAKRT DSTEKATEENRDRTSCENTT RKRMTSPFRRLRERMLSRER LVNSQKEDTDHNQATESCEK VKDVGSNIKDEKGSAIFNSN SQGNSNTLNCFYTRFKSKRR KTL in isoform 2. Ref.1
VSP_050610
Alternative sequence1392 – 1601210Missing in isoform 2. Ref.1
VSP_050611
Alternative sequence1489 – 1593105Missing in isoform 3 and isoform 5. Ref.3
VSP_050609
Natural variant5701S → A.
Corresponds to variant rs3756293 [ dbSNP | Ensembl ].
VAR_057168
Natural variant5941A → P.
Corresponds to variant rs34112735 [ dbSNP | Ensembl ].
VAR_057169
Natural variant13531I → V.
Corresponds to variant rs7717835 [ dbSNP | Ensembl ].
VAR_057170
Natural variant14521Q → R. Ref.1 Ref.2 Ref.3
Corresponds to variant rs1291602 [ dbSNP | Ensembl ].
VAR_059793
Natural variant15591V → E.
Corresponds to variant rs1064539 [ dbSNP | Ensembl ].
VAR_057171

Experimental info

Sequence conflict5661K → E in AAL79915. Ref.1
Sequence conflict5661K → E in AAL79916. Ref.1
Sequence conflict6191L → P in AAL79915. Ref.1
Sequence conflict6191L → P in AAL79916. Ref.1
Sequence conflict6371E → K in AAL79915. Ref.1
Sequence conflict6371E → K in AAL79916. Ref.1
Sequence conflict6691V → A in AAL79915. Ref.1
Sequence conflict6691V → A in AAL79916. Ref.1
Sequence conflict7491P → A in AAI42965. Ref.5

Secondary structure

1 ............................. 1601
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PDZ-GEF2A) [UniParc].

Last modified November 30, 2010. Version 2.
Checksum: CF4C5407EB61EEE2

FASTA1,601179,423
        10         20         30         40         50         60 
MNSPVDPGAR QALRKKPPER TPEDLNTIYS YLHGMEILSN LREHQLRLMS ARARYERYSG 

        70         80         90        100        110        120 
NQVLFCSETI ARCWYILLSG SVLVKGSMVL PPCSFGKQFG GKRGCDCLVL EPSEMIVVEN 

       130        140        150        160        170        180 
AKDNEDSILQ REIPARQSRR RFRKINYKGE RQTITDDVEV NSYLSLPADL TKMHLTENPH 

       190        200        210        220        230        240 
PQVTHVSSSQ SGCSIASDSG SSSLSDIYQA TESEVGDVDL TRLPEGPVDS EDDEEEDEEI 

       250        260        270        280        290        300 
DRTDPLQGRD LVRECLEKEP ADKTDDDIEQ LLEFMHQLPA FANMTMSVRR ELCSVMIFEV 

       310        320        330        340        350        360 
VEQAGAIILE DGQELDSWYV ILNGTVEISH PDGKVENLFM GNSFGITPTL DKQYMHGIVR 

       370        380        390        400        410        420 
TKVDDCQFVC IAQQDYWRIL NHVEKNTHKV EEEGEIVMVH EHRELDRSGT RKGHIVIKAT 

       430        440        450        460        470        480 
PERLIMHLIE EHSIVDPTYI EDFLLTYRTF LESPLDVGIK LLEWFKIDSL RDKVTRIVLL 

       490        500        510        520        530        540 
WVNNHFNDFE GDPAMTRFLE EFEKNLEDTK MNGHLRLLNI ACAAKAKWRQ VVLQKASRES 

       550        560        570        580        590        600 
PLQFSLNGGS EKGFGIFVEG VEPGSKAADS GLKRGDQIME VNGQNFENIT FMKAVEILRN 

       610        620        630        640        650        660 
NTHLALTVKT NIFVFKELLF RTEQEKSGVP HIPKIAEKKS NRHSIQHVPG DIEQTSQEKG 

       670        680        690        700        710        720 
SKKVKANTVS GGRNKIRKIL DKTRFSILPP KLFSDGGLSQ SQDDSIVGTR HCRHSLAIMP 

       730        740        750        760        770        780 
IPGTLSSSSP DLLQPTTSML DFSNPSDIPD QVIRVFKVDQ QSCYIIISKD TTAKEVVFHA 

       790        800        810        820        830        840 
VHEFGLTGAS DTYSLCEVSV TPEGVIKQRR LPDQFSKLAD RIQLNGRYYL KNNMETETLC 

       850        860        870        880        890        900 
SDEDAQELVK ESQLSMLQLS TIEVATQLSM RDFDLFRNIE PTEYIDDLFK LNSKTGNTHL 

       910        920        930        940        950        960 
KRFEDIVNQE TFWVASEILT EANQLKRMKI IKHFIKIALH CRECKNFNSM FAIISGLNLA 

       970        980        990       1000       1010       1020 
SVARLRGTWE KLPSKYEKHL QDLQDIFDPS RNMAKYRNIL SSQSMQPPII PLFPVVKKDM 

      1030       1040       1050       1060       1070       1080 
TFLHEGNDSK VDGLVNFEKL RMISKEIRQV VRMTSANMDP AMMFRQRSLS QGSTNSNMLD 

      1090       1100       1110       1120       1130       1140 
VQGGAHKKRA RRSSLLNAKK LYEDAQMARK VKQYLSSLDV ETDEEKFQMM SLQWEPAYGT 

      1150       1160       1170       1180       1190       1200 
LTKNLSEKRS AKSSEMSPVP MRSAGQTTKA HLHQPHRVSQ VLQVPAVNLH PIRKKGQTKD 

      1210       1220       1230       1240       1250       1260 
PALNTSLPQK VLGTTEEISG KKHTEDTISV ASSLHSSPPA SPQGSPHKGY TLIPSAKSDN 

      1270       1280       1290       1300       1310       1320 
LSDSSHSEIS SRSSIVSNCS VDSMSAALQD ERCSSQALAV PESTGALEKT EHASGIGDHS 

      1330       1340       1350       1360       1370       1380 
QHGPGWTLLK PSLIKCLAVS SSVSNEEISQ EHIIIEAADS GRGSWTSCSS SSHDNFQSLP 

      1390       1400       1410       1420       1430       1440 
NPKSWDFLNS YRHTHLDDPI AEVEPTDSEP YSCSKSCSRT CGQCKGSLER KSWTSSSSLS 

      1450       1460       1470       1480       1490       1500 
DTYEPNYGTV KQRVLESTPA ESSEGLDPKD ATDPVYKTVT SSTEKGLIVY CVTSPKKDDR 

      1510       1520       1530       1540       1550       1560 
YREPPPTPPG YLGISLADLK EGPHTHLKPP DYSVAVQRSK MMHNSLSRLP PASLSSNLVA 

      1570       1580       1590       1600 
CVPSKIVTQP QRHNLQPFHP KLGDVTDADS EADENEQVSA V

« Hide

Isoform 2 (PDZ-GEF2B) [UniParc].

Checksum: 479E95ACE48D3938
Show »

FASTA1,391157,540
Isoform 3 [UniParc].

Checksum: 726CDBA718C65649
Show »

FASTA1,509169,500
Isoform 4 [UniParc].

Checksum: 2674B9180DEB7FCC
Show »

FASTA1,609180,435
Isoform 5 [UniParc].

Checksum: 52E76A090032E29F
Show »

FASTA1,504168,914
Isoform 6 [UniParc].

Checksum: 2EF5931EDE350449
Show »

FASTA82793,442

References

« Hide 'large scale' references
[1]"Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2."
Kuiperij H.B., de Rooij J., Rehmann H., van Triest M., Wittinghofer A., Bos J.L., Zwartkruis F.J.T.
Biochim. Biophys. Acta 1593:141-149(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, VARIANT ARG-1452.
[2]"A PDZ domain containing guanine exchange factor (GEF) interacts with the second PDZ domain of human PTP1e."
Banville D., Murthy K., Shen S., Clark K., Fortin Y.
Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT, VARIANT ARG-1452.
[3]"Identification and characterization of RA-GEF-2, a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras."
Gao X., Satoh T., Liao Y., Song C., Hu C.-D., Kariya K., Kataoka T.
J. Biol. Chem. 276:42219-42225(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT ARG-1452.
Tissue: Fetal brain.
[4]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4; 5 AND 6).
Tissue: Brain.
[6]"Solution structure of the cNMP-binding domain of human Rap guanine nucleotide exchange factor 6."
RIKEN structural genomics initiative (RSGI)
Submitted (JUN-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 265-386.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF478468 mRNA. Translation: AAL79915.1.
AF478469 mRNA. Translation: AAL79916.1.
AF478567 mRNA. Translation: AAM21637.1.
AF394782 mRNA. Translation: AAK83368.1.
AC004227 Genomic DNA. No translation available.
AC004622 Genomic DNA. No translation available.
AC008497 Genomic DNA. No translation available.
AC008695 Genomic DNA. No translation available.
AC026754 Genomic DNA. No translation available.
BC133703 mRNA. Translation: AAI33704.1.
BC142964 mRNA. Translation: AAI42965.1.
BC144627 mRNA. Translation: AAI44628.1.
IPIIPI00291839.
IPI00337694.
IPI00872771.
IPI00943807.
IPI00943887.
RefSeqNP_001157858.1. NM_001164386.1.
NP_001157859.1. NM_001164387.1.
NP_001157860.1. NM_001164388.1.
NP_001157861.1. NM_001164389.1.
NP_001157862.1. NM_001164390.1.
NP_057424.3. NM_016340.5.
UniGeneHs.483329.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2D93NMR-A265-385[»]
3LNYX-ray1.30B1596-1601[»]
ProteinModelPortalQ8TEU7.
SMRQ8TEU7. Positions 268-386.
ModBaseSearch...

Protein-protein interaction databases

IntActQ8TEU7. 2 interactions.
STRING9606.ENSP00000296859.

PTM databases

PhosphoSiteQ8TEU7.

Polymorphism databases

DMDM34395686.

Proteomic databases

PaxDbQ8TEU7.
PRIDEQ8TEU7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296859; ENSP00000296859; ENSG00000158987.
ENST00000307984; ENSP00000309298; ENSG00000158987.
ENST00000308008; ENSP00000311419; ENSG00000158987.
ENST00000507093; ENSP00000426081; ENSG00000158987.
ENST00000509018; ENSP00000421684; ENSG00000158987.
ENST00000510071; ENSP00000425389; ENSG00000158987.
GeneID51735.
KEGGhsa:51735.
UCSCuc003kvn.2. human.
uc003kvo.2. human.
uc003kvr.3. human.

Organism-specific databases

CTD51735.
GeneCardsGC05M130759.
H-InvDBHIX0005150.
HIX0078163.
HGNCHGNC:20655. RAPGEF6.
HPAHPA037982.
MIM610499. gene.
neXtProtNX_Q8TEU7.
PharmGKBPA134885793.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307777.
HOVERGENHBG056658.
KOK08020.
OMAIMSLQCE.
PhylomeDBQ8TEU7.

Gene expression databases

ArrayExpressQ8TEU7.
BgeeQ8TEU7.
CleanExHS_RAPGEF6.
GenevestigatorQ8TEU7.
GermOnlineENSG00000158987. Homo sapiens.

Family and domain databases

Gene3D1.10.840.10. 1 hit.
2.60.120.10. 2 hits.
InterProIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR001478. PDZ.
IPR000159. Ras-assoc.
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR008937. Ras_GEF.
IPR023578. Ras_GEF_dom.
IPR001895. RasGRF_CDC25.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PANTHERPTHR23113. PTHR23113. 1 hit.
PfamPF00027. cNMP_binding. 1 hit.
PF00595. PDZ. 1 hit.
PF00788. RA. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
SMARTSM00100. cNMP. 1 hit.
SM00228. PDZ. 1 hit.
SM00314. RA. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMSSF51206. cNMP_binding. 2 hits.
SSF50156. PDZ. 1 hit.
SSF48366. Ras_GEF. 1 hit.
PROSITEPS50042. CNMP_BINDING_3. 1 hit.
PS50106. PDZ. 1 hit.
PS50200. RA. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRAPGEF6. human.
EvolutionaryTraceQ8TEU7.
GenomeRNAi51735.
NextBio55804.
SOURCESearch...

Entry information

Entry nameRPGF6_HUMAN
AccessionPrimary (citable) accession number: Q8TEU7
Secondary accession number(s): A3KN82 expand/collapse secondary AC list , A5PLL6, B7ZML2, E9PDV7, Q8NI21, Q8TEU6, Q96PC1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: November 30, 2010
Last modified: April 3, 2013
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents