Q12967 (GNDS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ral guanine nucleotide dissociation stimulator
Short name=RalGDS

Alternative name(s):
Ral guanine nucleotide exchange factor
Short name=RalGEF

Gene names

Name:	RALGDS
Synonyms:	KIAA1308, RGF

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	914 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Stimulates the dissociation of GDP from the Ras-related RalA and RalB GTPases which allows GTP binding and activation of the GTPases. Interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap.
Subunit structure	Interacts with RIT1 and RIT2 By similarity.
Domain	The Ras-associating domain interacts with Ras.
Sequence similarities	Contains 1 N-terminal Ras-GEF domain. Contains 1 Ras-associating domain. Contains 1 Ras-GEF domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Ras protein signal transduction Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome regulation of small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	Ral guanyl-nucleotide exchange factor activity Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q12967-1)

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: Q12967-2)

The sequence of this isoform differs from the canonical sequence as follows:
     738-912: FWESASQSSP...KQKGLKIAKG → VTACPSPQYP...KEQPCKAPRS

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 914

914

Ral guanine nucleotide dissociation stimulator

PRO_0000068877

Regions

Domain

112 – 249

138

N-terminal Ras-GEF

Domain

386 – 648

263

Ras-GEF

Domain

798 – 885

88

Ras-associating

Compositional bias

714 – 717

4

Poly-Ser

Compositional bias

753 – 765

13

Poly-Ser

Compositional bias

839 – 844

6

Poly-Glu

Amino acid modifications

Modified residue

586

1

Phosphotyrosine Ref.6

Natural variations

Alternative sequence

738 – 912

175

FWESA…KIAKG → VTACPSPQYPFPSPHSKSMH GARKPWILNTASRRFPIWQL AWGAPTGQWDLLILPSPSVL GISLTVIPGDLRHQLSLQQH LVLLSLHHARGCHTHPQALC LRALQLQLRAAALQPAGGRL LYHPRQPGRGQWQHVQEHPG KPAGVAWVPPSTGGKCTLNT VHHPCPPGVYLVVGGEGQMS ARYRNEEGSDQGQGWPEGRG GGKEQPCKAPRS in isoform 2.

VSP_035301

Natural variant

496

1

R → L in a colorectal cancer sample; somatic mutation. Ref.9

VAR_035822

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

914

Helix Strand Turn

Details...

Beta strand

800 – 809

10

Beta strand

814 – 819

6

Helix

825 – 835

11

Turn

843 – 845

3

Beta strand

846 – 855

10

Beta strand

857 – 860

4

Beta strand

862 – 864

3

Helix

866 – 869

4

Beta strand

877 – 882

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 20, 2001. Version 2. Checksum: EA5A5CF25AF3D523	FASTA	914	100,607
	10 20 30 40 50 60 MVQRMWAEAA GPAGGAEPLF PGSRRSRSVW DAVRLEVGVP DSCPVVLHSF TQLDPDLPRP 70 80 90 100 110 120 ESSTQEIGEE LINGVIYSIS LRKVQLHHGG NKGQRWLGYE NESALNLYET CKVRTVKAGT 130 140 150 160 170 180 LEKLVEHLVP AFQGSDLSYV TIFLCTYRAF TTTQQVLDLL FKRYGRCDAL TASSRYGCIL 190 200 210 220 230 240 PYSDEDGGPQ DQLKNAISSI LGTWLDQYSE DFCQPPDFPC LKQLVAYVQL NMPGSDLERR 250 260 270 280 290 300 AHLLLAQLEH SEPIEAEPEA LSPVPALKPT PELELALTPA RAPSPVPAPA PEPEPAPTPA 310 320 330 340 350 360 PGSELEVAPA PAPELQQAPE PAVGLESAPA PALELEPAPE QDPAPSQTLE LEPAPAPVPS 370 380 390 400 410 420 LQPSWPSPVV AENGLSEEKP HLLVFPPDLV AEQFTLMDAE LFKKVVPYHC LGSIWSQRDK 430 440 450 460 470 480 KGKEHLAPTI RATVTQFNSV ANCVITTCLG NRSTKAPDRA RVVEHWIEVA RECRILKNFS 490 500 510 520 530 540 SLYAILSALQ SNSIHRLKKT WEDVSRDSFR IFQKLSEIFS DENNYSLSRE LLIKEGTSKF 550 560 570 580 590 600 ATLEMNPKRA QKRPKETGII QGTVPYLGTF LTDLVMLDTA MKDYLYGRLI NFEKRRKEFE 610 620 630 640 650 660 VIAQIKLLQS ACNNYSIAPD EQFGAWFRAV ERLSETESYN LSCELEPPSE SASNTLRTKK 670 680 690 700 710 720 NTAIVKRWSD RQAPSTELST SGSSHSKSCD QLRCGPYLSS GDIADALSVH SAGSSSSDVE 730 740 750 760 770 780 EINISFVPES PDGQEKKFWE SASQSSPETS GISSASSSTS SSSASTTPVA ATRTHKRSVS 790 800 810 820 830 840 GLCNSSSALP LYNQQVGDCC IIRVSLDVDN GNMYKSILVT SQDKAPAVIR KAMDKHNLEE 850 860 870 880 890 900 EEPEDYELLQ ILSDDRKLKI PENANVFYAM NSTANYDFVL KKRTFTKGVK VKHGASSTLP 910 RMKQKGLKIA KGIF
	Isoform 2 [UniParc]. Checksum: 18593341C7EB71D5	FASTA	951	104,602
	10 20 30 40 50 60 MVQRMWAEAA GPAGGAEPLF PGSRRSRSVW DAVRLEVGVP DSCPVVLHSF TQLDPDLPRP 70 80 90 100 110 120 ESSTQEIGEE LINGVIYSIS LRKVQLHHGG NKGQRWLGYE NESALNLYET CKVRTVKAGT 130 140 150 160 170 180 LEKLVEHLVP AFQGSDLSYV TIFLCTYRAF TTTQQVLDLL FKRYGRCDAL TASSRYGCIL 190 200 210 220 230 240 PYSDEDGGPQ DQLKNAISSI LGTWLDQYSE DFCQPPDFPC LKQLVAYVQL NMPGSDLERR 250 260 270 280 290 300 AHLLLAQLEH SEPIEAEPEA LSPVPALKPT PELELALTPA RAPSPVPAPA PEPEPAPTPA 310 320 330 340 350 360 PGSELEVAPA PAPELQQAPE PAVGLESAPA PALELEPAPE QDPAPSQTLE LEPAPAPVPS 370 380 390 400 410 420 LQPSWPSPVV AENGLSEEKP HLLVFPPDLV AEQFTLMDAE LFKKVVPYHC LGSIWSQRDK 430 440 450 460 470 480 KGKEHLAPTI RATVTQFNSV ANCVITTCLG NRSTKAPDRA RVVEHWIEVA RECRILKNFS 490 500 510 520 530 540 SLYAILSALQ SNSIHRLKKT WEDVSRDSFR IFQKLSEIFS DENNYSLSRE LLIKEGTSKF 550 560 570 580 590 600 ATLEMNPKRA QKRPKETGII QGTVPYLGTF LTDLVMLDTA MKDYLYGRLI NFEKRRKEFE 610 620 630 640 650 660 VIAQIKLLQS ACNNYSIAPD EQFGAWFRAV ERLSETESYN LSCELEPPSE SASNTLRTKK 670 680 690 700 710 720 NTAIVKRWSD RQAPSTELST SGSSHSKSCD QLRCGPYLSS GDIADALSVH SAGSSSSDVE 730 740 750 760 770 780 EINISFVPES PDGQEKKVTA CPSPQYPFPS PHSKSMHGAR KPWILNTASR RFPIWQLAWG 790 800 810 820 830 840 APTGQWDLLI LPSPSVLGIS LTVIPGDLRH QLSLQQHLVL LSLHHARGCH THPQALCLRA 850 860 870 880 890 900 LQLQLRAAAL QPAGGRLLYH PRQPGRGQWQ HVQEHPGKPA GVAWVPPSTG GKCTLNTVHH 910 920 930 940 950 PCPPGVYLVV GGEGQMSARY RNEEGSDQGQ GWPEGRGGGK EQPCKAPRSI F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1." Humphrey D., Kwiatkowska J., Henske E.P., Haines J.L., Halley D., van Slegtenhorst M., Kwiatkowski D.J. Ann. Hum. Genet. 61:299-305(1997) [PubMed: 9365783] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed: 10718198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 205-912 (ISOFORM 2). Tissue: Brain.
[5]	"Activated Ras interacts with the Ral guanine nucleotide dissociation stimulator." Hofer F., Fields S., Schneider C., Martin G.S. Proc. Natl. Acad. Sci. U.S.A. 91:11089-11093(1994) [PubMed: 7972015] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 587-914 (ISOFORM 1).
[6]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-586, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Structure of the Ras-binding domain of RalGEF and implications for Ras binding and signalling." Geyer M., Herrmann C., Wohlgemuth S., Wittinghofer A., Kalbitzer H.R. Nat. Struct. Biol. 4:694-699(1997) [PubMed: 9302994] [Abstract] Cited for: STRUCTURE BY NMR OF 788-884.
[8]	"High-resolution structure of the RA-domain of human RalGDS and a dynamics study of its binding loop to Ras." Mueller T.D., Handel L., Schmieder P., Oschkinat H. Submitted (MAR-1999) to the PDB data bank Cited for: STRUCTURE BY NMR OF 771-886.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-496.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF295773 mRNA. Translation: AAG02122.1.
AF295775, AF295778 Genomic DNA. Translation: AAG10221.1.
AF295780 Genomic DNA. Translation: AAG10225.1.
AL162417 Genomic DNA. Translation: CAI13415.1.
CH471090 Genomic DNA. Translation: EAW88042.1.
AB037729 mRNA. Translation: BAA92546.1.
U14417 mRNA. Translation: AAA52360.1.

IPI

IPI00290395.
IPI00902660.

PIR

I38853.

RefSeq

NP_006257.1. NM_006266.2.

UniGene

Hs.106185.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RAX	NMR	-	A	780-886	[»]
2B3A	NMR	-	A	798-884	[»]
2RGF	NMR	-	A	788-884	[»]
3KH0	X-ray	2.10	A/B	793-914	[»]

ProteinModelPortal

Q12967.

SMR

Q12967. Positions 385-648, 793-885.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31375N.

IntAct

Q12967. 7 interactions.

STRING

Q12967.

PTM databases

PhosphoSite

Q12967.

Polymorphism databases

DMDM

14549162.

Proteomic databases

PRIDE

Q12967.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372050; ENSP00000361120; ENSG00000160271.

GeneID

5900.

KEGG

hsa:5900.

UCSC

uc004cco.1. human.

Organism-specific databases

CTD

5900.

GeneCards

GC09M135973.

H-InvDB

HIX0018166.

HGNC

HGNC:9842. RALGDS.

MIM

601619. gene.

neXtProt

NX_Q12967.

PharmGKB

PA34200.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06006.

HOVERGEN

HBG005864.

OMA

KVKHGAS.

OrthoDB

EOG4KWJSF.

PhylomeDB

Q12967.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q12967.

Bgee

Q12967.

CleanEx

HS_RALGDS.

Genevestigator

Q12967.

GermOnline

ENSG00000160271. Homo sapiens.

Family and domain databases

InterPro

IPR015758. RalGDS.
IPR000159. Ras-assoc.
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

K08732.

PANTHER

PTHR23113:SF35. RalGDS. 1 hit.
PTHR23113. Ras_GEF. 1 hit.

Pfam

PF00788. RA. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]

SMART

SM00314. RA. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]

SUPFAM

SSF48366. Ras_GEF. 1 hit.

PROSITE

PS50200. RA. 1 hit.
PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

22950.

SOURCE

Search...

Entry information

Entry name

GNDS_HUMAN

Accession

Primary (citable) accession number: Q12967
Secondary accession number(s): Q5T7V4 , Q9HAX7, Q9HAY1, Q9HCT1, Q9P2N8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	June 20, 2001
Last modified:	January 25, 2012
This is version 115 of the entry and version 2 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.