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P11233 (RALA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ras-related protein Ral-A
Gene names
Name:RALA
Synonyms:RAL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length206 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. Plays a role in the early stages of cytokinesis and is required to tether the exocyst to the cytokinetic furrow. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. Key regulator of LPAR1 signaling and competes with ADRBK1 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells. Ref.13 Ref.14 Ref.15

Enzyme regulation

Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).

Subunit structure

Interacts with RALBP1 via its effector domain. Interacts with EXOC8 and EXOC2. EXOC2 and EXOC8 have overlapping binding sites and compete for RALA binding. Interacts with Clostridium exoenzyme C3. Interacts with RALGPS1. Interacts with LPAR1 and LPAR2. Interacts with ADRBK1 in response to LPAR1 activation. RALA and ADRBK1 mutually inhibit each other's binding to LPAR1. Ref.9 Ref.10 Ref.11 Ref.14 Ref.17

Subcellular location

Cell surface. Cell membrane; Lipid-anchor; Cytoplasmic side. Cleavage furrow. Midbody. Note: Prior to LPA treatment found predominantly at the cell surface and in the presence of LPA colocalizes with LPAR1 and LPAR2 in the endocytic vesicles. During early cytokinesis localizes at the cleavage furrow membrane. Colocalizes with EXOC2 at the early midbody ring and persists there till maturation of the midbody. Ref.12 Ref.13 Ref.14

Induction

Activated in an LPA-dependent manner by LPAR1 and in an LPA-independent manner by LPAR2. Ref.14

Post-translational modification

Prenylation is essential for membrane localization. The geranylgeranylated form and the farnesylated mutant does not undergo alternative prenylation in response to geranylgeranyltransferase I inhibitors (GGTIs) and farnesyltransferase I inhibitors (FTIs).

Sequence similarities

Belongs to the small GTPase superfamily. Ras family.

Ontologies

Keywords
   Biological processCell cycle
Cell division
Exocytosis
Host-virus interaction
   Cellular componentCell membrane
Membrane
   LigandGTP-binding
Nucleotide-binding
   PTMLipoprotein
Methylation
Prenylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRas protein signal transduction

Traceable author statement. Source: Reactome

actin cytoskeleton reorganization

Inferred from direct assay PubMed 10051605. Source: BHF-UCL

chemotaxis

Traceable author statement PubMed 10848592. Source: ProtInc

cytokinesis

Inferred from direct assay Ref.13. Source: UniProtKB

exocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

membrane organization

Traceable author statement. Source: Reactome

membrane raft localization

Inferred from direct assay Ref.15. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of filopodium assembly

Inferred from direct assay PubMed 10051605. Source: BHF-UCL

regulation of exocytosis

Inferred from direct assay Ref.15. Source: UniProtKB

signal transduction

Traceable author statement PubMed 10848592Ref.2. Source: ProtInc

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcell surface

Inferred from direct assay Ref.14. Source: UniProtKB

cleavage furrow

Inferred from direct assay Ref.13. Source: UniProtKB

cytoplasmic vesicle membrane

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708PubMed 20458337. Source: UniProt

midbody

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay Ref.12. Source: UniProtKB

   Molecular_functionEdg-2 lysophosphatidic acid receptor binding

Inferred from direct assay Ref.14. Source: UniProtKB

GTP binding

Traceable author statement Ref.2. Source: ProtInc

GTPase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Exoc2O549212EBI-1036803,EBI-1036795From a different organism.
PPP2R1BP301546EBI-1036803,EBI-357094

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 203203Ras-related protein Ral-A
PRO_0000082693
Propeptide204 – 2063Removed in mature form By similarity
PRO_0000281344

Regions

Nucleotide binding24 – 296GTP
Nucleotide binding40 – 467GTP
Nucleotide binding127 – 1304GTP
Motif43 – 519Effector region

Amino acid modifications

Modified residue2031Cysteine methyl ester By similarity
Lipidation2031S-geranylgeranyl cysteine Ref.8 Ref.12

Experimental info

Mutagenesis471K → E: Strongly reduces interaction with EXOC8. Ref.17
Mutagenesis471K → I: No effect on interaction with EXOC8. Ref.17
Mutagenesis481A → W: Strongly reduces interaction with EXOC8. Ref.17
Mutagenesis501S → W: Strongly reduces interaction with EXOC8. Ref.17
Mutagenesis521R → A: Strongly reduces interaction with EXOC8. Ref.17
Mutagenesis521R → W: No effect on interaction with EXOC8. Ref.17
Mutagenesis811N → A: No effect on interaction with EXOC8. Ref.17
Mutagenesis811N → R: Strongly reduces interaction with EXOC8. Ref.17
Mutagenesis2031C → S: Loss of geranylgeranylation and membrane localization. Ref.12
Mutagenesis2061L → S: Converts geranyl-geranylation to farnesylation. No effect on membrane localization. Fails to deflect GGTI-induced apoptosis of adherent cell cultures, but rescues anchorage-independent cell proliferation. Ref.12
Sequence conflict1 – 22MA → MVDYL Ref.2
Sequence conflict1 – 22MA → MVDYL Ref.3

Secondary structure

........................... 206
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11233 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 6974341EA18C1975

FASTA20623,567
        10         20         30         40         50         60 
MAANKPKGQN SLALHKVIMV GSGGVGKSAL TLQFMYDEFV EDYEPTKADS YRKKVVLDGE 

        70         80         90        100        110        120 
EVQIDILDTA GQEDYAAIRD NYFRSGEGFL CVFSITEMES FAATADFREQ ILRVKEDENV 

       130        140        150        160        170        180 
PFLLVGNKSD LEDKRQVSVE EAKNRAEQWN VNYVETSAKT RANVDKVFFD LMREIRARKM 

       190        200 
EDSKEKNGKK KRKSLAKRIR ERCCIL 

« Hide

References

« Hide 'large scale' references
[1]"Coding sequences of human ralA and ralB cDNAs."
Chardin P., Tavitian A.
Nucleic Acids Res. 17:4380-4380(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Identification of the ral and rac1 gene products, low molecular mass GTP-binding proteins from human platelets."
Polakis P.G., Weber R.F., Nevins B., Didsbury J.R., Evans T., Snyderman R.
J. Biol. Chem. 264:16383-16389(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Platelet.
[3]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[4]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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].
[6]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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].
Tissue: Eye.
[8]"Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins encoded by rac1, rac2, and ralA."
Kinsella B.T., Erdman R.A., Maltese W.A.
J. Biol. Chem. 266:9786-9794(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: ISOPRENYLATION AT CYS-203.
[9]"Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity."
Jullien-Flores V., Dorseuil O., Romero F., Letourneur F., Saragosti S., Berger R., Tavitian A., Gacon G., Camonis J.H.
J. Biol. Chem. 270:22473-22477(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RALBP1.
[10]"Identification and characterization of a new family of guanine nucleotide exchange factors for the ras-related GTPase Ral."
Rebhun J.F., Chen H., Quilliam L.A.
J. Biol. Chem. 275:13406-13410(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RALGPS1.
[11]"Ral GTPases regulate exocyst assembly through dual subunit interactions."
Moskalenko S., Tong C., Rosse C., Mirey G., Formstecher E., Daviet L., Camonis J., White M.A.
J. Biol. Chem. 278:51743-51748(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXOC8.
[12]"Geranylgeranyltransferase I inhibitors target RalB to inhibit anchorage-dependent growth and induce apoptosis and RalA to inhibit anchorage-independent growth."
Falsetti S.C., Wang D.A., Peng H., Carrico D., Cox A.D., Der C.J., Hamilton A.D., Sebti S.M.
Mol. Cell. Biol. 27:8003-8014(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-203, MUTAGENESIS OF CYS-203 AND LEU-206.
[13]"Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs."
Cascone I., Selimoglu R., Ozdemir C., Del Nery E., Yeaman C., White M., Camonis J.
EMBO J. 27:2375-2387(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]"Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK."
Aziziyeh A.I., Li T.T., Pape C., Pampillo M., Chidiac P., Possmayer F., Babwah A.V., Bhattacharya M.
Cell. Signal. 21:1207-1217(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, INTERACTION WITH LPAR1; LPAR2 AND ADRBK1.
[15]"RalA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling."
Balasubramanian N., Meier J.A., Scott D.W., Norambuena A., White M.A., Schwartz M.A.
Curr. Biol. 20:75-79(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase."
Jin R., Junutula J.R., Matern H.T., Ervin K.E., Scheller R.H., Brunger A.T.
EMBO J. 24:2064-2074(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 9-183 IN COMPLEX WITH EXOC8 AND GTP ANALOG, INTERACTION WITH EXOC2, MUTAGENESIS OF LYS-47; ALA-48; SER-50; ARG-52 AND ASN-81.
[18]"Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme."
Pautsch A., Vogelsgesang M., Traenkle J., Herrmann C., Aktories K.
EMBO J. 24:3670-3680(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 9-183 IN COMPLEX WITH GTP AND CLOSTRIDIUM EXOENZYME C3.
[19]"Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase."
Holbourn K.P., Sutton J.M., Evans H.R., Shone C.C., Acharya K.R.
Proc. Natl. Acad. Sci. U.S.A. 102:5357-5362(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) IN COMPLEX WITH GTP AND CLOSTRIDIUM EXOENZYME C3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15014 mRNA. Translation: CAA33118.1.
M29893 mRNA. Translation: AAA36542.1.
AF493910 mRNA. Translation: AAM12624.1.
AC004837 Genomic DNA. No translation available.
CH236951 Genomic DNA. Translation: EAL23994.1.
CH471073 Genomic DNA. Translation: EAW94123.1.
BC039858 mRNA. Translation: AAH39858.1.
PIRTVHUAA. S04596.
RefSeqNP_005393.2. NM_005402.3.
UniGeneHs.6906.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UADX-ray2.10A/B9-183[»]
1ZC3X-ray2.00A/C9-183[»]
1ZC4X-ray2.50A/C9-183[»]
2A78X-ray1.81A9-183[»]
2A9KX-ray1.73A9-183[»]
2BOVX-ray2.66A1-206[»]
DisProtDP00581.
ProteinModelPortalP11233.
SMRP11233. Positions 13-182.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111834. 39 interactions.
IntActP11233. 7 interactions.
MINTMINT-238571.
STRING9606.ENSP00000005257.

PTM databases

PhosphoSiteP11233.

Polymorphism databases

DMDM131834.

Proteomic databases

PaxDbP11233.
PRIDEP11233.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000005257; ENSP00000005257; ENSG00000006451.
GeneID5898.
KEGGhsa:5898.
UCSCuc003thd.3. human.

Organism-specific databases

CTD5898.
GeneCardsGC07P039663.
HGNCHGNC:9839. RALA.
MIM179550. gene.
neXtProtNX_P11233.
PharmGKBPA34197.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233973.
HOVERGENHBG009351.
InParanoidP11233.
KOK07834.
OMADRCKKRR.
OrthoDBEOG7QVM41.
PhylomeDBP11233.
TreeFamTF312796.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpressP11233.
BgeeP11233.
CleanExHS_RALA.
GenevestigatorP11233.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR028412. Ral.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERPTHR24070. PTHR24070. 1 hit.
PTHR24070:SF3. PTHR24070:SF3. 1 hit.
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRala. human.
EvolutionaryTraceP11233.
GeneWikiRALA.
GenomeRNAi5898.
NextBio22942.
PROP11233.
SOURCESearch...

Entry information

Entry nameRALA_HUMAN
AccessionPrimary (citable) accession number: P11233
Secondary accession number(s): A4D1W3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 152 of the entry and version 1 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM