P11233 (RALA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-related protein Ral-A

Gene names

Name:	RALA
Synonyms:	RAL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	206 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Alternate 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 co-localizes 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 process	Cell cycle Cell division Exocytosis Host-virus interaction
Cellular component	Cell membrane Membrane
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Prenylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Traceable author statement. Source: Reactome actin cytoskeleton reorganization Inferred from direct assay PubMed 10051605. Source: BHF-UCL cell cycle Inferred from electronic annotation. Source: UniProtKB-KW 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 raft localization Inferred from direct assay Ref.15. Source: UniProtKB nerve growth factor 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 virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cell surface Inferred from direct assay Ref.14. Source: UniProtKB cleavage furrow Inferred from direct assay Ref.13. Source: UniProtKB midbody Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay Ref.12. Source: UniProtKB
Molecular_function	Edg-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
Exoc2	O54921	2	EBI-1036803,EBI-1036795	From a different organism.
PPP2R1B	P30154	6	EBI-1036803,EBI-357094

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 203

203

Ras-related protein Ral-A

PRO_0000082693

Propeptide

204 – 206

3

Removed in mature form By similarity

PRO_0000281344

Regions

Nucleotide binding

24 – 29

6

GTP

Nucleotide binding

40 – 46

7

GTP

Nucleotide binding

127 – 130

4

GTP

Motif

43 – 51

9

Effector region By similarity

Amino acid modifications

Modified residue

203

1

Cysteine methyl ester

Lipidation

203

1

S-geranylgeranyl cysteine Ref.8 Ref.12

Experimental info

Mutagenesis

47

1

K → E: Strongly reduces interaction with EXOC8. Ref.17

Mutagenesis

47

1

K → I: No effect on interaction with EXOC8. Ref.17

Mutagenesis

48

1

A → W: Strongly reduces interaction with EXOC8. Ref.17

Mutagenesis

50

1

S → W: Strongly reduces interaction with EXOC8. Ref.17

Mutagenesis

52

1

R → A: Strongly reduces interaction with EXOC8. Ref.17

Mutagenesis

52

1

R → W: No effect on interaction with EXOC8. Ref.17

Mutagenesis

81

1

N → A: No effect on interaction with EXOC8. Ref.17

Mutagenesis

81

1

N → R: Strongly reduces interaction with EXOC8. Ref.17

Mutagenesis

203

1

C → S: Loss of geranylgeranylation and membrane localization. Ref.12

Mutagenesis

206

1

L → 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 conflict

1 – 2

2

MA → MVDYL Ref.2

Sequence conflict

1 – 2

2

MA → MVDYL Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

206

Helix Strand Turn

Details...

Beta strand

14 – 20

7

Helix

27 – 36

10

Beta strand

49 – 57

9

Beta strand

60 – 68

9

Helix

76 – 85

10

Beta strand

87 – 94

8

Helix

98 – 115

18

Beta strand

122 – 127

6

Helix

129 – 134

6

Helix

139 – 148

10

Beta strand

152 – 155

4

Turn

158 – 160

3

Helix

164 – 180

17

Sequences

	Sequence		Length	Mass (Da)
	P11233 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 6974341EA18C1975	FASTA	206	23,567
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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.

IPI

IPI00217519.

PIR

TVHUAA. S04596.

RefSeq

NP_005393.2. NM_005402.3.

UniGene

Hs.6906.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UAD	X-ray	2.10	A/B	9-183	[»]
1ZC3	X-ray	2.00	A/C	9-183	[»]
1ZC4	X-ray	2.50	A/C	9-183	[»]
2A78	X-ray	1.81	A	9-183	[»]
2A9K	X-ray	1.73	A	9-183	[»]
2BOV	X-ray	2.66	A	1-206	[»]

ProteinModelPortal

P11233.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11233. 5 interactions.

MINT

MINT-238571.

STRING

9606.ENSP00000005257.

PTM databases

PhosphoSite

P11233.

Polymorphism databases

DMDM

131834.

Proteomic databases

PaxDb

P11233.

PRIDE

P11233.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000005257; ENSP00000005257; ENSG00000006451.

GeneID

5898.

KEGG

hsa:5898.

UCSC

uc003thd.3. human.

Organism-specific databases

CTD

5898.

GeneCards

GC07P039663.

HGNC

HGNC:9839. RALA.

MIM

179550. gene.

neXtProt

NX_P11233.

PharmGKB

PA34197.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOGENOM

HOG000233973.

HOVERGEN

HBG009351.

InParanoid

P11233.

KO

K07834.

OMA

SKATSGR.

OrthoDB

EOG4HX524.

PhylomeDB

P11233.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6_traffickingpathway. Arf6 trafficking events.
foxopathway. FoxO family signaling.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.

Reactome

REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

P11233.

Bgee

P11233.

CleanEx

HS_RALA.

Genevestigator

P11233.

GermOnline

ENSG00000006451. Homo sapiens.

Family and domain databases

InterPro

IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]

PANTHER

PTHR24070. PTHR24070. 1 hit.

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00173. RAS. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51421. RAS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

Rala. human.

EvolutionaryTrace

P11233.

GenomeRNAi

5898.

NextBio

22942.

SOURCE

Search...

Entry information

Entry name

RALA_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 142 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.