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Protein

Ras-related protein Ral-A

Gene

RALA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 GRK2 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells.3 Publications

Enzyme regulationi

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).

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi24 – 29GTP2 Publications6
Nucleotide bindingi40 – 46GTP2 Publications7
Nucleotide bindingi127 – 130GTP2 Publications4

GO - Molecular functioni

  • ATPase binding Source: UniProtKB
  • Edg-2 lysophosphatidic acid receptor binding Source: UniProtKB
  • GDP binding Source: UniProtKB
  • GTPase activity Source: Ensembl
  • GTP binding Source: UniProtKB
  • myosin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton reorganization Source: BHF-UCL
  • chemotaxis Source: ProtInc
  • cytokinesis Source: UniProtKB
  • exocytosis Source: UniProtKB-KW
  • membrane organization Source: Reactome
  • membrane raft localization Source: UniProtKB
  • neural tube closure Source: Ensembl
  • positive regulation of filopodium assembly Source: BHF-UCL
  • Ras protein signal transduction Source: InterPro
  • regulation of exocytosis Source: UniProtKB
  • signal transduction Source: ProtInc
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Exocytosis, Host-virus interaction

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006451-MONOMER.
ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
R-HSA-171007. p38MAPK events.
SIGNORiP11233.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Ral-A
Gene namesi
Name:RALA
Synonyms:RAL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:9839. RALA.

Subcellular locationi

  • 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.

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cleavage furrow Source: UniProtKB
  • cytoplasmic vesicle membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • midbody Source: UniProtKB-SubCell
  • myelin sheath Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi47K → E: Strongly reduces interaction with EXOC8. 1 Publication1
Mutagenesisi47K → I: No effect on interaction with EXOC8. 1 Publication1
Mutagenesisi48A → W: Strongly reduces interaction with EXOC8. 1 Publication1
Mutagenesisi50S → W: Strongly reduces interaction with EXOC8. 1 Publication1
Mutagenesisi52R → A: Strongly reduces interaction with EXOC8. 1 Publication1
Mutagenesisi52R → W: No effect on interaction with EXOC8. 1 Publication1
Mutagenesisi81N → A: No effect on interaction with EXOC8. 1 Publication1
Mutagenesisi81N → R: Strongly reduces interaction with EXOC8. 1 Publication1
Mutagenesisi203C → S: Loss of geranylgeranylation and membrane localization. 1 Publication1
Mutagenesisi206L → 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. 1 Publication1

Organism-specific databases

DisGeNETi5898.
OpenTargetsiENSG00000006451.
PharmGKBiPA34197.

Polymorphism and mutation databases

BioMutaiRALA.
DMDMi131834.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000826931 – 203Ras-related protein Ral-AAdd BLAST203
PropeptideiPRO_0000281344204 – 206Removed in mature formBy similarity3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei203Cysteine methyl esterBy similarity1
Lipidationi203S-geranylgeranyl cysteine2 Publications1

Post-translational modificationi

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).2 Publications

Keywords - PTMi

Lipoprotein, Methylation, Prenylation

Proteomic databases

EPDiP11233.
MaxQBiP11233.
PaxDbiP11233.
PeptideAtlasiP11233.
PRIDEiP11233.

PTM databases

iPTMnetiP11233.
PhosphoSitePlusiP11233.
SwissPalmiP11233.

Expressioni

Inductioni

Activated in an LPA-dependent manner by LPAR1 and in an LPA-independent manner by LPAR2.1 Publication

Gene expression databases

BgeeiENSG00000006451.
CleanExiHS_RALA.
ExpressionAtlasiP11233. baseline and differential.
GenevisibleiP11233. HS.

Organism-specific databases

HPAiHPA047037.
HPA065232.

Interactioni

Subunit structurei

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 GRK2 in response to LPAR1 activation. RALA and GRK2 mutually inhibit each other's binding to LPAR1.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Exoc2O549212EBI-1036803,EBI-1036795From a different organism.
PPP2R1BP301546EBI-1036803,EBI-357094

GO - Molecular functioni

  • ATPase binding Source: UniProtKB
  • Edg-2 lysophosphatidic acid receptor binding Source: UniProtKB
  • myosin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111834. 66 interactors.
IntActiP11233. 32 interactors.
MINTiMINT-238571.
STRINGi9606.ENSP00000005257.

Structurei

Secondary structure

1206
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi14 – 20Combined sources7
Helixi27 – 36Combined sources10
Beta strandi49 – 57Combined sources9
Beta strandi60 – 68Combined sources9
Helixi76 – 85Combined sources10
Beta strandi87 – 94Combined sources8
Helixi98 – 115Combined sources18
Beta strandi122 – 127Combined sources6
Helixi129 – 134Combined sources6
Helixi139 – 148Combined sources10
Beta strandi152 – 155Combined sources4
Turni158 – 160Combined sources3
Helixi164 – 180Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
DisProtiDP00581.
ProteinModelPortaliP11233.
SMRiP11233.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11233.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi43 – 51Effector region9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133672.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP11233.
KOiK07834.
OMAiSECQSRA.
OrthoDBiEOG091G0UAU.
PhylomeDBiP11233.
TreeFamiTF312796.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR028412. Ral.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PTHR24070:SF174. PTHR24070:SF174. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P11233-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAANKPKGQN SLALHKVIMV GSGGVGKSAL TLQFMYDEFV EDYEPTKADS
60 70 80 90 100
YRKKVVLDGE EVQIDILDTA GQEDYAAIRD NYFRSGEGFL CVFSITEMES
110 120 130 140 150
FAATADFREQ ILRVKEDENV PFLLVGNKSD LEDKRQVSVE EAKNRAEQWN
160 170 180 190 200
VNYVETSAKT RANVDKVFFD LMREIRARKM EDSKEKNGKK KRKSLAKRIR

ERCCIL
Length:206
Mass (Da):23,567
Last modified:July 1, 1989 - v1
Checksum:i6974341EA18C1975
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 2MA → MVDYL (PubMed:2550440).Curated2
Sequence conflicti1 – 2MA → MVDYL (Ref. 3) Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5460.1.
PIRiS04596. TVHUAA.
RefSeqiNP_005393.2. NM_005402.3.
XP_006715825.1. XM_006715762.2.
XP_011513768.1. XM_011515466.1.
UniGeneiHs.6906.

Genome annotation databases

EnsembliENST00000005257; ENSP00000005257; ENSG00000006451.
GeneIDi5898.
KEGGihsa:5898.
UCSCiuc003thd.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5460.1.
PIRiS04596. TVHUAA.
RefSeqiNP_005393.2. NM_005402.3.
XP_006715825.1. XM_006715762.2.
XP_011513768.1. XM_011515466.1.
UniGeneiHs.6906.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
DisProtiDP00581.
ProteinModelPortaliP11233.
SMRiP11233.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111834. 66 interactors.
IntActiP11233. 32 interactors.
MINTiMINT-238571.
STRINGi9606.ENSP00000005257.

PTM databases

iPTMnetiP11233.
PhosphoSitePlusiP11233.
SwissPalmiP11233.

Polymorphism and mutation databases

BioMutaiRALA.
DMDMi131834.

Proteomic databases

EPDiP11233.
MaxQBiP11233.
PaxDbiP11233.
PeptideAtlasiP11233.
PRIDEiP11233.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000005257; ENSP00000005257; ENSG00000006451.
GeneIDi5898.
KEGGihsa:5898.
UCSCiuc003thd.4. human.

Organism-specific databases

CTDi5898.
DisGeNETi5898.
GeneCardsiRALA.
HGNCiHGNC:9839. RALA.
HPAiHPA047037.
HPA065232.
MIMi179550. gene.
neXtProtiNX_P11233.
OpenTargetsiENSG00000006451.
PharmGKBiPA34197.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133672.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP11233.
KOiK07834.
OMAiSECQSRA.
OrthoDBiEOG091G0UAU.
PhylomeDBiP11233.
TreeFamiTF312796.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006451-MONOMER.
ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
R-HSA-171007. p38MAPK events.
SIGNORiP11233.

Miscellaneous databases

ChiTaRSiRALA. human.
EvolutionaryTraceiP11233.
GeneWikiiRALA.
GenomeRNAii5898.
PROiP11233.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000006451.
CleanExiHS_RALA.
ExpressionAtlasiP11233. baseline and differential.
GenevisibleiP11233. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR028412. Ral.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PTHR24070:SF174. PTHR24070:SF174. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRALA_HUMAN
AccessioniPrimary (citable) accession number: P11233
Secondary accession number(s): A4D1W3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 30, 2016
This is version 182 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.