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Protein

Ras-related protein Ral-A

Gene

RALA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling (PubMed:20005108). 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 (PubMed:19306925). During mitosis, supports the stabilization and elongation of the intracellular bridge between dividing cells. Cooperates with EXOC2 to recruit other components of the exocyst to the early midbody (PubMed:18756269).3 Publications

Activity 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: InterPro
  • GTP binding Source: UniProtKB
  • myosin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processCell cycle, Cell division, Exocytosis
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-171007 p38MAPK events
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
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

EuPathDBiHostDB:ENSG00000006451.7
HGNCiHGNC:9839 RALA
MIMi179550 gene
neXtProtiNX_P11233

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1 – 11Missing : Impaired cytokinesis, as shown by increased number of binucleate cells. Impaired cytokinesis; when associated with L-72. 1 PublicationAdd BLAST11
Mutagenesisi23G → V: Impaired cytokinesis, as shown by increased number of binucleate cells. No effect on interaction with EXOC2 and EXOC8. No effect on cytokinesis; when associated with R-38 or W-48. Decreased interaction with EXOC2 and EXOC8; when associated with R-38 or W-48. 1 Publication1
Mutagenesisi38E → R: Impaired cytokinesis, as shown by increased number of binucleate cells. No effect on cytokinesis; when associated with V-23. Decreased interaction with EXOC2 and EXOC8; when associated with V-23. 1 Publication1
Mutagenesisi47K → E: Strongly reduces interaction with EXOC8. 1 Publication1
Mutagenesisi47K → I: No effect on interaction with EXOC8. 1 Publication1
Mutagenesisi48A → W: Impaired cytokinesis, as shown by increased number of binucleate cells. No effect on cytokinesis; when associated with V-23. Decreased interaction with EXOC2 and EXOC8; when associated with V-23. 1 Publication1
Mutagenesisi48A → W: Strongly reduces interaction with EXOC8. 1 Publication1
Mutagenesisi49D → E: No effect on cytokinesis; when associated with L-72. 1 Publication1
Mutagenesisi49D → N: No effect on cytokinesis. Impaired cytokinesis, as shown by increased number of binucleate cells; when associated with L-72. 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
Mutagenesisi72Q → L: Impaired cytokinesis, as shown by increased number of binucleate cells. Impaired cytokinesis; when associated with N-49 or 1-M--S-11. No effect on cytokinesis; when associated with E-49. 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

Chemistry databases

ChEMBLiCHEMBL3879855
DrugBankiDB04315 Guanosine-5'-Diphosphate

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 do 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
ProteomicsDBi52726

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 Expressed in 228 organ(s), highest expression level in forebrain
CleanExiHS_RALA
ExpressionAtlasiP11233 baseline and differential
GenevisibleiP11233 HS

Organism-specific databases

HPAiHPA065232

Interactioni

Subunit structurei

Interacts (via effector domain) with RALBP1 (PubMed:7673236). Interacts with EXOC2/Sec5 and EXOC8/Exo84; binding to EXOC2 and EXOC8 is mutually exclusive (PubMed:14525976, PubMed:18756269, PubMed:15920473). Interacts with Clostridium exoenzyme C3 (PubMed:16177825, PubMed:15809419). Interacts with RALGPS1 (PubMed:10747847). Interacts with LPAR1 and LPAR2. Interacts with GRK2 in response to LPAR1 activation. RALA and GRK2 binding to LPAR1 is mutually exclusive (PubMed:19306925). Interacts with CDC42 (By similarity).By similarity8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111834, 71 interactors
IntActiP11233, 34 interactors
MINTiP11233
STRINGi9606.ENSP00000005257

Structurei

Secondary structure

1206
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiQSRAQQW
OrthoDBiEOG091G0UAU
PhylomeDBiP11233
TreeFamiTF312796

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR028412 Ral
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PTHR24070:SF174 PTHR24070:SF174, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C3P7H7C3P7_HUMAN
Ras-related protein Ral-A
RALA
164Annotation score:
C9JPE8C9JPE8_HUMAN
Ras-related protein Ral-A
RALA
101Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 2MA → MVDYL in AAA36542 (PubMed:2550440).Curated2
Sequence conflicti1 – 2MA → MVDYL in AAM12624 (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

Similar proteinsi

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, 71 interactors
IntActiP11233, 34 interactors
MINTiP11233
STRINGi9606.ENSP00000005257

Chemistry databases

ChEMBLiCHEMBL3879855
DrugBankiDB04315 Guanosine-5'-Diphosphate

PTM databases

iPTMnetiP11233
PhosphoSitePlusiP11233
SwissPalmiP11233

Polymorphism and mutation databases

BioMutaiRALA
DMDMi131834

Proteomic databases

EPDiP11233
MaxQBiP11233
PaxDbiP11233
PeptideAtlasiP11233
PRIDEiP11233
ProteomicsDBi52726

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5898
DisGeNETi5898
EuPathDBiHostDB:ENSG00000006451.7
GeneCardsiRALA
HGNCiHGNC:9839 RALA
HPAiHPA065232
MIMi179550 gene
neXtProtiNX_P11233
OpenTargetsiENSG00000006451
PharmGKBiPA34197
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-171007 p38MAPK events
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
SIGNORiP11233

Miscellaneous databases

ChiTaRSiRALA human
EvolutionaryTraceiP11233
GeneWikiiRALA
GenomeRNAii5898
PROiPR:P11233
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000006451 Expressed in 228 organ(s), highest expression level in forebrain
CleanExiHS_RALA
ExpressionAtlasiP11233 baseline and differential
GenevisibleiP11233 HS

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR028412 Ral
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PTHR24070:SF174 PTHR24070:SF174, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRALA_HUMAN
AccessioniPrimary (citable) accession number: P11233
Secondary accession number(s): A4D1W3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: September 12, 2018
This is version 199 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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