P11234 (RALB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-related protein Ral-B

Gene names

Name:

RALB

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	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	Multifuntional 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. Required both to stabilize the assembly of the exocyst complex and to localize functional exocyst complexes to the leading edge of migrating cells. Plays a role in the late stages of cytokinesis and is required for the abscission of the bridge joining the sister cells emerging from mitosis. Required for suppression of apoptosis. Ref.9
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 EXOC2 and EXOC8. Interacts with RALBP1 via its effector domain. Ref.6 Ref.7 Ref.11
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side. Note: During late cytokinesis localizes at the midbody. Ref.8 Ref.9
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	Apoptosis Cell cycle Cell division
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 apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cytokinesis Inferred from direct assay Ref.9. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome regulation of exocyst assembly Inferred from sequence or structural similarity. Source: UniProtKB regulation of exocyst localization Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome midbody Inferred from direct assay Ref.9. Source: UniProtKB plasma membrane Inferred from direct assay Ref.8. Source: UniProtKB
Molecular function	GTP binding Inferred from direct assay Ref.11. Source: UniProtKB GTPase activity Inferred from direct assay Ref.11. Source: UniProtKB protein binding Inferred from physical interaction Ref.11Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 203

203

Ras-related protein Ral-B

PRO_0000082698

Propeptide

204 – 206

3

Removed in mature form By similarity

PRO_0000281349

Regions

Nucleotide binding

21 – 29

9

GTP

Nucleotide binding

68 – 72

5

GTP

Nucleotide binding

128 – 131

4

GTP

Nucleotide binding

158 – 160

3

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

Experimental info

Mutagenesis

46

1

T → A: Reduces the binding affinity to EXOC2 effector. Ref.11

Mutagenesis

46

1

T → S: Reduces the binding affinity to EXOC2 effector. Ref.11

Mutagenesis

72

1

Q → L: Loss of GTPase activity. Ref.11

Mutagenesis

203

1

C → S: Loss of geranylgeranylation and membrane localization. Ref.8

Mutagenesis

206

1

L → S: Converts geranyl-geranylation to farnesylation. No effect on membrane localization. Confers resistance to GGTI-induced pancreatic cancer cell apoptosis, but not to GGTI-dependent inhibition of anchorage-independent proliferation. Ref.8

Secondary structure

1

.

.

.

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.

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206

Helix Strand Turn

Details...

Beta strand

14 – 20

7

Helix

28 – 36

9

Beta strand

51 – 56

6

Beta strand

61 – 68

8

Beta strand

74 – 77

4

Helix

78 – 84

7

Beta strand

90 – 92

3

Helix

98 – 114

17

Beta strand

124 – 126

3

Helix

140 – 148

9

Turn

159 – 161

3

Helix

165 – 179

15

Turn

180 – 182

3

Sequences

	Sequence		Length	Mass (Da)
	P11234 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: E0AC95130FB6452C	FASTA	206	23,409
	10 20 30 40 50 60 MAANKSKGQS SLALHKVIMV GSGGVGKSAL TLQFMYDEFV EDYEPTKADS YRKKVVLDGE 70 80 90 100 110 120 EVQIDILDTA GQEDYAAIRD NYFRSGEGFL LVFSITEHES FTATAEFREQ ILRVKAEEDK 130 140 150 160 170 180 IPLLVVGNKS DLEERRQVPV EEARSKAEEW GVQYVETSAK TRANVDKVFF DLMREIRTKK 190 200 MSENKDKNGK KSSKNKKSFK ERCCLL

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: 2662142] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Chromosomal localization and cDNA sequence of human ralB, a GTP binding protein." Hsieh C.-L., Swaroop A., Francke U. Somat. Cell Mol. Genet. 16:407-410(1990) [PubMed: 2120779] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[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: Brain.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[6]	"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: 7673236] [Abstract] Cited for: INTERACTION WITH RALBP1.
[7]	"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: 14525976] [Abstract] Cited for: INTERACTION WITH EXOC8.
[8]	"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: 17875936] [Abstract] Cited for: SUBCELLULAR LOCATION, ISOPRENYLATION, ISOPRENYLATION AT CYS-203, MUTAGENESIS OF CYS-203 AND LEU-206.
[9]	"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: 18756269] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Solution structure and dynamics of the small GTPase RalB in its active conformation: significance for effector protein binding." Fenwick R.B., Prasannan S., Campbell L.J., Nietlispach D., Evetts K.A., Camonis J., Mott H.R., Owen D. Biochemistry 48:2192-2206(2009) [PubMed: 19166349] [Abstract] Cited for: STRUCTURE BY NMR OF 12-185 IN COMPLEX WITH GTP ANALOG, INTERACTION WITH EXOC2, MUTAGENESIS OF THR-46 AND GLN-72.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X15015 mRNA. Translation: CAA33119.1.
M35416 mRNA. Translation: AAA60250.1.
AF493911 mRNA. Translation: AAM12625.1.
BT006953 mRNA. Translation: AAP35599.1.
BC018163 mRNA. Translation: AAH18163.1.

IPI

IPI01015571.

PIR

TVHUAB. S04597.

RefSeq

NP_002872.1. NM_002881.2.

UniGene

Hs.469820.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KE5	NMR	-	A	12-185	[»]
2KWI	NMR	-	A	8-185	[»]

ProteinModelPortal

P11234.

SMR

P11234. Positions 8-185.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11234. 10 interactions.

MINT

MINT-5000915.

STRING

P11234.

PTM databases

PhosphoSite

P11234.

Polymorphism databases

DMDM

131835.

Proteomic databases

PRIDE

P11234.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000272519; ENSP00000272519; ENSG00000144118.
ENST00000420510; ENSP00000414224; ENSG00000144118.

GeneID

5899.

KEGG

hsa:5899.

UCSC

uc002tmk.1. human.

Organism-specific databases

CTD

5899.

GeneCards

GC02P120997.

H-InvDB

HIX0002418.

HGNC

HGNC:9840. RALB.

HPA

CAB026010.

MIM

179551. gene.

neXtProt

NX_P11234.

PharmGKB

PA34198.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15904.

HOVERGEN

HBG009351.

OrthoDB

EOG4HX524.

PhylomeDB

P11234.

Enzyme and pathway databases

Pathway_Interaction_DB

foxopathway. FoxO family signaling.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P11234.

Bgee

P11234.

CleanEx

HS_RALB.

Genevestigator

P11234.

GermOnline

ENSG00000144118. Homo sapiens.

Family and domain databases

InterPro

IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR015591. Small_GTPase_Ral.
IPR020849. Small_GTPase_Ras.
[Graphical view]

KO

K07835.

PANTHER

PTHR24070. PTHR24070. 1 hit.
PTHR24070:SF124. PTHR24070:SF124. 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

NextBio

22946.

SOURCE

Search...

Entry information

Entry name

RALB_HUMAN

Accession

Primary (citable) accession number: P11234

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	January 25, 2012
This is version 129 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.