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Protein

Ras-related protein Rab-10

Gene

rab-10

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:23100538, PubMed:26394140, PubMed:26633194). Required for basolateral endocytic recycling, the return of macromolecules and fluid from endosomes to the plasma membrane, in polarized epithelial cells of the intestine upstream of rme-1 (PubMed:16394106). Involved in the formation of the endosomal tubular network that is required for basolateral recycling of clathrin-independent endocytic cargo such as daf-4 in the intestine (PubMed:25301900). Required for the recruitment of cnt-1 effector to endosomal membranes in the intestinal epithelium, which is important for the regulation of levels of endosomal phosphatidylinositol-4,5-bisphosphate, a key phosphoinositide in membrane traffic, and for the recruitment of endosomal membrane-bending proteins, rme-1 and sdpn-1 (PubMed:22869721). Recruits the rab-5 GTPase-activating protein tbc-2 to endosomes where it then inactivates rab-5 resulting in removal of rab-5 from membranes, which is necessary for cargo transport from early endosomes to recycling endosomes in the basolateral intestine (PubMed:26393361). Regulates recycling of synaptic membrane AMPA glutamate receptor, glr-1, from intracellular endosomal compartments back to synapses in a cholesterol-dependent endocytosis pathway functioning after clathrin-independent endocytosis in command interneurons (PubMed:17761527). Regulates neuropeptide release from dense core vesicles (DCVs) of cholinergic motoneurons in cooperation with rab-5. They reciprocally recruite each other's inactivating GAP molecule leading to local exclusion of one or the other rab protein at the Golgi-endosomal interphase at an essential stage during DCV sorting (PubMed:23100538). Regulates membrane trafficking of membranes and dendrite proteins from the Golgi and/or endosomal compartments to plasma membrane during dendrite morphogenesis together with the exocyst complex in the multi-dendritic PVD sensory neurons acting in a cell-autonomous manner and requiring its GTPase activity (PubMed:26394140). Functions cell-autonomously together with the exocyst complex to regulate dendrite morphogenesis and anterior-posterior patterning of the PVD neurons dendritic arbor by balancing the anterograde and retrograde transport via molecular motors unc-116 (kinesin heavy chain) and dhc-1 (dynein heavy chain) to appropriately transport branching factors, such as dma-1, to the specific subcellular regions of the developing dendrite in its GTPase activity-dependent manner (PubMed:26633194).8 Publications

Enzyme regulationi

Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). Tbc-4 is a likely GAP of this rab (PubMed:23100538). Denn-4 is a putative GEF of this rab (PubMed:26633194).By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi16 – 23GTPBy similarity8
Nucleotide bindingi64 – 68GTPBy similarity5
Nucleotide bindingi122 – 125GTPBy similarity4
Nucleotide bindingi152 – 154GTPBy similarity3

GO - Molecular functioni

  • GTPase activating protein binding Source: UniProtKB
  • GTP binding Source: UniProtKB-KW

GO - Biological processi

  • cellular response to insulin stimulus Source: GO_Central
  • endocytic recycling Source: WormBase
  • protein transport Source: UniProtKB-KW
  • receptor recycling Source: WormBase
  • small GTPase mediated signal transduction Source: InterPro
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-CEL-1445148. Translocation of GLUT4 to the plasma membrane.
R-CEL-6798695. Neutrophil degranulation.
R-CEL-8876198. RAB GEFs exchange GTP for GDP on RABs.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rab-10Curated
Short name:
Rab-101 Publication
Gene namesi
Name:rab-101 PublicationImported
ORF Names:T23H2.5Imported
OrganismiCaenorhabditis elegansImported
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome I

Organism-specific databases

WormBaseiT23H2.5; CE14114; WBGene00004273; rab-10.

Subcellular locationi

GO - Cellular componenti

  • axon Source: WormBase
  • dense core granule Source: WormBase
  • early endosome Source: WormBase
  • early endosome membrane Source: UniProtKB-SubCell
  • endosome Source: WormBase
  • Golgi apparatus Source: WormBase
  • Golgi medial cisterna Source: WormBase
  • Golgi membrane Source: UniProtKB-SubCell
  • insulin-responsive compartment Source: GO_Central
  • late endosome membrane Source: UniProtKB-SubCell
  • neuronal cell body Source: WormBase
  • recycling endosome Source: WormBase
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Intestinal cells exhibit abnormally abundant rab-5 and rab-7 positive enlarged early endosomes, which accumulate basolaterally recycling transmembrane cargo molecules and fluid indicating a block in basolateral transport (PubMed:16394106, PubMed:20573983). On the other hand, rme-1 positive recycling endosomes are missing. No endocytic trafficking defects in oocytes or coelomocytes (PubMed:16394106). Almost complete loss of cnt-1 endosomal localization in the intestinal epithelium. Overaccumulation of endosomal phosphatidylinositol-4,5-bisphosphate (PubMed:22869721). Nearly complete loss of basolateral endosomal tubule extensions of the intestine (PubMed:25301900). The endosomal localization of tbc-2 is strongly reduced leading to increased rab-5 association with membranes in the intestinal epithelia (PubMed:26393361). Cholesterol-dependent accumulation of glr-1 in large accretions running along the length of the ventral cord neurite bundle while synapses don't have general formation defects. Animals display a decreased frequency of locomotional reversals and significantly reduced response to nose-touch suggesting reduced glr-1 signaling (PubMed:17761527, PubMed:20573983). Rab-10 lin-10 double mutant displays additive glr-1 trafficking defects indicating that they both regulate endocytic recycling of AMPA receptors to synapses, but most probably along distinct regulatory pathways (PubMed:17761527). Complete loss of dense core vesicles (DCVs) secretion of neuropeptides from DA/DB motoneurons, while synaptic ultrastructure and synaptic vesicles (SV) exocytosis as well as coelomocyte function are unaffected (PubMed:23100538). Severely reduced proximal dendritic arborization in multi-dendritic PVD sensory neurons, but minimal effect on dendritic branching and growth on the distal area of the PVD. The growth of PVD axon is normal. Reduced dendritic growth of the multi-dendritic FLP neurons, but no effect on the dendritic growth of unbranched dendrites of the OLL, AWB and AWC neurons. Accumulates dendritic membrane proteins dma-1 and hpo-30 within intracellular vesicles within the growing PVD dendrites and have decreased dendrite membrane localization of these proteins. Rab-10 rab-8 double deletion mutant has enhanced dendritic arborization defects than rab-10 deletion alone in PVD neurons (PubMed:26394140). PVD dendritic branches are reduced in the posterior region of the cell, but are excessive in the distal anterior region of the cell. Dma-1 fails to localize to the plasma membrane in the posterior dendrite (PubMed:26633194). Rab-10 rab-8 double deletion mutant has disrupted transport of membrane proteins to the plasma membrane of the nonpolarized germline cells (PubMed:20573983).9 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23T → N: Dominant-negative mutant. Mislocalizes to the cytoplasm instead of membranes. Hardly any basolateral endosomal tubules of the intestine. No interaction with catalytically inactive tbc-4 A-155 mutant. Does not rescue rab-10 null mutant, and fails to rescue the proximal PVD defects in rab-10 deletion mutants, but also disrupts the distal dendrite arbor and further reduces branch complexity in the anterior region in wild-type animals. 7 Publications1
Mutagenesisi68Q → L: Constitutively active mutant unable to hydrolyze GTP. Associates correctly with membranes. Displays more extensive network of basolateral endosomal tubules of the intestine. Strongly reduced DCV secretion in dorsally projecting cholinergic DA/DB motoneurons. Interacts with the catalytically inactive tbc-4 A-155 mutant, but not with the catalytically active tbc-4. Partially rescues rab-10 null mutant and fully rescues the PVD dendrite morphogenesis defects in rab-10 deletion mutants. 8 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004380741 – 201Ras-related protein Rab-10Add BLAST201

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi200S-geranylgeranyl cysteineBy similarity1
Lipidationi201S-geranylgeranyl cysteineBy similarity1

Keywords - PTMi

Lipoprotein, Prenylation

Proteomic databases

EPDiQ94148.
PaxDbiI7FXD6.
Q94148.

Expressioni

Tissue specificityi

Almost ubiquitously expressed. Expressed in intestine, hypodermis, seam cells, body-wall muscles, many neurons, oviduct sheath cell, spermatheca, coelomocytes and pharyngeal and nerve ring.1 Publication

Gene expression databases

BgeeiWBGene00004273.

Interactioni

Subunit structurei

Interacts (GTP-bound form) with ehbp-1 (via C-terminal coiled coil) (PubMed:20573983, PubMed:22869721). Interacts (GTP-bound form) with cnt-1 (via C-terminal ankyrin repeat) (PubMed:22869721). Interacts (GTP-bound form) with rab-5 GAP, tbc-2 (via putative coiled coil domain) (PubMed:23100538, PubMed:26393361). Interacts (GTP-bound form) with amph-1 (PubMed:26393361).4 Publications

GO - Molecular functioni

  • GTPase activating protein binding Source: UniProtKB

Protein-protein interaction databases

STRINGi6239.T23H2.5.1.

Structurei

3D structure databases

ProteinModelPortaliQ94148.
SMRiQ94148.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi38 – 46Effector regionCurated9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rab family.Curated

Phylogenomic databases

eggNOGiKOG0078. Eukaryota.
ENOG410XPUI. LUCA.
GeneTreeiENSGT00860000133675.
HOGENOMiHOG000233968.
InParanoidiQ94148.
KOiK07903.
OMAiHVDTAFY.
OrthoDBiEOG091G0LA6.
PhylomeDBiQ94148.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
[Graphical view]
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.

Sequencei

Sequence statusi: Complete.

Q94148-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARRPYDMLF KLLLIGDSGV GKTCILYRFS DDAFNTTFIS TIGIDFKIKT
60 70 80 90 100
IELKGKKIKL QIWDTAGQER FHTITTSYYR GAMGIMLVYD ITNAKSFDNI
110 120 130 140 150
AKWLRNIDEH ASEDVVKMIL GNKCDMSDRR VVSRERGEKI AQDHGISFHE
160 170 180 190 200
TSAKLNVHVD TAFYDLAEAI LAKMPDSTDE QSRDTVNPVQ PQRQSSSGGC

C
Length:201
Mass (Da):22,712
Last modified:January 1, 1998 - v2
Checksum:i2D205ABF751EBF1A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX284601 Genomic DNA. Translation: CCD70773.1.
JQ235188 mRNA. Translation: AFP33152.1.
PIRiT28971.
RefSeqiNP_491857.1. NM_059456.4.
UniGeneiCel.17301.

Genome annotation databases

EnsemblMetazoaiT23H2.5.1; T23H2.5.1; WBGene00004273.
T23H2.5.2; T23H2.5.2; WBGene00004273.
GeneIDi266836.
KEGGicel:CELE_T23H2.5.
UCSCiT23H2.5.1. c. elegans.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX284601 Genomic DNA. Translation: CCD70773.1.
JQ235188 mRNA. Translation: AFP33152.1.
PIRiT28971.
RefSeqiNP_491857.1. NM_059456.4.
UniGeneiCel.17301.

3D structure databases

ProteinModelPortaliQ94148.
SMRiQ94148.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi6239.T23H2.5.1.

Proteomic databases

EPDiQ94148.
PaxDbiI7FXD6.
Q94148.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiT23H2.5.1; T23H2.5.1; WBGene00004273.
T23H2.5.2; T23H2.5.2; WBGene00004273.
GeneIDi266836.
KEGGicel:CELE_T23H2.5.
UCSCiT23H2.5.1. c. elegans.

Organism-specific databases

CTDi266836.
WormBaseiT23H2.5; CE14114; WBGene00004273; rab-10.

Phylogenomic databases

eggNOGiKOG0078. Eukaryota.
ENOG410XPUI. LUCA.
GeneTreeiENSGT00860000133675.
HOGENOMiHOG000233968.
InParanoidiQ94148.
KOiK07903.
OMAiHVDTAFY.
OrthoDBiEOG091G0LA6.
PhylomeDBiQ94148.

Enzyme and pathway databases

ReactomeiR-CEL-1445148. Translocation of GLUT4 to the plasma membrane.
R-CEL-6798695. Neutrophil degranulation.
R-CEL-8876198. RAB GEFs exchange GTP for GDP on RABs.

Gene expression databases

BgeeiWBGene00004273.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
[Graphical view]
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRAB10_CAEEL
AccessioniPrimary (citable) accession number: Q94148
Secondary accession number(s): I7FXD6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 2, 2016
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. 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.