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Protein

Ras-related protein Rab-35

Gene

RAB35

Organism
Homo sapiens (Human)
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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth.2 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) (PubMed:20154091). That Rab is activated by the guanine exchange factors DENND1A, DENND1B and DENND1C (PubMed:20154091).1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 22GTPBy similarity8
Nucleotide bindingi63 – 67GTPBy similarity5
Nucleotide bindingi120 – 123GTPBy similarity4

GO - Molecular functioni

  • GDP binding Source: UniProtKB
  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB

GO - Biological processi

  • antigen processing and presentation Source: UniProtKB
  • cellular response to nerve growth factor stimulus Source: UniProtKB
  • cytokinesis Source: UniProtKB
  • endocytic recycling Source: GO_Central
  • endosomal transport Source: UniProtKB
  • ER to Golgi vesicle-mediated transport Source: GO_Central
  • neuron projection development Source: UniProtKB
  • plasma membrane to endosome transport Source: UniProtKB
  • protein localization Source: UniProtKB
  • protein localization to endosome Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • 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

BioCyciZFISH:ENSG00000111737-MONOMER.
ReactomeiR-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rab-35
Alternative name(s):
GTP-binding protein RAY
Ras-related protein Rab-1C
Gene namesi
Name:RAB35
Synonyms:RAB1C, RAY
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:9774. RAB35.

Subcellular locationi

GO - Cellular componenti

  • cell projection membrane Source: UniProtKB
  • clathrin-coated endocytic vesicle Source: UniProtKB
  • clathrin-coated pit Source: UniProtKB
  • endosome membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • intercellular bridge Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • mitochondrion Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Cytoplasmic vesicle, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22S → N: Destabilization of the intercellular bridge during cytokinesis. Strong reduction in fast recycling. 1 Publication1
Mutagenesisi67Q → L: Loss of GTPase activity. Increased fast recycling. 1 Publication1

Organism-specific databases

DisGeNETi11021.
OpenTargetsiENSG00000111737.
PharmGKBiPA34127.

Polymorphism and mutation databases

BioMutaiRAB35.
DMDMi3024525.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001212451 – 201Ras-related protein Rab-35Add BLAST201

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei72PhosphothreonineCombined sources1
Modified residuei75O-(2-cholinephosphoryl)serine; by Legionella AnkX2 Publications1
Modified residuei77O-AMP-tyrosine; by Legionella DrrA1 Publication1
Lipidationi200S-geranylgeranyl cysteineBy similarity1
Lipidationi201S-geranylgeranyl cysteineBy similarity1

Post-translational modificationi

AMPylation at Tyr-77 by L.pneumophila DrrA occurs in the switch 2 region and leads to moderate inactivation of the GTPase activity. It appears to prolong the lifetime of the GTP state of RAB1B by restricting access of GTPase effectors to switch 2 and blocking effector-stimulated GTP hydrolysis, thereby rendering RAB35 constitutively active.2 Publications
Phosphocholinated by L.pneumophila AnkX. Both GDP-bound and GTP-bound forms can be phosphocholinated. Phosphocholination inhibits the GEF activity of DENND1A.

Keywords - PTMi

Lipoprotein, Phosphoprotein, Prenylation

Proteomic databases

EPDiQ15286.
MaxQBiQ15286.
PaxDbiQ15286.
PeptideAtlasiQ15286.
PRIDEiQ15286.
TopDownProteomicsiQ15286-1. [Q15286-1]
Q15286-2. [Q15286-2]

PTM databases

iPTMnetiQ15286.
PhosphoSitePlusiQ15286.
SwissPalmiQ15286.

Expressioni

Gene expression databases

BgeeiENSG00000111737.
CleanExiHS_RAB35.
ExpressionAtlasiQ15286. baseline and differential.
GenevisibleiQ15286. HS.

Organism-specific databases

HPAiHPA054146.

Interactioni

Subunit structurei

Interacts with DENND1A and DENND1B; in a nucleotide-dependent manner (PubMed:20154091, PubMed:22065758). Interacts with DENND1C; weak interaction which is nucleotide-independent (PubMed:20154091). Interacts (GTP-bound form) with ACAP2 and MICALL1; the interaction is direct and probably recruits ACAP2 and MICALL1 to membranes (PubMed:21951725). Interacts with EHD1; the interaction is indirect through MICALL1 and probably recruits EHD1 to membranes (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MICALL1Q8N3F82EBI-722275,EBI-1056885

Protein-protein interaction databases

BioGridi116211. 28 interactors.
IntActiQ15286. 26 interactors.
MINTiMINT-1370578.
STRINGi9606.ENSP00000229340.

Structurei

Secondary structure

1201
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 14Combined sources8
Helixi21 – 28Combined sources8
Turni38 – 40Combined sources3
Beta strandi41 – 52Combined sources12
Beta strandi55 – 64Combined sources10
Helixi67 – 69Combined sources3
Helixi75 – 78Combined sources4
Beta strandi82 – 89Combined sources8
Helixi93 – 109Combined sources17
Beta strandi113 – 120Combined sources8
Helixi125 – 127Combined sources3
Helixi132 – 142Combined sources11
Beta strandi146 – 148Combined sources3
Turni151 – 154Combined sources4
Helixi157 – 175Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TW8X-ray2.10B/D1-180[»]
ProteinModelPortaliQ15286.
SMRiQ15286.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi37 – 45Effector regionBy similarity9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rab family.Curated

Phylogenomic databases

eggNOGiKOG0079. Eukaryota.
ENOG4111IWZ. LUCA.
GeneTreeiENSGT00860000133677.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiQ15286.
KOiK07876.
OMAiLRVKLQI.
OrthoDBiEOG091G0LA6.
PhylomeDBiQ15286.
TreeFamiTF105954.

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.
PROSITEiPS51419. RAB. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15286-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MARDYDHLFK LLIIGDSGVG KSSLLLRFAD NTFSGSYITT IGVDFKIRTV
60 70 80 90 100
EINGEKVKLQ IWDTAGQERF RTITSTYYRG THGVIVVYDV TSAESFVNVK
110 120 130 140 150
RWLHEINQNC DDVCRILVGN KNDDPERKVV ETEDAYKFAG QMGIQLFETS
160 170 180 190 200
AKENVNVEEM FNCITELVLR AKKDNLAKQQ QQQQNDVVKL TKNSKRKKRC

C
Length:201
Mass (Da):23,025
Last modified:November 1, 1996 - v1
Checksum:i31EB15D6D42E076E
GO
Isoform 2 (identifier: Q15286-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     118-201: VGNKNDDPER...KNSKRKKRCC → DVQLHHGAGPPSKERQPGKTAAATTERCGEAHEEQ

Note: No experimental confirmation available.
Show »
Length:152
Mass (Da):17,058
Checksum:i711F975E26440998
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042918118 – 201VGNKN…KKRCC → DVQLHHGAGPPSKERQPGKT AAATTERCGEAHEEQ in isoform 2. 1 PublicationAdd BLAST84

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X79781 mRNA. Translation: CAA56177.1.
AF498960 mRNA. Translation: AAM21108.1.
BT020024 mRNA. Translation: AAV38827.1.
CR536486 mRNA. Translation: CAG38725.1.
CR541683 mRNA. Translation: CAG46484.1.
AK304620 mRNA. Translation: BAG65402.1.
AK312538 mRNA. Translation: BAG35437.1.
AC004812 Genomic DNA. Translation: AAC83182.1.
CH471054 Genomic DNA. Translation: EAW98163.1.
CH471054 Genomic DNA. Translation: EAW98164.1.
BC015931 mRNA. Translation: AAH15931.1.
CCDSiCCDS41846.1. [Q15286-1]
CCDS53836.1. [Q15286-2]
PIRiJC2488.
RefSeqiNP_001161078.1. NM_001167606.1. [Q15286-2]
NP_006852.1. NM_006861.6. [Q15286-1]
UniGeneiHs.524788.

Genome annotation databases

EnsembliENST00000229340; ENSP00000229340; ENSG00000111737. [Q15286-1]
ENST00000534951; ENSP00000441883; ENSG00000111737. [Q15286-2]
GeneIDi11021.
KEGGihsa:11021.
UCSCiuc001txm.2. human. [Q15286-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X79781 mRNA. Translation: CAA56177.1.
AF498960 mRNA. Translation: AAM21108.1.
BT020024 mRNA. Translation: AAV38827.1.
CR536486 mRNA. Translation: CAG38725.1.
CR541683 mRNA. Translation: CAG46484.1.
AK304620 mRNA. Translation: BAG65402.1.
AK312538 mRNA. Translation: BAG35437.1.
AC004812 Genomic DNA. Translation: AAC83182.1.
CH471054 Genomic DNA. Translation: EAW98163.1.
CH471054 Genomic DNA. Translation: EAW98164.1.
BC015931 mRNA. Translation: AAH15931.1.
CCDSiCCDS41846.1. [Q15286-1]
CCDS53836.1. [Q15286-2]
PIRiJC2488.
RefSeqiNP_001161078.1. NM_001167606.1. [Q15286-2]
NP_006852.1. NM_006861.6. [Q15286-1]
UniGeneiHs.524788.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TW8X-ray2.10B/D1-180[»]
ProteinModelPortaliQ15286.
SMRiQ15286.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116211. 28 interactors.
IntActiQ15286. 26 interactors.
MINTiMINT-1370578.
STRINGi9606.ENSP00000229340.

PTM databases

iPTMnetiQ15286.
PhosphoSitePlusiQ15286.
SwissPalmiQ15286.

Polymorphism and mutation databases

BioMutaiRAB35.
DMDMi3024525.

Proteomic databases

EPDiQ15286.
MaxQBiQ15286.
PaxDbiQ15286.
PeptideAtlasiQ15286.
PRIDEiQ15286.
TopDownProteomicsiQ15286-1. [Q15286-1]
Q15286-2. [Q15286-2]

Protocols and materials databases

DNASUi11021.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229340; ENSP00000229340; ENSG00000111737. [Q15286-1]
ENST00000534951; ENSP00000441883; ENSG00000111737. [Q15286-2]
GeneIDi11021.
KEGGihsa:11021.
UCSCiuc001txm.2. human. [Q15286-1]

Organism-specific databases

CTDi11021.
DisGeNETi11021.
GeneCardsiRAB35.
HGNCiHGNC:9774. RAB35.
HPAiHPA054146.
MIMi604199. gene.
neXtProtiNX_Q15286.
OpenTargetsiENSG00000111737.
PharmGKBiPA34127.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0079. Eukaryota.
ENOG4111IWZ. LUCA.
GeneTreeiENSGT00860000133677.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiQ15286.
KOiK07876.
OMAiLRVKLQI.
OrthoDBiEOG091G0LA6.
PhylomeDBiQ15286.
TreeFamiTF105954.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000111737-MONOMER.
ReactomeiR-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Miscellaneous databases

ChiTaRSiRAB35. human.
GeneWikiiRAB35.
GenomeRNAii11021.
PROiQ15286.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111737.
CleanExiHS_RAB35.
ExpressionAtlasiQ15286. baseline and differential.
GenevisibleiQ15286. HS.

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.
PROSITEiPS51419. RAB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRAB35_HUMAN
AccessioniPrimary (citable) accession number: Q15286
Secondary accession number(s): B2R6E0, B4E390
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 163 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 12
    Human chromosome 12: 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.