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Protein

Ras-related protein Rab-35

Gene

RAB35

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes.By similarity2 Publications

Activity 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 – 23GTPBy similarity9
Nucleotide bindingi33 – 40GTPBy similarity8
Nucleotide bindingi63 – 67GTPBy similarity5
Nucleotide bindingi120 – 123GTPBy similarity4
Nucleotide bindingi150 – 152GTPBy similarity3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processProtein transport, Transport
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-8854214 TBC/RABGAPs
R-HSA-8873719 RAB geranylgeranylation
R-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

EuPathDBiHostDB:ENSG00000111737.11
HGNCiHGNC:9774 RAB35
MIMi604199 gene
neXtProtiNX_Q15286

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, 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)serine2 Publications1
Modified residuei77O-AMP-tyrosine1 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
ProteomicsDBi60512
60513 [Q15286-2]
TopDownProteomicsiQ15286-1 [Q15286-1]
Q15286-2 [Q15286-2]

PTM databases

iPTMnetiQ15286
PhosphoSitePlusiQ15286
SwissPalmiQ15286

Expressioni

Gene expression databases

BgeeiENSG00000111737 Expressed in 208 organ(s), highest expression level in frontal cortex
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, 34 interactors
IntActiQ15286, 29 interactors
MINTiQ15286
STRINGi9606.ENSP00000229340

Structurei

Secondary structure

1201
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
GeneTreeiENSGT00900000140786
HOGENOMiHOG000233968
HOVERGENiHBG009351
InParanoidiQ15286
KOiK07876
OMAiLRVKLQI
OrthoDBiEOG091G0LA6
PhylomeDBiQ15286
TreeFamiTF105954

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51419 RAB, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

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

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H157F5H157_HUMAN
Ras-related protein Rab-35
RAB35
185Annotation score:
F5H7F8F5H7F8_HUMAN
Ras-related protein Rab-35
RAB35
147Annotation score:

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

Similar proteinsi

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, 34 interactors
IntActiQ15286, 29 interactors
MINTiQ15286
STRINGi9606.ENSP00000229340

PTM databases

iPTMnetiQ15286
PhosphoSitePlusiQ15286
SwissPalmiQ15286

Polymorphism and mutation databases

BioMutaiRAB35
DMDMi3024525

Proteomic databases

EPDiQ15286
MaxQBiQ15286
PaxDbiQ15286
PeptideAtlasiQ15286
PRIDEiQ15286
ProteomicsDBi60512
60513 [Q15286-2]
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
EuPathDBiHostDB:ENSG00000111737.11
GeneCardsiRAB35
HGNCiHGNC:9774 RAB35
HPAiHPA054146
MIMi604199 gene
neXtProtiNX_Q15286
OpenTargetsiENSG00000111737
PharmGKBiPA34127
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0079 Eukaryota
ENOG4111IWZ LUCA
GeneTreeiENSGT00900000140786
HOGENOMiHOG000233968
HOVERGENiHBG009351
InParanoidiQ15286
KOiK07876
OMAiLRVKLQI
OrthoDBiEOG091G0LA6
PhylomeDBiQ15286
TreeFamiTF105954

Enzyme and pathway databases

ReactomeiR-HSA-8854214 TBC/RABGAPs
R-HSA-8873719 RAB geranylgeranylation
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs

Miscellaneous databases

ChiTaRSiRAB35 human
GeneWikiiRAB35
GenomeRNAii11021
PROiPR:Q15286
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111737 Expressed in 208 organ(s), highest expression level in frontal cortex
CleanExiHS_RAB35
ExpressionAtlasiQ15286 baseline and differential
GenevisibleiQ15286 HS

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51419 RAB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRAB35_HUMAN
AccessioniPrimary (citable) accession number: Q15286
Secondary accession number(s): B2R6E0, B4E390
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 181 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 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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