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Protein

ADP-ribosylation factor-like protein 6

Gene

ARL6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in membrane protein trafficking at the base of the ciliary organelle. Mediates recruitment onto plasma membrane of the BBSome complex which would constitute a coat complex required for sorting of specific membrane proteins to the primary cilia (PubMed:20603001). Together with BBS1, is necessary for correct trafficking of PKD1 to primary cilia (By similarity). Together with the BBSome complex and LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation (PubMed:22072986). May regulate cilia assembly and disassembly and subsequent ciliary signaling events such as the Wnt signaling cascade (PubMed:20207729). Isoform 2 may be required for proper retinal function and organization (By similarity).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi31Magnesium1 Publication1
Metal bindingi50Magnesium1 Publication1
Binding sitei50GTP1 Publication1
Binding sitei72GTP; via amide nitrogen1 Publication1
Binding sitei164GTP; via amide nitrogen1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi24 – 31GTP1 Publication8
Nucleotide bindingi69 – 73GTPBy similarity5
Nucleotide bindingi130 – 133GTP1 Publication4

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cilium biogenesis/degradation, Protein transport, Sensory transduction, Transport, Vision

Keywords - Ligandi

GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113966-MONOMER.
ReactomeiR-HSA-5620922. BBSome-mediated cargo-targeting to cilium.

Names & Taxonomyi

Protein namesi
Recommended name:
ADP-ribosylation factor-like protein 6
Alternative name(s):
Bardet-Biedl syndrome 3 protein
Gene namesi
Name:ARL6
Synonyms:BBS3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:13210. ARL6.

Subcellular locationi

GO - Cellular componenti

  • axonemal microtubule Source: UniProtKB
  • axoneme Source: UniProtKB
  • cilium Source: MGI
  • cytoplasm Source: UniProtKB
  • cytosol Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • membrane coat Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Bardet-Biedl syndrome 3 (BBS3)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease.
See also OMIM:600151
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02764331T → M in BBS3; abrogates the GTP-binding ability without affecting GDP-binding/dissociating properties; increased proteasomal degradation. 3 PublicationsCorresponds to variant rs104893680dbSNPEnsembl.1
Natural variantiVAR_02764431T → R in BBS3; locked in a GDP-bound state that differs from its wild-type counterpart which is mainly GTP-bound; increased proteasomal degradation. 3 PublicationsCorresponds to variant rs104893680dbSNPEnsembl.1
Natural variantiVAR_07140594I → T in BBS3. 1 PublicationCorresponds to variant rs771054395dbSNPEnsembl.1
Natural variantiVAR_027645169G → A in BBS3; abrogates the GTP-binding ability; increased proteasomal degradation. 3 PublicationsCorresponds to variant rs104893679dbSNPEnsembl.1
Natural variantiVAR_027646170L → W in BBS3; abrogates the GTP-binding ability; increased proteasomal degradation. 3 PublicationsCorresponds to variant rs104893681dbSNPEnsembl.1
Retinitis pigmentosa 55 (RP55)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
See also OMIM:613575
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06418489A → V in RP55. 1 PublicationCorresponds to variant rs587777805dbSNPEnsembl.1

Keywords - Diseasei

Bardet-Biedl syndrome, Ciliopathy, Disease mutation, Mental retardation, Obesity, Retinitis pigmentosa

Organism-specific databases

DisGeNETi84100.
MalaCardsiARL6.
MIMi600151. phenotype.
613575. phenotype.
OpenTargetsiENSG00000113966.
Orphaneti110. Bardet-Biedl syndrome.
791. Retinitis pigmentosa.
PharmGKBiPA134931939.

Polymorphism and mutation databases

DMDMi14547903.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedSequence analysis
ChainiPRO_00002074722 – 186ADP-ribosylation factor-like protein 6Add BLAST185

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineSequence analysis1

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

EPDiQ9H0F7.
MaxQBiQ9H0F7.
PaxDbiQ9H0F7.
PeptideAtlasiQ9H0F7.
PRIDEiQ9H0F7.

PTM databases

iPTMnetiQ9H0F7.
PhosphoSitePlusiQ9H0F7.

Expressioni

Gene expression databases

BgeeiENSG00000113966.
CleanExiHS_ARL6.
ExpressionAtlasiQ9H0F7. baseline and differential.
GenevisibleiQ9H0F7. HS.

Organism-specific databases

HPAiHPA019361.

Interactioni

Subunit structurei

Interacts with SEC61B, ARL6IP1, ARL6IP2, ARL6IP3, ARL6IP4 ARL6IP5 and ARL6IP6. Interacts (GTP-bound form) with the BBSome a complex that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts (GTP-free form) with IFT27.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BBS1Q8NFJ94EBI-2891949,EBI-1805484

Protein-protein interaction databases

BioGridi123889. 6 interactors.
DIPiDIP-61535N.
IntActiQ9H0F7. 18 interactors.
STRINGi9606.ENSP00000337722.

Structurei

Secondary structure

1186
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi18 – 24Combined sources7
Helixi30 – 36Combined sources7
Helixi40 – 42Combined sources3
Beta strandi51 – 59Combined sources9
Beta strandi64 – 70Combined sources7
Turni74 – 76Combined sources3
Helixi77 – 86Combined sources10
Beta strandi88 – 95Combined sources8
Helixi99 – 114Combined sources16
Turni116 – 120Combined sources5
Beta strandi125 – 130Combined sources6
Helixi140 – 147Combined sources8
Helixi149 – 151Combined sources3
Beta strandi157 – 161Combined sources5
Turni164 – 167Combined sources4
Helixi170 – 180Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H57X-ray2.00A/B/C16-186[»]
ProteinModelPortaliQ9H0F7.
SMRiQ9H0F7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H0F7.

Family & Domainsi

Sequence similaritiesi

Belongs to the small GTPase superfamily. Arf family.Curated

Phylogenomic databases

eggNOGiKOG0070. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133732.
HOGENOMiHOG000163691.
HOVERGENiHBG002073.
InParanoidiQ9H0F7.
KOiK07951.
OMAiNCQGIIY.
OrthoDBiEOG091G0MVB.
PhylomeDBiQ9H0F7.
TreeFamiTF105466.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR024156. Small_GTPase_ARF.
IPR006689. Small_GTPase_ARF/SAR.
[Graphical view]
PfamiPF00025. Arf. 1 hit.
[Graphical view]
PRINTSiPR00328. SAR1GTPBP.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51417. ARF. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

Isoform 1 (identifier: Q9H0F7-1) [UniParc]FASTAAdd to basket
Also known as: BBS3

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
MGLLDRLSVL LGLKKKEVHV LCLGLDNSGK TTIINKLKPS NAQSQNILPT
60 70 80 90 100
IGFSIEKFKS SSLSFTVFDM SGQGRYRNLW EHYYKEGQAI IFVIDSSDRL
110 120 130 140 150
RMVVAKEELD TLLNHPDIKH RRIPILFFAN KMDLRDAVTS VKVSQLLCLE
160 170 180
NIKDKPWHIC ASDAIKGEGL QEGVDWLQDQ IQTVKT
Length:186
Mass (Da):21,097
Last modified:March 1, 2001 - v1
Checksum:i42E37FC7886BF1F0
GO
Isoform 2 (identifier: Q9H0F7-2) [UniParc]FASTAAdd to basket
Also known as: BBS3L

The sequence of this isoform differs from the canonical sequence as follows:
     179-186: DQIQTVKT → EKTIQSDPDCEDMKR

Note: Gene prediction based on EST data.
Show »
Length:193
Mass (Da):21,960
Checksum:i4C6C43101CE360C1
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02764331T → M in BBS3; abrogates the GTP-binding ability without affecting GDP-binding/dissociating properties; increased proteasomal degradation. 3 PublicationsCorresponds to variant rs104893680dbSNPEnsembl.1
Natural variantiVAR_02764431T → R in BBS3; locked in a GDP-bound state that differs from its wild-type counterpart which is mainly GTP-bound; increased proteasomal degradation. 3 PublicationsCorresponds to variant rs104893680dbSNPEnsembl.1
Natural variantiVAR_06418489A → V in RP55. 1 PublicationCorresponds to variant rs587777805dbSNPEnsembl.1
Natural variantiVAR_07140594I → T in BBS3. 1 PublicationCorresponds to variant rs771054395dbSNPEnsembl.1
Natural variantiVAR_027645169G → A in BBS3; abrogates the GTP-binding ability; increased proteasomal degradation. 3 PublicationsCorresponds to variant rs104893679dbSNPEnsembl.1
Natural variantiVAR_027646170L → W in BBS3; abrogates the GTP-binding ability; increased proteasomal degradation. 3 PublicationsCorresponds to variant rs104893681dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_040511179 – 186DQIQTVKT → EKTIQSDPDCEDMKR in isoform 2. Curated8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136815 mRNA. Translation: CAB66749.1.
AK292958 mRNA. Translation: BAF85647.1.
AC110491 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79880.1.
CH471052 Genomic DNA. Translation: EAW79881.1.
CH471052 Genomic DNA. Translation: EAW79882.1.
CH471052 Genomic DNA. Translation: EAW79883.1.
CH471052 Genomic DNA. Translation: EAW79884.1.
BC024239 mRNA. Translation: AAH24239.1.
CCDSiCCDS2928.1. [Q9H0F7-1]
RefSeqiNP_001265222.1. NM_001278293.2. [Q9H0F7-1]
NP_001310442.1. NM_001323513.1. [Q9H0F7-2]
NP_115522.1. NM_032146.5. [Q9H0F7-1]
NP_816931.1. NM_177976.3. [Q9H0F7-1]
XP_016862800.1. XM_017007311.1. [Q9H0F7-1]
UniGeneiHs.373801.
Hs.682062.

Genome annotation databases

EnsembliENST00000335979; ENSP00000337722; ENSG00000113966. [Q9H0F7-1]
ENST00000394206; ENSP00000377756; ENSG00000113966. [Q9H0F7-1]
ENST00000463745; ENSP00000419619; ENSG00000113966. [Q9H0F7-1]
ENST00000493990; ENSP00000418057; ENSG00000113966. [Q9H0F7-1]
GeneIDi84100.
KEGGihsa:84100.
UCSCiuc003dru.4. human. [Q9H0F7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136815 mRNA. Translation: CAB66749.1.
AK292958 mRNA. Translation: BAF85647.1.
AC110491 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79880.1.
CH471052 Genomic DNA. Translation: EAW79881.1.
CH471052 Genomic DNA. Translation: EAW79882.1.
CH471052 Genomic DNA. Translation: EAW79883.1.
CH471052 Genomic DNA. Translation: EAW79884.1.
BC024239 mRNA. Translation: AAH24239.1.
CCDSiCCDS2928.1. [Q9H0F7-1]
RefSeqiNP_001265222.1. NM_001278293.2. [Q9H0F7-1]
NP_001310442.1. NM_001323513.1. [Q9H0F7-2]
NP_115522.1. NM_032146.5. [Q9H0F7-1]
NP_816931.1. NM_177976.3. [Q9H0F7-1]
XP_016862800.1. XM_017007311.1. [Q9H0F7-1]
UniGeneiHs.373801.
Hs.682062.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H57X-ray2.00A/B/C16-186[»]
ProteinModelPortaliQ9H0F7.
SMRiQ9H0F7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123889. 6 interactors.
DIPiDIP-61535N.
IntActiQ9H0F7. 18 interactors.
STRINGi9606.ENSP00000337722.

PTM databases

iPTMnetiQ9H0F7.
PhosphoSitePlusiQ9H0F7.

Polymorphism and mutation databases

DMDMi14547903.

Proteomic databases

EPDiQ9H0F7.
MaxQBiQ9H0F7.
PaxDbiQ9H0F7.
PeptideAtlasiQ9H0F7.
PRIDEiQ9H0F7.

Protocols and materials databases

DNASUi84100.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000335979; ENSP00000337722; ENSG00000113966. [Q9H0F7-1]
ENST00000394206; ENSP00000377756; ENSG00000113966. [Q9H0F7-1]
ENST00000463745; ENSP00000419619; ENSG00000113966. [Q9H0F7-1]
ENST00000493990; ENSP00000418057; ENSG00000113966. [Q9H0F7-1]
GeneIDi84100.
KEGGihsa:84100.
UCSCiuc003dru.4. human. [Q9H0F7-1]

Organism-specific databases

CTDi84100.
DisGeNETi84100.
GeneCardsiARL6.
GeneReviewsiARL6.
HGNCiHGNC:13210. ARL6.
HPAiHPA019361.
MalaCardsiARL6.
MIMi600151. phenotype.
608845. gene.
613575. phenotype.
neXtProtiNX_Q9H0F7.
OpenTargetsiENSG00000113966.
Orphaneti110. Bardet-Biedl syndrome.
791. Retinitis pigmentosa.
PharmGKBiPA134931939.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0070. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133732.
HOGENOMiHOG000163691.
HOVERGENiHBG002073.
InParanoidiQ9H0F7.
KOiK07951.
OMAiNCQGIIY.
OrthoDBiEOG091G0MVB.
PhylomeDBiQ9H0F7.
TreeFamiTF105466.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113966-MONOMER.
ReactomeiR-HSA-5620922. BBSome-mediated cargo-targeting to cilium.

Miscellaneous databases

ChiTaRSiARL6. human.
EvolutionaryTraceiQ9H0F7.
GeneWikiiARL6.
GenomeRNAii84100.
PROiQ9H0F7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113966.
CleanExiHS_ARL6.
ExpressionAtlasiQ9H0F7. baseline and differential.
GenevisibleiQ9H0F7. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR024156. Small_GTPase_ARF.
IPR006689. Small_GTPase_ARF/SAR.
[Graphical view]
PfamiPF00025. Arf. 1 hit.
[Graphical view]
PRINTSiPR00328. SAR1GTPBP.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51417. ARF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARL6_HUMAN
AccessioniPrimary (citable) accession number: Q9H0F7
Secondary accession number(s): A8KA93, D3DN31
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 152 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 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.