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Protein

ADP-ribosylation factor-like protein 2

Gene

ARL2

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

Functioni

Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Regulates formation of new microtubules and centrosome integrity. Prevents the TBCD-induced microtubule destruction. Participates in association with TBCD, in the disassembly of the apical junction complexes. Antagonizes the effect of TBCD on epithelial cell detachment and tight and adherens junctions disassembly. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. Component of a regulated secretory pathway involved in Ca2+-dependent release of acetylcholine. Required for normal progress through the cell cycle.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei68GTP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi23 – 30GTPBy similarity8
Nucleotide bindingi66 – 70GTPBy similarity5
Nucleotide bindingi125 – 128GTPBy similarity4

GO - Molecular functioni

  • GDP binding Source: Ensembl
  • GTPase activity Source: UniProtKB
  • GTPase inhibitor activity Source: ProtInc
  • GTP binding Source: UniProtKB

GO - Biological processi

  • bicellular tight junction assembly Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • centrosome organization Source: UniProtKB
  • maintenance of protein location in nucleus Source: UniProtKB
  • negative regulation of GTPase activity Source: UniProtKB
  • positive regulation of cell-substrate adhesion Source: UniProtKB
  • positive regulation of microtubule polymerization Source: UniProtKB
  • regulation of insulin secretion Source: Reactome
  • regulation of microtubule polymerization Source: UniProtKB
  • small GTPase mediated signal transduction Source: InterPro
  • tubulin complex assembly Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-389977. Post-chaperonin tubulin folding pathway.
R-HSA-422356. Regulation of insulin secretion.

Names & Taxonomyi

Protein namesi
Recommended name:
ADP-ribosylation factor-like protein 2
Gene namesi
Name:ARL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:693. ARL2.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • lateral plasma membrane Source: UniProtKB
  • mitochondrial intermembrane space Source: UniProtKB
  • mitochondrial matrix Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3L → A: Reduces interaction with ARL2BP. 1 Publication1
Mutagenesisi3L → D: Reduces interaction with ARL2BP. 1 Publication1
Mutagenesisi4L → A: Does not reduce interaction with ARL2BP. 1 Publication1
Mutagenesisi4L → D: Reduces interaction with ARL2BP. 1 Publication1
Mutagenesisi6I → R: Reduces interaction with ARL2BP. 1 Publication1
Mutagenesisi7L → A: Does not reduce interaction with ARL2BP. 1 Publication1
Mutagenesisi7L → D: Reduces interaction with ARL2BP. 1 Publication1
Mutagenesisi30T → N: Does not inhibit the interaction with TBCD and rescues the TBCD-induced microtubule destruction. Reduces interaction with ARL2BP. Inhibits accumulation of STAT3 in the nucleus. 2 Publications1
Mutagenesisi47T → A: Does not inhibit the interaction with TBCD and rescues the TBCD-induced microtubule destruction. 1 Publication1
Mutagenesisi50F → A: Reduces interaction with ARL2BP. Inhibits the interaction with TBCD and rescues the TBCD-induced microtubule destruction. 2 Publications1
Mutagenesisi70Q → L: Induces cell cycle arrest, reduces ability to form microtubules and centrosome fragmentation. Inhibits the interaction with TBCD and does not rescue the TBCD-induced microtubule destruction. Interacts with ARL2BP and PDE6D. 4 Publications1
Mutagenesisi76Y → A: Does not reduce interaction with ARL2BP. 1 Publication1
Mutagenesisi80Y → A: Reduces interaction with ARL2BP. 1 Publication1

Organism-specific databases

DisGeNETi402.
OpenTargetsiENSG00000213465.
PharmGKBiPA24986.

Polymorphism and mutation databases

BioMutaiARL2.
DMDMi116241255.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedSequence analysis
ChainiPRO_00002074532 – 184ADP-ribosylation factor-like protein 2Add BLAST183

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineSequence analysis1
Modified residuei45PhosphoserineBy similarity1
Cross-linki71Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Post-translational modificationi

Not N-myristoylated.

Keywords - PTMi

Isopeptide bond, Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP36404.
PaxDbiP36404.
PeptideAtlasiP36404.
PRIDEiP36404.

PTM databases

iPTMnetiP36404.
PhosphoSitePlusiP36404.

Expressioni

Gene expression databases

BgeeiENSG00000213465.
CleanExiHS_ARL2.
ExpressionAtlasiP36404. baseline and differential.
GenevisibleiP36404. HS.

Organism-specific databases

HPAiHPA044610.

Interactioni

Subunit structurei

Found in a complex with ARL2, ARL2BP and SLC25A6. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Found in a complex with ARL2, ARL2BP and SLC25A4. The GTP-bound form interacts with PDE6D. Interacts with ELMOD2. The GTP-bound form interacts with ARL2BP. Interacts, preferentially in its GDP-bound state, with TBCD. Interacts with UNC119.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARL2BPQ9Y2Y011EBI-752365,EBI-3449344
PDE6DO4392414EBI-752365,EBI-712685
TBL1XR1Q9BZK73EBI-752365,EBI-765729
UNC119Q134328EBI-752365,EBI-711260

Protein-protein interaction databases

BioGridi106895. 24 interactors.
DIPiDIP-47535N.
IntActiP36404. 10 interactors.
MINTiMINT-6602180.
STRINGi9606.ENSP00000246747.

Structurei

Secondary structure

1184
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 9Combined sources7
Beta strandi16 – 22Combined sources7
Helixi29 – 37Combined sources9
Beta strandi48 – 54Combined sources7
Beta strandi60 – 67Combined sources8
Helixi71 – 80Combined sources10
Beta strandi85 – 92Combined sources8
Helixi96 – 98Combined sources3
Helixi99 – 110Combined sources12
Helixi113 – 115Combined sources3
Beta strandi119 – 125Combined sources7
Helixi135 – 140Combined sources6
Helixi141 – 146Combined sources6
Beta strandi152 – 156Combined sources5
Turni159 – 162Combined sources4
Helixi165 – 184Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3DOEX-ray2.25A1-184[»]
3DOFX-ray3.30A1-184[»]
ProteinModelPortaliP36404.
SMRiP36404.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP36404.

Family & Domainsi

Sequence similaritiesi

Belongs to the small GTPase superfamily. Arf family.Curated

Phylogenomic databases

eggNOGiKOG0073. Eukaryota.
ENOG410XRG9. LUCA.
GeneTreeiENSGT00780000121855.
HOGENOMiHOG000163691.
HOVERGENiHBG002073.
InParanoidiP36404.
KOiK07943.
OMAiFEQTDAL.
OrthoDBiEOG091G0O6V.
PhylomeDBiP36404.
TreeFamiTF105462.

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: P36404-1) [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
MGLLTILKKM KQKERELRLL MLGLDNAGKT TILKKFNGED IDTISPTLGF
60 70 80 90 100
NIKTLEHRGF KLNIWDVGGQ KSLRSYWRNY FESTDGLIWV VDSADRQRMQ
110 120 130 140 150
DCQRELQSLL VEERLAGATL LIFANKQDLP GALSSNAIRE VLELDSIRSH
160 170 180
HWCIQGCSAV TGENLLPGID WLLDDISSRI FTAD
Length:184
Mass (Da):20,878
Last modified:October 17, 2006 - v4
Checksum:i0823F005719C17F9
GO
Isoform 2 (identifier: P36404-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     113-139: Missing.

Show »
Length:157
Mass (Da):18,056
Checksum:i3EB9385F9C57941B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028056141V → A.3 PublicationsCorresponds to variant rs664226dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047278113 – 139Missing in isoform 2. 1 PublicationAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13687 mRNA. Translation: AAC37606.1.
AF493888 mRNA. Translation: AAM12602.1.
CN338497 mRNA. No translation available.
AP000436 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74333.1.
BC002530 mRNA. Translation: AAH02530.1.
CCDSiCCDS55770.1. [P36404-2]
CCDS8088.1. [P36404-1]
PIRiA48259.
RefSeqiNP_001186674.1. NM_001199745.1. [P36404-2]
NP_001658.2. NM_001667.3. [P36404-1]
UniGeneiHs.502836.

Genome annotation databases

EnsembliENST00000246747; ENSP00000246747; ENSG00000213465. [P36404-1]
ENST00000529384; ENSP00000436021; ENSG00000213465. [P36404-1]
ENST00000533729; ENSP00000432971; ENSG00000213465. [P36404-2]
GeneIDi402.
KEGGihsa:402.
UCSCiuc021qlc.2. human. [P36404-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13687 mRNA. Translation: AAC37606.1.
AF493888 mRNA. Translation: AAM12602.1.
CN338497 mRNA. No translation available.
AP000436 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74333.1.
BC002530 mRNA. Translation: AAH02530.1.
CCDSiCCDS55770.1. [P36404-2]
CCDS8088.1. [P36404-1]
PIRiA48259.
RefSeqiNP_001186674.1. NM_001199745.1. [P36404-2]
NP_001658.2. NM_001667.3. [P36404-1]
UniGeneiHs.502836.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3DOEX-ray2.25A1-184[»]
3DOFX-ray3.30A1-184[»]
ProteinModelPortaliP36404.
SMRiP36404.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106895. 24 interactors.
DIPiDIP-47535N.
IntActiP36404. 10 interactors.
MINTiMINT-6602180.
STRINGi9606.ENSP00000246747.

PTM databases

iPTMnetiP36404.
PhosphoSitePlusiP36404.

Polymorphism and mutation databases

BioMutaiARL2.
DMDMi116241255.

Proteomic databases

EPDiP36404.
PaxDbiP36404.
PeptideAtlasiP36404.
PRIDEiP36404.

Protocols and materials databases

DNASUi402.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000246747; ENSP00000246747; ENSG00000213465. [P36404-1]
ENST00000529384; ENSP00000436021; ENSG00000213465. [P36404-1]
ENST00000533729; ENSP00000432971; ENSG00000213465. [P36404-2]
GeneIDi402.
KEGGihsa:402.
UCSCiuc021qlc.2. human. [P36404-1]

Organism-specific databases

CTDi402.
DisGeNETi402.
GeneCardsiARL2.
H-InvDBHIX0079396.
HGNCiHGNC:693. ARL2.
HPAiHPA044610.
MIMi601175. gene.
neXtProtiNX_P36404.
OpenTargetsiENSG00000213465.
PharmGKBiPA24986.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0073. Eukaryota.
ENOG410XRG9. LUCA.
GeneTreeiENSGT00780000121855.
HOGENOMiHOG000163691.
HOVERGENiHBG002073.
InParanoidiP36404.
KOiK07943.
OMAiFEQTDAL.
OrthoDBiEOG091G0O6V.
PhylomeDBiP36404.
TreeFamiTF105462.

Enzyme and pathway databases

ReactomeiR-HSA-389977. Post-chaperonin tubulin folding pathway.
R-HSA-422356. Regulation of insulin secretion.

Miscellaneous databases

EvolutionaryTraceiP36404.
GeneWikiiARL2.
GenomeRNAii402.
PROiP36404.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213465.
CleanExiHS_ARL2.
ExpressionAtlasiP36404. baseline and differential.
GenevisibleiP36404. 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 nameiARL2_HUMAN
AccessioniPrimary (citable) accession number: P36404
Secondary accession number(s): G3V184, Q9BUK8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 162 of the entry and version 4 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 11
    Human chromosome 11: 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.