ARF6_RAT
ID ARF6_RAT Reviewed; 175 AA.
AC P62332; P26438; Q5BKA5;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=ADP-ribosylation factor 6;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P62330};
GN Name=Arf6;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8813705; DOI=10.1007/bf00226058;
RA Price S.R., Nightingale M.S., Tsuchiya M., Moss J., Vaughan M.;
RT "Interspecies relationships among ADP-ribosylation factors (ARFs): evidence
RT of evolutionary pressure to maintain individual identities.";
RL Mol. Cell. Biochem. 159:15-23(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH ASAP2.
RX PubMed=10022920; DOI=10.1128/mcb.19.3.2338;
RA Andreev J., Simon J.-P., Sabatini D.D., Kam J., Plowman G., Randazzo P.A.,
RA Schlessinger J.;
RT "Identification of a new Pyk2 target protein with Arf-GAP activity.";
RL Mol. Cell. Biol. 19:2338-2350(1999).
RN [4]
RP FUNCTION AS REGULATOR OF DENDRITIC SPINE DEVELOPMENT.
RX PubMed=16672654; DOI=10.1523/jneurosci.4182-05.2006;
RA Choi S., Ko J., Lee J.R., Lee H.W., Kim K., Chung H.S., Kim H., Kim E.;
RT "ARF6 and EFA6A regulate the development and maintenance of dendritic
RT spines.";
RL J. Neurosci. 26:4811-4819(2006).
RN [5]
RP INTERACTION WITH GGA3, ACTIVITY REGULATION, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=26446845; DOI=10.1091/mbc.e15-02-0087;
RA Li X., Lavigne P., Lavoie C.;
RT "GGA3 mediates TrkA endocytic recycling to promote sustained Akt
RT phosphorylation and cell survival.";
RL Mol. Biol. Cell 26:4412-4426(2015).
CC -!- FUNCTION: GTP-binding protein involved in protein trafficking that
CC regulates endocytic recycling and cytoskeleton remodeling
CC (PubMed:26446845). Required for normal completion of mitotic
CC cytokinesis. Involved in the regulation of dendritic spine development,
CC contributing to the regulation of dendritic branching and filopodia
CC extension (PubMed:16672654). Plays an important role in membrane
CC trafficking, during junctional remodeling and epithelial polarization.
CC Regulates surface levels of adherens junction proteins such as CDH1.
CC Required for NTRK1 sorting to the recycling pathway from early
CC endosomes (PubMed:26446845). {ECO:0000250|UniProtKB:P62331,
CC ECO:0000269|PubMed:16672654, ECO:0000269|PubMed:26446845}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P62330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P62330};
CC -!- ACTIVITY REGULATION: Activation is generally mediated by guanine
CC exchange factor (GEF), while inactivation through hydrolysis of bound
CC GTP is catalyzed by GTPases activating protein (GAP). Inactivated by
CC ACAP1 and ACAP2 (By similarity). Activated by NGF via NTRK1
CC (PubMed:26446845). {ECO:0000250|UniProtKB:P62330,
CC ECO:0000269|PubMed:26446845}.
CC -!- SUBUNIT: Interacts (when activated) with GGA1, GGA2 and GGA3; the
CC interaction is required for proper subcellular location of GGA1, GGA2
CC and GGA3 (By similarity). Interacts with PIP5K1C. Interacts with USP6
CC (via Rab-GAP TBC domain). Interacts with RAB11FIP3 and RAB11FIP4.
CC Interacts with HERC1. Interacts with ARHGAP21. Interacts with ASAP3;
CC the interaction is stabilized by calcium ions. Interacts with NCS1/FREQ
CC at the plasma membrane. Interacts with TBC1D24. Interacts with ECPAS.
CC Interacts with MICALL1. Interacts with SPAG9 homodimers, forming
CC heterotetramers. Interacts with CYTH3 (By similarity). Interacts with
CC ASAP2 (PubMed:10022920). Interacts with UACA (By similarity). Interacts
CC with KIF23, forming heterodimers and heterotetramers (By similarity).
CC Interacts with C9orf72 (By similarity). Interacts (GTP-bound form) with
CC TJAP1/PILT (By similarity). {ECO:0000250|UniProtKB:P62330,
CC ECO:0000250|UniProtKB:P62331, ECO:0000269|PubMed:10022920}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P62330}. Cell membrane
CC {ECO:0000250|UniProtKB:P62330}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62330}. Endosome membrane
CC {ECO:0000250|UniProtKB:P62330}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62330}. Recycling endosome membrane
CC {ECO:0000269|PubMed:26446845}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62330}. Cell projection, filopodium membrane
CC {ECO:0000250|UniProtKB:P62330}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62330}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:P62330}. Cleavage furrow
CC {ECO:0000250|UniProtKB:P62330}. Midbody, Midbody ring
CC {ECO:0000250|UniProtKB:P62330}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P62331}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62331}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000250|UniProtKB:P62331}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62331}. Note=Distributed uniformly on the
CC plasma membrane, as well as throughout the cytoplasm during metaphase.
CC Subsequently concentrated at patches in the equatorial region at the
CC onset of cytokinesis, and becomes distributed in the equatorial region
CC concurrent with cleavage furrow ingression. In late stages of
CC cytokinesis, concentrates at the midbody ring/Flemming body (By
CC similarity). Recruitment to the midbody ring requires both activation
CC by PSD/EFA6A and interaction with KIF23/MKLP1 (By similarity). After
CC abscission of the intercellular bridge, incorporated into one of the
CC daughter cells as a midbody remnant and localizes to punctate
CC structures beneath the plasma membrane (By similarity). Recruited to
CC the cell membrane in association with CYTH2 and ARL4C. Colocalizes with
CC DAB2IP at the plasma membrane and endocytic vesicles (By similarity).
CC Myristoylation is required for proper localization to membranes:
CC myristoylation on Lys-3 allows ARF6 to remain on membranes during the
CC GTPase cycle (By similarity). {ECO:0000250|UniProtKB:P62330,
CC ECO:0000250|UniProtKB:P62331}.
CC -!- PTM: GTP-bound form is myristoylated on Lys-3 by NMT1 and NMT2,
CC allowing ARF6 to remain on membranes during the GTPase cycle, thereby
CC promoting its activity. GDP-bound inactive form is demyristoylated on
CC Lys-3 by SIRT2 at early endosomes or endocytic recycling compartment to
CC allow its efficient activation by a guanine exchange factor (GEF) after
CC GDP release. {ECO:0000250|UniProtKB:P62330}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
CC {ECO:0000305}.
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DR EMBL; L12385; AAA40690.1; -; mRNA.
DR EMBL; BC091146; AAH91146.1; -; mRNA.
DR RefSeq; NP_077066.1; NM_024152.2.
DR AlphaFoldDB; P62332; -.
DR SMR; P62332; -.
DR BioGRID; 249405; 5.
DR IntAct; P62332; 2.
DR STRING; 10116.ENSRNOP00000006355; -.
DR iPTMnet; P62332; -.
DR PhosphoSitePlus; P62332; -.
DR jPOST; P62332; -.
DR PaxDb; P62332; -.
DR PRIDE; P62332; -.
DR Ensembl; ENSRNOT00000097511; ENSRNOP00000079011; ENSRNOG00000070951.
DR Ensembl; ENSRNOT00000101767; ENSRNOP00000077772; ENSRNOG00000070951.
DR Ensembl; ENSRNOT00000115929; ENSRNOP00000080368; ENSRNOG00000070951.
DR GeneID; 79121; -.
DR KEGG; rno:79121; -.
DR UCSC; RGD:621279; rat.
DR CTD; 382; -.
DR RGD; 621279; Arf6.
DR eggNOG; KOG0071; Eukaryota.
DR GeneTree; ENSGT00940000156593; -.
DR HOGENOM; CLU_040729_9_4_1; -.
DR InParanoid; P62332; -.
DR OMA; WSVIPTI; -.
DR OrthoDB; 1362554at2759; -.
DR PhylomeDB; P62332; -.
DR TreeFam; TF300808; -.
DR Reactome; R-RNO-8854214; TBC/RABGAPs.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-8875656; MET receptor recycling.
DR PRO; PR:P62332; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000004791; Expressed in esophagus and 20 other tissues.
DR Genevisible; P62332; RN.
DR GO; GO:0005938; C:cell cortex; ISO:RGD.
DR GO; GO:0032154; C:cleavage furrow; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0031527; C:filopodium membrane; ISO:RGD.
DR GO; GO:0090543; C:Flemming body; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:RGD.
DR GO; GO:0003925; F:G protein activity; ISS:UniProtKB.
DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0031996; F:thioesterase binding; ISO:RGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:RGD.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0032456; P:endocytic recycling; IDA:UniProtKB.
DR GO; GO:1902217; P:erythrocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0090162; P:establishment of epithelial cell polarity; ISO:RGD.
DR GO; GO:0097284; P:hepatocyte apoptotic process; ISO:RGD.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0099562; P:maintenance of postsynaptic density structure; IDA:SynGO.
DR GO; GO:0033028; P:myeloid cell apoptotic process; ISO:RGD.
DR GO; GO:2000171; P:negative regulation of dendrite development; IMP:RGD.
DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISO:RGD.
DR GO; GO:0120183; P:positive regulation of focal adhesion disassembly; ISO:RGD.
DR GO; GO:0051549; P:positive regulation of keratinocyte migration; ISO:RGD.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:RGD.
DR GO; GO:0034394; P:protein localization to cell surface; ISO:RGD.
DR GO; GO:0036010; P:protein localization to endosome; ISS:UniProtKB.
DR GO; GO:0060998; P:regulation of dendritic spine development; IMP:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; ISO:RGD.
DR GO; GO:0010975; P:regulation of neuron projection development; ISO:RGD.
DR GO; GO:1905606; P:regulation of presynapse assembly; IDA:SynGO.
DR GO; GO:0035020; P:regulation of Rac protein signal transduction; ISO:RGD.
DR GO; GO:0097178; P:ruffle assembly; ISO:RGD.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IDA:SynGO.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd04149; Arf6; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR041838; Arf6.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR024156; Small_GTPase_ARF.
DR InterPro; IPR006689; Small_GTPase_ARF/SAR.
DR PANTHER; PTHR11711; PTHR11711; 1.
DR Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00178; SAR; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51417; ARF; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasm; Differentiation; Endosome;
KW Golgi apparatus; GTP-binding; Hydrolase; Lipoprotein; Membrane; Myristate;
KW Neurogenesis; Nucleotide-binding; Protein transport; Reference proteome;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P62330"
FT CHAIN 2..175
FT /note="ADP-ribosylation factor 6"
FT /id="PRO_0000207402"
FT BINDING 23..28
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62330"
FT BINDING 41..44
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62330"
FT BINDING 63..67
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62330"
FT BINDING 122..125
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62330"
FT BINDING 155..156
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62330"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P62330"
FT LIPID 3
FT /note="N6-myristoyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P62330"
SQ SEQUENCE 175 AA; 20082 MW; 49E38E59AEA52B98 CRC64;
MGKVLSKIFG NKEMRILMLG LDAAGKTTIL YKLKLGQSVT TIPTVGFNVE TVTYKNVKFN
VWDVGGQDKI RPLWRHYYTG TQGLIFVVDC ADRDRIDEAR QELHRIINDR EMRDAIILIF
ANKQDLPDAM KPHEIQEKLG LTRIRDRNWY VQPSCATSGD GLYEGLTWLT SNYKS
