ARF4_HUMAN
ID ARF4_HUMAN Reviewed; 180 AA.
AC P18085; B2R7J7; P21371;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=ADP-ribosylation factor 4;
GN Name=ARF4; Synonyms=ARF2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2107548; DOI=10.1073/pnas.87.6.2206;
RA Monaco L., Murtagh J.J. Jr., Newman K.B., Tsai S.-C., Moss J., Vaughan M.;
RT "Selective amplification of an mRNA and related pseudogene for a human ADP-
RT ribosylation factor, a guanine nucleotide-dependent protein activator of
RT cholera toxin.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2206-2210(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1899243; DOI=10.1016/s0021-9258(18)52288-2;
RA Kahn R.A., Kern F.G., Clark J., Gelmann E.P., Rulka C.;
RT "Human ADP-ribosylation factors. A functionally conserved family of GTP-
RT binding proteins.";
RL J. Biol. Chem. 266:2606-2614(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10524252; DOI=10.1016/s0378-1119(99)00290-5;
RA Lebeda R.A., Haun R.S.;
RT "Cloning and characterization of the human ADP-ribosylation factor 4
RT gene.";
RL Gene 237:209-214(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, Placenta, Skin, and Urinary bladder;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-147, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH GDP.
RG Structural genomics consortium (SGC);
RT "Structure of human ADP-ribosylation factor 4.";
RL Submitted (APR-2005) to the PDB data bank.
CC -!- FUNCTION: GTP-binding protein that functions as an allosteric activator
CC of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.
CC Involved in protein trafficking; may modulate vesicle budding and
CC uncoating within the Golgi apparatus.
CC -!- INTERACTION:
CC P18085; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-1237085, EBI-350590;
CC P18085; O75154-1: RAB11FIP3; NbExp=2; IntAct=EBI-1237085, EBI-15605207;
CC P18085; Q96PM5: RCHY1; NbExp=3; IntAct=EBI-1237085, EBI-947779;
CC P18085; Q9H190: SDCBP2; NbExp=3; IntAct=EBI-1237085, EBI-742426;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Membrane {ECO:0000305}; Lipid-
CC anchor {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be ARF2. {ECO:0000305}.
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DR EMBL; M36341; AAA53081.1; -; mRNA.
DR EMBL; AF104238; AAD54674.1; -; Genomic_DNA.
DR EMBL; AF104233; AAD54674.1; JOINED; Genomic_DNA.
DR EMBL; AF104234; AAD54674.1; JOINED; Genomic_DNA.
DR EMBL; AF104235; AAD54674.1; JOINED; Genomic_DNA.
DR EMBL; AF104236; AAD54674.1; JOINED; Genomic_DNA.
DR EMBL; AF104237; AAD54674.1; JOINED; Genomic_DNA.
DR EMBL; AF493883; AAM12597.1; -; mRNA.
DR EMBL; AK313008; BAG35844.1; -; mRNA.
DR EMBL; BC003364; AAH03364.1; -; mRNA.
DR EMBL; BC008753; AAH08753.1; -; mRNA.
DR EMBL; BC016325; AAH16325.1; -; mRNA.
DR EMBL; BC022866; AAH22866.1; -; mRNA.
DR CCDS; CCDS2884.1; -.
DR PIR; B38622; B38622.
DR RefSeq; NP_001651.1; NM_001660.3.
DR PDB; 1Z6X; X-ray; 2.70 A; A/B=1-180.
DR PDBsum; 1Z6X; -.
DR AlphaFoldDB; P18085; -.
DR SMR; P18085; -.
DR BioGRID; 106873; 167.
DR DIP; DIP-38214N; -.
DR IntAct; P18085; 52.
DR MINT; P18085; -.
DR STRING; 9606.ENSP00000306010; -.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR iPTMnet; P18085; -.
DR MetOSite; P18085; -.
DR PhosphoSitePlus; P18085; -.
DR SwissPalm; P18085; -.
DR BioMuta; ARF4; -.
DR DMDM; 114123; -.
DR EPD; P18085; -.
DR jPOST; P18085; -.
DR MassIVE; P18085; -.
DR MaxQB; P18085; -.
DR PaxDb; P18085; -.
DR PeptideAtlas; P18085; -.
DR PRIDE; P18085; -.
DR ProteomicsDB; 53547; -.
DR TopDownProteomics; P18085; -.
DR Antibodypedia; 46310; 240 antibodies from 32 providers.
DR DNASU; 378; -.
DR Ensembl; ENST00000303436.11; ENSP00000306010.6; ENSG00000168374.11.
DR GeneID; 378; -.
DR KEGG; hsa:378; -.
DR MANE-Select; ENST00000303436.11; ENSP00000306010.6; NM_001660.4; NP_001651.1.
DR UCSC; uc003dix.5; human.
DR CTD; 378; -.
DR DisGeNET; 378; -.
DR GeneCards; ARF4; -.
DR HGNC; HGNC:655; ARF4.
DR HPA; ENSG00000168374; Low tissue specificity.
DR MIM; 601177; gene.
DR neXtProt; NX_P18085; -.
DR OpenTargets; ENSG00000168374; -.
DR PharmGKB; PA24937; -.
DR VEuPathDB; HostDB:ENSG00000168374; -.
DR eggNOG; KOG0070; Eukaryota.
DR GeneTree; ENSGT00940000156297; -.
DR HOGENOM; CLU_040729_9_1_1; -.
DR InParanoid; P18085; -.
DR OMA; CATQGEG; -.
DR OrthoDB; 1362554at2759; -.
DR PhylomeDB; P18085; -.
DR TreeFam; TF300808; -.
DR PathwayCommons; P18085; -.
DR Reactome; R-HSA-5620916; VxPx cargo-targeting to cilium.
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR Reactome; R-HSA-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR SignaLink; P18085; -.
DR BioGRID-ORCS; 378; 460 hits in 1047 CRISPR screens.
DR ChiTaRS; ARF4; human.
DR EvolutionaryTrace; P18085; -.
DR GeneWiki; ARF4; -.
DR GenomeRNAi; 378; -.
DR Pharos; P18085; Tbio.
DR PRO; PR:P18085; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P18085; protein.
DR Bgee; ENSG00000168374; Expressed in tibia and 213 other tissues.
DR ExpressionAtlas; P18085; baseline and differential.
DR Genevisible; P18085; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; TAS:Reactome.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome.
DR GO; GO:0031584; P:activation of phospholipase D activity; IDA:UniProtKB.
DR GO; GO:0045176; P:apical protein localization; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; TAS:Reactome.
DR GO; GO:0060996; P:dendritic spine development; IDA:MGI.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IEA:Ensembl.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006471; P:protein ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0061512; P:protein localization to cilium; IEA:Ensembl.
DR GO; GO:0099175; P:regulation of postsynapse organization; IEA:Ensembl.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IGI:WormBase.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd04150; Arf1_5_like; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR045872; Arf1-5-like.
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 3D-structure; ER-Golgi transport; Golgi apparatus; GTP-binding;
KW Lipoprotein; Membrane; Myristate; Nucleotide-binding; Phosphoprotein;
KW Protein transport; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..180
FT /note="ADP-ribosylation factor 4"
FT /id="PRO_0000207391"
FT BINDING 24..31
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 67..71
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 126..129
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805"
FT VARIANT 68
FT /note="V -> A (in dbSNP:rs11550597)"
FT /id="VAR_048317"
FT HELIX 5..8
FT /evidence="ECO:0007829|PDB:1Z6X"
FT TURN 9..12
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 18..25
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 30..37
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 59..67
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 83..95
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 100..112
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:1Z6X"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:1Z6X"
FT HELIX 166..177
FT /evidence="ECO:0007829|PDB:1Z6X"
SQ SEQUENCE 180 AA; 20511 MW; 3A43EB1F37A81BD9 CRC64;
MGLTISSLFS RLFGKKQMRI LMVGLDAAGK TTILYKLKLG EIVTTIPTIG FNVETVEYKN
ICFTVWDVGG QDRIRPLWKH YFQNTQGLIF VVDSNDRERI QEVADELQKM LLVDELRDAV
LLLFANKQDL PNAMAISEMT DKLGLQSLRN RTWYVQATCA TQGTGLYEGL DWLSNELSKR
