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 27-MAR-2024, entry version 226. 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 FUNCTION, INTERACTION WITH RAB11FIP3; RAB11A; ASAP1; RAB3IP AND RHO, AND RP SUBCELLULAR LOCATION. RX PubMed=25673879; DOI=10.1242/jcs.162925; RA Wang J., Deretic D.; RT "The Arf and Rab11 effector FIP3 acts synergistically with ASAP1 to direct RT Rabin8 in ciliary receptor targeting."; RL J. Cell Sci. 128:1375-1385(2015). RN [12] RP INTERACTION WITH RAB3IP; RAB11A AND RAB11FIP3. RX PubMed=26258637; DOI=10.1038/nsmb.3065; RA Vetter M., Stehle R., Basquin C., Lorentzen E.; RT "Structure of Rab11-FIP3-Rabin8 reveals simultaneous binding of FIP3 and RT Rabin8 effectors to Rab11."; RL Nat. Struct. Mol. Biol. 22:695-702(2015). RN [13] 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 [14] 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. Part of the ciliary targeting CC complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, CC which direct preciliary vesicle trafficking to mother centriole and CC ciliogenesis initiation (PubMed:25673879). CC {ECO:0000269|PubMed:25673879}. CC -!- SUBUNIT: Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 CC and ARF4; the complex promotes preciliary trafficking; the complex CC binds to RHO in photoreceptor cells and promotes RHO ciliary transport. CC {ECO:0000269|PubMed:25673879, ECO:0000269|PubMed:26258637}. 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 {ECO:0000269|PubMed:25673879}. CC Membrane {ECO:0000305}; Lipid-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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 279. DR DIP; DIP-38214N; -. DR IntAct; P18085; 80. DR MINT; P18085; -. DR STRING; 9606.ENSP00000306010; -. DR DrugBank; DB04315; Guanosine-5'-Diphosphate. DR GlyGen; P18085; 3 sites, 1 O-linked glycan (3 sites). 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; 9606-ENSP00000306010; -. DR PeptideAtlas; P18085; -. DR PRIDE; P18085; -. DR ProteomicsDB; 53547; -. DR Pumba; P18085; -. DR TopDownProteomics; P18085; -. DR Antibodypedia; 46310; 269 antibodies from 33 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 AGR; HGNC:655; -. 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; GRKWYIQ; -. DR OrthoDB; 5474610at2759; -. 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 SIGNOR; P18085; -. DR BioGRID-ORCS; 378; 494 hits in 1128 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 215 other cell types or tissues. DR ExpressionAtlas; P18085; baseline and differential. 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:0000139; C:Golgi membrane; IDA:UniProtKB. 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:0106274; F:NAD+-protein-arginine ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:1990583; F:phospholipase D activator 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:0061512; P:protein localization to cilium; IEA:Ensembl. DR GO; GO:1902017; P:regulation of cilium assembly; IDA:UniProtKB. 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; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR045872; Arf1-5-like. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR006689; Small_GTPase_ARF/SAR. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR11711; ADP RIBOSYLATION FACTOR-RELATED; 1. DR PANTHER; PTHR11711:SF110; ADP-RIBOSYLATION FACTOR 4; 1. DR Pfam; PF00025; Arf; 1. DR PRINTS; PR00328; SAR1GTPBP. DR SMART; SM00177; ARF; 1. DR SMART; SM00175; RAB; 1. DR SMART; SM00178; SAR; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51417; ARF; 1. DR Genevisible; P18085; HS. 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 //