ARL4A_HUMAN
ID ARL4A_HUMAN Reviewed; 200 AA.
AC P40617; A4D119; P80418; Q49AF5;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=ADP-ribosylation factor-like protein 4A;
GN Name=ARL4A; Synonyms=ARL4;
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].
RC TISSUE=Umbilical vein endothelial cell;
RA Rosenwald A.G., Kahn R.A.;
RL Submitted (JAN-1995) to UniProtKB.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Choe I.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [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 GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Melanoma;
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 [8]
RP SUBCELLULAR LOCATION.
RX PubMed=10462049; DOI=10.1016/s0014-5793(99)00759-0;
RA Jacobs S., Schilf C., Fliegert F., Koling S., Weber Y., Schurmann A.,
RA Joost H.-G.;
RT "ADP-ribosylation factor (ARF)-like 4, 6, and 7 represent a subgroup of the
RT ARF family characterization by rapid nucleotide exchange and a nuclear
RT localization signal.";
RL FEBS Lett. 456:384-388(1999).
RN [9]
RP FUNCTION, MYRISTOYLATION, INTERACTION WITH KPNA2, MUTAGENESIS OF THR-34 AND
RP GLN-79, AND SUBCELLULAR LOCATION.
RX PubMed=10980193; DOI=10.1074/jbc.m002470200;
RA Lin C.Y., Huang P.H., Liao W.L., Cheng H.J., Huang C.F., Kuo J.C.,
RA Patton W.A., Massenburg D., Moss J., Lee F.J.;
RT "ARL4, an ARF-like protein that is developmentally regulated and localized
RT to nuclei and nucleoli.";
RL J. Biol. Chem. 275:37815-37823(2000).
RN [10]
RP LACK OF INTERACTION WITH ARL4A.
RX PubMed=10831612; DOI=10.1083/jcb.149.5.1087;
RA Bhamidipati A., Lewis S.A., Cowan N.J.;
RT "ADP ribosylation factor-like protein 2 (Arl2) regulates the interaction of
RT tubulin-folding cofactor D with native tubulin.";
RL J. Cell Biol. 149:1087-1096(2000).
RN [11]
RP FUNCTION, INTERACTION WITH CYTH2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP THR-34 AND GLN-79.
RX PubMed=17398095; DOI=10.1016/j.cub.2007.03.007;
RA Hofmann I., Thompson A., Sanderson C.M., Munro S.;
RT "The Arl4 family of small G proteins can recruit the cytohesin Arf6
RT exchange factors to the plasma membrane.";
RL Curr. Biol. 17:711-716(2007).
CC -!- FUNCTION: Small GTP-binding protein which cycles between an inactive
CC GDP-bound and an active GTP-bound form, and the rate of cycling is
CC regulated by guanine nucleotide exchange factors (GEF) and GTPase-
CC activating proteins (GAP). GTP-binding protein that does not act as an
CC allosteric activator of the cholera toxin catalytic subunit. Recruits
CC CYTH1, CYTH2, CYTH3 and CYTH4 to the plasma membrane in GDP-bound form.
CC {ECO:0000269|PubMed:10980193, ECO:0000269|PubMed:17398095}.
CC -!- SUBUNIT: Interacts with CYTH2. Interacts with KPNA2; the interaction is
CC direct. Does not interacts with ARL4A. {ECO:0000269|PubMed:10980193,
CC ECO:0000269|PubMed:17398095}.
CC -!- INTERACTION:
CC P40617; Q68D86: CCDC102B; NbExp=3; IntAct=EBI-2875746, EBI-10171570;
CC P40617; Q2TAC2: CCDC57; NbExp=3; IntAct=EBI-2875746, EBI-2808286;
CC P40617; O60447: EVI5; NbExp=3; IntAct=EBI-2875746, EBI-852291;
CC P40617; Q08379: GOLGA2; NbExp=6; IntAct=EBI-2875746, EBI-618309;
CC P40617; P08727: KRT19; NbExp=3; IntAct=EBI-2875746, EBI-742756;
CC P40617; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-2875746, EBI-11522433;
CC P40617; Q8WVV4-1: POF1B; NbExp=3; IntAct=EBI-2875746, EBI-11986735;
CC P40617; Q9H0A9: SPATC1L; NbExp=3; IntAct=EBI-2875746, EBI-372911;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Cytoplasm. Nucleus, nucleolus.
CC Note=Localization in the nucleolus is dependent by nucleotide binding.
CC -!- PTM: Myristoylated. {ECO:0000269|PubMed:10980193}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
CC {ECO:0000305}.
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DR EMBL; U73960; AAB39713.1; -; mRNA.
DR EMBL; AK313233; BAG36044.1; -; mRNA.
DR EMBL; AF493890; AAM12604.1; -; mRNA.
DR EMBL; CH236948; EAL24295.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW93650.1; -; Genomic_DNA.
DR EMBL; BC001111; AAH01111.1; -; mRNA.
DR EMBL; BC003027; AAH03027.1; -; mRNA.
DR CCDS; CCDS5359.1; -.
DR RefSeq; NP_001032241.1; NM_001037164.2.
DR RefSeq; NP_001182325.1; NM_001195396.1.
DR RefSeq; NP_005729.1; NM_005738.4.
DR RefSeq; NP_997625.1; NM_212460.3.
DR AlphaFoldDB; P40617; -.
DR SMR; P40617; -.
DR BioGRID; 115428; 19.
DR IntAct; P40617; 10.
DR STRING; 9606.ENSP00000379898; -.
DR GlyGen; P40617; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P40617; -.
DR PhosphoSitePlus; P40617; -.
DR BioMuta; ARL4A; -.
DR DMDM; 1168495; -.
DR EPD; P40617; -.
DR jPOST; P40617; -.
DR MassIVE; P40617; -.
DR PaxDb; P40617; -.
DR PeptideAtlas; P40617; -.
DR PRIDE; P40617; -.
DR ProteomicsDB; 55376; -.
DR Antibodypedia; 25147; 202 antibodies from 32 providers.
DR DNASU; 10124; -.
DR Ensembl; ENST00000356797.7; ENSP00000349250.3; ENSG00000122644.13.
DR Ensembl; ENST00000396662.5; ENSP00000379897.1; ENSG00000122644.13.
DR Ensembl; ENST00000396663.2; ENSP00000379898.1; ENSG00000122644.13.
DR Ensembl; ENST00000396664.2; ENSP00000379899.2; ENSG00000122644.13.
DR Ensembl; ENST00000404894.1; ENSP00000385236.1; ENSG00000122644.13.
DR Ensembl; ENST00000651779.1; ENSP00000498350.1; ENSG00000122644.13.
DR GeneID; 10124; -.
DR KEGG; hsa:10124; -.
DR MANE-Select; ENST00000651779.1; ENSP00000498350.1; NM_005738.5; NP_005729.1.
DR UCSC; uc003ssp.4; human.
DR CTD; 10124; -.
DR DisGeNET; 10124; -.
DR GeneCards; ARL4A; -.
DR HGNC; HGNC:695; ARL4A.
DR HPA; ENSG00000122644; Tissue enhanced (testis).
DR MIM; 604786; gene.
DR neXtProt; NX_P40617; -.
DR OpenTargets; ENSG00000122644; -.
DR PharmGKB; PA24988; -.
DR VEuPathDB; HostDB:ENSG00000122644; -.
DR eggNOG; KOG0070; Eukaryota.
DR GeneTree; ENSGT00940000154546; -.
DR HOGENOM; CLU_040729_9_3_1; -.
DR InParanoid; P40617; -.
DR OMA; FEWIAAN; -.
DR OrthoDB; 1457094at2759; -.
DR PhylomeDB; P40617; -.
DR TreeFam; TF105464; -.
DR PathwayCommons; P40617; -.
DR SignaLink; P40617; -.
DR BioGRID-ORCS; 10124; 69 hits in 1009 CRISPR screens.
DR ChiTaRS; ARL4A; human.
DR GeneWiki; ARL4A; -.
DR GenomeRNAi; 10124; -.
DR Pharos; P40617; Tbio.
DR PRO; PR:P40617; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P40617; protein.
DR Bgee; ENSG00000122644; Expressed in left testis and 100 other tissues.
DR ExpressionAtlas; P40617; baseline and differential.
DR Genevisible; P40617; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 3.40.50.300; -; 1.
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 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; Cytoplasm; GTP-binding; Lipoprotein; Membrane; Myristate;
KW Nucleotide-binding; Nucleus; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..200
FT /note="ADP-ribosylation factor-like protein 4A"
FT /id="PRO_0000207459"
FT BINDING 27..34
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 75..79
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 134..137
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT MUTAGEN 34
FT /note="T->N: Inhibits relocalization of CYTH2 to the plasma
FT membrane. Strongly localized in the nucleolus."
FT /evidence="ECO:0000269|PubMed:10980193,
FT ECO:0000269|PubMed:17398095"
FT MUTAGEN 79
FT /note="Q->L: Localized in the nucleus and nucleolus."
FT /evidence="ECO:0000269|PubMed:10980193,
FT ECO:0000269|PubMed:17398095"
SQ SEQUENCE 200 AA; 22615 MW; 8D93A8C003BD16CF CRC64;
MGNGLSDQTS ILSNLPSFQS FHIVILGLDC AGKTTVLYRL QFNEFVNTVP TKGFNTEKIK
VTLGNSKTVT FHFWDVGGQE KLRPLWKSYT RCTDGIVFVV DSVDVERMEE AKTELHKITR
ISENQGVPVL IVANKQDLRN SLSLSEIEKL LAMGELSSST PWHLQPTCAI IGDGLKEGLE
KLHDMIIKRR KMLRQQKKKR
