ARL4C_HUMAN
ID ARL4C_HUMAN Reviewed; 192 AA.
AC P56559; Q4A519; Q53R10; Q9BVN1; Q9UQ34;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=ADP-ribosylation factor-like protein 4C;
DE AltName: Full=ADP-ribosylation factor-like protein 7;
DE AltName: Full=ADP-ribosylation factor-like protein LAK;
GN Name=ARL4C; Synonyms=ARL7;
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] (ISOFORM 1).
RC TISSUE=Testis;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INDUCTION,
RP MUTAGENESIS OF GLY-2, AND SUBCELLULAR LOCATION.
RX PubMed=15147902; DOI=10.1016/j.febslet.2004.04.048;
RA Engel T., Lueken A., Bode G., Hobohm U., Lorkowski S., Schlueter B.,
RA Rust S., Cullen P., Pech M., Assmann G., Seedorf U.;
RT "ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol
RT loading and participates in apolipoprotein AI-dependent cholesterol
RT export.";
RL FEBS Lett. 566:241-246(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney, and 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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-192 (ISOFORM 1).
RA Abe Y., Nezu K., Ueda N.;
RT "ADP-ribosylation factor-like protein LAK.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP FUNCTION, INTERACTION WITH CYTH2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLY-2 AND LYS-34.
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).
RN [11]
RP FUNCTION, INTERACTION WITH ALPHA TUBULIN, MUTAGENESIS OF THR-27 AND GLN-72,
RP AND TISSUE SPECIFICITY.
RX PubMed=19409876; DOI=10.1016/j.bbrc.2009.04.125;
RA Wei S.M., Xie C.G., Abe Y., Cai J.T.;
RT "ADP-ribosylation factor like 7 (ARL7) interacts with alpha-tubulin and
RT modulates intracellular vesicular transport.";
RL Biochem. Biophys. Res. Commun. 384:352-356(2009).
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. May be
CC involved in transport between a perinuclear compartment and the plasma
CC membrane, apparently linked to the ABCA1-mediated cholesterol secretion
CC pathway. Recruits CYTH1, CYTH2, CYTH3 and CYTH4 to the plasma membrane
CC in the GDP-bound form. Regulates the microtubule-dependent
CC intracellular vesicular transport from early endosome to recycling
CC endosome process. {ECO:0000269|PubMed:15147902,
CC ECO:0000269|PubMed:17398095, ECO:0000269|PubMed:19409876}.
CC -!- SUBUNIT: Interacts with CYTH2. Interacts with alpha tubulin;
CC interaction is independent on the ARL4C GTP or GDP binding status.
CC {ECO:0000269|PubMed:17398095, ECO:0000269|PubMed:19409876}.
CC -!- SUBCELLULAR LOCATION: Cell projection, filopodium. Cell membrane.
CC Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56559-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56559-2; Sequence=VSP_055120;
CC -!- TISSUE SPECIFICITY: Expressed in several tumor cell lines (at protein
CC level). Expressed in lung, brain, leukocytes and placenta.
CC {ECO:0000269|PubMed:19409876}.
CC -!- INDUCTION: By liver X-receptor/retinoid X receptor agonists or
CC cholesterol loading. {ECO:0000269|PubMed:15147902}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA75473.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; Y17804; CAB44355.1; -; mRNA.
DR EMBL; AJ579850; CAE30322.1; -; mRNA.
DR EMBL; AJ579851; CAE30323.1; -; mRNA.
DR EMBL; AF493892; AAM12606.1; -; mRNA.
DR EMBL; BT019378; AAV38185.1; -; mRNA.
DR EMBL; BT019379; AAV38186.1; -; mRNA.
DR EMBL; AK314119; BAG36810.1; -; mRNA.
DR EMBL; AC105145; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097713; AAX93114.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW71073.1; -; Genomic_DNA.
DR EMBL; BC001051; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC089043; AAH89043.1; -; mRNA.
DR EMBL; AB016811; BAA75473.1; ALT_INIT; mRNA.
DR CCDS; CCDS2512.1; -. [P56559-1]
DR CCDS; CCDS63169.1; -. [P56559-2]
DR RefSeq; NP_001269360.1; NM_001282431.1. [P56559-2]
DR RefSeq; NP_005728.2; NM_005737.3. [P56559-1]
DR AlphaFoldDB; P56559; -.
DR SMR; P56559; -.
DR BioGRID; 115427; 36.
DR ELM; P56559; -.
DR IntAct; P56559; 21.
DR STRING; 9606.ENSP00000339754; -.
DR iPTMnet; P56559; -.
DR PhosphoSitePlus; P56559; -.
DR BioMuta; ARL4C; -.
DR DMDM; 3913085; -.
DR EPD; P56559; -.
DR jPOST; P56559; -.
DR MassIVE; P56559; -.
DR MaxQB; P56559; -.
DR PaxDb; P56559; -.
DR PeptideAtlas; P56559; -.
DR PRIDE; P56559; -.
DR ProteomicsDB; 56928; -. [P56559-1]
DR Antibodypedia; 34460; 92 antibodies from 20 providers.
DR DNASU; 10123; -.
DR Ensembl; ENST00000339728.6; ENSP00000339754.3; ENSG00000188042.8. [P56559-2]
DR Ensembl; ENST00000390645.2; ENSP00000375057.2; ENSG00000188042.8. [P56559-1]
DR GeneID; 10123; -.
DR KEGG; hsa:10123; -.
DR MANE-Select; ENST00000339728.6; ENSP00000339754.3; NM_001282431.2; NP_001269360.1. [P56559-2]
DR UCSC; uc002vvm.6; human. [P56559-1]
DR CTD; 10123; -.
DR DisGeNET; 10123; -.
DR GeneCards; ARL4C; -.
DR HGNC; HGNC:698; ARL4C.
DR HPA; ENSG00000188042; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 604787; gene.
DR neXtProt; NX_P56559; -.
DR OpenTargets; ENSG00000188042; -.
DR PharmGKB; PA24991; -.
DR VEuPathDB; HostDB:ENSG00000188042; -.
DR eggNOG; KOG0070; Eukaryota.
DR GeneTree; ENSGT00940000160639; -.
DR HOGENOM; CLU_040729_9_2_1; -.
DR InParanoid; P56559; -.
DR OMA; RVQPACA; -.
DR OrthoDB; 1457094at2759; -.
DR PhylomeDB; P56559; -.
DR TreeFam; TF105464; -.
DR PathwayCommons; P56559; -.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR SignaLink; P56559; -.
DR BioGRID-ORCS; 10123; 17 hits in 1073 CRISPR screens.
DR ChiTaRS; ARL4C; human.
DR GenomeRNAi; 10123; -.
DR Pharos; P56559; Tbio.
DR PRO; PR:P56559; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P56559; protein.
DR Bgee; ENSG00000188042; Expressed in pons and 196 other tissues.
DR ExpressionAtlas; P56559; baseline and differential.
DR Genevisible; P56559; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc.
DR GO; GO:0032456; P:endocytic recycling; IDA:UniProtKB.
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 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 Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW GTP-binding; Lipoprotein; Membrane; Myristate; Nucleotide-binding;
KW Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..192
FT /note="ADP-ribosylation factor-like protein 4C"
FT /id="PRO_0000207462"
FT BINDING 20..27
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 68..72
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 127..130
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 VAR_SEQ 192
FT /note="R -> RTGDLRSCEV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15147902"
FT /id="VSP_055120"
FT MUTAGEN 2
FT /note="G->A: Cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:15147902,
FT ECO:0000269|PubMed:17398095"
FT MUTAGEN 27
FT /note="T->N: Does not interact with alpha tubulin."
FT /evidence="ECO:0000269|PubMed:19409876"
FT MUTAGEN 34
FT /note="K->N: Cytoplasmic localization. Increases GDP-form."
FT /evidence="ECO:0000269|PubMed:17398095"
FT MUTAGEN 72
FT /note="Q->L: Does not interact with alpha tubulin.
FT Activates transferrin transport from early endosome to
FT recycling endosome."
FT /evidence="ECO:0000269|PubMed:19409876"
SQ SEQUENCE 192 AA; 21487 MW; 389BD49CF9E6D10D CRC64;
MGNISSNISA FQSLHIVMLG LDSAGKTTVL YRLKFNEFVN TVPTIGFNTE KIKLSNGTAK
GISCHFWDVG GQEKLRPLWK SYSRCTDGII YVVDSVDVDR LEEAKTELHK VTKFAENQGT
PLLVIANKQD LPKSLPVAEI EKQLALHELI PATTYHVQPA CAIIGEGLTE GMDKLYEMIL
KRRKSLKQKK KR
