RUFY4_HUMAN
ID RUFY4_HUMAN Reviewed; 571 AA.
AC Q6ZNE9; Q6ZR96;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=RUN and FYVE domain-containing protein 4;
GN Name=RUFY4;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 155-571 (ISOFORM 1).
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 [4]
RP FUNCTION, INDUCTION, DOMAIN FYVE AND RUN, INTERACTION WITH RAB7A, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26416964; DOI=10.1083/jcb.201501059;
RA Terawaki S., Camosseto V., Prete F., Wenger T., Papadopoulos A.,
RA Rondeau C., Combes A., Rodriguez Rodrigues C., Vu Manh T.P., Fallet M.,
RA English L., Santamaria R., Soares A.R., Weil T., Hammad H., Desjardins M.,
RA Gorvel J.P., Santos M.A., Gatti E., Pierre P.;
RT "RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome
RT tethering in response to Interleukin-4.";
RL J. Cell Biol. 210:1133-1152(2015).
CC -!- FUNCTION: Positively regulates macroautophagy in primary dendritic
CC cells. Increases autophagic flux, probably by stimulating both
CC autophagosome formation and facilitating tethering with lysosomes.
CC Binds to phosphatidylinositol 3-phosphate (PtdIns3P) through its FYVE-
CC type zinc finger. {ECO:0000269|PubMed:26416964}.
CC -!- SUBUNIT: Interacts (via RUN domain) with RAB7A.
CC {ECO:0000269|PubMed:26416964}.
CC -!- INTERACTION:
CC Q6ZNE9; P55273: CDKN2D; NbExp=3; IntAct=EBI-10181525, EBI-745859;
CC Q6ZNE9; G5E9A7: DMWD; NbExp=3; IntAct=EBI-10181525, EBI-10976677;
CC Q6ZNE9; P14136: GFAP; NbExp=3; IntAct=EBI-10181525, EBI-744302;
CC Q6ZNE9; P42858: HTT; NbExp=3; IntAct=EBI-10181525, EBI-466029;
CC Q6ZNE9; P02545: LMNA; NbExp=3; IntAct=EBI-10181525, EBI-351935;
CC Q6ZNE9; Q8TBB1: LNX1; NbExp=6; IntAct=EBI-10181525, EBI-739832;
CC Q6ZNE9; Q9BXW4: MAP1LC3C; NbExp=3; IntAct=EBI-10181525, EBI-2603996;
CC Q6ZNE9; O14777: NDC80; NbExp=7; IntAct=EBI-10181525, EBI-715849;
CC Q6ZNE9; P35240: NF2; NbExp=3; IntAct=EBI-10181525, EBI-1014472;
CC Q6ZNE9; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-10181525, EBI-5235340;
CC Q6ZNE9; Q86WV8: TSC1; NbExp=3; IntAct=EBI-10181525, EBI-12806590;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome
CC {ECO:0000269|PubMed:26416964}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZNE9-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZNE9-3; Sequence=VSP_035815, VSP_035816;
CC -!- INDUCTION: By IL4/interleukin-4 in dendritic cells.
CC {ECO:0000269|PubMed:26416964}.
CC -!- DOMAIN: The RUN domain and the FYVE-type zinc finger are essential for
CC its function in the positive regulation of macroautophagy.
CC {ECO:0000269|PubMed:26416964}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI13713.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC87417.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR EMBL; AK128393; BAC87417.1; ALT_SEQ; mRNA.
DR EMBL; AC124768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113712; AAI13713.1; ALT_INIT; mRNA.
DR RefSeq; NP_940885.2; NM_198483.3. [Q6ZNE9-2]
DR RefSeq; XP_011509316.1; XM_011511014.2. [Q6ZNE9-2]
DR RefSeq; XP_016859385.1; XM_017003896.1. [Q6ZNE9-2]
DR AlphaFoldDB; Q6ZNE9; -.
DR SMR; Q6ZNE9; -.
DR BioGRID; 130035; 15.
DR IntAct; Q6ZNE9; 12.
DR STRING; 9606.ENSP00000363270; -.
DR iPTMnet; Q6ZNE9; -.
DR PhosphoSitePlus; Q6ZNE9; -.
DR BioMuta; RUFY4; -.
DR DMDM; 215273875; -.
DR EPD; Q6ZNE9; -.
DR jPOST; Q6ZNE9; -.
DR PaxDb; Q6ZNE9; -.
DR PeptideAtlas; Q6ZNE9; -.
DR PRIDE; Q6ZNE9; -.
DR Antibodypedia; 34256; 60 antibodies from 16 providers.
DR DNASU; 285180; -.
DR Ensembl; ENST00000344321.8; ENSP00000345900.7; ENSG00000188282.12. [Q6ZNE9-2]
DR Ensembl; ENST00000457754.6; ENSP00000410091.2; ENSG00000188282.12. [Q6ZNE9-3]
DR GeneID; 285180; -.
DR KEGG; hsa:285180; -.
DR UCSC; uc061shp.1; human. [Q6ZNE9-2]
DR CTD; 285180; -.
DR DisGeNET; 285180; -.
DR GeneCards; RUFY4; -.
DR HGNC; HGNC:24804; RUFY4.
DR HPA; ENSG00000188282; Tissue enhanced (brain, lymphoid tissue).
DR neXtProt; NX_Q6ZNE9; -.
DR OpenTargets; ENSG00000188282; -.
DR PharmGKB; PA147357421; -.
DR VEuPathDB; HostDB:ENSG00000188282; -.
DR eggNOG; KOG1729; Eukaryota.
DR GeneTree; ENSGT00940000154044; -.
DR HOGENOM; CLU_1562395_0_0_1; -.
DR InParanoid; Q6ZNE9; -.
DR OMA; KRERRCP; -.
DR PhylomeDB; Q6ZNE9; -.
DR PathwayCommons; Q6ZNE9; -.
DR SignaLink; Q6ZNE9; -.
DR BioGRID-ORCS; 285180; 1 hit in 216 CRISPR screens.
DR GenomeRNAi; 285180; -.
DR Pharos; Q6ZNE9; Tbio.
DR PRO; PR:Q6ZNE9; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6ZNE9; protein.
DR Bgee; ENSG00000188282; Expressed in granulocyte and 89 other tissues.
DR ExpressionAtlas; Q6ZNE9; baseline and differential.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProtKB.
DR GO; GO:0071353; P:cellular response to interleukin-4; IDA:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:UniProtKB.
DR Gene3D; 1.20.58.900; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR042939; RUFY4.
DR InterPro; IPR004012; Run_dom.
DR InterPro; IPR037213; Run_dom_sf.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR47732; PTHR47732; 1.
DR Pfam; PF02759; RUN; 1.
DR SMART; SM00593; RUN; 1.
DR SUPFAM; SSF140741; SSF140741; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50826; RUN; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasmic vesicle; Metal-binding;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..571
FT /note="RUN and FYVE domain-containing protein 4"
FT /id="PRO_0000284671"
FT DOMAIN 33..166
FT /note="RUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00178"
FT ZN_FING 474..567
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 174..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 521
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 524
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 537
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 540
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 545
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 548
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 559
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 562
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT VAR_SEQ 94..172
FT /note="LKTPLGKGRAFIRFCLARGQLAEALQLCLLNSELTREWYGPRSPLLCPERQE
FT DILDSLYALNGVAFELDLQQPDLDGAW -> GMVWTPEPSALPRTPRRHPGLSLCSQWG
FT GLRVGPPAARPGWSLAHVLRVTLLQFHPNPGKETQKKQRCPKEDPSRIWRA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_035815"
FT VAR_SEQ 173..571
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_035816"
SQ SEQUENCE 571 AA; 64350 MW; 7B45C3BB8685F515 CRC64;
MAEEGAILKV TKDLRAAVSA ILQGYGDGQG PVTDTSAELH RLCGCLELLL QFDQKEQKSF
LGPRKDYWDF LCTALRRQRG NMEPIHFVRS QDKLKTPLGK GRAFIRFCLA RGQLAEALQL
CLLNSELTRE WYGPRSPLLC PERQEDILDS LYALNGVAFE LDLQQPDLDG AWPMFSESRC
SSSTQTQGRR PRKNKDAPKK IPAAYGGPEN VQIEDSHTSQ AICLQDAPSG QQLAGLPRSQ
QQRHLPFFLE KKGESSRKHR YPQSMWEPEG KELQLDQEER APWIEIFLGN STPSTQGQGK
GAMGTQKEVI GMEAEVTGVL LVAEGQRTTE GTHKKEAEWS HVQRLLMPSP RGAVEGAVSG
SRQGSGGSSI LGEPWVLQGH ATKEDSTVEN PQVQTEVTLV ARREEQAEVS LQDEIKSLRL
GLRKAEEQAQ RQEQLLREQE GELQALREQL SRCQEERAEL QAQLEQKQQE AERRDAMYQE
ELGGQRDLVQ AMKRRVLELI QEKDRLWQRL QHLSSMAPEC CVACSKIFGR FSRRYPCRLC
GGLLCHACSM DYKKRDRCCP PCAQGREAQV T
