TMM59_HUMAN
ID TMM59_HUMAN Reviewed; 323 AA.
AC Q9BXS4; B3KQL7; O75393; Q4VBP9; Q5T705; Q96KX7;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Transmembrane protein 59;
DE AltName: Full=Liver membrane-bound protein;
DE Flags: Precursor;
GN Name=TMEM59; Synonyms=C1orf8; ORFNames=HSPC001, UNQ169/PRO195;
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=Fetal liver;
RA Qu X., Zhang C., Zhai Y., Wu S., Yu Y., Wei H., Xing G., Lu C., Zhou G.,
RA Dong C., He F.;
RT "Homo sapiens liver membrane-bound protein mRNA.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46.
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Lung;
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 FUNCTION, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=20427278; DOI=10.1074/jbc.m109.055608;
RA Ullrich S., Munch A., Neumann S., Kremmer E., Tatzelt J.,
RA Lichtenthaler S.F.;
RT "The novel membrane protein TMEM59 modulates complex glycosylation, cell
RT surface expression, and secretion of the amyloid precursor protein.";
RL J. Biol. Chem. 285:20664-20674(2010).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, INTERACTION
RP WITH ATG16L1, AND MUTAGENESIS OF TYR-268; GLU-272; TYR-277 AND LEU-280.
RX PubMed=23376921; DOI=10.1038/emboj.2013.8;
RA Boada-Romero E., Letek M., Fleischer A., Pallauf K., Ramon-Barros C.,
RA Pimentel-Muinos F.X.;
RT "TMEM59 defines a novel ATG16L1-binding motif that promotes local
RT activation of LC3.";
RL EMBO J. 32:566-582(2013).
RN [10]
RP FUNCTION, INTERACTION WITH ATG16L1, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF TYR-268; VAL-269; GLU-272; LYS-273; TYR-277; GLY-278 AND LEU-280.
RX PubMed=27273576; DOI=10.1038/ncomms11821;
RA Boada-Romero E., Serramito-Gomez I., Sacristan M.P., Boone D.L.,
RA Xavier R.J., Pimentel-Muinos F.X.;
RT "The T300A Crohn's disease risk polymorphism impairs function of the WD40
RT domain of ATG16L1.";
RL Nat. Commun. 7:11821-11821(2016).
CC -!- FUNCTION: Acts as a regulator of autophagy in response to S.aureus
CC infection by promoting activation of LC3 (MAP1LC3A, MAP1LC3B or
CC MAP1LC3C). Acts by interacting with ATG16L1, leading to promote a
CC functional complex between LC3 and ATG16L1 and promoting LC3 lipidation
CC and subsequent activation of autophagy (PubMed:27273576,
CC PubMed:23376921). Modulates the O-glycosylation and complex N-
CC glycosylation steps occurring during the Golgi maturation of several
CC proteins such as APP, BACE1, SEAP or PRNP (PubMed:20427278). Inhibits
CC APP transport to the cell surface and further shedding
CC (PubMed:20427278). {ECO:0000269|PubMed:20427278,
CC ECO:0000269|PubMed:23376921, ECO:0000269|PubMed:27273576}.
CC -!- SUBUNIT: Interacts with ATG16L1 (via WD repeats).
CC {ECO:0000269|PubMed:23376921, ECO:0000269|PubMed:27273576}.
CC -!- INTERACTION:
CC Q9BXS4; Q676U5: ATG16L1; NbExp=6; IntAct=EBI-7054441, EBI-535909;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:23376921, ECO:0000269|PubMed:27273576}; Single-pass
CC type I membrane protein {ECO:0000255}. Lysosome membrane
CC {ECO:0000269|PubMed:23376921, ECO:0000269|PubMed:27273576}; Single-pass
CC type I membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000269|PubMed:23376921}; Single-pass type I membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:20427278};
CC Single-pass type I membrane protein {ECO:0000255}. Note=Mainly
CC localizes to late endosomes/lysosomes. Probably first exported to the
CC cell surface and then actively endocytosed to transiently localize in
CC early endosomes on its way to the late endosomal/lysosomal compartment
CC where it becomes quickly degraded. {ECO:0000269|PubMed:23376921}.
CC -!- DOMAIN: The ATG16L1-binding motif mediates interaction with ATG16L1 and
CC promotes autophagy. {ECO:0000269|PubMed:23376921}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20427278}.
CC -!- SIMILARITY: Belongs to the TMEM59 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC39890.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH03106.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF290615; AAK28026.1; -; mRNA.
DR EMBL; AF047439; AAC39890.1; ALT_FRAME; mRNA.
DR EMBL; AY359029; AAQ89388.1; -; mRNA.
DR EMBL; AK075187; BAG52079.1; -; mRNA.
DR EMBL; AK075505; BAC11658.1; -; mRNA.
DR EMBL; AL353898; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06707.1; -; Genomic_DNA.
DR EMBL; BC003106; AAH03106.1; ALT_INIT; mRNA.
DR EMBL; BC016374; AAH16374.1; -; mRNA.
DR EMBL; BC095464; AAH95464.1; -; mRNA.
DR CCDS; CCDS586.1; -.
DR RefSeq; NP_001291972.1; NM_001305043.1.
DR RefSeq; NP_001291978.1; NM_001305049.1.
DR RefSeq; NP_001291979.1; NM_001305050.1.
DR RefSeq; NP_001291980.1; NM_001305051.1.
DR RefSeq; NP_001291981.1; NM_001305052.1.
DR RefSeq; NP_001291995.1; NM_001305066.1.
DR RefSeq; NP_004863.2; NM_004872.4.
DR AlphaFoldDB; Q9BXS4; -.
DR BioGRID; 114904; 233.
DR IntAct; Q9BXS4; 11.
DR MINT; Q9BXS4; -.
DR STRING; 9606.ENSP00000234831; -.
DR TCDB; 8.A.84.1.4; the insulin secretion regulator tmem59 (tmem59) family.
DR GlyGen; Q9BXS4; 1 site.
DR iPTMnet; Q9BXS4; -.
DR PhosphoSitePlus; Q9BXS4; -.
DR SwissPalm; Q9BXS4; -.
DR BioMuta; TMEM59; -.
DR DMDM; 18202737; -.
DR EPD; Q9BXS4; -.
DR jPOST; Q9BXS4; -.
DR MassIVE; Q9BXS4; -.
DR MaxQB; Q9BXS4; -.
DR PaxDb; Q9BXS4; -.
DR PeptideAtlas; Q9BXS4; -.
DR PRIDE; Q9BXS4; -.
DR ProteomicsDB; 79491; -.
DR Antibodypedia; 46893; 99 antibodies from 28 providers.
DR DNASU; 9528; -.
DR Ensembl; ENST00000234831.10; ENSP00000234831.5; ENSG00000116209.12.
DR GeneID; 9528; -.
DR KEGG; hsa:9528; -.
DR MANE-Select; ENST00000234831.10; ENSP00000234831.5; NM_004872.5; NP_004863.2.
DR UCSC; uc001cwp.4; human.
DR CTD; 9528; -.
DR DisGeNET; 9528; -.
DR GeneCards; TMEM59; -.
DR HGNC; HGNC:1239; TMEM59.
DR HPA; ENSG00000116209; Low tissue specificity.
DR neXtProt; NX_Q9BXS4; -.
DR OpenTargets; ENSG00000116209; -.
DR PharmGKB; PA25620; -.
DR VEuPathDB; HostDB:ENSG00000116209; -.
DR eggNOG; ENOG502QUIS; Eukaryota.
DR GeneTree; ENSGT00390000008279; -.
DR HOGENOM; CLU_059747_1_0_1; -.
DR InParanoid; Q9BXS4; -.
DR OMA; INSSWIL; -.
DR OrthoDB; 1102891at2759; -.
DR PhylomeDB; Q9BXS4; -.
DR TreeFam; TF331226; -.
DR PathwayCommons; Q9BXS4; -.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; Q9BXS4; -.
DR BioGRID-ORCS; 9528; 9 hits in 1027 CRISPR screens.
DR ChiTaRS; TMEM59; human.
DR GeneWiki; TMEM59; -.
DR GenomeRNAi; 9528; -.
DR Pharos; Q9BXS4; Tbio.
DR PRO; PR:Q9BXS4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BXS4; protein.
DR Bgee; ENSG00000116209; Expressed in olfactory segment of nasal mucosa and 206 other tissues.
DR ExpressionAtlas; Q9BXS4; baseline and differential.
DR Genevisible; Q9BXS4; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000137; C:Golgi cis cisterna; IDA:UniProtKB.
DR GO; GO:0005797; C:Golgi medial cisterna; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000138; C:Golgi trans cisterna; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; IEA:Ensembl.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; IDA:UniProtKB.
DR InterPro; IPR022065; Uncharacterised_TMEM59.
DR PANTHER; PTHR28652; PTHR28652; 1.
DR Pfam; PF12280; BSMAP; 1.
PE 1: Evidence at protein level;
KW Autophagy; Cell membrane; Endosome; Glycoprotein; Golgi apparatus;
KW Lysosome; Membrane; Phosphoprotein; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..323
FT /note="Transmembrane protein 59"
FT /id="PRO_0000003003"
FT TOPO_DOM 36..238
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..323
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 263..281
FT /note="ATG16L1-binding motif"
FT /evidence="ECO:0000269|PubMed:23376921,
FT ECO:0000269|PubMed:27273576"
FT MOD_RES 303
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9QY73"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:20427278"
FT VARIANT 46
FT /note="A -> V (in dbSNP:rs41294776)"
FT /evidence="ECO:0000269|PubMed:11042152"
FT /id="VAR_063397"
FT MUTAGEN 268
FT /note="Y->A,F: Impaired ability to activate LC3. Impaired
FT interaction with ATG16L1."
FT /evidence="ECO:0000269|PubMed:23376921,
FT ECO:0000269|PubMed:27273576"
FT MUTAGEN 268
FT /note="Y->W: Does not affect ability to activate LC3."
FT /evidence="ECO:0000269|PubMed:23376921"
FT MUTAGEN 269
FT /note="V->A: No effect on interaction with ATG16L1."
FT /evidence="ECO:0000269|PubMed:27273576"
FT MUTAGEN 272
FT /note="E->A,D: Does not affect ability to activate LC3. No
FT effect on interaction with ATG16L1."
FT /evidence="ECO:0000269|PubMed:23376921,
FT ECO:0000269|PubMed:27273576"
FT MUTAGEN 273
FT /note="K->A: No effect on interaction with ATG16L1."
FT /evidence="ECO:0000269|PubMed:27273576"
FT MUTAGEN 277
FT /note="Y->A: Impaired ability to activate LC3. Impaired
FT interaction with ATG16L1."
FT /evidence="ECO:0000269|PubMed:23376921,
FT ECO:0000269|PubMed:27273576"
FT MUTAGEN 277
FT /note="Y->W,F: Does not affect ability to activate LC3."
FT /evidence="ECO:0000269|PubMed:23376921"
FT MUTAGEN 278
FT /note="G->A: No effect on interaction with ATG16L1."
FT /evidence="ECO:0000269|PubMed:27273576"
FT MUTAGEN 280
FT /note="L->A,V: Impaired ability to activate LC3. Impaired
FT interaction with ATG16L1."
FT /evidence="ECO:0000269|PubMed:23376921,
FT ECO:0000269|PubMed:27273576"
FT CONFLICT 209
FT /note="Y -> SD (in Ref. 7; AAH16374)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 323 AA; 36223 MW; 0926AB7D12D1B902 CRC64;
MAAPKGSLWV RTQLGLPPLL LLTMALAGGS GTASAEAFDS VLGDTASCHR ACQLTYPLHT
YPKEEELYAC QRGCRLFSIC QFVDDGIDLN RTKLECESAC TEAYSQSDEQ YACHLGCQNQ
LPFAELRQEQ LMSLMPKMHL LFPLTLVRSF WSDMMDSAQS FITSSWTFYL QADDGKIVIF
QSKPEIQYAP HLEQEPTNLR ESSLSKMSYL QMRNSQAHRN FLEDGESDGF LRCLSLNSGW
ILTTTLVLSV MVLLWICCAT VATAVEQYVP SEKLSIYGDL EFMNEQKLNR YPASSLVVVR
SKTEDHEEAG PLPTKVNLAH SEI
