ID TMM74_HUMAN Reviewed; 305 AA. AC Q96NL1; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 24-JAN-2024, entry version 130. DE RecName: Full=Transmembrane protein 74; GN Name=TMEM74; 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]. 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [3] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=18294959; DOI=10.1016/j.bbrc.2008.02.055; RA Yu C., Wang L., Lv B., Lu Y., Zeng L., Chen Y., Ma D., Shi T., Wang L.; RT "TMEM74, a lysosome and autophagosome protein, regulates autophagy."; RL Biochem. Biophys. Res. Commun. 369:622-629(2008). RN [4] RP FUNCTION. RX PubMed=19029833; DOI=10.4161/auto.5.1.7247; RA He P., Peng Z., Luo Y., Wang L., Yu P., Deng W., An Y., Shi T., Ma D.; RT "High-throughput functional screening for autophagy-related genes and RT identification of TM9SF1 as an autophagosome-inducing gene."; RL Autophagy 5:52-60(2009). CC -!- FUNCTION: Plays an essential role in autophagy. TMEM74-induced CC autophagy may involve PI3K signal transduction. CC {ECO:0000269|PubMed:18294959, ECO:0000269|PubMed:19029833}. CC -!- INTERACTION: CC Q96NL1; Q13520: AQP6; NbExp=3; IntAct=EBI-10292091, EBI-13059134; CC Q96NL1; Q969F0: FATE1; NbExp=3; IntAct=EBI-10292091, EBI-743099; CC Q96NL1; Q9H400: LIME1; NbExp=3; IntAct=EBI-10292091, EBI-2830566; CC Q96NL1; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-10292091, EBI-12070086; CC Q96NL1; Q69YG0: TMEM42; NbExp=3; IntAct=EBI-10292091, EBI-12038591; CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:18294959}; CC Multi-pass membrane protein {ECO:0000269|PubMed:18294959}. Cytoplasmic CC vesicle, autophagosome membrane {ECO:0000269|PubMed:18294959}; Multi- CC pass membrane protein {ECO:0000269|PubMed:18294959}. CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, and placenta. CC {ECO:0000269|PubMed:18294959}. CC -!- SIMILARITY: Belongs to the TMEM74 family. {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; AK055230; BAB70881.1; -; mRNA. DR EMBL; BC030710; AAH30710.1; -; mRNA. DR CCDS; CCDS6310.1; -. DR RefSeq; NP_694560.1; NM_153015.2. DR AlphaFoldDB; Q96NL1; -. DR BioGRID; 127621; 124. DR IntAct; Q96NL1; 5. DR STRING; 9606.ENSP00000297459; -. DR TCDB; 8.A.122.2.1; the vesicular membrane neurensin/tmem74 (neurensin/tmem74) family. DR PhosphoSitePlus; Q96NL1; -. DR BioMuta; TMEM74; -. DR DMDM; 74732587; -. DR MassIVE; Q96NL1; -. DR PaxDb; 9606-ENSP00000297459; -. DR PeptideAtlas; Q96NL1; -. DR ProteomicsDB; 77529; -. DR Antibodypedia; 3040; 105 antibodies from 22 providers. DR DNASU; 157753; -. DR Ensembl; ENST00000297459.4; ENSP00000297459.3; ENSG00000164841.5. DR GeneID; 157753; -. DR KEGG; hsa:157753; -. DR MANE-Select; ENST00000297459.4; ENSP00000297459.3; NM_153015.3; NP_694560.1. DR UCSC; uc003ymy.2; human. DR AGR; HGNC:26409; -. DR CTD; 157753; -. DR DisGeNET; 157753; -. DR GeneCards; TMEM74; -. DR HGNC; HGNC:26409; TMEM74. DR HPA; ENSG00000164841; Tissue enhanced (brain, retina). DR MIM; 613935; gene. DR neXtProt; NX_Q96NL1; -. DR OpenTargets; ENSG00000164841; -. DR PharmGKB; PA142670785; -. DR VEuPathDB; HostDB:ENSG00000164841; -. DR eggNOG; ENOG502QUYY; Eukaryota. DR GeneTree; ENSGT00530000063880; -. DR HOGENOM; CLU_079915_0_0_1; -. DR InParanoid; Q96NL1; -. DR OMA; GRKVCNC; -. DR OrthoDB; 5313320at2759; -. DR PhylomeDB; Q96NL1; -. DR TreeFam; TF335735; -. DR PathwayCommons; Q96NL1; -. DR SignaLink; Q96NL1; -. DR BioGRID-ORCS; 157753; 9 hits in 1149 CRISPR screens. DR ChiTaRS; TMEM74; human. DR GenomeRNAi; 157753; -. DR Pharos; Q96NL1; Tbio. DR PRO; PR:Q96NL1; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q96NL1; Protein. DR Bgee; ENSG00000164841; Expressed in secondary oocyte and 104 other cell types or tissues. DR ExpressionAtlas; Q96NL1; baseline and differential. DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl. DR GO; GO:0051867; P:general adaptation syndrome, behavioral process; IEA:Ensembl. DR GO; GO:0016236; P:macroautophagy; IMP:HGNC. DR InterPro; IPR029695; TMEM74-like. DR PANTHER; PTHR16125; TRANSMEMBRANE PROTEIN 74; 1. DR PANTHER; PTHR16125:SF3; TRANSMEMBRANE PROTEIN 74; 1. DR Pfam; PF14927; Neurensin; 1. DR Genevisible; Q96NL1; HS. PE 1: Evidence at protein level; KW Autophagy; Cytoplasmic vesicle; Lysosome; Membrane; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1..305 FT /note="Transmembrane protein 74" FT /id="PRO_0000259600" FT TRANSMEM 178..198 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 232..252 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 52..88 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 123..143 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 52..79 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 305 AA; 33338 MW; 9521A382F126B683 CRC64; MELHYLAKKS NQADLCDARD WSSRGLPGDQ ADTAATRAAL CCQKQCASTP RATEMEGSKL SSSPASPSSS LQNSTLQPDA FPPGLLHSGN NQITAERKVC NCCSQELETS FTYVDKNINL EQRNRSSPSA KGHNHPGELG WENPNEWSQE AAISLISEEE DDTSSEATSS GKSIDYGFIS AILFLVTGIL LVIISYIVPR EVTVDPNTVA AREMERLEKE SARLGAHLDR CVIAGLCLLT LGGVILSCLL MMSMWKGELY RRNRFASSKE SAKLYGSFNF RMKTSTNENT LELSLVEEDA LAVQS //