ID DERL1_HUMAN Reviewed; 251 AA. AC Q9BUN8; B3KW41; E9PH19; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 27-MAR-2024, entry version 183. DE RecName: Full=Derlin-1 {ECO:0000303|PubMed:15215855}; DE AltName: Full=Degradation in endoplasmic reticulum protein 1; DE Short=DERtrin-1; DE AltName: Full=Der1-like protein 1 {ECO:0000303|PubMed:15215855}; GN Name=DERL1 {ECO:0000312|HGNC:HGNC:28454}; Synonyms=DER1; GN ORFNames=UNQ243/PRO276 {ECO:0000312|EMBL:AAQ89177.1}; 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 1). 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 47-131 (ISOFORM 2). RC TISSUE=Esophagus; 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 [5] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION (MICROBIAL INFECTION), RP SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, TISSUE SPECIFICITY, AND RP INTERACTION WITH US11 (MICROBIAL INFECTION). RX PubMed=15215855; DOI=10.1038/nature02592; RA Lilley B.N., Ploegh H.L.; RT "A membrane protein required for dislocation of misfolded proteins from the RT ER."; RL Nature 429:834-840(2004). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND RP INTERACTION WITH US11 AND SELENOS. RX PubMed=15215856; DOI=10.1038/nature02656; RA Ye Y., Shibata Y., Yun C., Ron D., Rapoport T.A.; RT "A membrane protein complex mediates retro-translocation from the ER lumen RT into the cytosol."; RL Nature 429:841-847(2004). RN [7] RP INTERACTION WITH VCP AND SYVN1. RX PubMed=16289116; DOI=10.1016/j.jmb.2005.10.020; RA Schulze A., Standera S., Buerger E., Kikkert M., van Voorden S., Wiertz E., RA Koning F., Kloetzel P.-M., Seeger M.; RT "The ubiquitin-domain protein HERP forms a complex with components of the RT endoplasmic reticulum associated degradation pathway."; RL J. Mol. Biol. 354:1021-1027(2005). RN [8] RP INTERACTION WITH NGLY1. RX PubMed=16055502; DOI=10.1091/mbc.e05-04-0345; RA Katiyar S., Joshi S., Lennarz W.J.; RT "The retrotranslocation protein derlin-1 binds peptide:N-glycanase to the RT endoplasmic reticulum."; RL Mol. Biol. Cell 16:4584-4594(2005). RN [9] RP HOMOOLIGOMERIZATION, AND INTERACTION WITH AMFR; SYVN1; VCP AND SELENOS. RX PubMed=16186510; DOI=10.1073/pnas.0505006102; RA Ye Y., Shibata Y., Kikkert M., van Voorden S., Wiertz E., Rapoport T.A.; RT "Recruitment of the p97 ATPase and ubiquitin ligases to the site of RT retrotranslocation at the endoplasmic reticulum membrane."; RL Proc. Natl. Acad. Sci. U.S.A. 102:14132-14138(2005). RN [10] RP SUBCELLULAR LOCATION, OLIGOMERIZATION, AND INTERACTION WITH SELENOS; VCP; RP SEL1L AND SYVN1. RX PubMed=16186509; DOI=10.1073/pnas.0505014102; RA Lilley B.N., Ploegh H.L.; RT "Multiprotein complexes that link dislocation, ubiquitination, and RT extraction of misfolded proteins from the endoplasmic reticulum membrane."; RL Proc. Natl. Acad. Sci. U.S.A. 102:14296-14301(2005). RN [11] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH DERL3 AND RP VCP. RX PubMed=16449189; DOI=10.1083/jcb.200507057; RA Oda Y., Okada T., Yoshida H., Kaufman R.J., Nagata K., Mori K.; RT "Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein RT response and are required for ER-associated degradation."; RL J. Cell Biol. 172:383-393(2006). RN [12] RP INTERACTION WITH RNF103. RX PubMed=18675248; DOI=10.1016/j.bbrc.2008.07.126; RA Maruyama Y., Yamada M., Takahashi K., Yamada M.; RT "Ubiquitin ligase Kf-1 is involved in the endoplasmic reticulum-associated RT degradation pathway."; RL Biochem. Biophys. Res. Commun. 374:737-741(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [14] RP INTERACTION WITH UBXN6. RX PubMed=19275885; DOI=10.1016/j.bbrc.2009.03.012; RA Nagahama M., Ohnishi M., Kawate Y., Matsui T., Miyake H., Yuasa K., RA Tani K., Tagaya M., Tsuji A.; RT "UBXD1 is a VCP-interacting protein that is involved in ER-associated RT degradation."; RL Biochem. Biophys. Res. Commun. 382:303-308(2009). RN [15] RP INTERACTION WITH TRAM1. RX PubMed=19121997; DOI=10.1074/jbc.m807568200; RA Oresic K., Ng C.L., Tortorella D.; RT "TRAM1 participates in human cytomegalovirus US2- and US11-mediated RT dislocation of an endoplasmic reticulum membrane glycoprotein."; RL J. Biol. Chem. 284:5905-5914(2009). RN [16] RP INTERACTION WITH YOD1. RX PubMed=19818707; DOI=10.1016/j.molcel.2009.09.016; RA Ernst R., Mueller B., Ploegh H.L., Schlieker C.; RT "The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to RT facilitate protein dislocation from the ER."; RL Mol. Cell 36:28-38(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP INTERACTION WITH SELENOK AND SELENOS. RX PubMed=22016385; DOI=10.1074/jbc.m111.310920; RA Shchedrina V.A., Everley R.A., Zhang Y., Gygi S.P., Hatfield D.L., RA Gladyshev V.N.; RT "Selenoprotein K binds multiprotein complexes and is involved in the RT regulation of endoplasmic reticulum homeostasis."; RL J. Biol. Chem. 286:42937-42948(2011). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201 AND SER-226, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP INTERACTION WITH ZFAND2B. RX PubMed=24160817; DOI=10.1042/bj20130710; RA Glinka T., Alter J., Braunstein I., Tzach L., Wei Sheng C., Geifman S., RA Edelmann M.J., Kessler B.M., Stanhill A.; RT "Signal-peptide-mediated translocation is regulated by a p97-AIRAPL RT complex."; RL Biochem. J. 457:253-261(2014). RN [22] RP INTERACTION WITH HM13 AND XBP1, AND MUTAGENESIS OF GLY-180. RX PubMed=25239945; DOI=10.15252/embj.201488208; RA Chen C.Y., Malchus N.S., Hehn B., Stelzer W., Avci D., Langosch D., RA Lemberg M.K.; RT "Signal peptide peptidase functions in ERAD to cleave the unfolded protein RT response regulator XBP1u."; RL EMBO J. 33:2492-2506(2014). RN [23] RP FUNCTION, AND SUBUNIT. RX PubMed=26565908; DOI=10.1016/j.celrep.2015.09.047; RA Kadowaki H., Nagai A., Maruyama T., Takami Y., Satrimafitrah P., Kato H., RA Honda A., Hatta T., Natsume T., Sato T., Kai H., Ichijo H., Nishitoh H.; RT "Pre-emptive quality control protects the ER from protein overload via the RT proximity of ERAD components and SRP."; RL Cell Rep. 13:944-956(2015). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [25] RP FUNCTION. RX PubMed=26692333; DOI=10.1038/nm.4013; RA Osorio F.G., Soria-Valles C., Santiago-Fernandez O., Bernal T., RA Mittelbrunn M., Colado E., Rodriguez F., Bonzon-Kulichenko E., Vazquez J., RA Porta-de-la-Riva M., Ceron J., Fueyo A., Li J., Green A.R., Freije J.M., RA Lopez-Otin C.; RT "Loss of the proteostasis factor AIRAPL causes myeloid transformation by RT deregulating IGF-1 signaling."; RL Nat. Med. 22:91-96(2016). RN [26] RP INTERACTION WITH C18ORF32. RX PubMed=29275994; DOI=10.1016/j.devcel.2017.11.020; RA Bersuker K., Peterson C.W.H., To M., Sahl S.J., Savikhin V., Grossman E.A., RA Nomura D.K., Olzmann J.A.; RT "A Proximity Labeling Strategy Provides Insights into the Composition and RT Dynamics of Lipid Droplet Proteomes."; RL Dev. Cell 44:97-112(2018). RN [27] {ECO:0007744|PDB:5GLF} RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 239-250 IN COMPLEX WITH VCP, RP INTERACTION WITH VCP, SHP MOTIF, AND MUTAGENESIS OF 243-GLY--GLY-245; RP ARG-247 AND LEU-248. RX PubMed=27714797; DOI=10.1002/1873-3468.12447; RA Lim J.J., Lee Y., Yoon S.Y., Ly T.T., Kang J.Y., Youn H.S., An J.Y., RA Lee J.G., Park K.R., Kim T.G., Yang J.K., Jun Y., Eom S.H.; RT "Structural insights into the interaction of human p97 N-terminal domain RT and SHP motif in Derlin-1 rhomboid pseudoprotease."; RL FEBS Lett. 590:4402-4413(2016). RN [28] {ECO:0007744|PDB:7CZB} RP STRUCTURE BY ELECTRON MICROSCOPY (3.8 ANGSTROMS), FUNCTION, SUBUNIT, RP TRANSMEMBRANE DOMAINS, AND MUTAGENESIS OF PHE-70; LEU-73; TYR-164 AND RP ILE-165. RX PubMed=33658201; DOI=10.1126/sciadv.abe8591; RA Rao B., Li S., Yao D., Wang Q., Xia Y., Jia Y., Shen Y., Cao Y.; RT "The cryo-EM structure of an ERAD protein channel formed by tetrameric RT human Derlin-1."; RL Sci. Adv. 7:0-0(2021). CC -!- FUNCTION: Functional component of endoplasmic reticulum-associated CC degradation (ERAD) for misfolded lumenal proteins (PubMed:15215856, CC PubMed:33658201). Forms homotetramers which encircle a large channel CC traversing the endoplasmic reticulum (ER) membrane (PubMed:33658201). CC This allows the retrotranslocation of misfolded proteins from the ER CC into the cytosol where they are ubiquitinated and degraded by the CC proteasome (PubMed:33658201). The channel has a lateral gate within the CC membrane which provides direct access to membrane proteins with no need CC to reenter the ER lumen first (PubMed:33658201). May mediate the CC interaction between VCP and the misfolded protein (PubMed:15215856). CC Also involved in endoplasmic reticulum stress-induced pre-emptive CC quality control, a mechanism that selectively attenuates the CC translocation of newly synthesized proteins into the endoplasmic CC reticulum and reroutes them to the cytosol for proteasomal degradation CC (PubMed:26565908). By controlling the steady-state expression of the CC IGF1R receptor, indirectly regulates the insulin-like growth factor CC receptor signaling pathway (PubMed:26692333). CC {ECO:0000269|PubMed:15215856, ECO:0000269|PubMed:26565908, CC ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:33658201}. CC -!- FUNCTION: (Microbial infection) In case of infection by CC cytomegaloviruses, it plays a central role in the export from the ER CC and subsequent degradation of MHC class I heavy chains via its CC interaction with US11 viral protein, which recognizes and associates CC with MHC class I heavy chains. Also participates in the degradation CC process of misfolded cytomegalovirus US2 protein. CC {ECO:0000269|PubMed:15215855, ECO:0000269|PubMed:15215856}. CC -!- SUBUNIT: Homotetramer (PubMed:33658201). The four subunits of the CC tetramer are arranged in a twofold symmetry (PubMed:33658201). Forms CC heterooligomers with DERL2 and DERL3; binding to DERL3 is poorer than CC that between DERL2 and DERL3. Interacts (via SHP-box motif) with VCP CC (PubMed:16289116, PubMed:16186510, PubMed:16186509, PubMed:16449189, CC PubMed:27714797). Interacts with AMFR, SELENOS, SEL1L, SELENOK and CC SYVN1, as well as with SEL1L-SYVN1 and VCP-SELENOS protein complexes; CC this interaction is weaker than that observed between DERL2 and these CC complexes. Interacts with NGLY1 and YOD1. Does not bind to EDEM1. CC Interacts with DNAJB9. Interacts with RNF103 (PubMed:15215856, CC PubMed:16055502, PubMed:16186509, PubMed:16186510, PubMed:16289116, CC PubMed:16449189, PubMed:18675248, PubMed:19818707, PubMed:22016385). CC Interacts with HM13 (PubMed:25239945). Interacts with XBP1 isoform 1 CC (via luminal/ectodomain domain); the interaction obviates the need for CC ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage CC (PubMed:25239945). Interacts with the signal recognition particle/SRP CC and the SRP receptor; in the process of endoplasmic reticulum stress- CC induced pre-emptive quality control (PubMed:26565908). May interact CC with UBXN6 (PubMed:19275885). Interacts with ZFAND2B; probably through CC VCP (PubMed:24160817). Interacts with CCDC47 (By similarity). Interacts CC with C18orf32 (PubMed:29275994). May interact with TRAM1 CC (PubMed:19121997). {ECO:0000250|UniProtKB:Q99J56, CC ECO:0000269|PubMed:15215856, ECO:0000269|PubMed:16055502, CC ECO:0000269|PubMed:16186509, ECO:0000269|PubMed:16186510, CC ECO:0000269|PubMed:16289116, ECO:0000269|PubMed:16449189, CC ECO:0000269|PubMed:18675248, ECO:0000269|PubMed:19121997, CC ECO:0000269|PubMed:19275885, ECO:0000269|PubMed:19818707, CC ECO:0000269|PubMed:22016385, ECO:0000269|PubMed:24160817, CC ECO:0000269|PubMed:25239945, ECO:0000269|PubMed:26565908, CC ECO:0000269|PubMed:27714797, ECO:0000269|PubMed:29275994, CC ECO:0000269|PubMed:33658201}. CC -!- SUBUNIT: (Microbial infection) Interacts with the cytomegalovirus US11 CC protein. {ECO:0000269|PubMed:15215855, ECO:0000269|PubMed:15215856}. CC -!- INTERACTION: CC Q9BUN8; Q8TB40: ABHD4; NbExp=3; IntAct=EBI-398977, EBI-7131019; CC Q9BUN8; Q13520: AQP6; NbExp=3; IntAct=EBI-398977, EBI-13059134; CC Q9BUN8; P51572: BCAP31; NbExp=3; IntAct=EBI-398977, EBI-77683; CC Q9BUN8; P13569: CFTR; NbExp=8; IntAct=EBI-398977, EBI-349854; CC Q9BUN8; Q9H5X1: CIAO2A; NbExp=3; IntAct=EBI-398977, EBI-752069; CC Q9BUN8; Q96PJ5: FCRL4; NbExp=3; IntAct=EBI-398977, EBI-4314687; CC Q9BUN8; O15552: FFAR2; NbExp=3; IntAct=EBI-398977, EBI-2833872; CC Q9BUN8; Q05329: GAD2; NbExp=3; IntAct=EBI-398977, EBI-9304251; CC Q9BUN8; Q8TCT9: HM13; NbExp=6; IntAct=EBI-398977, EBI-347472; CC Q9BUN8; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-398977, EBI-749265; CC Q9BUN8; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-398977, EBI-739832; CC Q9BUN8; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-398977, EBI-7545592; CC Q9BUN8; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-398977, EBI-10192441; CC Q9BUN8; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-398977, EBI-17247926; CC Q9BUN8; Q14973: SLC10A1; NbExp=3; IntAct=EBI-398977, EBI-3923031; CC Q9BUN8; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-398977, EBI-18159983; CC Q9BUN8; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-398977, EBI-10262251; CC Q9BUN8; Q8TBB6: SLC7A14; NbExp=3; IntAct=EBI-398977, EBI-5235586; CC Q9BUN8; Q9UHI5: SLC7A8; NbExp=3; IntAct=EBI-398977, EBI-13292283; CC Q9BUN8; Q9BQ70: TCF25; NbExp=3; IntAct=EBI-398977, EBI-745182; CC Q9BUN8; Q53QW1: TEX44; NbExp=3; IntAct=EBI-398977, EBI-10278496; CC Q9BUN8; Q6PL24: TMED8; NbExp=3; IntAct=EBI-398977, EBI-11603430; CC Q9BUN8; Q9Y320: TMX2; NbExp=3; IntAct=EBI-398977, EBI-6447886; CC Q9BUN8; Q13049: TRIM32; NbExp=3; IntAct=EBI-398977, EBI-742790; CC Q9BUN8; Q9Y385: UBE2J1; NbExp=3; IntAct=EBI-398977, EBI-988826; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:15215855, ECO:0000269|PubMed:15215856, CC ECO:0000269|PubMed:16186509, ECO:0000269|PubMed:16449189}; Multi-pass CC membrane protein {ECO:0000269|PubMed:15215855, CC ECO:0000269|PubMed:15215856, ECO:0000269|PubMed:16186509, CC ECO:0000269|PubMed:16449189}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BUN8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BUN8-2; Sequence=VSP_041329; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15215855, CC ECO:0000269|PubMed:16449189}. CC -!- SIMILARITY: Belongs to the derlin 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; AY358818; AAQ89177.1; -; mRNA. DR EMBL; AC104316; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC002457; AAH02457.1; -; mRNA. DR EMBL; AK124086; BAG54003.1; -; mRNA. DR CCDS; CCDS47915.1; -. [Q9BUN8-2] DR CCDS; CCDS6337.1; -. [Q9BUN8-1] DR RefSeq; NP_001128143.1; NM_001134671.2. [Q9BUN8-2] DR RefSeq; NP_077271.1; NM_024295.5. [Q9BUN8-1] DR PDB; 5GLF; X-ray; 2.25 A; B/D/F/H=239-250. DR PDB; 7CZB; EM; 3.80 A; A/B/C/D=1-251. DR PDB; 7Y4W; EM; 3.67 A; W/X/Y/Z=1-251. DR PDB; 7Y53; EM; 3.61 A; W/X/Y/Z=1-251. DR PDB; 7Y59; EM; 4.51 A; W/X/Y/Z=1-251. DR PDBsum; 5GLF; -. DR PDBsum; 7CZB; -. DR PDBsum; 7Y4W; -. DR PDBsum; 7Y53; -. DR PDBsum; 7Y59; -. DR AlphaFoldDB; Q9BUN8; -. DR EMDB; EMD-30508; -. DR EMDB; EMD-33608; -. DR EMDB; EMD-33611; -. DR EMDB; EMD-33613; -. DR SMR; Q9BUN8; -. DR BioGRID; 122559; 493. DR CORUM; Q9BUN8; -. DR IntAct; Q9BUN8; 53. DR MINT; Q9BUN8; -. DR STRING; 9606.ENSP00000259512; -. DR TCDB; 3.A.16.1.1; the endoplasmic reticular retrotranslocon (er-rt) family. DR iPTMnet; Q9BUN8; -. DR MetOSite; Q9BUN8; -. DR PhosphoSitePlus; Q9BUN8; -. DR SwissPalm; Q9BUN8; -. DR BioMuta; DERL1; -. DR DMDM; 50400630; -. DR EPD; Q9BUN8; -. DR jPOST; Q9BUN8; -. DR MassIVE; Q9BUN8; -. DR MaxQB; Q9BUN8; -. DR PaxDb; 9606-ENSP00000259512; -. DR PeptideAtlas; Q9BUN8; -. DR ProteomicsDB; 79114; -. [Q9BUN8-1] DR ProteomicsDB; 79115; -. [Q9BUN8-2] DR Pumba; Q9BUN8; -. DR TopDownProteomics; Q9BUN8-1; -. [Q9BUN8-1] DR Antibodypedia; 13772; 264 antibodies from 27 providers. DR DNASU; 79139; -. DR Ensembl; ENST00000259512.9; ENSP00000259512.3; ENSG00000136986.10. [Q9BUN8-1] DR Ensembl; ENST00000405944.7; ENSP00000384289.3; ENSG00000136986.10. [Q9BUN8-2] DR GeneID; 79139; -. DR KEGG; hsa:79139; -. DR MANE-Select; ENST00000259512.9; ENSP00000259512.3; NM_024295.6; NP_077271.1. DR UCSC; uc003ypl.3; human. [Q9BUN8-1] DR AGR; HGNC:28454; -. DR CTD; 79139; -. DR DisGeNET; 79139; -. DR GeneCards; DERL1; -. DR HGNC; HGNC:28454; DERL1. DR HPA; ENSG00000136986; Low tissue specificity. DR MIM; 608813; gene. DR neXtProt; NX_Q9BUN8; -. DR OpenTargets; ENSG00000136986; -. DR PharmGKB; PA134926638; -. DR VEuPathDB; HostDB:ENSG00000136986; -. DR eggNOG; KOG0858; Eukaryota. DR GeneTree; ENSGT00530000063156; -. DR InParanoid; Q9BUN8; -. DR OMA; LWRCVTS; -. DR OrthoDB; 1123482at2759; -. DR PhylomeDB; Q9BUN8; -. DR TreeFam; TF354297; -. DR BRENDA; 3.4.21.105; 2681. DR PathwayCommons; Q9BUN8; -. DR Reactome; R-HSA-382556; ABC-family proteins mediated transport. DR Reactome; R-HSA-532668; N-glycan trimming in the ER and Calnexin/Calreticulin cycle. DR Reactome; R-HSA-5678895; Defective CFTR causes cystic fibrosis. DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins. DR SignaLink; Q9BUN8; -. DR SIGNOR; Q9BUN8; -. DR BioGRID-ORCS; 79139; 57 hits in 1161 CRISPR screens. DR ChiTaRS; DERL1; human. DR GenomeRNAi; 79139; -. DR Pharos; Q9BUN8; Tbio. DR PRO; PR:Q9BUN8; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9BUN8; Protein. DR Bgee; ENSG00000136986; Expressed in secondary oocyte and 204 other cell types or tissues. DR ExpressionAtlas; Q9BUN8; baseline and differential. DR GO; GO:0036513; C:Derlin-1 retrotranslocation complex; IDA:UniProtKB. DR GO; GO:0036502; C:Derlin-1-VIMP complex; IDA:ParkinsonsUK-UCL. DR GO; GO:0005769; C:early endosome; IEA:Ensembl. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IEA:Ensembl. DR GO; GO:0000839; C:Hrd1p ubiquitin ligase ERAD-L complex; IBA:GO_Central. DR GO; GO:0005770; C:late endosome; IEA:Ensembl. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0051117; F:ATPase binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0042288; F:MHC class I protein binding; IDA:UniProtKB. DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB. DR GO; GO:0005047; F:signal recognition particle binding; IDA:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:1990381; F:ubiquitin-specific protease binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0071218; P:cellular response to misfolded protein; IMP:ParkinsonsUK-UCL. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB. DR GO; GO:0036503; P:ERAD pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0045184; P:establishment of protein localization; TAS:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:ParkinsonsUK-UCL. DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB. DR GO; GO:0006986; P:response to unfolded protein; IMP:MGI. DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IDA:UniProtKB. DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IDA:UniProtKB. DR InterPro; IPR007599; DER1. DR InterPro; IPR035952; Rhomboid-like_sf. DR PANTHER; PTHR11009; DER1-LIKE PROTEIN, DERLIN; 1. DR PANTHER; PTHR11009:SF1; DERLIN-1; 1. DR Pfam; PF04511; DER1; 1. DR SUPFAM; SSF144091; Rhomboid-like; 1. DR Genevisible; Q9BUN8; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Endoplasmic reticulum; KW Host-virus interaction; Membrane; Phosphoprotein; Protein transport; KW Reference proteome; Transmembrane; Transmembrane helix; Transport; KW Unfolded protein response. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895" FT CHAIN 2..251 FT /note="Derlin-1" FT /id="PRO_0000219042" FT TOPO_DOM 2..15 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33658201" FT TRANSMEM 16..31 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:33658201" FT TOPO_DOM 32..69 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:33658201" FT TRANSMEM 70..89 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:33658201" FT TOPO_DOM 90..94 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33658201" FT TRANSMEM 95..115 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:33658201" FT TOPO_DOM 116..122 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:33658201" FT TRANSMEM 123..137 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:33658201" FT TOPO_DOM 138..154 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33658201" FT TRANSMEM 155..166 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:33658201" FT TOPO_DOM 167..170 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:33658201" FT TRANSMEM 171..189 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:33658201" FT TOPO_DOM 190..251 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33658201" FT REGION 229..251 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 241..248 FT /note="SHP-box" FT /evidence="ECO:0000305|PubMed:27714797" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 201 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 202 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 226 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 170..189 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041329" FT VARIANT 171 FT /note="I -> V (in dbSNP:rs2272722)" FT /id="VAR_019516" FT MUTAGEN 70 FT /note="F->C: Impaired ERAD substrate degradation." FT /evidence="ECO:0000269|PubMed:33658201" FT MUTAGEN 73 FT /note="L->A: Impaired ERAD substrate degradation." FT /evidence="ECO:0000269|PubMed:33658201" FT MUTAGEN 164 FT /note="Y->A: Impaired ERAD substrate degradation." FT /evidence="ECO:0000269|PubMed:33658201" FT MUTAGEN 165 FT /note="I->A: Impaired ERAD substrate degradation." FT /evidence="ECO:0000269|PubMed:33658201" FT MUTAGEN 180 FT /note="G->V: Reduces interaction with and proteolysis of FT XBP1 isoform 1." FT /evidence="ECO:0000269|PubMed:25239945" FT MUTAGEN 243..245 FT /note="GQG->AQA: Significantly reduced binding to VCP." FT /evidence="ECO:0000269|PubMed:27714797" FT MUTAGEN 247 FT /note="R->A: Significantly reduced binding to VCP." FT /evidence="ECO:0000269|PubMed:27714797" FT MUTAGEN 248 FT /note="L->A: Significantly reduced binding to VCP." FT /evidence="ECO:0000269|PubMed:27714797" FT STRAND 245..247 FT /evidence="ECO:0007829|PDB:5GLF" SQ SEQUENCE 251 AA; 28801 MW; 4A6E0DB68D9AF244 CRC64; MSDIGDWFRS IPAITRYWFA ATVAVPLVGK LGLISPAYLF LWPEAFLYRF QIWRPITATF YFPVGPGTGF LYLVNLYFLY QYSTRLETGA FDGRPADYLF MLLFNWICIV ITGLAMDMQL LMIPLIMSVL YVWAQLNRDM IVSFWFGTRF KACYLPWVIL GFNYIIGGSV INELIGNLVG HLYFFLMFRY PMDLGGRNFL STPQFLYRWL PSRRGGVSGF GVPPASMRRA ADQNGGGGRH NWGQGFRLGD Q //