DERL1_HUMAN
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 03-AUG-2022, entry version 174.
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=2; 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}.
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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 PDBsum; 5GLF; -.
DR PDBsum; 7CZB; -.
DR AlphaFoldDB; Q9BUN8; -.
DR SMR; Q9BUN8; -.
DR BioGRID; 122559; 480.
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; Q9BUN8; -.
DR PeptideAtlas; Q9BUN8; -.
DR PRIDE; Q9BUN8; -.
DR ProteomicsDB; 79114; -. [Q9BUN8-1]
DR ProteomicsDB; 79115; -. [Q9BUN8-2]
DR TopDownProteomics; Q9BUN8-1; -. [Q9BUN8-1]
DR Antibodypedia; 13772; 240 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 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; GTRFKAM; -.
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; 56 hits in 1085 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 202 other tissues.
DR ExpressionAtlas; Q9BUN8; baseline and differential.
DR Genevisible; Q9BUN8; HS.
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:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
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:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005770; C:late endosome; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
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:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0036503; P:ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045184; P:establishment of protein localization; TAS:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:ParkinsonsUK-UCL.
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 Pfam; PF04511; DER1; 1.
DR SUPFAM; SSF144091; SSF144091; 1.
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
