DERL1_MOUSE
ID DERL1_MOUSE Reviewed; 251 AA.
AC Q99J56; Q3U6Z2; Q9D918;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Derlin-1 {ECO:0000303|PubMed:16186509};
DE AltName: Full=Degradation in endoplasmic reticulum protein 1;
DE AltName: Full=Der1-like protein 1 {ECO:0000303|PubMed:16186509};
GN Name=Derl1 {ECO:0000312|MGI:MGI:1915069}; Synonyms=Der1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Cerebellum, and Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary tumor;
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 TISSUE SPECIFICITY, AND INDUCTION.
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 [4]
RP INDUCTION.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
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 [7]
RP INTERACTION WITH DNAJB9.
RX PubMed=22267725; DOI=10.1074/jbc.m111.311290;
RA Lai C.W., Otero J.H., Hendershot L.M., Snapp E.;
RT "ERdj4 protein is a soluble endoplasmic reticulum (ER) DnaJ family protein
RT that interacts with ER-associated degradation machinery.";
RL J. Biol. Chem. 287:7969-7978(2012).
RN [8]
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 [9]
RP INTERACTION WITH CCDC47.
RX PubMed=25009997; DOI=10.1016/j.ydbio.2014.06.024;
RA Yamamoto S., Yamazaki T., Komazaki S., Yamashita T., Osaki M.,
RA Matsubayashi M., Kidoya H., Takakura N., Yamazaki D., Kakizawa S.;
RT "Contribution of calumin to embryogenesis through participation in the
RT endoplasmic reticulum-associated degradation activity.";
RL Dev. Biol. 393:33-43(2014).
CC -!- FUNCTION: Functional component of endoplasmic reticulum-associated
CC degradation (ERAD) for misfolded lumenal proteins. Forms homotetramers
CC which encircle a large channel traversing the endoplasmic reticulum
CC (ER) membrane. This allows the retrotranslocation of misfolded proteins
CC from the ER into the cytosol where they are ubiquitinated and degraded
CC by the proteasome. The channel has a lateral gate within the membrane
CC which provides direct access to membrane proteins with no need to
CC reenter the ER lumen first. May mediate the interaction between VCP and
CC the misfolded protein. Also involved in endoplasmic reticulum stress-
CC induced pre-emptive quality control, a mechanism that selectively
CC attenuates the translocation of newly synthesized proteins into the
CC endoplasmic reticulum and reroutes them to the cytosol for proteasomal
CC degradation. By controlling the steady-state expression of the IGF1R
CC receptor, indirectly regulates the insulin-like growth factor receptor
CC signaling pathway. {ECO:0000250|UniProtKB:Q9BUN8}.
CC -!- SUBUNIT: Homotetramer (By similarity). The four subunits of the
CC tetramer are arranged in a twofold symmetry (By similarity). Forms
CC homo- and heterooligomers with DERL2 and DERL3; binding to DERL3 is
CC poorer than that between DERL2 and DERL3. Interacts (via SHP-box motif)
CC with VCP (By similarity). Interacts with AMFR, SELENOS, SEL1L, SELENOK
CC and SYVN1, as well as with SEL1L-SYVN1 and VCP-SELENOS protein
CC complexes; this interaction is weaker than that observed between DERL2
CC and these complexes. Interacts with NGLY1 and YOD1. Does not bind to
CC EDEM1 (By similarity). Interacts with DNAJB9 (PubMed:22267725).
CC Interacts with RNF103. Interacts with HM13. Interacts with XBP1 isoform
CC 1 (via luminal/ectodomain domain); the interaction obviates the need
CC for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1
CC cleavage. Interacts with the signal recognition particle/SRP and the
CC SRP receptor; in the process of endoplasmic reticulum stress-induced
CC pre-emptive quality control. May interact with UBXN6 (By similarity).
CC Interacts with ZFAND2B; probably through VCP (PubMed:24160817).
CC Interacts with CCDC47 (PubMed:25009997). Interacts with C18orf32 (By
CC similarity). May interact with TRAM1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9BUN8, ECO:0000269|PubMed:22267725,
CC ECO:0000269|PubMed:24160817, ECO:0000269|PubMed:25009997}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9BUN8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9BUN8}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with lowest levels in brain and
CC heart. {ECO:0000269|PubMed:16186509}.
CC -!- INDUCTION: Up-regulated in response to endoplasmic reticulum stress via
CC the ERN1-XBP1 pathway of the unfolded protein response (UPR).
CC {ECO:0000269|PubMed:16186509, ECO:0000269|PubMed:16449189}.
CC -!- SIMILARITY: Belongs to the derlin family. {ECO:0000305}.
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DR EMBL; AK007435; BAB25036.1; -; mRNA.
DR EMBL; AK043420; BAC31545.1; -; mRNA.
DR EMBL; AK075631; BAC35868.1; -; mRNA.
DR EMBL; AK152197; BAE31026.1; -; mRNA.
DR EMBL; AK152901; BAE31582.1; -; mRNA.
DR EMBL; BC003454; AAH03454.1; -; mRNA.
DR EMBL; BC085490; AAH85490.1; -; mRNA.
DR CCDS; CCDS27484.1; -.
DR RefSeq; NP_077169.1; NM_024207.4.
DR AlphaFoldDB; Q99J56; -.
DR SMR; Q99J56; -.
DR BioGRID; 212459; 5.
DR STRING; 10090.ENSMUSP00000022993; -.
DR iPTMnet; Q99J56; -.
DR PhosphoSitePlus; Q99J56; -.
DR SwissPalm; Q99J56; -.
DR EPD; Q99J56; -.
DR jPOST; Q99J56; -.
DR MaxQB; Q99J56; -.
DR PaxDb; Q99J56; -.
DR PRIDE; Q99J56; -.
DR ProteomicsDB; 279627; -.
DR Antibodypedia; 13772; 240 antibodies from 27 providers.
DR DNASU; 67819; -.
DR Ensembl; ENSMUST00000022993; ENSMUSP00000022993; ENSMUSG00000022365.
DR GeneID; 67819; -.
DR KEGG; mmu:67819; -.
DR UCSC; uc007vsq.1; mouse.
DR CTD; 79139; -.
DR MGI; MGI:1915069; Derl1.
DR VEuPathDB; HostDB:ENSMUSG00000022365; -.
DR eggNOG; KOG0858; Eukaryota.
DR GeneTree; ENSGT00530000063156; -.
DR HOGENOM; CLU_051898_3_1_1; -.
DR InParanoid; Q99J56; -.
DR OMA; GTRFKAM; -.
DR OrthoDB; 1609512at2759; -.
DR PhylomeDB; Q99J56; -.
DR TreeFam; TF354297; -.
DR Reactome; R-MMU-382556; ABC-family proteins mediated transport.
DR Reactome; R-MMU-532668; N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
DR BioGRID-ORCS; 67819; 10 hits in 72 CRISPR screens.
DR ChiTaRS; Derl1; mouse.
DR PRO; PR:Q99J56; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q99J56; protein.
DR Bgee; ENSMUSG00000022365; Expressed in vestibular membrane of cochlear duct and 259 other tissues.
DR Genevisible; Q99J56; MM.
DR GO; GO:0036513; C:Derlin-1 retrotranslocation complex; ISO:MGI.
DR GO; GO:0036502; C:Derlin-1-VIMP complex; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005770; C:late endosome; IDA:MGI.
DR GO; GO:0051117; F:ATPase binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042288; F:MHC class I protein binding; ISS:UniProtKB.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0005047; F:signal recognition particle binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; ISO:MGI.
DR GO; GO:0034620; P:cellular response to unfolded protein; IMP:MGI.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; ISO:MGI.
DR GO; GO:0036503; P:ERAD pathway; ISO:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; ISO:MGI.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; ISS:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS: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 Acetylation; Endoplasmic reticulum; Membrane; Phosphoprotein;
KW Protein transport; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport; Unfolded protein response.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT CHAIN 2..251
FT /note="Derlin-1"
FT /id="PRO_0000219043"
FT TOPO_DOM 2..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TRANSMEM 16..31
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TOPO_DOM 32..69
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TRANSMEM 70..89
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TOPO_DOM 90..94
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TRANSMEM 95..115
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TOPO_DOM 116..122
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TRANSMEM 123..137
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TOPO_DOM 138..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TRANSMEM 155..166
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TOPO_DOM 167..170
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TRANSMEM 171..189
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT TOPO_DOM 190..251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
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:0000250|UniProtKB:Q9BUN8"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT MOD_RES 201
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 202
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BUN8"
FT CONFLICT 13
FT /note="A -> V (in Ref. 1; BAB25036)"
FT /evidence="ECO:0000305"
FT CONFLICT 17
FT /note="Y -> N (in Ref. 1; BAB25036)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="A -> V (in Ref. 1; BAB25036)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 251 AA; 28835 MW; 2E1B79DEAFD3FDC8 CRC64;
MSDIGDWFRS IPAITRYWFA ATVAVPLIGK LGIISPAYFF LWPEAFLYRF QIWRPFTATF
YFPVGPGTGF LYLVNLYFLY QYSTRLEAGA FDGRPADYLF MLLFNWICIV ITGLAMDMQL
LMIPLIMSVL YVWAQLNRDL IVSFWFGTRF KACYLPWVIL GFNYIIGGSV INELIGNLVG
HLYFFLMFRY PMDLGGRNFL STPQFLYRWL PSRRGGVSGF GVPPASMRRA ADQNGGGGRH
NWGQGFRLGD Q
