DERL2_MOUSE
ID DERL2_MOUSE Reviewed; 239 AA.
AC Q8BNI4; Q920I5; Q99J12;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Derlin-2 {ECO:0000303|PubMed:16186509};
DE AltName: Full=Degradation in endoplasmic reticulum protein 2;
DE AltName: Full=Der1-like protein 2 {ECO:0000303|PubMed:16186509};
DE AltName: Full=F-LANa {ECO:0000303|PubMed:11500051};
GN Name=Derl2 {ECO:0000312|MGI:MGI:2151483};
GN Synonyms=Der2, Flana {ECO:0000305|PubMed:11500051};
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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=11500051; DOI=10.1006/bbrc.2001.5390;
RA Ying H., Yu Y., Xu Y.;
RT "Cloning and characterization of F-LANa, upregulated in human liver
RT cancer.";
RL Biochem. Biophys. Res. Commun. 286:394-400(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Embryo, and Head;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC 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 [4]
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 [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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 [7]
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 [8]
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 glycoproteins, but not that of
CC misfolded nonglycoproteins. May act by forming a channel that allows
CC the retrotranslocation of misfolded glycoproteins into the cytosol
CC where they are ubiquitinated and degraded by the proteasome. May
CC mediate the interaction between VCP and misfolded glycoproteins. May
CC also be 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 {ECO:0000250|UniProtKB:Q9GZP9}.
CC -!- SUBUNIT: Forms homo- and heterooligomers with DERL3 and, to a lesser
CC extent, with DERL1 (By similarity). Interacts with the SEL1L/SYVN1 and
CC VCP/SELENOS protein complexes (PubMed:22016385). Mediates association
CC between VCP and EDEM1, as well as that between VCP and the misfolded
CC glycoproteins (By similarity). Interacts with OS9 (By similarity).
CC Interacts with SELENOK and SELENOS (PubMed:22016385). Interacts with
CC the signal recognition particle/SRP and the SRP receptor; in the
CC process of endoplasmic reticulum stress-induced pre-emptive quality
CC control (By similarity). Interacts with CCDC47 (PubMed:25009997).
CC {ECO:0000250|UniProtKB:Q9GZP9, ECO:0000269|PubMed:22016385,
CC ECO:0000269|PubMed:25009997}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9GZP9}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9GZP9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BNI4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BNI4-2; Sequence=VSP_011085;
CC -!- TISSUE SPECIFICITY: Widely expressed, with lowest levels in brain and
CC heart. {ECO:0000269|PubMed:11500051, 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; AF208064; AAL14868.1; -; mRNA.
DR EMBL; AK048627; BAC33399.1; -; mRNA.
DR EMBL; AK077659; BAC36934.1; -; mRNA.
DR EMBL; AK082564; BAC38533.1; -; mRNA.
DR EMBL; AK083632; BAC38974.1; -; mRNA.
DR EMBL; BC005682; AAH05682.1; -; mRNA.
DR CCDS; CCDS24972.1; -. [Q8BNI4-1]
DR RefSeq; NP_001278075.1; NM_001291146.1.
DR RefSeq; NP_001278076.1; NM_001291147.1.
DR RefSeq; NP_001278077.1; NM_001291148.1.
DR RefSeq; NP_291040.1; NM_033562.4. [Q8BNI4-1]
DR AlphaFoldDB; Q8BNI4; -.
DR SMR; Q8BNI4; -.
DR BioGRID; 228066; 3.
DR IntAct; Q8BNI4; 1.
DR STRING; 10090.ENSMUSP00000117052; -.
DR iPTMnet; Q8BNI4; -.
DR PhosphoSitePlus; Q8BNI4; -.
DR EPD; Q8BNI4; -.
DR MaxQB; Q8BNI4; -.
DR PaxDb; Q8BNI4; -.
DR PeptideAtlas; Q8BNI4; -.
DR PRIDE; Q8BNI4; -.
DR ProteomicsDB; 277978; -. [Q8BNI4-1]
DR ProteomicsDB; 277979; -. [Q8BNI4-2]
DR Antibodypedia; 23707; 141 antibodies from 23 providers.
DR DNASU; 116891; -.
DR Ensembl; ENSMUST00000108523; ENSMUSP00000104163; ENSMUSG00000018442. [Q8BNI4-2]
DR Ensembl; ENSMUST00000143850; ENSMUSP00000117052; ENSMUSG00000018442. [Q8BNI4-1]
DR GeneID; 116891; -.
DR KEGG; mmu:116891; -.
DR UCSC; uc007jxi.2; mouse. [Q8BNI4-2]
DR UCSC; uc007jxj.2; mouse. [Q8BNI4-1]
DR CTD; 51009; -.
DR MGI; MGI:2151483; Derl2.
DR VEuPathDB; HostDB:ENSMUSG00000018442; -.
DR eggNOG; KOG0858; Eukaryota.
DR GeneTree; ENSGT00530000063156; -.
DR HOGENOM; CLU_051898_5_2_1; -.
DR InParanoid; Q8BNI4; -.
DR OMA; WSRKNPD; -.
DR OrthoDB; 1609512at2759; -.
DR PhylomeDB; Q8BNI4; -.
DR TreeFam; TF314715; -.
DR Reactome; R-MMU-382556; ABC-family proteins mediated transport.
DR Reactome; R-MMU-5358346; Hedgehog ligand biogenesis.
DR BioGRID-ORCS; 116891; 14 hits in 72 CRISPR screens.
DR ChiTaRS; Derl2; mouse.
DR PRO; PR:Q8BNI4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8BNI4; protein.
DR Bgee; ENSMUSG00000018442; Expressed in cumulus cell and 253 other tissues.
DR ExpressionAtlas; Q8BNI4; baseline and differential.
DR Genevisible; Q8BNI4; MM.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
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:0005770; C:late endosome; IDA:MGI.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
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:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:1904153; P:negative regulation of retrograde protein transport, ER to cytosol; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IMP:MGI.
DR GO; GO:0001967; P:suckling behavior; IMP:MGI.
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 Alternative splicing; Endoplasmic reticulum; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Unfolded protein response.
FT CHAIN 1..239
FT /note="Derlin-2"
FT /id="PRO_0000219046"
FT TOPO_DOM 1..57
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..78
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..96
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..150
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..171
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 172
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 214..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 233..239
FT /note="EGQRLGG -> WNKTDLD (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_011085"
FT CONFLICT 228
FT /note="G -> A (in Ref. 1; AAL14868)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 239 AA; 27640 MW; D702B14B47516A8C CRC64;
MAYQSLRLEY LQIPPVSRAY TTACVLTTAA VQLELITPFQ LYFNPELIFK HFQIWRLITN
FLFFGPVGFN FLFNMIFLYR YCRMLEEGSF RGRTADFVFM FLFGGFLMTL FGLFVSLVFL
GQAFTIMLVY VWSRRNPYVR MNFFGLLNFQ APFLPWVLMG FSLLLGNSII VDLLGIAVGH
IYFFLEDIFP NQPGGIRILK TPSILRTIFD TPDEDPNYNP LPEERPGGFA WGEGQRLGG
