DERL2_HUMAN
ID DERL2_HUMAN Reviewed; 239 AA.
AC Q9GZP9; Q9Y3A7;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Derlin-2 {ECO:0000303|PubMed:15215855};
DE AltName: Full=Degradation in endoplasmic reticulum protein 2;
DE Short=DERtrin-2;
DE AltName: Full=Der1-like protein 2 {ECO:0000303|PubMed:15215855};
DE AltName: Full=F-LAN-1 {ECO:0000312|EMBL:AAG43049.1};
DE AltName: Full=F-LANa {ECO:0000303|PubMed:11500051};
GN Name=DERL2 {ECO:0000312|HGNC:HGNC:17943};
GN Synonyms=DER2, FLANA {ECO:0000305|PubMed:11500051};
GN ORFNames=CGI-101 {ECO:0000312|EMBL:AAD34096.1},
GN SBBI53 {ECO:0000312|EMBL:AAF99603.1};
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 [MRNA], 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].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Dendritic cell;
RA Zhang W., Wan T., Cao X.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP FUNCTION (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
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 [7]
RP FUNCTION, OLIGOMERIZATION, AND INTERACTION WITH SELENOS; 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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, TISSUE SPECIFICITY,
RP INDUCTION, OLIGOMERIZATION, AND INTERACTION WITH VCP AND EDEM1.
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 [9]
RP INTERACTION WITH OS9.
RX PubMed=19084021; DOI=10.1016/j.jmb.2008.11.045;
RA Alcock F., Swanton E.;
RT "Mammalian OS-9 is upregulated in response to endoplasmic reticulum stress
RT and facilitates ubiquitination of misfolded glycoproteins.";
RL J. Mol. Biol. 385:1032-1042(2009).
RN [10]
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 [11]
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).
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
CC (PubMed:16186509, PubMed:16449189). May also be involved in endoplasmic
CC reticulum stress-induced pre-emptive quality control, a mechanism that
CC selectively attenuates the translocation of newly synthesized proteins
CC into the endoplasmic reticulum and reroutes them to the cytosol for
CC proteasomal degradation (PubMed:26565908).
CC {ECO:0000269|PubMed:16186509, ECO:0000269|PubMed:16449189,
CC ECO:0000269|PubMed:26565908}.
CC -!- FUNCTION: (Microbial infection) In contrast to DERL1, it is not
CC involved in the degradation of MHC class I heavy chains following
CC infection by cytomegaloviruses. {ECO:0000269|PubMed:15215855}.
CC -!- SUBUNIT: Forms homo- and heterooligomers with DERL3 and, to a lesser
CC extent, with DERL1 (PubMed:16186509). Interacts with the SEL1L/SYVN1
CC and VCP/SELENOS protein complexes (PubMed:16186509). Mediates
CC association between VCP and EDEM1, as well as that between VCP and the
CC misfolded glycoproteins (PubMed:16449189). Interacts with OS9
CC (PubMed:19084021). Interacts with SELENOK and SELENOS
CC (PubMed:22016385). 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). Interacts with
CC CCDC47 (By similarity). {ECO:0000250|UniProtKB:Q8BNI4,
CC ECO:0000269|PubMed:16186509, ECO:0000269|PubMed:16449189,
CC ECO:0000269|PubMed:19084021, ECO:0000269|PubMed:22016385,
CC ECO:0000269|PubMed:26565908}.
CC -!- INTERACTION:
CC Q9GZP9; Q9NR28: DIABLO; NbExp=3; IntAct=EBI-7962814, EBI-517508;
CC Q9GZP9; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-7962814, EBI-713304;
CC Q9GZP9; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-7962814, EBI-10172290;
CC Q9GZP9; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-7962814, EBI-10171774;
CC Q9GZP9; Q00013: MPP1; NbExp=3; IntAct=EBI-7962814, EBI-711788;
CC Q9GZP9; P43378: PTPN9; NbExp=3; IntAct=EBI-7962814, EBI-742898;
CC Q9GZP9; Q8N0V3: RBFA; NbExp=3; IntAct=EBI-7962814, EBI-3232108;
CC Q9GZP9; Q8WV19: SFT2D1; NbExp=3; IntAct=EBI-7962814, EBI-2854842;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15215855, ECO:0000269|PubMed:16449189}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:15215855,
CC ECO:0000269|PubMed:16449189}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Overexpressed in various
CC hepatocarcinomas. {ECO:0000269|PubMed:11500051,
CC ECO:0000269|PubMed:16449189}.
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:16449189}.
CC -!- SIMILARITY: Belongs to the derlin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34096.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF132289; AAG43049.1; -; mRNA.
DR EMBL; AF208065; AAL14869.1; -; mRNA.
DR EMBL; AF151859; AAD34096.1; ALT_FRAME; mRNA.
DR EMBL; AF242523; AAF99603.1; -; mRNA.
DR EMBL; CR457202; CAG33483.1; -; mRNA.
DR EMBL; BC010890; AAH10890.1; -; mRNA.
DR CCDS; CCDS11073.1; -.
DR PIR; JC7752; JC7752.
DR RefSeq; NP_001291708.1; NM_001304779.1.
DR RefSeq; NP_057125.2; NM_016041.4.
DR AlphaFoldDB; Q9GZP9; -.
DR SMR; Q9GZP9; -.
DR BioGRID; 119216; 142.
DR CORUM; Q9GZP9; -.
DR IntAct; Q9GZP9; 57.
DR MINT; Q9GZP9; -.
DR STRING; 9606.ENSP00000158771; -.
DR TCDB; 3.A.16.1.4; the endoplasmic reticular retrotranslocon (er-rt) family.
DR GlyGen; Q9GZP9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9GZP9; -.
DR PhosphoSitePlus; Q9GZP9; -.
DR BioMuta; DERL2; -.
DR DMDM; 50400648; -.
DR EPD; Q9GZP9; -.
DR jPOST; Q9GZP9; -.
DR MassIVE; Q9GZP9; -.
DR MaxQB; Q9GZP9; -.
DR PaxDb; Q9GZP9; -.
DR PeptideAtlas; Q9GZP9; -.
DR PRIDE; Q9GZP9; -.
DR ProteomicsDB; 80110; -.
DR Antibodypedia; 23707; 141 antibodies from 23 providers.
DR DNASU; 51009; -.
DR Ensembl; ENST00000158771.9; ENSP00000158771.4; ENSG00000072849.11.
DR GeneID; 51009; -.
DR KEGG; hsa:51009; -.
DR MANE-Select; ENST00000158771.9; ENSP00000158771.4; NM_016041.5; NP_057125.2.
DR UCSC; uc002gcc.2; human.
DR CTD; 51009; -.
DR DisGeNET; 51009; -.
DR GeneCards; DERL2; -.
DR HGNC; HGNC:17943; DERL2.
DR HPA; ENSG00000072849; Low tissue specificity.
DR MIM; 610304; gene.
DR neXtProt; NX_Q9GZP9; -.
DR OpenTargets; ENSG00000072849; -.
DR PharmGKB; PA134896343; -.
DR VEuPathDB; HostDB:ENSG00000072849; -.
DR eggNOG; KOG0858; Eukaryota.
DR GeneTree; ENSGT00530000063156; -.
DR HOGENOM; CLU_051898_5_2_1; -.
DR InParanoid; Q9GZP9; -.
DR OMA; WSRKNPD; -.
DR OrthoDB; 1609512at2759; -.
DR PhylomeDB; Q9GZP9; -.
DR TreeFam; TF314715; -.
DR PathwayCommons; Q9GZP9; -.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-HSA-5362768; Hh mutants are degraded by ERAD.
DR Reactome; R-HSA-5678895; Defective CFTR causes cystic fibrosis.
DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC).
DR SignaLink; Q9GZP9; -.
DR BioGRID-ORCS; 51009; 157 hits in 1075 CRISPR screens.
DR ChiTaRS; DERL2; human.
DR GeneWiki; Derlin-2; -.
DR GenomeRNAi; 51009; -.
DR Pharos; Q9GZP9; Tbio.
DR PRO; PR:Q9GZP9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9GZP9; protein.
DR Bgee; ENSG00000072849; Expressed in right testis and 194 other tissues.
DR ExpressionAtlas; Q9GZP9; baseline and differential.
DR Genevisible; Q9GZP9; HS.
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: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:0005770; C:late endosome; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
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:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB.
DR GO; GO:1904153; P:negative regulation of retrograde protein transport, ER to cytosol; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IMP:UniProtKB.
DR GO; GO:0001967; P:suckling behavior; IEA:Ensembl.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP: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 Endoplasmic reticulum; Host-virus interaction; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix;
KW Unfolded protein response.
FT CHAIN 1..239
FT /note="Derlin-2"
FT /id="PRO_0000219045"
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 215..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 239 AA; 27567 MW; CAA228487C3CCB5C CRC64;
MAYQSLRLEY LQIPPVSRAY TTACVLTTAA VQLELITPFQ LYFNPELIFK HFQIWRLITN
FLFFGPVGFN FLFNMIFLYR YCRMLEEGSF RGRTADFVFM FLFGGFLMTL FGLFVSLVFL
GQAFTIMLVY VWSRRNPYVR MNFFGLLNFQ APFLPWVLMG FSLLLGNSII VDLLGIAVGH
IYFFLEDVFP NQPGGIRILK TPSILKAIFD TPDEDPNYNP LPEERPGGFA WGEGQRLGG
