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Protein

Derlin-2

Gene

DERL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal glycoproteins, but not that of misfolded nonglycoproteins. May act by forming a channel that allows the retrotranslocation of misfolded glycoproteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and the degradation substrate. In contrast to DERL1, it is not involved in the degradation of MHC class I heavy chains following infection by cytomegaloviruses. May play a role in cell proliferation.3 Publications

GO - Biological processi

  • cellular protein metabolic process Source: Reactome
  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • negative regulation of retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL
  • positive regulation of cell growth Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • post-translational protein modification Source: Reactome
  • protein folding Source: Reactome
  • protein N-linked glycosylation via asparagine Source: Reactome
  • retrograde protein transport, ER to cytosol Source: UniProtKB
  • suckling behavior Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Unfolded protein response

Enzyme and pathway databases

ReactomeiR-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362768. Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
R-HSA-901032. ER Quality Control Compartment (ERQC).

Names & Taxonomyi

Protein namesi
Recommended name:
Derlin-2
Alternative name(s):
Degradation in endoplasmic reticulum protein 2
Short name:
DERtrin-2
Der1-like protein 2
F-LAN-1
F-LANa
Gene namesi
Name:DERL2
Synonyms:DER2, FLANA
ORF Names:CGI-101, SBBI53
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:17943. DERL2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5757CytoplasmicSequence analysisAdd
BLAST
Transmembranei58 – 7821Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini79 – 9618LumenalSequence analysisAdd
BLAST
Transmembranei97 – 11721Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini118 – 15033CytoplasmicSequence analysisAdd
BLAST
Transmembranei151 – 17121Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini172 – 1721LumenalSequence analysis
Transmembranei173 – 19321Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini194 – 23946CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • early endosome Source: Ensembl
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: Reactome
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • late endosome Source: Ensembl
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134896343.

Polymorphism and mutation databases

BioMutaiDERL2.
DMDMi50400648.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 239239Derlin-2PRO_0000219045Add
BLAST

Proteomic databases

EPDiQ9GZP9.
MaxQBiQ9GZP9.
PaxDbiQ9GZP9.
PeptideAtlasiQ9GZP9.
PRIDEiQ9GZP9.

PTM databases

iPTMnetiQ9GZP9.
PhosphoSiteiQ9GZP9.

Expressioni

Tissue specificityi

Ubiquitous. Overexpressed in various hepatocarcinomas.2 Publications

Inductioni

Up-regulated in response to endoplasmic reticulum stress via the ERN1-XBP1 pathway of the unfolded protein response (UPR).By similarity

Gene expression databases

BgeeiQ9GZP9.
CleanExiHS_DERL2.
ExpressionAtlasiQ9GZP9. baseline and differential.
GenevisibleiQ9GZP9. HS.

Organism-specific databases

HPAiCAB037287.
HPA048957.
HPA056551.

Interactioni

Subunit structurei

Forms homo- and heterooligomers with DERL3 and, to a lesser extent, with DERL1. Interacts with SELK, VIMP, VCP and EDEM1. Mediates association between VCP and EDEM1, as well as that between VCP and the degradation substrate. Interacts with the SEL1L/SYVN1 and VCP/VIMP protein complexes. Interacts with OS9. Part of a complex which includes CANX, DERL1, DERL2, DDOST/OST48, RPN1, RPN2, SELK, VIMP, STT3A AND VCP.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KRTAP10-7P604093EBI-7962814,EBI-10172290
KRTAP10-8P604103EBI-7962814,EBI-10171774

Protein-protein interaction databases

BioGridi119216. 44 interactions.
IntActiQ9GZP9. 12 interactions.
MINTiMINT-3065126.
STRINGi9606.ENSP00000158771.

Structurei

3D structure databases

ProteinModelPortaliQ9GZP9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the derlin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0858. Eukaryota.
COG5291. LUCA.
GeneTreeiENSGT00530000063156.
HOGENOMiHOG000200948.
HOVERGENiHBG051338.
InParanoidiQ9GZP9.
OMAiVSPFQLY.
OrthoDBiEOG73RBC2.
PhylomeDBiQ9GZP9.
TreeFamiTF314715.

Family and domain databases

InterProiIPR007599. DER1.
[Graphical view]
PANTHERiPTHR11009. PTHR11009. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9GZP9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAYQSLRLEY LQIPPVSRAY TTACVLTTAA VQLELITPFQ LYFNPELIFK
60 70 80 90 100
HFQIWRLITN FLFFGPVGFN FLFNMIFLYR YCRMLEEGSF RGRTADFVFM
110 120 130 140 150
FLFGGFLMTL FGLFVSLVFL GQAFTIMLVY VWSRRNPYVR MNFFGLLNFQ
160 170 180 190 200
APFLPWVLMG FSLLLGNSII VDLLGIAVGH IYFFLEDVFP NQPGGIRILK
210 220 230
TPSILKAIFD TPDEDPNYNP LPEERPGGFA WGEGQRLGG
Length:239
Mass (Da):27,567
Last modified:March 1, 2001 - v1
Checksum:iCAA228487C3CCB5C
GO

Sequence cautioni

The sequence AAD34096.1 differs from that shown. Reason: Frameshift at positions 122, 128 and 136. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132289 mRNA. Translation: AAG43049.1.
AF208065 mRNA. Translation: AAL14869.1.
AF151859 mRNA. Translation: AAD34096.1. Frameshift.
AF242523 mRNA. Translation: AAF99603.1.
CR457202 mRNA. Translation: CAG33483.1.
BC010890 mRNA. Translation: AAH10890.1.
CCDSiCCDS11073.1.
PIRiJC7752.
RefSeqiNP_001291708.1. NM_001304779.1.
NP_057125.2. NM_016041.4.
UniGeneiHs.286131.
Hs.730726.

Genome annotation databases

EnsembliENST00000158771; ENSP00000158771; ENSG00000072849.
GeneIDi51009.
UCSCiuc002gcc.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132289 mRNA. Translation: AAG43049.1.
AF208065 mRNA. Translation: AAL14869.1.
AF151859 mRNA. Translation: AAD34096.1. Frameshift.
AF242523 mRNA. Translation: AAF99603.1.
CR457202 mRNA. Translation: CAG33483.1.
BC010890 mRNA. Translation: AAH10890.1.
CCDSiCCDS11073.1.
PIRiJC7752.
RefSeqiNP_001291708.1. NM_001304779.1.
NP_057125.2. NM_016041.4.
UniGeneiHs.286131.
Hs.730726.

3D structure databases

ProteinModelPortaliQ9GZP9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119216. 44 interactions.
IntActiQ9GZP9. 12 interactions.
MINTiMINT-3065126.
STRINGi9606.ENSP00000158771.

PTM databases

iPTMnetiQ9GZP9.
PhosphoSiteiQ9GZP9.

Polymorphism and mutation databases

BioMutaiDERL2.
DMDMi50400648.

Proteomic databases

EPDiQ9GZP9.
MaxQBiQ9GZP9.
PaxDbiQ9GZP9.
PeptideAtlasiQ9GZP9.
PRIDEiQ9GZP9.

Protocols and materials databases

DNASUi51009.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000158771; ENSP00000158771; ENSG00000072849.
GeneIDi51009.
UCSCiuc002gcc.2. human.

Organism-specific databases

CTDi51009.
GeneCardsiDERL2.
HGNCiHGNC:17943. DERL2.
HPAiCAB037287.
HPA048957.
HPA056551.
MIMi610304. gene.
neXtProtiNX_Q9GZP9.
PharmGKBiPA134896343.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0858. Eukaryota.
COG5291. LUCA.
GeneTreeiENSGT00530000063156.
HOGENOMiHOG000200948.
HOVERGENiHBG051338.
InParanoidiQ9GZP9.
OMAiVSPFQLY.
OrthoDBiEOG73RBC2.
PhylomeDBiQ9GZP9.
TreeFamiTF314715.

Enzyme and pathway databases

ReactomeiR-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362768. Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
R-HSA-901032. ER Quality Control Compartment (ERQC).

Miscellaneous databases

GeneWikiiDerlin-2.
GenomeRNAii51009.
NextBioi53490.
PROiQ9GZP9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9GZP9.
CleanExiHS_DERL2.
ExpressionAtlasiQ9GZP9. baseline and differential.
GenevisibleiQ9GZP9. HS.

Family and domain databases

InterProiIPR007599. DER1.
[Graphical view]
PANTHERiPTHR11009. PTHR11009. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of F-LANa, upregulated in human liver cancer."
    Ying H., Yu Y., Xu Y.
    Biochem. Biophys. Res. Commun. 286:394-400(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Liver.
  2. "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics."
    Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.
    Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. Zhang W., Wan T., Cao X.
    Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Dendritic cell.
  4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  6. "A membrane protein required for dislocation of misfolded proteins from the ER."
    Lilley B.N., Ploegh H.L.
    Nature 429:834-840(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  7. "Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane."
    Lilley B.N., Ploegh H.L.
    Proc. Natl. Acad. Sci. U.S.A. 102:14296-14301(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, OLIGOMERIZATION, INTERACTION WITH VIMP; SEL1L AND SYVN1.
  8. "Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation."
    Oda Y., Okada T., Yoshida H., Kaufman R.J., Nagata K., Mori K.
    J. Cell Biol. 172:383-393(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, TISSUE SPECIFICITY, INDUCTION, OLIGOMERIZATION, INTERACTION WITH VCP AND EDEM1.
  9. "Mammalian OS-9 is upregulated in response to endoplasmic reticulum stress and facilitates ubiquitination of misfolded glycoproteins."
    Alcock F., Swanton E.
    J. Mol. Biol. 385:1032-1042(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH OS9.
  10. "Selenoprotein K binds multiprotein complexes and is involved in the regulation of endoplasmic reticulum homeostasis."
    Shchedrina V.A., Everley R.A., Zhang Y., Gygi S.P., Hatfield D.L., Gladyshev V.N.
    J. Biol. Chem. 286:42937-42948(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SELK AND VIMP, IDENTIFICATION IN A COMPLEX WITH CANX; DERL2; DDOST; RPN1; RPN2; SELK; STT3A; VCP AND VIMP.

Entry informationi

Entry nameiDERL2_HUMAN
AccessioniPrimary (citable) accession number: Q9GZP9
Secondary accession number(s): Q9Y3A7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: March 1, 2001
Last modified: April 13, 2016
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.