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Protein

Derlin-1

Gene

DERL1

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

Functioni

Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by forming a channel that allows the retrotranslocation of misfolded proteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and the misfolded protein (PubMed:15215856). Also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333).3 Publications
(Microbial infection) In case of infection by cytomegaloviruses, it plays a central role in the export from the ER and subsequent degradation of MHC class I heavy chains via its interaction with US11 viral protein, which recognizes and associates with MHC class I heavy chains. Also participates in the degradation process of misfolded cytomegalovirus US2 protein.2 Publications

GO - Molecular functioni

  • ATPase binding Source: ParkinsonsUK-UCL
  • MHC class I protein binding Source: UniProtKB
  • protease binding Source: UniProtKB
  • signaling receptor activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • ERAD pathway Source: ParkinsonsUK-UCL
  • ER-associated misfolded protein catabolic process Source: ParkinsonsUK-UCL
  • establishment of protein localization Source: UniProtKB
  • positive regulation of protein binding Source: ParkinsonsUK-UCL
  • positive regulation of protein ubiquitination Source: ParkinsonsUK-UCL
  • protein destabilization Source: UniProtKB
  • protein folding Source: Reactome
  • protein homooligomerization Source: ParkinsonsUK-UCL
  • protein ubiquitination Source: Reactome
  • response to unfolded protein Source: MGI
  • retrograde protein transport, ER to cytosol Source: UniProtKB
  • transmembrane transport Source: Reactome
  • ubiquitin-dependent ERAD pathway Source: UniProtKB
  • viral process Source: UniProtKB-KW

Keywordsi

Biological processHost-virus interaction, Protein transport, Transport, Unfolded protein response

Enzyme and pathway databases

BRENDAi3.4.21.105 2681
ReactomeiR-HSA-382556 ABC-family proteins mediated transport
R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins

Protein family/group databases

TCDBi3.A.16.1.1 the endoplasmic reticular retrotranslocon (er-rt) family

Names & Taxonomyi

Protein namesi
Recommended name:
Derlin-11 Publication
Alternative name(s):
Degradation in endoplasmic reticulum protein 1
Short name:
DERtrin-1
Der1-like protein 11 Publication
Gene namesi
Name:DERL1Imported
Synonyms:DER1
ORF Names:UNQ243/PRO276Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000136986.9
HGNCiHGNC:28454 DERL1
MIMi608813 gene
neXtProtiNX_Q9BUN8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 22CytoplasmicSequence analysisAdd BLAST21
Transmembranei23 – 43Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini44 – 59LumenalSequence analysisAdd BLAST16
Transmembranei60 – 80Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini81 – 105CytoplasmicSequence analysisAdd BLAST25
Transmembranei106 – 126Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini127 – 154LumenalSequence analysisAdd BLAST28
Transmembranei155 – 175Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini176 – 251CytoplasmicSequence analysisAdd BLAST76

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi180G → V: Reduces interaction with and proteolysis of XBP1 isoform 1. 1 Publication1

Organism-specific databases

DisGeNETi79139
OpenTargetsiENSG00000136986
PharmGKBiPA134926638

Polymorphism and mutation databases

DMDMi50400630

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002190422 – 251Derlin-1Add BLAST250

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei201PhosphoserineCombined sources1
Modified residuei202PhosphothreonineCombined sources1
Modified residuei226PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9BUN8
MaxQBiQ9BUN8
PaxDbiQ9BUN8
PeptideAtlasiQ9BUN8
PRIDEiQ9BUN8
TopDownProteomicsiQ9BUN8-1 [Q9BUN8-1]

PTM databases

iPTMnetiQ9BUN8
PhosphoSitePlusiQ9BUN8

Expressioni

Tissue specificityi

Ubiquitous.2 Publications

Gene expression databases

BgeeiENSG00000136986
CleanExiHS_DERL1
ExpressionAtlasiQ9BUN8 baseline and differential
GenevisibleiQ9BUN8 HS

Organism-specific databases

HPAiCAB037269
HPA016562

Interactioni

Subunit structurei

Forms homo- and heterooligomers with DERL2 and DERL3; binding to DERL3 is poorer than that between DERL2 and DERL3. Interacts with AMFR, SELENOS, SEL1L, SELENOK, SYVN1 and VCP, as well as with SEL1L-SYVN1 and VCP-SELENOS protein complexes; this interaction is weaker than that observed between DERL2 and these complexes. Interacts with NGLY1 and YOD1. Does not bind to EDEM1. Interacts with DNAJB9. Interacts with RNF103 (PubMed:15215856, PubMed:16055502, PubMed:16186509, PubMed:16186510, PubMed:16289116, PubMed:16449189, PubMed:18675248, PubMed:19818707, PubMed:22016385). Interacts with HM13 (PubMed:25239945). Interacts with XBP1 isoform 1 (via luminal/ectodomain domain); the interaction obviates the need for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage (PubMed:25239945). Interact with the signal recognition particle/SRP and the SRP receptor; in the process of endoplasmic reticulum stress-induced pre-emptive quality control (PubMed:26565908). May interact with UBXN6 (PubMed:19275885). Interacts with ZFAND2B; probably through VCP (PubMed:24160817).13 Publications
(Microbial infection) Interacts with the cytomegalovirus US11 protein.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ATPase binding Source: ParkinsonsUK-UCL
  • MHC class I protein binding Source: UniProtKB
  • protease binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi122559, 129 interactors
CORUMiQ9BUN8
IntActiQ9BUN8, 17 interactors
MINTiQ9BUN8
STRINGi9606.ENSP00000259512

Structurei

Secondary structure

1251
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi245 – 247Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5GLFX-ray2.25B/D/F/H239-250[»]
ProteinModelPortaliQ9BUN8
SMRiQ9BUN8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the derlin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0858 Eukaryota
COG5291 LUCA
GeneTreeiENSGT00530000063156
HOGENOMiHOG000200949
HOVERGENiHBG105143
InParanoidiQ9BUN8
KOiK11519
OMAiTYIWCQL
OrthoDBiEOG091G0EP1
PhylomeDBiQ9BUN8
TreeFamiTF354297

Family and domain databases

InterProiView protein in InterPro
IPR007599 DER1
PANTHERiPTHR11009 PTHR11009, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BUN8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSDIGDWFRS IPAITRYWFA ATVAVPLVGK LGLISPAYLF LWPEAFLYRF
60 70 80 90 100
QIWRPITATF YFPVGPGTGF LYLVNLYFLY QYSTRLETGA FDGRPADYLF
110 120 130 140 150
MLLFNWICIV ITGLAMDMQL LMIPLIMSVL YVWAQLNRDM IVSFWFGTRF
160 170 180 190 200
KACYLPWVIL GFNYIIGGSV INELIGNLVG HLYFFLMFRY PMDLGGRNFL
210 220 230 240 250
STPQFLYRWL PSRRGGVSGF GVPPASMRRA ADQNGGGGRH NWGQGFRLGD

Q
Length:251
Mass (Da):28,801
Last modified:June 1, 2001 - v1
Checksum:i4A6E0DB68D9AF244
GO
Isoform 2 (identifier: Q9BUN8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     170-189: Missing.

Show »
Length:231
Mass (Da):26,423
Checksum:iE0D0982FDD620F1F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019516171I → V. Corresponds to variant dbSNP:rs2272722Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041329170 – 189Missing in isoform 2. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358818 mRNA Translation: AAQ89177.1
AC104316 Genomic DNA No translation available.
BC002457 mRNA Translation: AAH02457.1
AK124086 mRNA Translation: BAG54003.1
CCDSiCCDS47915.1 [Q9BUN8-2]
CCDS6337.1 [Q9BUN8-1]
RefSeqiNP_001128143.1, NM_001134671.2 [Q9BUN8-2]
NP_077271.1, NM_024295.5 [Q9BUN8-1]
UniGeneiHs.241576

Genome annotation databases

EnsembliENST00000259512; ENSP00000259512; ENSG00000136986 [Q9BUN8-1]
ENST00000405944; ENSP00000384289; ENSG00000136986 [Q9BUN8-2]
GeneIDi79139
KEGGihsa:79139
UCSCiuc003ypl.3 human [Q9BUN8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDERL1_HUMAN
AccessioniPrimary (citable) accession number: Q9BUN8
Secondary accession number(s): B3KW41, E9PH19
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: June 1, 2001
Last modified: May 23, 2018
This is version 150 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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