Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Derlin-1

Gene

DERL1

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 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 degradation substrate. 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
  • 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
  • ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • establishment of protein localization Source: UniProtKB
  • intracellular transport of viral protein in host cell Source: UniProtKB
  • positive regulation of protein binding Source: ParkinsonsUK-UCL
  • positive regulation of protein ubiquitination Source: ParkinsonsUK-UCL
  • protein destabilization Source: UniProtKB
  • protein homooligomerization Source: ParkinsonsUK-UCL
  • response to unfolded protein Source: MGI
  • retrograde protein transport, ER to cytosol Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Protein transport, Transport, Unfolded protein response

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136986-MONOMER.
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.

Protein family/group databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Derlin-1
Alternative name(s):
Degradation in endoplasmic reticulum protein 1
Short name:
DERtrin-1
Der1-like protein 1
Gene namesi
Name:DERL1
Synonyms:DER1
ORF Names:UNQ243/PRO276
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:28454. DERL1.

Subcellular locationi

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

GO - Cellular componenti

  • Derlin-1 retrotranslocation complex Source: UniProtKB
  • Derlin-1-VIMP complex Source: ParkinsonsUK-UCL
  • early endosome Source: Ensembl
  • endoplasmic reticulum Source: UniProtKB
  • host cell Source: GOC
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: MGI
  • late endosome Source: Ensembl
  • membrane Source: UniProtKB
Complete GO annotation...

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

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

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, VIMP/SELS, SEL1L, SELK, SYVN1 and VCP, as well as with SEL1L-SYVN1 and VCP-VIMP protein complexes; this interaction is weaker than that observed between DERL2 and these complexes. Interacts with the cytomegalovirus US11 protein. Interacts with NGLY1 and YOD1. Does not bind to EDEM1. Interacts with DNAJB9 and RNF103. Part of a complex which includes CANX, DERL1, DERL2, DDOST/OST48, RPN1, RPN2, SELK, VIMP, STT3A AND VCP (PubMed:15215855, 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).11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BCAP31P515723EBI-398977,EBI-77683
CFTRP135692EBI-398977,EBI-349854
HM13Q8TCT96EBI-398977,EBI-347472
TCF25Q9BQ703EBI-398977,EBI-745182

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. 77 interactors.
IntActiQ9BUN8. 16 interactors.
STRINGi9606.ENSP00000259512.

Structurei

3D structure databases

ProteinModelPortaliQ9BUN8.
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.
OMAiQFKAHYL.
OrthoDBiEOG091G0EP1.
PhylomeDBiQ9BUN8.
TreeFamiTF354297.

Family and domain databases

InterProiIPR007599. DER1.
[Graphical view]
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 rs2272722dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ9BUN8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122559. 77 interactors.
IntActiQ9BUN8. 16 interactors.
STRINGi9606.ENSP00000259512.

Protein family/group databases

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

PTM databases

iPTMnetiQ9BUN8.
PhosphoSitePlusiQ9BUN8.

Polymorphism and mutation databases

DMDMi50400630.

Proteomic databases

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

Protocols and materials databases

DNASUi79139.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi79139.
DisGeNETi79139.
GeneCardsiDERL1.
HGNCiHGNC:28454. DERL1.
HPAiCAB037269.
HPA016562.
MIMi608813. gene.
neXtProtiNX_Q9BUN8.
OpenTargetsiENSG00000136986.
PharmGKBiPA134926638.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136986-MONOMER.
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.

Miscellaneous databases

GenomeRNAii79139.
PROiQ9BUN8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136986.
CleanExiHS_DERL1.
ExpressionAtlasiQ9BUN8. baseline and differential.
GenevisibleiQ9BUN8. HS.

Family and domain databases

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

Entry informationi

Entry nameiDERL1_HUMAN
AccessioniPrimary (citable) accession number: Q9BUN8
Secondary accession number(s): B3KW41, E9PH19
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: June 1, 2001
Last modified: November 30, 2016
This is version 136 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 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

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.