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3.A.16.1.1
Mammalian ER retrotranslocon. The Grp170 protein plays a role during ERAD, positioning this client-release factor at the retrotranslocation site, allowing a mechanism to couple client release from BiP and retrotranslocation (Inoue and Tsai, 2016). The cryo-EM structure of the ERAD protein channel, formed by tetrameric human Derlin-1, has been solved (Rao et al. 2021).  The structure shows that Derlin-1 forms a homotetramer that encircles a large tunnel traversing the ER membrane. The tunnel has a diameter of about 12 to 15 angstroms, large enough to allow an α-helix to pass through. The structure shows a lateral gate within the membrane, providing access of transmembrane proteins to the tunnel. Thus, Derlin-1 forms a protein channel for translocation of misfolded proteins. This structure is different from the monomeric yeast Derlin structure previously reported, which forms a semichannel with another protein (Rao et al. 2021).

Accession Number:Q9BUN8
Protein Name:Derlin-1
Length:251
Molecular Weight:28801.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

RefSeq: NP_001128143.1    NP_077271.1   
Entrez Gene ID: 79139   
Pfam: PF04511   
OMIM: 608813  gene
KEGG: hsa:79139   

Gene Ontology

GO:0030176 C:integral to endoplasmic reticulum membrane
GO:0042288 F:MHC class I protein binding
GO:0004872 F:receptor activity
GO:0030968 P:endoplasmic reticulum unfolded protein resp...
GO:0030433 P:ER-associated protein catabolic process
GO:0019060 P:intracellular transport of viral proteins i...
GO:0030970 P:retrograde protein transport, ER to cytosol

References (11)

[1] “The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.”  Clark H.F.et.al.   12975309
[2] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[3] “A membrane protein required for dislocation of misfolded proteins from the ER.”  Lilley B.N.et.al.   15215855
[4] “A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol.”  Ye Y.et.al.   15215856
[5] “The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway.”  Schulze A.et.al.   16289116
[6] “The retrotranslocation protein derlin-1 binds peptide:N-glycanase to the endoplasmic reticulum.”  Katiyar S.et.al.   16055502
[7] “Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane.”  Ye Y.et.al.   16186510
[8] “Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane.”  Lilley B.N.et.al.   16186509
[9] “Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.”  Oda Y.et.al.   16449189
[10] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[11] “The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER.”  Ernst R.et.al.   19818707
Structure:
5GLF     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MSDIGDWFRS IPAITRYWFA ATVAVPLVGK LGLISPAYLF LWPEAFLYRF QIWRPITATF 
61:	YFPVGPGTGF LYLVNLYFLY QYSTRLETGA FDGRPADYLF MLLFNWICIV ITGLAMDMQL 
121:	LMIPLIMSVL YVWAQLNRDM IVSFWFGTRF KACYLPWVIL GFNYIIGGSV INELIGNLVG 
181:	HLYFFLMFRY PMDLGGRNFL STPQFLYRWL PSRRGGVSGF GVPPASMRRA ADQNGGGGRH 
241:	NWGQGFRLGD Q