Derlin-1

Derlin 1
Identifiers
Symbols	DERL1 ; DER-1; DER1
External IDs	OMIM: 608813 MGI: 1915069 HomoloGene: 11483 GeneCards: DERL1 Gene
Gene ontology Molecular function • protease binding • receptor activity • protein binding • ubiquitin protein ligase binding • MHC class I protein binding • ATPase binding • ubiquitin-specific protease binding Cellular component • early endosome • late endosome • endoplasmic reticulum • membrane • integral component of membrane • integral component of endoplasmic reticulum membrane • VCP-NPL4-UFD1 AAA ATPase complex • Derlin-1-VIMP complex • Derlin-1 retrotranslocation complex • host cell Biological process • response to unfolded protein • intracellular transport of viral protein in host cell • ER-associated ubiquitin-dependent protein catabolic process • endoplasmic reticulum unfolded protein response • retrograde protein transport, ER to cytosol • positive regulation of protein ubiquitination • protein destabilization • positive regulation of protein binding • ERAD pathway • establishment of protein localization • protein homooligomerization • ER-associated misfolded protein catabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	79139	67819
Ensembl	ENSG00000136986	ENSMUSG00000022365
UniProt	Q9BUN8	Q99J56
RefSeq (mRNA)	NM_001134671	NM_024207
RefSeq (protein)	NP_001128143	NP_077169
Location (UCSC)	Chr 8: 123.01 – 123.04 Mb	Chr 15: 57.87 – 57.89 Mb
PubMed search

Derlin-1 also known as degradation in endoplasmic reticulum protein 1 is a protein that in humans is encoded by the DERL1 gene.^[1][2][3] It is a member of the rhomboid-like clan of polytopic membrane proteins.

Function

Derlin-1 is part of a complex (that includes VIMP, SEL1, HRD1, and HERP) that mediates endoplasmic-reticulum-associated degradation (ERAD) that detects misfolded proteins in the endoplasmic reticulum and targets them for destruction.^[4]

Clinical significance

Derlin 1 (DERL1) is up-regulated in metastatic canine mammary tumors as part of the unfolded protein response.^[5][6][7]

See also

• Derlin-2
• Derlin-3

References

1. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (Oct 2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
2. Lilley BN, Ploegh HL (Jun 2004). "A membrane protein required for dislocation of misfolded proteins from the ER". Nature 429 (6994): 834–40. doi:10.1038/nature02592. PMID 15215855.
3. "Entrez Gene: DERL1 Der1-like domain family, member 1".
4. Schaheen B, Dang H, Fares H (July 2009). "Derlin-dependent accumulation of integral membrane proteins at cell surfaces". J. Cell. Sci. 122 (Pt 13): 2228–39. doi:10.1242/jcs.048892. PMID 19509052.
5. Klopfleisch R, Klose P, Gruber AD. (2010). "The combined expression pattern of BMP2, LTBP4, and DERL1 discriminates malignant from benign canine mammary tumors.". Veterinary Pathology. 47 (3): 446–54. doi:10.1177/0300985810363904. PMID 20375427.
6. Klopfleisch R, Schütze M, Linzmann H, Brunnberg L, Gruber AD. (2010). "Increased Derlin-1 expression in metastases of canine mammary adenocarcinomas.". J Comp Pathol 142 (1): 79–83. doi:10.1016/j.jcpa.2009.06.006. PMID 19632687.
7. Klopfleisch R, Gruber AD. (2009). "Derlin-1 and stanniocalcin-1 are differentially regulated in metastasizing canine mammary adenocarcinomas.". J Comp Pathol. 141 (2): 113–120. doi:10.1016/j.jcpa.2008.09.010. PMID 19515379.

Further reading

• Andersson B, Wentland MA, Ricafrente JY; et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC; et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Ye Y, Shibata Y, Yun C; et al. (2004). "A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol.". Nature 429 (6994): 841–7. doi:10.1038/nature02656. PMID 15215856.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Katiyar S, Joshi S, Lennarz WJ (2006). "The retrotranslocation protein Derlin-1 binds peptide:N-glycanase to the endoplasmic reticulum.". Mol. Biol. Cell 16 (10): 4584–94. doi:10.1091/mbc.E05-04-0345. PMC 1237066. PMID 16055502.
• Lilley BN, Ploegh HL (2006). "Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane.". Proc. Natl. Acad. Sci. U.S.A. 102 (40): 14296–301. doi:10.1073/pnas.0505014102. PMC 1242303. PMID 16186509.
• Ye Y, Shibata Y, Kikkert M; et al. (2006). "Inaugural Article: Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane.". Proc. Natl. Acad. Sci. U.S.A. 102 (40): 14132–8. doi:10.1073/pnas.0505006102. PMC 1242302. PMID 16186510.
• Schulze A, Standera S, Buerger E; et al. (2006). "The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway.". J. Mol. Biol. 354 (5): 1021–7. doi:10.1016/j.jmb.2005.10.020. PMID 16289116.
• Oda Y, Okada T, Yoshida H; et al. (2006). "Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.". J. Cell Biol. 172 (3): 383–93. doi:10.1083/jcb.200507057. PMC 2063648. PMID 16449189.
• Schubert V, Da Silva JS, Dotti CG (2006). "Localized recruitment and activation of RhoA underlies dendritic spine morphology in a glutamate receptor-dependent manner.". J. Cell Biol. 172 (3): 453–67. doi:10.1083/jcb.200506136. PMC 2063654. PMID 16449195.
• Sun F, Zhang R, Gong X; et al. (2007). "Derlin-1 promotes the efficient degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR folding mutants.". J. Biol. Chem. 281 (48): 36856–63. doi:10.1074/jbc.M607085200. PMID 16954204.
• Crawshaw SG, Cross BC, Wilson CM, High S (2007). "The oligomeric state of Derlin-1 is modulated by endoplasmic reticulum stress.". Mol. Membr. Biol. 24 (2): 113–20. doi:10.1080/09687860600988727. PMID 17453418.