HERPUD1

Homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1
PDB rendering based on 1wgd.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1WGD​
Identifiers
Symbols	HERPUD1 ; HERP; Mif1; SUP
External IDs	OMIM: 608070 MGI: 1927406 HomoloGene: 40973 GeneCards: HERPUD1 Gene
Gene ontology Molecular function • molecular_function • protein binding • ion channel binding Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • membrane • calcium channel complex • Lewy body core Biological process • ubiquitin-dependent protein catabolic process • response to unfolded protein • endoplasmic reticulum unfolded protein response • retrograde protein transport, ER to cytosol • regulation of protein ubiquitination • positive regulation of protein binding • endoplasmic reticulum calcium ion homeostasis • response to endoplasmic reticulum stress • PERK-mediated unfolded protein response • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • cellular protein metabolic process • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • positive regulation of ER-associated ubiquitin-dependent protein catabolic process • negative regulation of intrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9709	64209
Ensembl	ENSG00000051108	ENSMUSG00000031770
UniProt	Q15011	Q9JJK5
RefSeq (mRNA)	NM_001010989	NM_022331
RefSeq (protein)	NP_001010989	NP_071726
Location (UCSC)	Chr 16: 56.93 – 56.94 Mb	Chr 8: 94.39 – 94.4 Mb
PubMed search

Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein is a protein that in humans is encoded by the HERPUD1 gene.^[1][2][3]

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response. This response includes the inhibition of translation to prevent further accumulation of unfolded proteins, the increased expression of proteins involved in polypeptide folding, known as the unfolded protein response (UPR), and the destruction of misfolded proteins by the ER-associated protein degradation (ERAD) system. This gene may play a role in both UPR and ERAD. Its expression is induced by UPR and it has an ER stress response element in its promoter region while the encoded protein has an N-terminal ubiquitin-like domain which may interact with the ERAD system. This protein has been shown to interact with presenilin proteins and to increase the level of amyloid-beta protein following its overexpression. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms. The full-length nature of all transcript variants has not been determined.^[3]

Interactions

HERPUD1 has been shown to interact with UBQLN1^[4] and UBQLN2.

References

1. Kokame K, Agarwala KL, Kato H, Miyata T (Nov 2000). "Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress". J Biol Chem 275 (42): 32846–53. doi:10.1074/jbc.M002063200. PMID 10922362.
2. van Laar T, Schouten T, Hoogervorst E, van Eck M, van der Eb AJ, Terleth C (Apr 2000). "The novel MMS-inducible gene Mif1/KIAA0025 is a target of the unfolded protein response pathway". FEBS Lett 469 (1): 123–31. doi:10.1016/S0014-5793(00)01253-9. PMID 10708769.
3. "Entrez Gene: HERPUD1 homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1".
4. Kim, Tae-Yeon; Kim Eunmin; Yoon Sungjoo Kim; Yoon Jong-Bok (May 2008). "Herp enhances ER-associated protein degradation by recruiting ubiquilins". Biochem. Biophys. Res. Commun. (United States) 369 (2): 741–6. doi:10.1016/j.bbrc.2008.02.086. PMID 18307982.

Further reading

• van Laar T, van der Eb AJ, Terleth C (2002). "Mif1: a missing link between the unfolded protein response pathway and ER-associated protein degradation?". Curr. Protein Pept. Sci. 2 (2): 169–90. doi:10.2174/1389203013381189. PMID 12370023.
• Nomura N, Miyajima N, Sazuka T, et al. (1995). "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.". DNA Res. 1 (1): 27–35. doi:10.1093/dnares/1.1.27. PMID 7584026.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• 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.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Kokame K, Kato H, Miyata T (2001). "Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response". J. Biol. Chem. 276 (12): 9199–205. doi:10.1074/jbc.M010486200. PMID 11112790.
• Sai X, Kawamura Y, Kokame K, et al. (2002). "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein". J. Biol. Chem. 277 (15): 12915–20. doi:10.1074/jbc.M112372200. PMID 11799129.
• Chtarbova S, Nimmrich I, Erdmann S, et al. (2002). "Murine Nr4a1 and Herpud1 are up-regulated by Wnt-1, but the homologous human genes are independent from beta-catenin activation". Biochem. J. 367 (Pt 3): 723–8. doi:10.1042/BJ20020699. PMC 1222938. PMID 12153396.
• 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.
• Sai X, Kokame K, Shiraishi H, et al. (2003). "The ubiquitin-like domain of Herp is involved in Herp degradation, but not necessary for its enhancement of amyloid beta-protein generation". FEBS Lett. 553 (1–2): 151–6. doi:10.1016/S0014-5793(03)01009-3. PMID 14550564.
• 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.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• 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.
• Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
• Liang G, Audas TE, Li Y, et al. (2007). "Luman/CREB3 Induces Transcription of the Endoplasmic Reticulum (ER) Stress Response Protein Herp through an ER Stress Response Element". Mol. Cell. Biol. 26 (21): 7999–8010. doi:10.1128/MCB.01046-06. PMC 1636730. PMID 16940180.
• Lenz B, Bleich S, Beutler S, et al. (2007). "Homocysteine regulates expression of Herp by DNA methylation involving the AARE and CREB binding sites". Exp. Cell Res. 312 (20): 4049–55. doi:10.1016/j.yexcr.2006.09.004. PMID 17020760.