From Wikipedia, the free encyclopedia
Jump to: navigation, search
Siah E3 ubiquitin protein ligase 1
Protein SIAH1 PDB 1k2f.png
PDB rendering based on 1k2f.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols SIAH1 ; SIAH1A
External IDs OMIM602212 MGI108064 HomoloGene20654 GeneCards: SIAH1 Gene
EC number 6.3.2.-
RNA expression pattern
PBB GE SIAH1 202980 s at tn.png
PBB GE SIAH1 202981 x at tn.png
More reference expression data
Species Human Mouse
Entrez 6477 20437
Ensembl ENSG00000196470 ENSMUSG00000036840
UniProt Q8IUQ4 P61092
RefSeq (mRNA) NM_001006610 NM_009172
RefSeq (protein) NP_001006611 NP_033198
Location (UCSC) Chr 16:
48.39 – 48.48 Mb
Chr 8:
86.72 – 86.75 Mb
PubMed search [1] [2]

E3 ubiquitin-protein ligase SIAH1 is an enzyme that in humans is encoded by the SIAH1 gene.[1][2]


This gene encodes for a polypeptide structure that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in the development of certain forms of Parkinson's disease, the regulation of the cellular response to hypoxia and induction of apoptosis. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.[3]


SIAH1 has been shown to interact with:


  1. ^ Hu G, Chung YL, Glover T, Valentine V, Look AT, Fearon ER (January 1998). "Characterization of human homologs of the Drosophila seven in absentia (sina) gene". Genomics 46 (1): 103–11. doi:10.1006/geno.1997.4997. PMID 9403064. 
  2. ^ Hu G, Zhang S, Vidal M, Baer JL, Xu T, Fearon ER (November 1997). "Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway". Genes Dev 11 (20): 2701–14. doi:10.1101/gad.11.20.2701. PMC 316613. PMID 9334332. 
  3. ^ "Entrez Gene: SIAH1 seven in absentia homolog 1 (Drosophila)". 
  4. ^ Liu J, Stevens J, Rote CA, Yost HJ, Hu Y, Neufeld KL, White RL, Matsunami N (2001). "Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein". Mol. Cell 7 (5): 927–36. doi:10.1016/S1097-2765(01)00241-6. PMID 11389840. 
  5. ^ Matsuzawa S, Takayama S, Froesch BA, Zapata JM, Reed JC (1998). "p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1". EMBO J. 17 (10): 2736–47. doi:10.1093/emboj/17.10.2736. PMC 1170614. PMID 9582267. 
  6. ^ Matsuzawa SI, Reed JC (2001). "Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses". Mol. Cell 7 (5): 915–26. doi:10.1016/S1097-2765(01)00242-8. PMID 11389839. 
  7. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  8. ^ Venables JP, Dalgliesh C, Paronetto MP, Skitt L, Thornton JK, Saunders PT, Sette C, Jones KT, Elliott DJ (2004). "SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome". Hum. Mol. Genet. 13 (14): 1525–34. doi:10.1093/hmg/ddh165. PMID 15163637. 
  9. ^ Germani A, Bruzzoni-Giovanelli H, Fellous A, Gisselbrecht S, Varin-Blank N, Calvo F (2000). "SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis". Oncogene 19 (52): 5997–6006. doi:10.1038/sj.onc.1204002. PMID 11146551. 
  10. ^ Susini L, Passer BJ, Amzallag-Elbaz N, Juven-Gershon T, Prieur S, Privat N, Tuynder M, Gendron MC, Israël A, Amson R, Oren M, Telerman A (2001). "Siah-1 binds and regulates the function of Numb". Proc. Natl. Acad. Sci. U.S.A. 98 (26): 15067–72. doi:10.1073/pnas.261571998. PMC 64984. PMID 11752454. 
  11. ^ Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y (2003). "Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1". Cancer Res. 63 (12): 3043–8. PMID 12810624. 
  12. ^ Relaix F, Wei Xj, Li W, Pan J, Lin Y, Bowtell DD, Sassoon DA, Wu X (2000). "Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis". Proc. Natl. Acad. Sci. U.S.A. 97 (5): 2105–10. doi:10.1073/pnas.040378897. PMC 15761. PMID 10681424. 
  13. ^ Tiedt R, Bartholdy BA, Matthias G, Newell JW, Matthias P (2001). "The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1". EMBO J. 20 (15): 4143–52. doi:10.1093/emboj/20.15.4143. PMC 149178. PMID 11483517. 
  14. ^ Germani A, Prabel A, Mourah S, Podgorniak MP, Di Carlo A, Ehrlich R, Gisselbrecht S, Varin-Blank N, Calvo F, Bruzzoni-Giovanelli H (2003). "SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway". Oncogene 22 (55): 8845–51. doi:10.1038/sj.onc.1206994. PMID 14654780. 
  15. ^ Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F (2008). "E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3". Cell. Signal. 20 (5): 942–8. doi:10.1016/j.cellsig.2008.01.010. PMID 18276110. 

Further reading[edit]