SIAH1

Siah E3 ubiquitin protein ligase 1
PDB rendering based on 1k2f.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2A25​, 4C9Z​, 4CA1​, 4I7B​, 4I7C​, 4I7D​, 4X3G​
Identifiers
Symbols	SIAH1 ; SIAH1A
External IDs	OMIM: 602212 MGI: 108064 HomoloGene: 20654 GeneCards: SIAH1 Gene
EC number	6.3.2.-
Gene ontology Molecular function • ubiquitin-protein transferase activity • protein binding • protein C-terminus binding • zinc ion binding • ligase activity • identical protein binding • ubiquitin protein ligase activity Cellular component • nucleus • cytoplasm • early endosome • cytosol • plasma membrane • beta-catenin destruction complex Biological process • ubiquitin-dependent protein catabolic process • apoptotic process • cell cycle • spermatogenesis • nervous system development • axon guidance • anatomical structure morphogenesis • protein catabolic process • protein destabilization • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • positive regulation of apoptotic process • proteasome-mediated ubiquitin-dependent protein catabolic process • neuron apoptotic process • positive regulation of intrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
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: 48.36 – 48.45 Mb	Chr 8: 86.72 – 86.75 Mb
PubMed search

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

Function

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]

Interactions

SIAH1 has been shown to interact with:

• APC,^[4]
• BAG1,^[5]
• CACYBP,^[6]
• KHDRBS3,^[7][8]
• KIF22,^[9]
• NUMB,^[10]
• PEG10,^[11]
• PEG3^[12]
• POU2AF1,^[13]
• RBBP8,^[14] and
• TRIB3.^[15]

References

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

• 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.
• Nemani M, Linares-Cruz G, Bruzzoni-Giovanelli H, et al. (1996). "Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression.". Proc. Natl. Acad. Sci. U.S.A. 93 (17): 9039–42. doi:10.1073/pnas.93.17.9039. PMC 38591. PMID 8799150.
• 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.
• Matsuzawa S, Takayama S, Froesch BA, et al. (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.
• Block KL, Vornlocher HP, Hershey JW (1998). "Characterization of cDNAs encoding the p44 and p35 subunits of human translation initiation factor eIF3.". J. Biol. Chem. 273 (48): 31901–8. doi:10.1074/jbc.273.48.31901. PMID 9822659.
• Hu G, Fearon ER (1999). "Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins.". Mol. Cell. Biol. 19 (1): 724–32. PMC 83929. PMID 9858595.
• Relaix F, Wei X, Li W, et al. (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.
• Tanikawa J, Ichikawa-Iwata E, Kanei-Ishii C, et al. (2000). "p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3.". J. Biol. Chem. 275 (20): 15578–85. doi:10.1074/jbc.M000372200. PMID 10747903.
• Medhioub M, Vaury C, Hamelin R, Thomas G (2000). "Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for this candidate tumor suppressor gene.". Int. J. Cancer 87 (6): 794–7. doi:10.1002/1097-0215(20000915)87:6<794::AID-IJC5>3.0.CO;2-B. PMID 10956387.
• Germani A, Bruzzoni-Giovanelli H, Fellous A, et al. (2001). "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.
• 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.
• Liu J, Stevens J, Rote CA, et al. (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.
• Tiedt R, Bartholdy BA, Matthias G, et al. (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.
• Boehm J, He Y, Greiner A, et al. (2001). "Regulation of BOB.1/OBF.1 stability by SIAH.". EMBO J. 20 (15): 4153–62. doi:10.1093/emboj/20.15.4153. PMC 149152. PMID 11483518.
• Susini L, Passer BJ, Amzallag-Elbaz N, et al. (2002). "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.
• Wheeler TC, Chin LS, Li Y, et al. (2002). "Regulation of synaptophysin degradation by mammalian homologues of seven in absentia.". J. Biol. Chem. 277 (12): 10273–82. doi:10.1074/jbc.M107857200. PMID 11786535.
• Maeda A, Yoshida T, Kusuzaki K, Sakai T (2002). "The characterization of the human Siah-1 promoter(1).". FEBS Lett. 512 (1-3): 223–6. doi:10.1016/S0014-5793(02)02265-2. PMID 11852084.
• Jarmuz A, Chester A, Bayliss J, et al. (2002). "An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22.". Genomics 79 (3): 285–96. doi:10.1006/geno.2002.6718. PMID 11863358.