SIAH1

Seven in absentia homolog 1 (Drosophila)

PDB rendering based on 1k2f.

Available structures
PDB	1k2f, 2a25, 2an6

Identifiers

Symbols

SIAH1; FLJ08065; SIAH1A

External IDs

OMIM: 602212 MGI: 108064 HomoloGene: 20654 GeneCards: SIAH1 Gene

EC number

6.3.2.-

Gene Ontology
Molecular function	• ubiquitin-protein ligase activity • protein binding • protein C-terminus binding • zinc ion binding • zinc ion binding • ligase activity • metal ion binding
Cellular component	• nucleus • cytoplasm • early endosome • cytosol • synaptic vesicle • beta-catenin destruction complex
Biological process	• proteolysis • apoptosis • cell cycle • multicellular organismal development • spermatogenesis • nervous system development • axon guidance • anatomical structure morphogenesis • cell differentiation • protein catabolic process • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • proteasomal ubiquitin-dependent protein catabolic process • neuron apoptosis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 16:
48.39 – 48.42 Mb

Chr 8:
89.25 – 89.27 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 a protein 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 PEG10,^[4] CACYBP,^[5] POU2AF1,^[6] RBBP8,^[7] BAG1,^[8] TRIB3,^[9] NUMB,^[10] KIF22,^[11] KHDRBS3,^[12]^[13] PEG3^[14] and APC.^[15]

References

^ Hu G, Chung YL, Glover T, Valentine V, Look AT, Fearon ER (Jan 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.
^ Hu G, Zhang S, Vidal M, Baer JL, Xu T, Fearon ER (Nov 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316613.
^ "Entrez Gene: SIAH1 seven in absentia homolog 1 (Drosophila)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6477.
^ Okabe, Hiroshi; Satoh Seiji, Furukawa Yoichi, Kato Tatsushi, Hasegawa Suguru, Nakajima Yumi, Yamaoka Yoshio, Nakamura Yusuke (Jun. 2003). "Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1". Cancer Res. (United States) 63 (12): 3043–8. ISSN 0008-5472. PMID 12810624.
^ Matsuzawa, S I; Reed J C (May. 2001). "Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses". Mol. Cell (United States) 7 (5): 915–26. doi:10.1016/S1097-2765(01)00242-8. ISSN 1097-2765. PMID 11389839.
^ Tiedt, R; Bartholdy B A, Matthias G, Newell J W, Matthias P (Aug. 2001). "The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1". EMBO J. (England) 20 (15): 4143–52. doi:10.1093/emboj/20.15.4143. ISSN 0261-4189. PMC 149178. PMID 11483517. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149178.
^ Germani, Antonia; Prabel Audrey, Mourah Samia, Podgorniak Marie-Pierre, Di Carlo Anna, Ehrlich Ricardo, Gisselbrecht Sylvie, Varin-Blank Nadine, Calvo Fabien, Bruzzoni-Giovanelli Heriberto (Dec. 2003). "SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway". Oncogene (England) 22 (55): 8845–51. doi:10.1038/sj.onc.1206994. ISSN 0950-9232. PMID 14654780.
^ Matsuzawa, S; Takayama S, Froesch B A, Zapata J M, Reed J C (May. 1998). "p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1". EMBO J. (ENGLAND) 17 (10): 2736–47. doi:10.1093/emboj/17.10.2736. ISSN 0261-4189. PMC 1170614. PMID 9582267. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170614.
^ Zhou, Ying; Li Lu, Liu Qiongming, Xing Guichun, Kuai Xuezhang, Sun Jing, Yin Xiushan, Wang Jian, Zhang Lingqiang, He Fuchu (May. 2008). "E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3". Cell. Signal. (England) 20 (5): 942–8. doi:10.1016/j.cellsig.2008.01.010. ISSN 0898-6568. PMID 18276110.
^ Susini, L; Passer B J, Amzallag-Elbaz N, Juven-Gershon T, Prieur S, Privat N, Tuynder M, Gendron M C, Israël A, Amson R, Oren M, Telerman A (Dec. 2001). "Siah-1 binds and regulates the function of Numb". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (26): 15067–72. doi:10.1073/pnas.261571998. ISSN 0027-8424. PMC 64984. PMID 11752454. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=64984.
^ Germani, A; Bruzzoni-Giovanelli H, Fellous A, Gisselbrecht S, Varin-Blank N, Calvo F (Dec. 2000). "SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis". Oncogene (England) 19 (52): 5997–6006. doi:10.1038/sj.onc.1204002. ISSN 0950-9232. PMID 11146551.
^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
^ Venables, Julian P; Dalgliesh Caroline, Paronetto Maria Paolo, Skitt Lindi, Thornton Jared K, Saunders Philippa T, Sette Claudio, Jones Keith T, Elliott David J (Jul. 2004). "SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome". Hum. Mol. Genet. (England) 13 (14): 1525–34. doi:10.1093/hmg/ddh165. ISSN 0964-6906. PMID 15163637.
^ Relaix, F; Wei X j, Li W, Pan J, Lin Y, Bowtell D D, Sassoon D A, Wu X (Feb. 2000). "Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (5): 2105–10. doi:10.1073/pnas.040378897. ISSN 0027-8424. PMC 15761. PMID 10681424. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15761.
^ Liu, J; Stevens J, Rote C A, Yost H J, Hu Y, Neufeld K L, White R L, Matsunami N (May. 2001). "Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein". Mol. Cell (United States) 7 (5): 927–36. doi:10.1016/S1097-2765(01)00241-6. ISSN 1097-2765. PMID 11389840.

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38591.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170614.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=83929.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15761.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149178.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149152.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=64984.
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.

PDB gallery

1k2f: siah, Seven In Absentia Homolog

2a25: Crystal structure of Siah1 SBD bound to the peptide EKPAAVVAPITTG from SIP

2an6: Protein-peptide complex