SIAH2 explained

E3 ubiquitin-protein ligase SIAH2 is an enzyme that in humans is encoded by the SIAH2 gene.^{[1] [2]}

Function

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 regulating cellular response to hypoxia.

Interactions

SIAH2 has been shown to interact with PEG10,^[3] Synaptophysin,^[4] PEG3^[5] and VAV1.^[6]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Hu G, Chung YL, Glover T, Valentine V, Look AT, Fearon ER . Characterization of human homologs of the Drosophila seven in absentia (sina) gene . Genomics . 46 . 1 . 103–11 . November 1997 . 9403064 . 10.1006/geno.1997.4997 . free .
• Hu G, Fearon ER . Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins . Molecular and Cellular Biology . 19 . 1 . 724–32 . January 1999 . 9858595 . 83929 . 10.1128/mcb.19.1.724.
• Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N . hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways . Molecular and Cellular Biology . 19 . 5 . 3798–807 . May 1999 . 10207103 . 84217 . 10.1128/mcb.19.5.3798.
• Relaix F, Wei XJ, Li W, Pan J, Lin Y, Bowtell DD, Sassoon DA, Wu X . Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis . Proceedings of the National Academy of Sciences of the United States of America . 97 . 5 . 2105–10 . February 2000 . 10681424 . 15761 . 10.1073/pnas.040378897 . 2000PNAS...97.2105R . free .
• Joensuu T, Hämäläinen R, Lehesjoki AE, de la Chapelle A, Sankila EM . A sequence-ready map of the Usher syndrome type III critical region on chromosome 3q . Genomics . 63 . 3 . 409–16 . February 2000 . 10704288 . 10.1006/geno.1999.6096 .
• Matsuzawa SI, Reed JC . Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses . Molecular Cell . 7 . 5 . 915–26 . May 2001 . 11389839 . 10.1016/S1097-2765(01)00242-8 . free .
• Boehm J, He Y, Greiner A, Staudt L, Wirth T . Regulation of BOB.1/OBF.1 stability by SIAH . The EMBO Journal . 20 . 15 . 4153–62 . August 2001 . 11483518 . 149152 . 10.1093/emboj/20.15.4153 .
• Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L . Regulation of synaptophysin degradation by mammalian homologues of seven in absentia . The Journal of Biological Chemistry . 277 . 12 . 10273–82 . March 2002 . 11786535 . 10.1074/jbc.M107857200 . free .
• Kutsenko AS, Gizatullin RZ, Al-Amin AN, Wang F, Kvasha SM, Podowski RM, Matushkin YG, Gyanchandani A, Muravenko OV, Levitsky VG, Kolchanov NA, Protopopov AI, Kashuba VI, Kisselev LL, Wasserman W, Wahlestedt C, Zabarovsky ER . NotI flanking sequences: a tool for gene discovery and verification of the human genome . Nucleic Acids Research . 30 . 14 . 3163–70 . July 2002 . 12136098 . 135748 . 10.1093/nar/gkf428 .
• Habelhah H, Frew IJ, Laine A, Janes PW, Relaix F, Sassoon D, Bowtell DD, Ronai Z . Stress-induced decrease in TRAF2 stability is mediated by Siah2 . The EMBO Journal . 21 . 21 . 5756–65 . November 2002 . 12411493 . 131073 . 10.1093/emboj/cdf576 .
• Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y . Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1 . Cancer Research . 63 . 12 . 3043–8 . June 2003 . 12810624 .
• Fanelli M, Fantozzi A, De Luca P, Caprodossi S, Matsuzawa S, Lazar MA, Pelicci PG, Minucci S . The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome . The Journal of Biological Chemistry . 279 . 7 . 5374–9 . February 2004 . 14645235 . 10.1074/jbc.M306407200 . free .
• Germani A, Prabel A, Mourah S, Podgorniak MP, Di Carlo A, Ehrlich R, Gisselbrecht S, Varin-Blank N, Calvo F, Bruzzoni-Giovanelli H . SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway . Oncogene . 22 . 55 . 8845–51 . December 2003 . 14654780 . 10.1038/sj.onc.1206994 . free .
• Nakayama K, Frew IJ, Hagensen M, Skals M, Habelhah H, Bhoumik A, Kadoya T, Erdjument-Bromage H, Tempst P, Frappell PB, Bowtell DD, Ronai Z . Siah2 regulates stability of prolyl-hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia . Cell . 117 . 7 . 941–52 . June 2004 . 15210114 . 10.1016/j.cell.2004.06.001 . 1447980 . free .

Notes and References

1. Hu G, Zhang S, Vidal M, Baer JL, Xu T, Fearon ER . Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway . Genes & Development . 11 . 20 . 2701–14 . October 1997 . 9334332 . 316613 . 10.1101/gad.11.20.2701 .
2. Web site: Entrez Gene: SIAH2 seven in absentia homolog 2 (Drosophila).
3. Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y . Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1 . Cancer Research . 63 . 12 . 3043–8 . June 2003 . 12810624 .
4. Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L . Regulation of synaptophysin degradation by mammalian homologues of seven in absentia . The Journal of Biological Chemistry . 277 . 12 . 10273–82 . March 2002 . 11786535 . 10.1074/jbc.M107857200 . free .
5. Relaix F, Wei XJ, Li W, Pan J, Lin Y, Bowtell DD, Sassoon DA, Wu X . Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis . Proceedings of the National Academy of Sciences of the United States of America . 97 . 5 . 2105–10 . February 2000 . 10681424 . 15761 . 10.1073/pnas.040378897 . 2000PNAS...97.2105R . free .
6. Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N . hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways . Molecular and Cellular Biology . 19 . 5 . 3798–807 . May 1999 . 10207103 . 84217 . 10.1128/mcb.19.5.3798.