# SIAH2

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Protein-coding gene in the species Homo sapiens

SIAH2 Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5H9M Identifiers Aliases SIAH2, hSiah2, siah E3 ubiquitin protein ligase 2 External IDs OMIM: 602213; MGI: 108062; HomoloGene: 21053; GeneCards: SIAH2; OMA:SIAH2 - orthologs Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q25.1 Start 150,741,125 bp[1] End 150,763,477 bp[1] Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 D|3 28.68 cM Start 58,582,359 bp[2] End 58,599,821 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal gland left adrenal cortex monocyte ectocervix right lobe of liver blood canal of the cervix bone marrow stromal cell of endometrium Top expressed in secondary oocyte zygote primary oocyte seminiferous tubule spermatid olfactory epithelium ankle joint parotid gland right kidney islet of Langerhans More reference expression data BioGPS n/a Gene ontology Molecular function transcription corepressor activity zinc ion binding metal ion binding protein binding ubiquitin conjugating enzyme binding transferase activity ubiquitin-protein transferase activity ubiquitin protein ligase activity Cellular component cytoplasm cytosol intracellular membrane-bounded organelle nucleoplasm soma early endosome neuron projection nucleus Biological process negative regulation of cysteine-type endopeptidase activity involved in apoptotic process small GTPase mediated signal transduction regulation of protein ubiquitination negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic process axon guidance multicellular organism development protein ubiquitination cell cycle negative regulation of canonical Wnt signaling pathway apoptotic process negative regulation of nucleic acid-templated transcription protein polyubiquitination protein deubiquitination ubiquitin-dependent protein catabolic process negative regulation of netrin-activated signaling pathway proteasome-mediated ubiquitin-dependent protein catabolic process regulation of circadian rhythm rhythmic process Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 6478 20439 Ensembl ENSG00000181788 ENSMUSG00000036432 UniProt O43255 Q06986 RefSeq (mRNA) NM_005067 NM_009174 RefSeq (protein) NP_005058 NP_033200 Location (UCSC) Chr 3: 150.74 – 150.76 Mb Chr 3: 58.58 – 58.6 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

**E3 ubiquitin-protein ligase SIAH2** is an [enzyme](/source/Enzyme) that in humans is encoded by the *SIAH2* [gene](/source/Gene).[5][6]

## Function

This gene encodes a protein that is a member of the [seven in absentia homolog](https://en.wikipedia.org/w/index.php?title=Seven_in_absentia_homolog&action=edit&redlink=1) (SIAH) family. The protein is an [E3 ligase](/source/E3_ligase) and is involved in [ubiquitination](/source/Ubiquitination) and proteasome-mediated degradation of specific proteins. The activity of this [ubiquitin ligase](/source/Ubiquitin_ligase) has been implicated in regulating cellular response to [hypoxia](/source/Hypoxia_(medical)).[6]

## Interactions

SIAH2 has been shown to [interact](/source/Protein-protein_interaction) with [PEG10](/source/PEG10),[7] [Synaptophysin](/source/Synaptophysin),[8] [PEG3](/source/PEG3)[9] and [VAV1](/source/VAV1).[10]

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000181788](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000181788) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000036432](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000036432) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=6478). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=20439). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-pmid9334332_5-0)** Hu G, Zhang S, Vidal M, Baer JL, Xu T, Fearon ER (October 1997). ["Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC316613). *Genes & Development*. **11** (20): 2701–14. [doi](/source/Doi_(identifier)):[10.1101/gad.11.20.2701](https://doi.org/10.1101%2Fgad.11.20.2701). [PMC](/source/PMC_(identifier)) [316613](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC316613). [PMID](/source/PMID_(identifier)) [9334332](https://pubmed.ncbi.nlm.nih.gov/9334332).

1. ^ [***a***](#cite_ref-entrez_6-0) [***b***](#cite_ref-entrez_6-1) ["Entrez Gene: SIAH2 seven in absentia homolog 2 (Drosophila)"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6478).

1. **[^](#cite_ref-pmid12810624_7-0)** Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y (June 2003). "Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1". *Cancer Research*. **63** (12): 3043–8. [PMID](/source/PMID_(identifier)) [12810624](https://pubmed.ncbi.nlm.nih.gov/12810624).

1. **[^](#cite_ref-pmid11786535_8-0)** Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L (March 2002). ["Regulation of synaptophysin degradation by mammalian homologues of seven in absentia"](https://doi.org/10.1074%2Fjbc.M107857200). *The Journal of Biological Chemistry*. **277** (12): 10273–82. [doi](/source/Doi_(identifier)):[10.1074/jbc.M107857200](https://doi.org/10.1074%2Fjbc.M107857200). [PMID](/source/PMID_(identifier)) [11786535](https://pubmed.ncbi.nlm.nih.gov/11786535).

1. **[^](#cite_ref-pmid10681424_9-0)** Relaix F, Wei XJ, Li W, Pan J, Lin Y, Bowtell DD, Sassoon DA, Wu X (February 2000). ["Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15761). *Proceedings of the National Academy of Sciences of the United States of America*. **97** (5): 2105–10. [Bibcode](/source/Bibcode_(identifier)):[2000PNAS...97.2105R](https://ui.adsabs.harvard.edu/abs/2000PNAS...97.2105R). [doi](/source/Doi_(identifier)):[10.1073/pnas.040378897](https://doi.org/10.1073%2Fpnas.040378897). [PMC](/source/PMC_(identifier)) [15761](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15761). [PMID](/source/PMID_(identifier)) [10681424](https://pubmed.ncbi.nlm.nih.gov/10681424).

1. **[^](#cite_ref-pmid10207103_10-0)** Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N (May 1999). ["hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84217). *Molecular and Cellular Biology*. **19** (5): 3798–807. [doi](/source/Doi_(identifier)):[10.1128/mcb.19.5.3798](https://doi.org/10.1128%2Fmcb.19.5.3798). [PMC](/source/PMC_(identifier)) [84217](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84217). [PMID](/source/PMID_(identifier)) [10207103](https://pubmed.ncbi.nlm.nih.gov/10207103).

## Further reading

- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". *Gene*. **138** (1–2): 171–4. [doi](/source/Doi_(identifier)):[10.1016/0378-1119(94)90802-8](https://doi.org/10.1016%2F0378-1119%2894%2990802-8). [PMID](/source/PMID_(identifier)) [8125298](https://pubmed.ncbi.nlm.nih.gov/8125298).

- Bonaldo MF, Lennon G, Soares MB (September 1996). ["Normalization and subtraction: two approaches to facilitate gene discovery"](https://doi.org/10.1101%2Fgr.6.9.791). *Genome Research*. **6** (9): 791–806. [doi](/source/Doi_(identifier)):[10.1101/gr.6.9.791](https://doi.org/10.1101%2Fgr.6.9.791). [PMID](/source/PMID_(identifier)) [8889548](https://pubmed.ncbi.nlm.nih.gov/8889548).

- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". *Gene*. **200** (1–2): 149–56. [doi](/source/Doi_(identifier)):[10.1016/S0378-1119(97)00411-3](https://doi.org/10.1016%2FS0378-1119%2897%2900411-3). [PMID](/source/PMID_(identifier)) [9373149](https://pubmed.ncbi.nlm.nih.gov/9373149).

- Hu G, Chung YL, Glover T, Valentine V, Look AT, Fearon ER (November 1997). ["Characterization of human homologs of the Drosophila seven in absentia (sina) gene"](https://doi.org/10.1006%2Fgeno.1997.4997). *Genomics*. **46** (1): 103–11. [doi](/source/Doi_(identifier)):[10.1006/geno.1997.4997](https://doi.org/10.1006%2Fgeno.1997.4997). [PMID](/source/PMID_(identifier)) [9403064](https://pubmed.ncbi.nlm.nih.gov/9403064).

- Hu G, Fearon ER (January 1999). ["Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC83929). *Molecular and Cellular Biology*. **19** (1): 724–32. [doi](/source/Doi_(identifier)):[10.1128/mcb.19.1.724](https://doi.org/10.1128%2Fmcb.19.1.724). [PMC](/source/PMC_(identifier)) [83929](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC83929). [PMID](/source/PMID_(identifier)) [9858595](https://pubmed.ncbi.nlm.nih.gov/9858595).

- Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N (May 1999). ["hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84217). *Molecular and Cellular Biology*. **19** (5): 3798–807. [doi](/source/Doi_(identifier)):[10.1128/mcb.19.5.3798](https://doi.org/10.1128%2Fmcb.19.5.3798). [PMC](/source/PMC_(identifier)) [84217](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84217). [PMID](/source/PMID_(identifier)) [10207103](https://pubmed.ncbi.nlm.nih.gov/10207103).

- Relaix F, Wei XJ, Li W, Pan J, Lin Y, Bowtell DD, Sassoon DA, Wu X (February 2000). ["Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15761). *Proceedings of the National Academy of Sciences of the United States of America*. **97** (5): 2105–10. [Bibcode](/source/Bibcode_(identifier)):[2000PNAS...97.2105R](https://ui.adsabs.harvard.edu/abs/2000PNAS...97.2105R). [doi](/source/Doi_(identifier)):[10.1073/pnas.040378897](https://doi.org/10.1073%2Fpnas.040378897). [PMC](/source/PMC_(identifier)) [15761](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15761). [PMID](/source/PMID_(identifier)) [10681424](https://pubmed.ncbi.nlm.nih.gov/10681424).

- Joensuu T, Hämäläinen R, Lehesjoki AE, de la Chapelle A, Sankila EM (February 2000). "A sequence-ready map of the Usher syndrome type III critical region on chromosome 3q". *Genomics*. **63** (3): 409–16. [doi](/source/Doi_(identifier)):[10.1006/geno.1999.6096](https://doi.org/10.1006%2Fgeno.1999.6096). [PMID](/source/PMID_(identifier)) [10704288](https://pubmed.ncbi.nlm.nih.gov/10704288).

- Matsuzawa SI, Reed JC (May 2001). ["Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses"](https://doi.org/10.1016%2FS1097-2765%2801%2900242-8). *Molecular Cell*. **7** (5): 915–26. [doi](/source/Doi_(identifier)):[10.1016/S1097-2765(01)00242-8](https://doi.org/10.1016%2FS1097-2765%2801%2900242-8). [PMID](/source/PMID_(identifier)) [11389839](https://pubmed.ncbi.nlm.nih.gov/11389839).

- Boehm J, He Y, Greiner A, Staudt L, Wirth T (August 2001). ["Regulation of BOB.1/OBF.1 stability by SIAH"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149152). *The EMBO Journal*. **20** (15): 4153–62. [doi](/source/Doi_(identifier)):[10.1093/emboj/20.15.4153](https://doi.org/10.1093%2Femboj%2F20.15.4153). [PMC](/source/PMC_(identifier)) [149152](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149152). [PMID](/source/PMID_(identifier)) [11483518](https://pubmed.ncbi.nlm.nih.gov/11483518).

- Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L (March 2002). ["Regulation of synaptophysin degradation by mammalian homologues of seven in absentia"](https://doi.org/10.1074%2Fjbc.M107857200). *The Journal of Biological Chemistry*. **277** (12): 10273–82. [doi](/source/Doi_(identifier)):[10.1074/jbc.M107857200](https://doi.org/10.1074%2Fjbc.M107857200). [PMID](/source/PMID_(identifier)) [11786535](https://pubmed.ncbi.nlm.nih.gov/11786535).

- 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 (July 2002). ["NotI flanking sequences: a tool for gene discovery and verification of the human genome"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC135748). *Nucleic Acids Research*. **30** (14): 3163–70. [doi](/source/Doi_(identifier)):[10.1093/nar/gkf428](https://doi.org/10.1093%2Fnar%2Fgkf428). [PMC](/source/PMC_(identifier)) [135748](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC135748). [PMID](/source/PMID_(identifier)) [12136098](https://pubmed.ncbi.nlm.nih.gov/12136098).

- Habelhah H, Frew IJ, Laine A, Janes PW, Relaix F, Sassoon D, Bowtell DD, Ronai Z (November 2002). ["Stress-induced decrease in TRAF2 stability is mediated by Siah2"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC131073). *The EMBO Journal*. **21** (21): 5756–65. [doi](/source/Doi_(identifier)):[10.1093/emboj/cdf576](https://doi.org/10.1093%2Femboj%2Fcdf576). [PMC](/source/PMC_(identifier)) [131073](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC131073). [PMID](/source/PMID_(identifier)) [12411493](https://pubmed.ncbi.nlm.nih.gov/12411493).

- Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y (June 2003). "Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1". *Cancer Research*. **63** (12): 3043–8. [PMID](/source/PMID_(identifier)) [12810624](https://pubmed.ncbi.nlm.nih.gov/12810624).

- Fanelli M, Fantozzi A, De Luca P, Caprodossi S, Matsuzawa S, Lazar MA, Pelicci PG, Minucci S (February 2004). ["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"](https://doi.org/10.1074%2Fjbc.M306407200). *The Journal of Biological Chemistry*. **279** (7): 5374–9. [doi](/source/Doi_(identifier)):[10.1074/jbc.M306407200](https://doi.org/10.1074%2Fjbc.M306407200). [PMID](/source/PMID_(identifier)) [14645235](https://pubmed.ncbi.nlm.nih.gov/14645235).

- Germani A, Prabel A, Mourah S, Podgorniak MP, Di Carlo A, Ehrlich R, Gisselbrecht S, Varin-Blank N, Calvo F, Bruzzoni-Giovanelli H (December 2003). ["SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway"](https://doi.org/10.1038%2Fsj.onc.1206994). *Oncogene*. **22** (55): 8845–51. [doi](/source/Doi_(identifier)):[10.1038/sj.onc.1206994](https://doi.org/10.1038%2Fsj.onc.1206994). [PMID](/source/PMID_(identifier)) [14654780](https://pubmed.ncbi.nlm.nih.gov/14654780).

- 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 (June 2004). ["Siah2 regulates stability of prolyl-hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia"](https://doi.org/10.1016%2Fj.cell.2004.06.001). *Cell*. **117** (7): 941–52. [doi](/source/Doi_(identifier)):[10.1016/j.cell.2004.06.001](https://doi.org/10.1016%2Fj.cell.2004.06.001). [PMID](/source/PMID_(identifier)) [15210114](https://pubmed.ncbi.nlm.nih.gov/15210114). [S2CID](/source/S2CID_(identifier)) [1447980](https://api.semanticscholar.org/CorpusID:1447980).

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Adapted from the Wikipedia article [SIAH2](https://en.wikipedia.org/wiki/SIAH2) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/SIAH2?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.