SIAH1 (siah E3 ubiquitin protein ligase 1)

Alias_names	seven in absentia homolog 1 (Drosophila)
Alias_symbol (synonym)	hSIAH1
Other alias	SIAH1A
HGNC (Hugo)	SIAH1
LocusID (NCBI)	6477
Atlas_Id	457
Location	16q12.1  [Link to chromosome band 16q12]
Location_base_pair	Starts at 48360543 and ends at 48385318 bp from pter ( according to hg19-Feb_2009)  [Mapping SIAH1.png]
	Map of chromosome 16 with region 16q12.1 highlighted as the location of the gene SIAH1.

Note	The human Siah1 gene is composed of 2 exons, separated by an intron of roughly 14,5 kb.
	Genomic structure and exon-intron boundaries for SIAH1. The relevant DNA sequences at exon-intron boundaries are indicated, and respective amino acid sequences are indicated below in single-letter code. The entire open reading frame of SIAH1 is in exon 2, and its initiating methionine is underlined.
Pseudogene	One pseudogene has been reported.

	Schema of Siah1 structure. Siah1 has RING domain at the N-terminus and the substrate binding domain (SBD) at the C-terminus. Some substrate proteins are recognized by this substrate binding domain directly, and receive ubiquitin-conjugation.
Expression	Siah1 mRNA is widely expressed in the human tissues. It is expressed at higher level in placenta, skeletal muscle and testis.
Localisation	Siah1 protein can be localized in both cytoplasm and nucleus.
Function	Siah1 is the mammalian homolog of Drosophia seven in absentia (SINA) protein (Carthew and Rubin, 1990). Siah1 protein plays a key role in biological processes such as the cell cycle, programmed cell death, and oncogenesis (Nemani et al., 1996). The Siah family of RING-domain proteins are components of ubiquitin ligase complexes, targeting proteins for proteasomal degradation. Numerous substrates targeted for degradation by Siah proteins have been reported; Synphilin-1 (Nagano et al., 2003), DCC (Hu et al., 1997), N-CoR (Zhang et al., 1998), BOB1/OBF1 (Boehm et al., 2001, Tiedt et al., 2001), c-Myb (Tanikawa et al., 2000), Kid (Germani et al., 2000) and CtIP (Germani et al., 2003). Siah1 expression is upregulated by p53, revealing a link between genotoxic injury and destruction of β-catenin and reduced T-cell factor/lymphoid enhancer factor (Tcf/Lef) activity (Liu et al., 2001; Jansen et al., 2009). Recent paper showed Siah1 expression facilitates ubiquitination and degradation of the tumor suppressor HIPK2 that is a key regulator of the apoptotic programme induced by DNA damage (Winter et al., 2008). It has been shown that the nuclear translocation and accumulation of GAPDH play important roles in early events leading to cell death initiation and execution (Sirover, 1999), resulting in the various degenerative diseases. Siah1 functions as a potential carrier/shuttle proteins for the induction of GAPDH nuclear translocation because of its nuclear location signal (NLS) domain in Siah1 (Hara et al., 2005). Siah1a knockout mice are growth-retarded, exhibit early lethality, and display spermatogenetic defects. They also exhibit high numbers of osteoclasts with low numbers of osteoblasts, resulting in severe osteopenia (Frew et al., 2004).
Homology	Human: Siah2. Mouse: Siah1a, Siah1b, Siah2.

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