SIAH1 protein expression summary - The Human Protein Atlas

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SIAH1

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STRUCT & INT

SIAH1

SIAH1 INFORMATION
Proteinⁱ Full gene name according to HGNC.	Siah E3 ubiquitin protein ligase 1
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	SIAH1 (hSIAH1)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s).	Disease related genes Enzymes Human disease related genes Metabolic proteins Plasma proteins Potential drug targets Transporters
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	4
Protein interactions	Interacting with 14 proteins

PROTEIN EXPRESSION AND LOCALIZATION
Tissue profileⁱ A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource. "Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.	General nuclear and cytoplasmic expression.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	Localized to the Mitochondria In addition localized to the Nucleoplasm
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.	Intracellular

TISSUE RNA EXPRESSION
Tissue specificityⁱ The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.	Low tissue specificity
Tissue expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Placenta - Pregnancy (mainly)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category	Low human brain regional specificity
Brain expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Transcription (mainly)

CELL TYPE RNA EXPRESSION
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Cell type enriched (Syncytiotrophoblasts)
Single cell type expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Syncytiotrophoblasts - Pregnancy (mainly)
Tissue cell type classificationⁱ Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.	Cell type enriched (Testis - Early spermatids)
Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Low immune cell specificity
Immune cell expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Eosinophils - Transcription (mainly)

CANCER & CELL LINES
Prognostic summary	SIAH1 is a prognostic marker in Kidney renal clear cell carcinoma, Liver hepatocellular carcinoma
Cancer specificityⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.	Low cancer specificity
Cell line expression clusterⁱ The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Cell cycle regulation (mainly)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Low cancer specificity

PROTEINS IN BLOOD
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.	No
Proximity extension assayⁱ Detectibility in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with six visits during two years. Read more	Not available

PROTEIN FUNCTION
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates 14, 15, 16, 17, 18, 19, 20, 21, 22, 23. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes 24, 25, 26, 27, 28, 29, 30, 31, 32, 33. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP 34, 35, 36, 37, 38, 39, 40, 41. Confers constitutive instability to HIPK2 through proteasomal degradation 42, 43. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling 44, 45, 46, 47, 48, 49, 50, 51, 52, 53. Has some overlapping function with SIAH2 54, 55, 56, 57, 58, 59, 60, 61, 62, 63. Induces apoptosis in cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus (By similarity). GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (By similarity). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (By similarity). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1 64, 65.... show less
Molecular function (UniProt)ⁱ Keywords assigned by UniProt to proteins due to their particular molecular function.	Developmental protein, Transferase
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Apoptosis, Cell cycle, Differentiation, Spermatogenesis, Ubl conjugation pathway
Ligand (UniProt)ⁱ Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.	Metal-binding, Zinc
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	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. [provided by RefSeq, Jul 2008]... show less

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