Details for: SIAH2

Gene ID: 6478

Symbol: SIAH2

Ensembl ID: ENSG00000181788

Description: siah E3 ubiquitin protein ligase 2

Associated with

Cells (max top 100)

(Cell Significance Index and respective Thresholds are uniquely calculated using our advanced thresholding algorithms to reveal cell-specific gene markers)

  • Cell Name: polychromatophilic erythroblast (CL0000550)
    Fold Change: 151.6601
    Cell Significance Index: -23.5900
  • Cell Name: hematopoietic oligopotent progenitor cell (CL0002032)
    Fold Change: 97.9722
    Cell Significance Index: -24.8500
  • Cell Name: smooth muscle fiber of ileum (CL1000278)
    Fold Change: 64.3053
    Cell Significance Index: -30.3600
  • Cell Name: mucosal type mast cell (CL0000485)
    Fold Change: 63.9496
    Cell Significance Index: -25.9800
  • Cell Name: peripheral blood mononuclear cell (CL2000001)
    Fold Change: 57.7291
    Cell Significance Index: -29.7000
  • Cell Name: ciliated cell of the bronchus (CL0002332)
    Fold Change: 27.6095
    Cell Significance Index: -26.3600
  • Cell Name: orthochromatic erythroblast (CL0000552)
    Fold Change: 20.3170
    Cell Significance Index: -25.0500
  • Cell Name: CD8-alpha-beta-positive, alpha-beta intraepithelial T cell (CL0000796)
    Fold Change: 9.7392
    Cell Significance Index: -26.0900
  • Cell Name: stromal cell of bone marrow (CL0010001)
    Fold Change: 7.2478
    Cell Significance Index: -28.6000
  • Cell Name: CD8-positive, alpha-beta regulatory T cell (CL0000795)
    Fold Change: 6.9804
    Cell Significance Index: -21.4400
  • Cell Name: cortical cell of adrenal gland (CL0002097)
    Fold Change: 5.0828
    Cell Significance Index: 136.2000
  • Cell Name: epidermal Langerhans cell (CL0002457)
    Fold Change: 4.6103
    Cell Significance Index: -10.0900
  • Cell Name: placental villous trophoblast (CL2000060)
    Fold Change: 3.0433
    Cell Significance Index: 81.2600
  • Cell Name: epithelial cell of stomach (CL0002178)
    Fold Change: 2.4095
    Cell Significance Index: 280.8000
  • Cell Name: early pro-B cell (CL0002046)
    Fold Change: 2.2847
    Cell Significance Index: 147.4000
  • Cell Name: basal cell of prostate epithelium (CL0002341)
    Fold Change: 1.6297
    Cell Significance Index: 44.3600
  • Cell Name: neoplastic cell (CL0001063)
    Fold Change: 1.3403
    Cell Significance Index: 265.9900
  • Cell Name: gut absorptive cell (CL0000677)
    Fold Change: 1.2060
    Cell Significance Index: 72.4000
  • Cell Name: tonsil germinal center B cell (CL2000006)
    Fold Change: 1.1294
    Cell Significance Index: 133.1900
  • Cell Name: intestinal crypt stem cell of colon (CL0009043)
    Fold Change: 1.0550
    Cell Significance Index: 114.7500
  • Cell Name: conjunctival epithelial cell (CL1000432)
    Fold Change: 0.9616
    Cell Significance Index: 13.1200
  • Cell Name: tuft cell of colon (CL0009041)
    Fold Change: 0.7920
    Cell Significance Index: 715.0800
  • Cell Name: bladder urothelial cell (CL1001428)
    Fold Change: 0.7414
    Cell Significance Index: 38.5200
  • Cell Name: L2/3-6 intratelencephalic projecting glutamatergic neuron (CL4023040)
    Fold Change: 0.6370
    Cell Significance Index: 127.7800
  • Cell Name: enterocyte of epithelium of small intestine (CL1000334)
    Fold Change: 0.5361
    Cell Significance Index: 15.4500
  • Cell Name: microfold cell of epithelium of small intestine (CL1000353)
    Fold Change: 0.5337
    Cell Significance Index: 36.9100
  • Cell Name: stromal cell of ovary (CL0002132)
    Fold Change: 0.4980
    Cell Significance Index: 68.3900
  • Cell Name: enterocyte of epithelium of large intestine (CL0002071)
    Fold Change: 0.4871
    Cell Significance Index: 22.0800
  • Cell Name: stem cell of epidermis (CL1000428)
    Fold Change: 0.4506
    Cell Significance Index: 1.3400
  • Cell Name: basal cell of urothelium (CL1000486)
    Fold Change: 0.4057
    Cell Significance Index: 49.8900
  • Cell Name: intermediate cell of urothelium (CL4030055)
    Fold Change: 0.4027
    Cell Significance Index: 72.6000
  • Cell Name: enteroendocrine cell of colon (CL0009042)
    Fold Change: 0.3284
    Cell Significance Index: 62.5000
  • Cell Name: cell in vitro (CL0001034)
    Fold Change: 0.3244
    Cell Significance Index: 177.1700
  • Cell Name: enteroendocrine cell of small intestine (CL0009006)
    Fold Change: 0.3116
    Cell Significance Index: 7.7900
  • Cell Name: glycinergic neuron (CL1001509)
    Fold Change: 0.3002
    Cell Significance Index: 15.7600
  • Cell Name: basal epithelial cell of tracheobronchial tree (CL0002329)
    Fold Change: 0.2970
    Cell Significance Index: 8.3000
  • Cell Name: luminal adaptive secretory precursor cell of mammary gland (CL4033057)
    Fold Change: 0.2601
    Cell Significance Index: 12.2300
  • Cell Name: progenitor cell of mammary luminal epithelium (CL0009116)
    Fold Change: 0.2485
    Cell Significance Index: 18.5200
  • Cell Name: obsolete caudal ganglionic eminence derived GABAergic cortical interneuron (CL4023070)
    Fold Change: 0.1953
    Cell Significance Index: 70.0700
  • Cell Name: hair follicular keratinocyte (CL2000092)
    Fold Change: 0.1720
    Cell Significance Index: 76.0500
  • Cell Name: acinar cell of salivary gland (CL0002623)
    Fold Change: 0.1617
    Cell Significance Index: 7.5400
  • Cell Name: neutrophil progenitor cell (CL0000834)
    Fold Change: 0.1465
    Cell Significance Index: 3.9200
  • Cell Name: lactocyte (CL0002325)
    Fold Change: 0.1126
    Cell Significance Index: 14.5500
  • Cell Name: cardiac muscle myoblast (CL0000513)
    Fold Change: 0.1053
    Cell Significance Index: 8.0800
  • Cell Name: pancreatic acinar cell (CL0002064)
    Fold Change: 0.0994
    Cell Significance Index: 16.9700
  • Cell Name: GABAergic interneuron (CL0011005)
    Fold Change: 0.0807
    Cell Significance Index: 55.8200
  • Cell Name: pigmented epithelial cell (CL0000529)
    Fold Change: 0.0737
    Cell Significance Index: 138.8100
  • Cell Name: indirect pathway medium spiny neuron (CL4023029)
    Fold Change: 0.0597
    Cell Significance Index: 2.6400
  • Cell Name: fibroblast of dermis (CL0002551)
    Fold Change: 0.0535
    Cell Significance Index: 1.1200
  • Cell Name: colon goblet cell (CL0009039)
    Fold Change: 0.0524
    Cell Significance Index: 5.1800
  • Cell Name: odontoblast (CL0000060)
    Fold Change: 0.0149
    Cell Significance Index: 1.9100
  • Cell Name: secondary lens fiber (CL0002225)
    Fold Change: 0.0137
    Cell Significance Index: 18.6800
  • Cell Name: ciliary muscle cell (CL1000443)
    Fold Change: 0.0071
    Cell Significance Index: 3.2100
  • Cell Name: non-pigmented ciliary epithelial cell (CL0002304)
    Fold Change: 0.0001
    Cell Significance Index: 0.0600
  • Cell Name: lens epithelial cell (CL0002224)
    Fold Change: -0.0041
    Cell Significance Index: -6.3200
  • Cell Name: pancreatic A cell (CL0000171)
    Fold Change: -0.0081
    Cell Significance Index: -6.0300
  • Cell Name: pulmonary alveolar epithelial cell (CL0000322)
    Fold Change: -0.0081
    Cell Significance Index: -6.1300
  • Cell Name: anterior lens cell (CL0002223)
    Fold Change: -0.0083
    Cell Significance Index: -15.3100
  • Cell Name: intestinal crypt stem cell of small intestine (CL0009017)
    Fold Change: -0.0141
    Cell Significance Index: -0.3000
  • Cell Name: pancreatic PP cell (CL0002275)
    Fold Change: -0.0150
    Cell Significance Index: -9.3600
  • Cell Name: type B pancreatic cell (CL0000169)
    Fold Change: -0.0242
    Cell Significance Index: -13.6800
  • Cell Name: kidney loop of Henle cortical thick ascending limb epithelial cell (CL1001109)
    Fold Change: -0.0259
    Cell Significance Index: -18.9600
  • Cell Name: small intestine goblet cell (CL1000495)
    Fold Change: -0.0327
    Cell Significance Index: -1.1500
  • Cell Name: abnormal cell (CL0001061)
    Fold Change: -0.0585
    Cell Significance Index: -5.9800
  • Cell Name: pigmented ciliary epithelial cell (CL0002303)
    Fold Change: -0.0740
    Cell Significance Index: -10.7600
  • Cell Name: pancreatic D cell (CL0000173)
    Fold Change: -0.0743
    Cell Significance Index: -15.6600
  • Cell Name: dopaminergic neuron (CL0000700)
    Fold Change: -0.0761
    Cell Significance Index: -21.9000
  • Cell Name: pancreatic endocrine cell (CL0008024)
    Fold Change: -0.0809
    Cell Significance Index: -9.2400
  • Cell Name: direct pathway medium spiny neuron (CL4023026)
    Fold Change: -0.0813
    Cell Significance Index: -3.0800
  • Cell Name: retinal progenitor cell (CL0002672)
    Fold Change: -0.1174
    Cell Significance Index: -6.5900
  • Cell Name: fibroblast of mammary gland (CL0002555)
    Fold Change: -0.1204
    Cell Significance Index: -3.4500
  • Cell Name: sebum secreting cell (CL0000317)
    Fold Change: -0.1210
    Cell Significance Index: -8.5600
  • Cell Name: smooth muscle cell of sphincter of pupil (CL0002243)
    Fold Change: -0.1292
    Cell Significance Index: -13.4600
  • Cell Name: pancreatic ductal cell (CL0002079)
    Fold Change: -0.1335
    Cell Significance Index: -15.3000
  • Cell Name: lung endothelial cell (CL1001567)
    Fold Change: -0.1423
    Cell Significance Index: -7.4100
  • Cell Name: paneth cell of epithelium of small intestine (CL1000343)
    Fold Change: -0.1560
    Cell Significance Index: -3.3800
  • Cell Name: forebrain neuroblast (CL1000042)
    Fold Change: -0.1638
    Cell Significance Index: -10.0700
  • Cell Name: transit amplifying cell of colon (CL0009011)
    Fold Change: -0.1645
    Cell Significance Index: -5.2700
  • Cell Name: centrilobular region hepatocyte (CL0019029)
    Fold Change: -0.1915
    Cell Significance Index: -3.2300
  • Cell Name: granulosa cell (CL0000501)
    Fold Change: -0.1936
    Cell Significance Index: -5.0900
  • Cell Name: transit amplifying cell of small intestine (CL0009012)
    Fold Change: -0.1981
    Cell Significance Index: -4.1100
  • Cell Name: hippocampal granule cell (CL0001033)
    Fold Change: -0.2142
    Cell Significance Index: -14.4000
  • Cell Name: mesenchymal cell (CL0008019)
    Fold Change: -0.2202
    Cell Significance Index: -3.6900
  • Cell Name: peg cell (CL4033014)
    Fold Change: -0.2446
    Cell Significance Index: -5.6500
  • Cell Name: mesonephric nephron tubule epithelial cell (CL1000022)
    Fold Change: -0.2990
    Cell Significance Index: -10.3900
  • Cell Name: kidney loop of Henle descending limb epithelial cell (CL1001021)
    Fold Change: -0.3367
    Cell Significance Index: -26.6700
  • Cell Name: syncytiotrophoblast cell (CL0000525)
    Fold Change: -0.3890
    Cell Significance Index: -3.7000
  • Cell Name: skeletal muscle fiber (CL0008002)
    Fold Change: -0.4093
    Cell Significance Index: -10.5200
  • Cell Name: intestinal tuft cell (CL0019032)
    Fold Change: -0.4272
    Cell Significance Index: -26.1900
  • Cell Name: pro-T cell (CL0000827)
    Fold Change: -0.4314
    Cell Significance Index: -11.0200
  • Cell Name: CD14-positive, CD16-negative classical monocyte (CL0002057)
    Fold Change: -0.4534
    Cell Significance Index: -8.3800
  • Cell Name: umbrella cell of urothelium (CL4030056)
    Fold Change: -0.4653
    Cell Significance Index: -4.2900
  • Cell Name: foveolar cell of stomach (CL0002179)
    Fold Change: -0.4678
    Cell Significance Index: -3.0500
  • Cell Name: cardiac muscle cell (CL0000746)
    Fold Change: -0.4877
    Cell Significance Index: -7.2000
  • Cell Name: cerebellar granule cell (CL0001031)
    Fold Change: -0.4966
    Cell Significance Index: -8.5100
  • Cell Name: fibro/adipogenic progenitor cell (CL0009099)
    Fold Change: -0.5290
    Cell Significance Index: -26.7300
  • Cell Name: stratified epithelial cell (CL0000079)
    Fold Change: -0.5789
    Cell Significance Index: -21.2500
  • Cell Name: paneth cell of colon (CL0009009)
    Fold Change: -0.5930
    Cell Significance Index: -8.8900
  • Cell Name: periportal region hepatocyte (CL0019026)
    Fold Change: -0.5959
    Cell Significance Index: -8.8000
  • Cell Name: corticothalamic-projecting glutamatergic cortical neuron (CL4023013)
    Fold Change: -0.6076
    Cell Significance Index: -19.3500

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Other Information

**Key Characteristics:** SIAH2 is a 90-kDa protein consisting of an N-terminal domain with a zinc-binding motif, followed by a coiled-coil region and an E3 ubiquitin ligase domain. This domain is responsible for recognizing and binding to specific target proteins, facilitating their ubiquitination and degradation. SIAH2 is highly expressed in cells involved in immune responses, such as germinal center B cells, early pro-B cells, and mural cells. **Pathways and Functions:** SIAH2 is involved in multiple signaling pathways, including: 1. **Adaptive Immune System:** SIAH2 regulates the ubiquitination and degradation of key immune proteins, such as MHC class I and II molecules, influencing antigen presentation and immune response. 2. **Apoptosis:** SIAH2 modulates the activity of pro-apoptotic proteins, such as BAX and BAK, by ubiquitinating and degrading them, thereby preventing excessive cell death. 3. **Canonical Wnt Signaling Pathway:** SIAH2 negatively regulates the Wnt/β-catenin pathway, which is involved in cell proliferation, differentiation, and survival. 4. **Deubiquitination:** SIAH2 acts as a deubiquitinating enzyme, removing ubiquitin from target proteins, thereby regulating their activity and localization. **Clinical Significance:** SIAH2's dysregulation has been implicated in various immune-related disorders, including: 1. **Autoimmune Diseases:** SIAH2 deficiency or dysfunction has been linked to autoimmune diseases, such as rheumatoid arthritis and lupus, due to impaired immune regulation. 2. **Cancer:** SIAH2's role in regulating apoptosis and cell cycle progression makes it a potential target for cancer therapy. 3. **Neurological Disorders:** SIAH2's involvement in axon guidance and neuronal development suggests its potential role in neurological disorders, such as autism and schizophrenia. In conclusion, SIAH2 is a multifaceted gene that plays a crucial role in immune regulation, apoptosis, and development. Its dysregulation has significant clinical implications for autoimmune diseases, cancer, and neurological disorders, highlighting the need for further research into the molecular mechanisms underlying SIAH2's functions.

Genular Protein ID: 3037535750

Symbol: SIAH2_HUMAN

Name: E3 ubiquitin-protein ligase SIAH2

UniProtKB Accession Codes:

O43255 O43270

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CORUM 1 CTD 1 ChEBI 8 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 EC 2 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 25 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 4 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9403064

Title: Characterization of human homologs of the Drosophila seven in absentia (sina) gene.

PubMed ID: 9403064

DOI: 10.1006/geno.1997.4997

PubMed ID: 10207103

Title: hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways.

PubMed ID: 10207103

DOI: 10.1128/mcb.19.5.3798

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9334332

Title: Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway.

PubMed ID: 9334332

DOI: 10.1101/gad.11.20.2701

PubMed ID: 11483518

Title: Regulation of BOB.1/OBF.1 stability by SIAH.

PubMed ID: 11483518

DOI: 10.1093/emboj/20.15.4153

PubMed ID: 11389839

Title: Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses.

PubMed ID: 11389839

DOI: 10.1016/s1097-2765(01)00242-8

PubMed ID: 12411493

Title: Stress-induced decrease in TRAF2 stability is mediated by Siah2.

PubMed ID: 12411493

DOI: 10.1093/emboj/cdf576

PubMed ID: 12810624

Title: Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1.

PubMed ID: 12810624

PubMed ID: 16509823

Title: Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiation.

PubMed ID: 16509823

DOI: 10.1042/bj20051996

PubMed ID: 19224863

Title: Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation.

PubMed ID: 19224863

DOI: 10.1074/jbc.m805990200

PubMed ID: 22878263

Title: Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways.

PubMed ID: 22878263

DOI: 10.1093/jmcb/mjs047

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 26392558

Title: Ubiquitin ligase Siah2 regulates RevErbalpha degradation and the mammalian circadian clock.

PubMed ID: 26392558

DOI: 10.1073/pnas.1501204112

PubMed ID: 28546513

Title: The SIAH E3 ubiquitin ligases promote Wnt/beta-catenin signaling through mediating Wnt-induced Axin degradation.

PubMed ID: 28546513

DOI: 10.1101/gad.300053.117

Sequence Information:

  • Length: 324
  • Mass: 34615
  • Checksum: 2D5DD845666EC924
  • Sequence:
    • MSRPSSTGPS ANKPCSKQPP PQPQHTPSPA APPAAATISA AGPGSSAVPA AAAVISGPGG 
GGGAGPVSPQ HHELTSLFEC PVCFDYVLPP ILQCQAGHLV CNQCRQKLSC CPTCRGALTP 
SIRNLAMEKV ASAVLFPCKY ATTGCSLTLH HTEKPEHEDI CEYRPYSCPC PGASCKWQGS 
LEAVMSHLMH AHKSITTLQG EDIVFLATDI NLPGAVDWVM MQSCFGHHFM LVLEKQEKYE 
GHQQFFAIVL LIGTRKQAEN FAYRLELNGN RRRLTWEATP RSIHDGVAAA IMNSDCLVFD 
TAIAHLFADN GNLGINVTIS TCCP

Database document:

This is a preview of the gene's schema. Only a few entries are kept for 'singleCellExpressions,' 'mRNAExpressions,' and other large data arrays for visualization purposes. You can zoom in with the mouse wheel for a closer view, and the text will adjust automatically if necessary. For the full schema, download it here.