Seroatlas · Human Serome Atlas

SIAH2

E3 ubiquitin-protein ligase SIAH2

Also known as: SIAH2_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O43255
Gene: SIAH2
Ensembl: ENSG00000181788
Chromosome: 3
Canonical length: 324 aa
Protein class: Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Transporters
Subcellular location: Nucleoplasm,Vesicles
Quaternary structure: Homodimer

OverviewNCBI Gene

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. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

324 residues, UniProt reviewed canonical sequence.

>O43255|SIAH2
     1  MSRPSSTGPS ANKPCSKQPP PQPQHTPSPA APPAAATISA AGPGSSAVPA AAAVISGPGG
    61  GGGAGPVSPQ HHELTSLFEC PVCFDYVLPP ILQCQAGHLV CNQCRQKLSC CPTCRGALTP
   121  SIRNLAMEKV ASAVLFPCKY ATTGCSLTLH HTEKPEHEDI CEYRPYSCPC PGASCKWQGS
   181  LEAVMSHLMH AHKSITTLQG EDIVFLATDI NLPGAVDWVM MQSCFGHHFM LVLEKQEKYE
   241  GHQQFFAIVL LIGTRKQAEN FAYRLELNGN RRRLTWEATP RSIHDGVAAA IMNSDCLVFD
   301  TAIAHLFADN GNLGINVTIS TCCP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SIAH2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.37
Highest tissue expression: 80 nTPM

Expression across tissuesHPA

Tissue

adrenal gland: 80 nTPM
liver: 63 nTPM
esophagus: 49 nTPM
cervix: 45 nTPM
tonsil: 43 nTPM
bone marrow: 42 nTPM

Single-cell type

syncytiotrophoblasts: 471 nCPM
adrenal cortex cells: 356 nCPM
esophageal apical cells: 351 nCPM
kupffer cells: 335 nCPM
platelets: 287 nCPM
cytotrophoblasts: 274 nCPM

Immune cell

basophil: 8.9 nTPM
eosinophil: 8.6 nTPM
neutrophil: 4.7 nTPM
memory CD4 T-cell: 2.8 nTPM
plasmacytoid DC: 2.6 nTPM
MAIT T-cell: 2.5 nTPM

Brain region

white matter: 43 nTPM
cerebral cortex: 31 nTPM
basal ganglia: 29 nTPM
pons: 26 nTPM
choroid plexus: 26 nTPM
cerebellum: 26 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.59
gnomAD pLI: 0.69
gnomAD missense Z: 2.43
DepMap mean gene effect: 0.1
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SIAH2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SIAH2 as an antibody target. Whether an autoantibody or antibody against SIAH2 could matter depends on whether native SIAH2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SIAH2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label SIAH2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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