SIX1
Homeobox protein SIX1
Also known as: DFNA23, SIX1_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q15475
- Gene
- SIX1
- Ensembl
- ENSG00000126778
- Chromosome
- 14
- Canonical length
- 284 aa
- Protein class
- Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm,Nucleoli
OverviewNCBI Gene
The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in limb development. Defects in this gene are a cause of autosomal dominant deafness type 23 (DFNA23) and branchiootic syndrome type 3 (BOS3). [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
284 residues, UniProt reviewed canonical sequence.
>Q15475|SIX1
1 MSMLPSFGFT QEQVACVCEV LQQGGNLERL GRFLWSLPAC DHLHKNESVL KAKAVVAFHR
61 GNFRELYKIL ESHQFSPHNH PKLQQLWLKA HYVEAEKLRG RPLGAVGKYR VRRKFPLPRT
121 IWDGEETSYC FKEKSRGVLR EWYAHNPYPS PREKRELAEA TGLTTTQVSN WFKNRRQRDR
181 AAEAKERENT ENNNSSSNKQ NQLSPLEGGK PLMSSSEEEF SPPQSPDQNS VLLLQGNMGH
241 ARSSNYSLPG LTASQPSHGL QTHQHQLQDS LLGPLTSSLV DLGSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against SIX1 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)
- 0.48
- Highest tissue expression
- 112 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 112 nTPM
- salivary gland: 48 nTPM
- parathyroid gland: 45 nTPM
- tongue: 43 nTPM
- pituitary gland: 20 nTPM
- cervix: 14 nTPM
Single-cell type
- myonuclei: 149 nCPM
- lacrimal acinar cells: 137 nCPM
- medullary thymic epithelial cells: 134 nCPM
- gonadotrophs: 125 nCPM
- pituitary stem cells: 110 nCPM
- myosatellite cells: 104 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- choroid plexus: 1.6 nTPM
- basal ganglia: 0.6 nTPM
- cerebellum: 0.6 nTPM
- cerebral cortex: 0.6 nTPM
- thalamus: 0.6 nTPM
- pons: 0.4 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about SIX1.
Disease | AllUniProt
Conditions SIX1 is implicated in, by any mechanism.
- Deafness, autosomal dominant, 23 (DFNA23) MIM:605192
- Branchiootic syndrome 3 (BOS3) MIM:608389
Disease | GeneticClinVar
26 pathogenic / likely-pathogenic of 278 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Branchiootic syndrome 3
- Autosomal dominant nonsyndromic hearing loss 23
- Inborn genetic diseases
- SIX1-related disorder
- Branchiootorenal syndrome 1
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)
- 0.52
- gnomAD pLI
- 0.65
- gnomAD missense Z
- 1.19
- DepMap mean gene effect
- -0.2
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- aorta morphogenesis
- apoptotic process
- branching involved in ureteric bud morphogenesis
- cellular response to 3,3',5-triiodo-L-thyronine
- cochlea morphogenesis
- embryonic cranial skeleton morphogenesis
- embryonic skeletal system morphogenesis
- endothelin receptor signaling pathway
- epithelial cell differentiation
- facial nerve morphogenesis
- fungiform papilla morphogenesis
- gene expression
- generation of neurons
- inner ear development
- inner ear morphogenesis
- kidney development
- metanephric mesenchyme development
- middle ear morphogenesis
- myoblast migration
- myoblast proliferation
- myotome development
- negative regulation of neuron apoptotic process
- negative regulation of transcription by RNA polymerase II
- neural crest cell differentiation
- neuron fate specification
- Notch signaling pathway
- olfactory placode formation
- organ induction
- otic vesicle development
- outflow tract morphogenesis
- pattern specification process
- pharyngeal system development
- positive regulation of branching involved in ureteric bud morphogenesis
- positive regulation of brown fat cell differentiation
- positive regulation of DNA-templated transcription
- positive regulation of mesenchymal cell proliferation involved in ureter development
- positive regulation of myoblast proliferation
- positive regulation of secondary heart field cardioblast proliferation
- positive regulation of transcription by RNA polymerase II
- positive regulation of ureteric bud formation
- protein localization to nucleus
- regulation of branch elongation involved in ureteric bud branching
- regulation of DNA-templated transcription
- regulation of epithelial cell proliferation
- regulation of neuron differentiation
- regulation of protein localization
- regulation of skeletal muscle cell differentiation
- regulation of skeletal muscle cell proliferation
- regulation of skeletal muscle satellite cell proliferation
- regulation of synaptic assembly at neuromuscular junction
- regulation of transcription by RNA polymerase II
- sensory perception of sound
- skeletal muscle fiber development
- skeletal muscle tissue development
- thymus development
- thyroid gland development
- trigeminal ganglion development
- ureter smooth muscle cell differentiation
- ureteric bud development
- mesenchymal cell proliferation involved in ureter development
- mesonephric tubule formation
Molecular functions
- chromatin binding
- DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
- transcription cis-regulatory region binding
- transcription coactivator binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of SIX1 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 SIX1 as an antibody target. Whether an autoantibody or antibody against SIX1 could matter depends on whether native SIX1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
SIX1 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 SIX1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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