Seroatlas · Human Serome Atlas

SIX4

Homeobox protein SIX4

Also known as: AREC3, SIX4_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q9UIU6
Gene
SIX4
Ensembl
ENSG00000100625
Chromosome
14
Canonical length
781 aa
Protein class
Predicted intracellular proteins, Transcription factors
Subcellular location
Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes a member of the homeobox family, subfamily SIX. The drosophila homolog is a nuclear homeoprotein required for eye development. Studies in mouse show that this gene product functions as a transcription factor, and may have a role in the differentiation or maturation of neuronal cells. [provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

781 residues, UniProt reviewed canonical sequence.

>Q9UIU6|SIX4
     1  MSSSSPTGQI ASAADIKQEN GMESASEGQE AHREVAGGAA VGLSPPAPAP FPLEPGDAAT
    61  AAARVSGEEG AVAAAAAGAA ADQVQLHSEL LGRHHHAAAA AAQTPLAFSP DHVACVCEAL
   121  QQGGNLDRLA RFLWSLPQSD LLRGNESLLK ARALVAFHQG IYPELYSILE SHSFESANHP
   181  LLQQLWYKAR YTEAERARGR PLGAVDKYRL RRKFPLPRTI WDGEETVYCF KEKSRNALKE
   241  LYKQNRYPSP AEKRHLAKIT GLSLTQVSNW FKNRRQRDRN PSETQSKSES DGNPSTEDES
   301  SKGHEDLSPH PLSSSSDGIT NLSLSSHMEP VYMQQIGNAK ISLSSSGVLL NGSLVPASTS
   361  PVFLNGNSFI QGPSGVILNG LNVGNTQAVA LNPPKMSSNI VSNGISMTDI LGSTSQDVKE
   421  FKVLQSSANS ATTTSYSPSV PVSFPGLIPS TEVKREGIQT VASQDGGSVV TFTTPVQINQ
   481  YGIVQIPNSG ANSQFLNGSI GFSPLQLPPV SVAASQGNIS VSSSTSDGST FTSESTTVQQ
   541  GKVFLSSLAP SAVVYTVPNT GQTIGSVKQE GLERSLVFSQ LMPVNQNAQV NANLSSENIS
   601  GSGLHPLASS LVNVSPTHNF SLSPSTLLNP TELNRDIADS QPMSAPVASK STVTSVSNTN
   661  YATLQNCSLI TGQDLLSVPM TQAALGEIVP TAEDQVGHPS PAVHQDFVQE HRLVLQSVAN
   721  MKENFLSNSE SKATSSLMML DSKSKYVLDG MVDTVCEDLE TDKKELAKLQ TVQLDEDMQD
   781  L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SIX4 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)
0.62
Highest tissue expression
15 nTPM

Expression across tissuesHPA

Tissue

  • tongue: 15 nTPM
  • parathyroid gland: 14 nTPM
  • skeletal muscle: 13 nTPM
  • salivary gland: 6.5 nTPM
  • pituitary gland: 2.5 nTPM
  • prostate: 2.5 nTPM

Single-cell type

  • conjunctival goblet cells: 65 nCPM
  • endometrial luminal cells: 62 nCPM
  • endometrial secretory cells: 59 nCPM
  • myonuclei: 50 nCPM
  • endometrial ciliated cells: 49 nCPM
  • epididymal basal cells: 48 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: 13 nTPM
  • cerebral cortex: 5.7 nTPM
  • pons: 5.2 nTPM
  • cerebellum: 4.3 nTPM
  • hypothalamus: 3.6 nTPM
  • midbrain: 3.6 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)
0.43
gnomAD pLI
0.69
gnomAD missense Z
1.49
DepMap mean gene effect
-0.02
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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 SIX4 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 SIX4 as an antibody target. Whether an autoantibody or antibody against SIX4 could matter depends on whether native SIX4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SIX4 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 SIX4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SIX4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

© 2026 · Seroatlas, Discover Oregon LLC · Terms of use

Loading the interactive Seroatlas protein explorer...