Affinage

SOWAHC

Ankyrin repeat domain-containing protein SOWAHC · UniProt Q53LP3

Round 2 corrected
Length
525 aa
Mass
55.7 kDa
Annotated
2026-04-28
33 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOWAHC encodes a nuclear-localizing ankyrin repeat domain-containing protein whose direct biochemical function remains uncharacterized. The mouse ortholog (TSC77, 76% amino acid identity) localizes to the nucleus in heterologous cells and is preferentially expressed in testis with developmental upregulation during spermatogenesis (PMID:17309138). The SOWAHC locus is embedded within a deeply conserved genomic regulatory block shared with Iroquois homeobox genes across bilaterians, where cis-regulatory modules for Iroquois transcription reside within or adjacent to the Sowah gene, imposing strong syntenic constraints over ~600 million years of evolution (PMID:22234889).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2007 Low

    Determining where SOWAHC protein resides and when it is expressed established that the mouse ortholog is a nuclear protein with testis-enriched expression during spermatogenesis, providing the first cellular context for its function.

    Evidence GFP-TSC77 fusion imaging in Cos-7 cells and RT-PCR/microarray developmental profiling in mouse tissues

    PMID:17309138

    Open questions at the time
    • Nuclear localization demonstrated by a single method (GFP fusion) in a heterologous cell line without endogenous antibody confirmation
    • No loss-of-function or gain-of-function experiments to test a role in spermatogenesis
    • No binding partners or enzymatic activity identified
  2. 2012 Medium

    Resolving why the SOWAHC locus is conserved in synteny with Iroquois genes revealed that Iroquois-specific cis-regulatory modules embedded within the Sowah locus impose deep genomic regulatory constraints, explaining locus architecture rather than SOWAHC protein function per se.

    Evidence Comparative genomics across 39 metazoan species identifying conserved non-coding elements and CRMs within Sowah introns

    PMID:22234889

    Open questions at the time
    • Does not address the molecular function of SOWAHC protein itself
    • Functional validation of the identified CRMs (e.g., reporter assays) was not performed in this study
    • Whether SOWAHC protein has any regulatory interplay with Iroquois genes is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct molecular activity, binding partners, and physiological role of SOWAHC protein remain entirely undefined; no loss-of-function model, interactome data, or enzymatic characterization exists.
  • No substrate, binding partner, or enzymatic activity has been identified
  • No knockout or knockdown phenotype reported in any organism
  • Role of the ankyrin repeat domain in protein–protein interactions is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005634 nucleus 1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 The mouse ortholog of SOWAHC (TSC77, homologous to human C2orf26/SOWAHC at 76% amino acid identity) localizes to the nucleus, as demonstrated by GFP-TSC77 fusion protein imaging in Cos-7 cells. The protein (681 aa, ~77 kDa) contains predicted NAD(P)-nitrite reductase (NirB), HcaD, and NADH dehydrogenase (Ndh) domains and is preferentially expressed in mouse testis, with expression increasing from postnatal day 9 to day 21, implicating it in spermatogenesis. GFP fusion protein subcellular localization (live imaging), RT-PCR tissue distribution, DNA microarray developmental expression profiling, bioinformatics domain analysis Croatian medical journal Low 17309138
2012 The SOWAHC locus (Sowah genes) is syntenic with Iroquois homeobox genes across nearly all studied bilaterians despite ~600 million years of independent evolution. Iroquois-specific cis-regulatory modules (CRMs) populate the Sowah locus, indicating that regulatory constraints imposed by these embedded CRMs underlie the conservation of the Iroquois-Sowah genomic regulatory block. In tetrapods, Sowah orthologs became intronless (via retroposition), allowing the physical decoupling of Sowah exons from the Iroquois regulatory landscape while retaining associated CRMs in gene deserts. Comparative genomics across 39 metazoan species, identification of conserved non-coding elements and CRMs within Sowah introns, analysis of retrogene replacement events in tetrapods Genome research Medium 22234889

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2010 An atlas of combinatorial transcriptional regulation in mouse and man. Cell 573 20211142
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2016 A High-Density Map for Navigating the Human Polycomb Complexome. Cell reports 216 27705803
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2019 Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes & development 110 31753913
2022 Identification and functional characterization of transcriptional activators in human cells. Molecular cell 98 35016035
2012 Charting the landscape of tandem BRCT domain-mediated protein interactions. Science signaling 92 22990118
2017 The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery. Nature communications 86 29180619
2014 DEPDC1B coordinates de-adhesion events and cell-cycle progression at mitosis. Developmental cell 78 25458010
2021 Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy. Acta pharmaceutica Sinica. B 66 35256949
2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature 66 15815621
2010 Identification of genes associated with chemosensitivity to SAHA/taxane combination treatment in taxane-resistant breast cancer cells. Breast cancer research and treatment 48 20224928
2019 PLEKHA4/kramer Attenuates Dishevelled Ubiquitination to Modulate Wnt and Planar Cell Polarity Signaling. Cell reports 42 31091453
2012 An ancient genomic regulatory block conserved across bilaterians and its dismantling in tetrapods by retrogene replacement. Genome research 32 22234889
2023 Antagonistic roles of canonical and Alternative-RPA in disease-associated tandem CAG repeat instability. Cell 23 37827155
2020 Methylation‑driven genes PMPCAP1, SOWAHC and ZNF454 as potential prognostic biomarkers in lung squamous cell carcinoma. Molecular medicine reports 18 32016477
2017 Expanding the Interactome of TES by Exploiting TES Modules with Different Subcellular Localizations. Journal of proteome research 11 28378594
2022 TRABID targets DDB2 for deubiquitination to promote proliferation of hepatocellular carcinoma cells. Biochemical and biophysical research communications 9 35944360
2023 Pulse-SILAC and Interactomics Reveal Distinct DDB1-CUL4-Associated Factors, Cellular Functions, and Protein Substrates. Molecular & cellular proteomics : MCP 8 37689310
2007 Identification of a novel testis-specific gene in mice and its potential roles in spermatogenesis. Croatian medical journal 5 17309138
2025 Genome-wide association study identifying immune markers in Qingyuan partridge chickens infected with avian Leukosis virus subgroup J. Poultry science 1 40876114
2025 Proximity-based proteomics (BioID) uncovers the Rho GTPase interactome in kidney podocytes. Frontiers in cell and developmental biology 1 41306285
2025 MYSM1 promotes lung adenocarcinoma progression via TRAF2/3-mediated activation of MAPK and non-canonical NF-κB pathways. NPJ precision oncology 0 41162619