Affinage

SNTB1

Beta-1-syntrophin · UniProt Q13884

Length
538 aa
Mass
58.1 kDa
Annotated
2026-06-10
41 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNTB1 (beta-1 syntrophin) is an intracellular scaffold protein that promotes gastrointestinal cancer proliferation, epithelial-mesenchymal transition (EMT), and metastasis by amplifying oncogenic signaling (PMID:34277816, PMID:39548564). In colorectal cancer cells it acts as a positive regulator of Wnt/β-catenin signaling, with knockdown lowering β-catenin pathway components (Wnt1, C-Jun, C-Myc, TCF7, cyclin D1), suppressing cancer stemness, proliferation, migration, invasion, and in vivo tumor growth and metastasis (PMID:34277816, PMID:37592763). SNTB1 operates upstream of YAP1, and YAP1 re-expression partially rescues the Wnt/β-catenin/MYC signaling and phenotypic defects caused by SNTB1 loss, linking SNTB1 to Hippo-YAP output (PMID:37592763, PMID:39548564). SNTB1 forms a physical complex with SRC kinase and engages TGF-β-mediated communication with enterocytes to drive EMT (PMID:39548564). Upstream, SNTB1 mRNA is subject to ZC3H13-mediated, YTHDF1-dependent m6A modification that post-transcriptionally elevates SNTB1 protein and promotes gastric cancer progression (PMID:40774945).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2021 Medium

    Established SNTB1 as a positive regulator of Wnt/β-catenin signaling in cancer rather than a passive scaffold, defining a functional role in tumor growth and stemness.

    Evidence siRNA knockdown with luciferase reporter, Western blot, agonist recovery, and xenograft in colorectal cancer cells

    PMID:34277816

    Open questions at the time
    • Molecular mechanism by which SNTB1 activates the pathway not defined
    • Direct binding partner within the Wnt cascade not identified
    • Single-lab finding
  2. 2023 Medium

    Placed SNTB1 upstream of YAP1 in driving Wnt/β-catenin/MYC signaling and EMT, identifying YAP1 as a downstream effector via rescue.

    Evidence siRNA knockdown plus YAP1 overexpression rescue, colony formation, migration/invasion, and xenograft/metastasis models in colorectal cancer cells

    PMID:37592763

    Open questions at the time
    • How SNTB1 controls YAP1 expression is unresolved
    • YAP1 rescue is partial, implying additional effectors
    • Single-lab finding
  3. 2024 Medium

    Identified a direct physical partner (SRC kinase) and a Hippo-YAP/TGF-β cell-communication axis, connecting SNTB1 scaffolding to a defined signaling kinase.

    Evidence Reciprocal co-immunoprecipitation, overexpression, caudal-vein metastasis model, and scRNA-seq/CellphoneDB in colon adenocarcinoma

    PMID:39548564

    Open questions at the time
    • Mechanism by which SNTB1 modulates SRC activity not dissected
    • Whether SRC binding mediates the YAP/Wnt effects untested
    • Single-lab finding
  4. 2025 Medium

    Defined how SNTB1 itself is upregulated, identifying m6A modification as a post-transcriptional control point.

    Evidence MeRIP-seq, immunoprecipitation, and functional rescue assays implicating ZC3H13 writer/YTHDF1 reader in gastric cancer

    PMID:40774945

    Open questions at the time
    • Specific m6A sites on SNTB1 mRNA not mapped
    • Whether m6A control operates in colorectal/colon contexts unknown
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SNTB1 mechanistically integrates SRC binding, Wnt/β-catenin activation, and YAP1 regulation into a single scaffold function remains unresolved.
  • No structural model of SNTB1 complexes
  • Causal ordering of SRC, YAP1, and β-catenin not established
  • Non-cancer physiological role not addressed in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3
Partners
SRC

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 SNTB1 (beta-1 syntrophin) positively regulates the Wnt/β-catenin signaling pathway in colorectal cancer cells; silencing SNTB1 decreased levels of β-catenin pathway components, suppressed tumor growth and cancer stemness in vitro, and reduced tumorigenesis in vivo, as assessed by luciferase reporter assay and agonist recovery experiments. siRNA knockdown, Western blot, luciferase reporter assay, agonist recovery assay, in vivo xenograft, flow cytometry (side population assay) Annals of translational medicine Medium 34277816
2023 SNTB1 knockdown in colorectal cancer cells decreased levels of Wnt1, C-Jun, C-Myc, TCF7, and cyclin D1, inhibited EMT, suppressed proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo; mechanistically, SNTB1 positively regulated YAP1 expression, and YAP1 partially rescued the effects of SNTB1 knockdown on Wnt/β-catenin/MYC signaling and CRC cell phenotypes. siRNA knockdown, Western blot, colony formation assay, migration/invasion assay, nude mouse xenograft/metastasis model, YAP1 overexpression rescue experiment Cell cycle (Georgetown, Tex.) Medium 37592763
2024 SNTB1 forms a physical complex with SRC kinase (demonstrated by co-immunoprecipitation), and SNTB1 overexpression activates the Hippo-YAP pathway in colon adenocarcinoma; overexpression of SNTB1 enhanced proliferation, migration and invasion of COAD cell lines and increased tumor metastasis to lung, liver and bone in nude mice; single-cell RNA-seq and CellphoneDB analysis indicated that SNTB1-high cancer cells communicate with enterocytes via TGF-β to promote EMT. Co-immunoprecipitation, Western blot, overexpression in cell lines, in vivo caudal vein injection metastasis model, scRNA-seq, CellphoneDB analysis Journal of translational medicine Medium 39548564
2025 ZC3H13, an m6A methyltransferase component, mediates YTHDF1-dependent m6A modification of SNTB1 mRNA, leading to post-transcriptional upregulation of SNTB1 protein; elevated SNTB1 promotes EMT and progression of gastric cancer cells in vitro and in vivo. MeRIP-seq (m6A sequencing), RNA-seq, immunoprecipitation, in vivo and in vitro functional assays, multi-omics analysis Cell death & disease Medium 40774945

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 The A1 and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5' splice site selection in vivo. Proceedings of the National Academy of Sciences of the United States of America 199 8041722
2009 Protein-cofactor interactions in bioenergetic complexes: the role of the A1A and A1B phylloquinones in Photosystem I. Biochimica et biophysica acta 103 19409369
2013 The yeast Snt2 protein coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress. Molecular and cellular biology 39 23878396
2014 Evidence that histidine forms a coordination bond to the A(0A) and A(0B) chlorophylls and a second H-bond to the A(1A) and A(1B) phylloquinones in M688H(PsaA) and M668H(PsaB) variants of Synechocystis sp. PCC 6803. Biochimica et biophysica acta 27 24747069
2000 Spatio-temporal expression of the trans-acting splicing factors SF2/ASF and heterogeneous ribonuclear proteins A1/A1B in the myometrium of the pregnant human uterus: a molecular mechanism for regulating regional protein isoform expression in vivo. The Journal of clinical endocrinology and metabolism 27 10843177
2019 Association of the ZC3H11B, ZFHX1B and SNTB1 genes with myopia of different severities. The British journal of ophthalmology 26 31300455
2007 Broad screening of the legume family for variability in seed insecticidal activities and for the occurrence of the A1b-like knottin peptide entomotoxins. Phytochemistry 25 17222873
2011 Inactivation of Snt2, a BAH/PHD-containing transcription factor, impairs pathogenicity and increases autophagosome abundance in Fusarium oxysporum. Molecular plant pathology 24 21535351
1986 Haemoprotein b-590 (Escherichia coli), a reducible catalase and peroxidase: evidence for its close relationship to hydroperoxidase I and a 'cytochrome a1b' preparation. Journal of general microbiology 23 3543208
2017 Exiguobacterium sp. A1b/GX59 isolated from a patient with community-acquired pneumonia and bacteremia: genomic characterization and literature review. BMC infectious diseases 22 28732529
2012 Exploring the electron transfer pathways in photosystem I by high-time-resolution electron paramagnetic resonance: observation of the B-side radical pair P700(+)A1B(-) in whole cells of the deuterated green alga Chlamydomonas reinhardtii at cryogenic temperatures. Journal of the American Chemical Society 22 22352450
2007 Toxicity, binding and internalization of the pea-A1b entomotoxin in Sf9 cells. Biochimie 16 17845830
1983 The existence of atypical blood group galactosyltransferase which causes an expression of A2 character in A1B red blood cells. American journal of human genetics 16 6418000
2009 Inducible 70 kDa heat shock proteins protect embryos from teratogen-induced exencephaly: Analysis using Hspa1a/a1b knockout mice. Birth defects research. Part A, Clinical and molecular teratology 15 19639652
1986 Limited tryptic digestion of Ca2+,Mg2+-adenosine triphosphatase of the sarcoplasmic reticulum: enzymatic properties of A1b + B complex. Journal of biochemistry 14 2944882
2004 A new ephrin-A1 isoform (ephrin-A1b) with altered receptor binding properties abrogates the cleavage of ephrin-A1a. The Biochemical journal 13 14692877
2004 SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation. Biochemical and biophysical research communications 12 15485655
1985 The A1B genotype expressed as A2B on the red cells of individuals with strong B gene-specific transferases. Results from two paternity cases. Transfusion 11 3918362
2023 SNTB1 regulates colorectal cancer cell proliferation and metastasis through YAP1 and the WNT/β-catenin pathway. Cell cycle (Georgetown, Tex.) 10 37592763
2021 Beta-1 syntrophin (SNTB1) regulates colorectal cancer progression and stemness via regulation of the Wnt/β-catenin signaling pathway. Annals of translational medicine 10 34277816
2017 Association and interaction of myopia with SNP markers rs13382811 and rs6469937 at ZFHX1B and SNTB1 in Han Chinese and European populations. Molecular vision 10 28848321
2021 hnRNP A1B, a Splice Variant of HNRNPA1, Is Spatially and Temporally Regulated. Frontiers in neuroscience 9 34630013
2018 Mango phenolics increase the serum apolipoprotein A1/B ratio in rats fed high cholesterol and sodium cholate diets. Journal of the science of food and agriculture 8 30187493
2021 Plasma Apolipoproteins A1/B and OxLDL Levels in Patients with Covid-19 As Possible Markers of the Disease. Cytology and genetics 6 34898734
2009 A protocol comparison for the analysis of heat shock protein A1B +A1538G SNP. Cell stress & chaperones 6 19657725
2015 Evaluation of group A1B erythrocytes converted to type as group O: studies of markers of function and compatibility. Blood transfusion = Trasfusione del sangue 5 26509826
2021 A1B and BB blood group genotypes are risk factors for pulmonary embolism. Wiener klinische Wochenschrift 4 34081189
2020 Association of SNTB1 with High Myopia. Current eye research 4 32452213
2024 Developing a mouse model of human coronavirus NL63 infection: comparison with rhinovirus-A1B and effects of prior rhinovirus infection. American journal of physiology. Lung cellular and molecular physiology 3 39189801
2015 Co-segregation of Freiberg's infraction with a familial translocation t(5;7)(p13.3;p22.2) ascertained by a child with cri du chat syndrome and brachydactyly type A1B. American journal of medical genetics. Part A 3 25756154
2023 Full genome sequence of a human rhinovirus A1B, obtained in Kazakhstan. Microbiology resource announcements 2 37796012
2023 The SNTB1 and ZFHX1B gene have susceptibility in northern Han Chinese populations with high myopia. Experimental eye research 2 37890754
2022 Detection of anti-B antibodies in a patient with A1B blood group: A case report and literature review. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 2 35469752
2015 Polymorphisms in Heat Shock Proteins A1B and A1L (HOM) as Risk Factors for Oesophageal Carcinoma in Northeast India. Asian Pacific journal of cancer prevention : APJCP 2 26745065
1982 Abnormal blood group galactosyltransferase in blood type A1B-subjects whose sera contain anti-B agglutinin. Human genetics 2 6818134
2024 Modulation of SRC by SNTB1 activates the Hippo-YAP pathway during colon adenocarcinoma metastasis. Journal of translational medicine 1 39548564
2024 Transient receptor potential a1b regulates primordial germ cell numbers and sex differentiation in developing zebrafish. Journal of fish biology 1 39587668
2025 ZC3H13 mediates N6-methyladenosine modification of SNTB1 to promote epithelial-mesenchymal transition in gastric cancer. Cell death & disease 0 40774945
2025 SNTB1 gene polymorphisms and risk of high myopia: meta-analysis and single-center validation. Molecular vision 0 41867379
1984 [Population genetics of taiga hunters and reindeer breeders in central Siberia. The biochemical markers of genes Hp, Tf, Gc, A1b, GLO1, PGM1, AcP and EsD]. Genetika 0 6542041
1978 [Some aspects of the allelic interaction in family studies of normal A1B and A2B subjects (author's transl)]. Nouvelle revue francaise d'hematologie 0 754172

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