SCGB2A2 (mammaglobin-A) is a small secreted secretoglobin (lipophilin subfamily) that forms disulfide-linked complexes and is highly expressed in mammary gland tissue. As a secreted secretoglobin, it is expected to bind hydrophobic ligands in extracellular fluids, although specific ligands and direct biochemical activity remain poorly defined.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005615
extracellular space
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: SCGB2A2 is a secreted protein; extracellular space annotation is appropriate.
Reason: Secreted secretoglobins function in the extracellular milieu.
Supporting Evidence:
UniProt:Q13296
SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
|
|
GO:0030521
androgen receptor signaling pathway
|
IBA
GO_REF:0000033 |
REMOVE |
Summary: No direct evidence links SCGB2A2 to androgen receptor signaling.
Reason: Neither UniProt nor the deep research summary provides evidence for androgen receptor pathway involvement; this appears to be an over-annotation for a secreted secretoglobin.
Supporting Evidence:
UniProt:Q13296
Belongs to the secretoglobin family. Lipophilin subfamily.
|
|
GO:0005576
extracellular region
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Secreted protein localized to the extracellular region.
Reason: Secreted localization is a core feature of mammaglobin-A.
Supporting Evidence:
UniProt:Q13296
SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
|
|
GO:0005515
protein binding
|
IPI
PMID:25416956 A proteome-scale map of the human interactome network. |
UNDECIDED |
Summary: High-throughput interactome study does not provide gene-specific evidence for SCGB2A2.
Reason: The cached PMID:25416956 text is a global interactome map without SCGB2A2-specific interaction evidence, so this annotation cannot be verified from the publication.
Supporting Evidence:
PMID:25416956
A proteome-scale map of the human interactome network.
UniProt:Q13296
Q13296; P50552: VASP; NbExp=3; IntAct=EBI-9058786, EBI-748201;
|
|
GO:0008289
lipid binding
|
IEA | NEW |
Summary: Secretoglobin family members are reported to bind steroid-like ligands.
Reason: Family-level evidence supports hydrophobic ligand binding as a molecular function.
Supporting Evidence:
file:human/SCGB2A2/SCGB2A2-deep-research-falcon.md
Member of the secretoglobin/uteroglobin superfamily; literature describes steroid-like ligand binding as a shared property in the family.
|
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Research plan and verification
We first verified the target. SCGB2A2 encodes Mammaglobin-A (MAM-A), a 93–amino-acid secreted protein in the secretoglobin (uteroglobin) family located in the chromosome 11q13 secretoglobin cluster. It forms a covalent complex with lipophilin B (SCGB1D2). The organism is human. These features align with UniProt Q13296 and published literature, confirming the correct gene/protein identity and family/domain assignment (zafrakas2006expressionanalysisof pages 1-2, milosevic2023theenigmaof pages 1-2).
Key concepts and definitions
- Gene/protein identity: SCGB2A2 (synonyms: MGB1, mammaglobin-A) encodes a small secreted secretoglobin (≈93 aa) with glycosylated species (~18 and ~25 kDa in tissue) and frequent covalent complexing with lipophilin B (SCGB1D2) (BMC Cancer, 2006; DOI: 10.1186/1471-2407-6-88) (zafrakas2006expressionanalysisof pages 1-2).
- Protein family/domains: Member of the secretoglobin/uteroglobin superfamily; literature describes steroid-like ligand binding as a shared property in the family. SCGB2A2 is reported largely hormone-independent in regulation and part of the 11q13 secretoglobin locus (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 1-2).
- Cellular/tissue localization and expression: Predominantly expressed in mammary epithelium and frequently overexpressed in breast carcinoma; expression also occurs in gynecologic tract tumors (endometrial, ovarian, cervical) and in salivary gland neoplasms, often co-expressed with lipophilin B (BMC Cancer, 2006; DOI: 10.1186/1471-2407-6-88; IJMS, 2023; DOI: 10.3390/ijms241713407) (zafrakas2006expressionanalysisof pages 1-2, milosevic2023theenigmaof pages 9-11).
- Complex/partners: Mammaglobin-A commonly forms a covalent complex with lipophilin B (SCGB1D2), supporting a heteromeric secretoglobin complex in tumors (BMC Cancer, 2006; DOI: 10.1186/1471-2407-6-88) (zafrakas2006expressionanalysisof pages 1-2).
Current understanding of molecular function and pathways
- Functional roles: Multiple experimental reports (summarized in recent review) link MAM-A to tumor cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and survival signaling. Pathways implicated include MAPK, FAK, matrix metalloproteinases, and NF-κB; MAM-A suppression reduces mesenchymal-gene expression (e.g., ZEB1, Snail, Twist), migration/invasion, growth, and anoikis resistance in model systems (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 9-11).
- Regulation: Expression has been described as largely independent of steroid hormones; proposed transcriptional regulation includes PEA3 family factors. Reported associations with ER/PR status vary across studies, with both positive and conflicting correlations noted (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 1-2, milosevic2023theenigmaof pages 5-6).
- Family context: Secretoglobins are small, secreted, often dimeric proteins with roles in epithelial biology and inflammation; SCGB2A2 fits these structural/functional patterns and forms a complex with SCGB1D2 consistent with secretoglobin heterodimers (BMC Cancer, 2006; DOI: 10.1186/1471-2407-6-88) (zafrakas2006expressionanalysisof pages 1-2).
Recent developments and latest research (emphasis 2023–2024)
- Biomarker synthesis: A 2023 review consolidates that MAM-A is detected in approximately 70–80% of primary/metastatic breast cancers overall (with histology-specific ranges, e.g., lobular carcinoma 59–100%, invasive carcinoma NOS 25–94%), and highlights evolving uses across tissue, blood, sentinel lymph node, and bone marrow contexts (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 3-5).
- Sensitivity advances in intraoperative assays: Real-time RT-PCR platforms for sentinel lymph node analysis are reported to detect rare disease, with claimed analytical sensitivity approaching one tumor cell among 10^6–10^7 leukocytes and operational intraoperative application; the GeneSearch Breast Lymph Node RT-PCR assay is cited historically for metastases >0.2 mm (IJMS, 2023; DOI: 10.3390/ijms241713407; Adv Clin Chem, 2014; DOI: 10.1016/b978-0-12-800263-6.00006-9) (milosevic2023theenigmaof pages 7-9, ghersevich2014mammaglobina pages 18-21).
- Tumor-type specificity updates: A 2023 review emphasizes that nearly all MAM-A–positive tumors arise within breast, gynecologic tract, or salivary gland, while also acknowledging variability by antibody, protocol, and scoring thresholds; this refines tissue-of-origin inference for metastasis workups (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 9-11).
- Translational immunotherapy: The 2023 synthesis details a completed phase I MAM-A DNA vaccine showing safety and induction of MAM-A–specific CD4+/CD8+ T cells, with increased ICOShi CD4+ and reduced FoxP3+ CD4+ after vaccination; multiple HLA-restricted epitopes (A2/A3/A24) and dendritic cell strategies are described for future trials (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 11-12).
Applications and real-world implementations
- Immunohistochemistry (IHC) for primary/metastatic diagnosis:
- Sensitivity/specificity: In a clinical chemistry review summarizing multicenter data, mammaglobin-A IHC sensitivity in primary breast carcinoma is reported at 93.1% (vs. GCDFP-15 84.5%), with performance in metastatic breast carcinoma around 76% sensitivity and 90% specificity, supporting use in tissue-of-origin panels (Adv Clin Chem, 2014; DOI: 10.1016/b978-0-12-800263-6.00006-9) (ghersevich2014mammaglobina pages 18-21).
- Tumor spectrum: Strongest utility in breast and gynecologic tract; co-expression with lipophilin B is common and supports paired-marker strategies. Specificity is high when integrated with morphology/other markers, though broader expression across gynecologic sites reduces absolute breast specificity (BMC Cancer, 2006; DOI: 10.1186/1471-2407-6-88; IJMS, 2023; DOI: 10.3390/ijms241713407) (zafrakas2006expressionanalysisof pages 1-2, milosevic2023theenigmaof pages 9-11).
- Molecular assays (RT-PCR) in sentinel nodes and blood:
- Sentinel lymph node: Real-time RT-PCR for MAM-A has been incorporated into intraoperative workflows to guide axillary dissection thresholds, with detection down to micro-metastatic disease (>0.2 mm) and claimed analytical sensitivity of 1 tumor cell per 10^6–10^7 WBC in spiking models (Adv Clin Chem, 2014; DOI: 10.1016/b978-0-12-800263-6.00006-9; IJMS, 2023; DOI: 10.3390/ijms241713407) (ghersevich2014mammaglobina pages 18-21, milosevic2023theenigmaof pages 7-9).
- Circulating assays: RT-PCR detection of MAM-A mRNA in blood is reported in ~25% of patients in mixed cohorts, and serum MAM-A protein reported in 33% of primary and 44% of metastatic cases; assays often improve sensitivity when combined with multi-gene panels (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 7-9).
- Imaging: A mammaglobin-A–directed near-infrared antibody-dye conjugate demonstrated in vivo detection of nodal metastases in preclinical models, suggesting feasibility for noninvasive/surgical guidance applications (Adv Clin Chem, 2014; DOI: 10.1016/b978-0-12-800263-6.00006-9) (ghersevich2014mammaglobina pages 18-21).
- Immunotherapy and vaccines: Phase I experience with a MAM-A DNA vaccine indicates acceptable safety and induction of antigen-specific cellular immunity, supporting ongoing development of peptide, DNA, and dendritic-cell approaches targeting MAM-A epitopes (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 11-12).
Expert opinions and analysis from authoritative sources
- Diagnostic positioning: Reviews converge that mammaglobin-A is one of the most breast-associated epithelial markers, outperforming or complementing GCDFP-15 and EpCAM in some series for metastatic attribution; however, standardization of antibodies, scoring, and pre-analytic variables remains essential to ensure reproducibility (Adv Clin Chem, 2014; DOI: 10.1016/b978-0-12-800263-6.00006-9) (ghersevich2014mammaglobina pages 18-21).
- Specificity caveat: The canonical view of “breast-specificity” is refined by large tumor surveys showing abundant expression in gynecologic malignancies and occasional non-breast sites; pairing SCGB2A2 with SCGB1D2 and a broader IHC panel increases tissue-of-origin confidence (BMC Cancer, 2006; DOI: 10.1186/1471-2407-6-88) (zafrakas2006expressionanalysisof pages 1-2).
- Biology and therapeutic potential: The protein’s context-dependent roles in EMT, migration/invasion, and immune recognition suggest both biomarker and therapeutic target potential, but definitive mechanistic elucidation and clinical validation (including prospective outcome associations) are still maturing (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 9-11, milosevic2023theenigmaof pages 11-12).
Statistics and quantitative data from recent studies
- Prevalence in breast cancer: Approximate overall positivity 70–80% (histology-dependent ranges reported: lobular 59–100%, invasive NOS 25–94%) (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 3-5).
- IHC performance: Sensitivity 93.1% in primary breast carcinoma; in metastatic breast carcinoma sensitivity/specificity ~76%/90% (Adv Clin Chem, 2014; DOI: 10.1016/b978-0-12-800263-6.00006-9) (ghersevich2014mammaglobina pages 18-21).
- Molecular assay sensitivity: RT-PCR detection limits reported down to one tumor cell among 10^6–10^7 leukocytes; sentinel-node intraoperative assays detect metastases >0.2 mm (IJMS, 2023; DOI: 10.3390/ijms241713407; Adv Clin Chem, 2014; DOI: 10.1016/b978-0-12-800263-6.00006-9) (milosevic2023theenigmaof pages 7-9, ghersevich2014mammaglobina pages 18-21).
- Circulating detection rates: Serum protein positivity ~33% (primary) and ~44% (metastatic); blood RT-PCR positivity around 25% in studied cohorts (IJMS, 2023; DOI: 10.3390/ijms241713407) (milosevic2023theenigmaof pages 7-9).
- Regulation across tumor panels: In matched tumor/normal arrays, SCGB2A2 was downregulated in 49% and upregulated in 12% of breast tumors; in endometrial tumors it was upregulated in ~47% and downregulated in ~22% (BMC Cancer, 2006; DOI: 10.1186/1471-2407-6-88) (zafrakas2006expressionanalysisof pages 1-2).
Summary of identity/family and domain alignment
- The protein is a human secreted secretoglobin, consistent with the UniProt domain annotations (Secretoglobin/uteroglobin family) and literature descriptions of small, dimeric, ligand-binding epithelial proteins. SCGB2A2 often heterodimerizes with SCGB1D2 (lipophilin B), matching the secretoglobin subfamily architecture (BMC Cancer, 2006; DOI: 10.1186/1471-2407-6-88) (zafrakas2006expressionanalysisof pages 1-2).
Table of key evidence
| Source (first author, journal) | Year | Focus | Key Findings / Statistics | URL |
|---|---:|---|---|---|
| Milosevic, International Journal of Molecular Sciences | 2023 | Comprehensive biomarker & translational review | Reported SCGB2A2 (Mammaglobin‑A) expression in ~70–80% of breast tumors; RT‑PCR claims: detect 1 tumor cell among 10^6–10^7 WBC; tissue positivity ranges (lobular 59–100%, invasive 25–94%); imaging (NIR antibody‑dye) concept described (diagnostic limitations noted). (milosevic2023theenigmaof pages 7-9, milosevic2023theenigmaof pages 3-5) | https://doi.org/10.3390/ijms241713407 |
| Ghersevich, Advances in Clinical Chemistry | 2014 | Diagnostic performance, IHC and molecular assays | IHC sensitivity reported 93.1% (vs GCDFP‑15 84.5%); metastatic breast carcinoma IHC sensitivity/specificity ~76% / 90%; commercial intraoperative real‑time RT‑PCR (Gene‑Search Breast Lymph Node Assay) detects metastases >0.2 mm; preclinical NIR imaging validated in mouse models. (ghersevich2014mammaglobina pages 18-21) | https://doi.org/10.1016/b978-0-12-800263-6.00006-9 |
| Zafrakas, BMC Cancer | 2006 | Tissue distribution and co‑expression with lipophilin B | SCGB2A2 forms covalent complex with lipophilin B (SCGB1D2); expression not restricted to breast—co‑expression abundant in endometrial/ovarian/cervical cancers; in breast tumors SCGB2A2 down‑regulated in 49% and up‑regulated in 12%; endometrial tumors up‑regulated in ~47%. (zafrakas2006expressionanalysisof pages 1-2) | https://doi.org/10.1186/1471-2407-6-88 |
| Milosevic (functional/tissue specificity), International Journal of Molecular Sciences | 2023 | Molecular function & tissue specificity | Describes MAM‑A as a 93‑aa secretoglobin implicated in proliferation, migration, invasion and EMT (pathways: MAPK, FAK, MMPs, NF‑κB); reports that ~99% of tumors positive for MAM‑A are from breast, gynecologic or salivary sites; highlights antibody/protocol variability in IHC. (milosevic2023theenigmaof pages 9-11, milosevic2023theenigmaof pages 3-5) | https://doi.org/10.3390/ijms241713407 |
| Milosevic (translational immunotherapy), International Journal of Molecular Sciences | 2023 | Immunotherapy / vaccines and translational applications | Summarizes phase I MAM‑A DNA vaccine data (n≈15): no severe toxicities; increased peripheral MAM‑A‑specific CD4+/CD8+ T cells, ICOShi CD4+ increase and decreased FoxP3+CD4+ at 6 months; candidate HLA‑A2/A3/A24 epitopes and DC/adjuvant strategies proposed. (milosevic2023theenigmaof pages 11-12) | https://doi.org/10.3390/ijms241713407 |
Table: Concise table summarizing major primary and review sources (2006–2024) on SCGB2A2 (Mammaglobin‑A), showing focus, key findings/statistics and URLs to support diagnostic, functional and translational claims.
Limitations and open questions
- Tissue specificity is high for breast but not absolute; significant expression in gynecologic tumors requires panel-based interpretation to avoid misclassification (zafrakas2006expressionanalysisof pages 1-2).
- Prognostic correlations are inconsistent across cohorts (associations both with less aggressive and more aggressive phenotypes reported), warranting larger, standardized, prospective studies (milosevic2023theenigmaof pages 5-6, milosevic2023theenigmaof pages 3-5).
- Mechanistic roles in signaling and EMT are supported by model systems but need further validation in clinical specimens and intervention studies (milosevic2023theenigmaof pages 9-11).
Citable sources with URLs and dates
- Milosevic B et al. The Enigma of Mammaglobin: Redefining the Biomarker Paradigm in Breast Carcinoma. International Journal of Molecular Sciences. 2023 Aug;24:13407. URL: https://doi.org/10.3390/ijms241713407 (milosevic2023theenigmaof pages 1-2, milosevic2023theenigmaof pages 9-11, milosevic2023theenigmaof pages 5-6, milosevic2023theenigmaof pages 3-5, milosevic2023theenigmaof pages 7-9).
- Ghersevich S, Ceballos MP. Mammaglobin A. Advances in Clinical Chemistry. 2014 Jan;64:241–268. URL: https://doi.org/10.1016/b978-0-12-800263-6.00006-9 (ghersevich2014mammaglobina pages 18-21).
- Zafrakas M et al. Expression analysis of mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2) in more than 300 human tumors and matching normal tissues reveals their co-expression in gynecologic malignancies. BMC Cancer. 2006 Apr;6:88. URL: https://doi.org/10.1186/1471-2407-6-88 (zafrakas2006expressionanalysisof pages 1-2).
References
(zafrakas2006expressionanalysisof pages 1-2): Menelaos Zafrakas, Beate Petschke, Andreas Donner, Florian Fritzsche, Glen Kristiansen, Ruth Knüchel, and Edgar Dahl. Expression analysis of mammaglobin a (scgb2a2) and lipophilin b (scgb1d2) in more than 300 human tumors and matching normal tissues reveals their co-expression in gynecologic malignancies. BMC Cancer, 6:88-88, Apr 2006. URL: https://doi.org/10.1186/1471-2407-6-88, doi:10.1186/1471-2407-6-88. This article has 125 citations and is from a peer-reviewed journal.
(milosevic2023theenigmaof pages 1-2): Bojan Milosevic, Bojan Stojanovic, Aleksandar Cvetkovic, Ivan Jovanovic, Marko Spasic, Milica Dimitrijevic Stojanovic, Vesna Stankovic, Marija Sekulic, Bojana S. Stojanovic, Natasa Zdravkovic, Minja Mitrovic, Jasmina Stojanovic, Darko Laketic, Maja Vulovic, and Danijela Cvetkovic. The enigma of mammaglobin: redefining the biomarker paradigm in breast carcinoma. International Journal of Molecular Sciences, 24:13407, Aug 2023. URL: https://doi.org/10.3390/ijms241713407, doi:10.3390/ijms241713407. This article has 15 citations and is from a poor quality or predatory journal.
(milosevic2023theenigmaof pages 9-11): Bojan Milosevic, Bojan Stojanovic, Aleksandar Cvetkovic, Ivan Jovanovic, Marko Spasic, Milica Dimitrijevic Stojanovic, Vesna Stankovic, Marija Sekulic, Bojana S. Stojanovic, Natasa Zdravkovic, Minja Mitrovic, Jasmina Stojanovic, Darko Laketic, Maja Vulovic, and Danijela Cvetkovic. The enigma of mammaglobin: redefining the biomarker paradigm in breast carcinoma. International Journal of Molecular Sciences, 24:13407, Aug 2023. URL: https://doi.org/10.3390/ijms241713407, doi:10.3390/ijms241713407. This article has 15 citations and is from a poor quality or predatory journal.
(milosevic2023theenigmaof pages 5-6): Bojan Milosevic, Bojan Stojanovic, Aleksandar Cvetkovic, Ivan Jovanovic, Marko Spasic, Milica Dimitrijevic Stojanovic, Vesna Stankovic, Marija Sekulic, Bojana S. Stojanovic, Natasa Zdravkovic, Minja Mitrovic, Jasmina Stojanovic, Darko Laketic, Maja Vulovic, and Danijela Cvetkovic. The enigma of mammaglobin: redefining the biomarker paradigm in breast carcinoma. International Journal of Molecular Sciences, 24:13407, Aug 2023. URL: https://doi.org/10.3390/ijms241713407, doi:10.3390/ijms241713407. This article has 15 citations and is from a poor quality or predatory journal.
(milosevic2023theenigmaof pages 3-5): Bojan Milosevic, Bojan Stojanovic, Aleksandar Cvetkovic, Ivan Jovanovic, Marko Spasic, Milica Dimitrijevic Stojanovic, Vesna Stankovic, Marija Sekulic, Bojana S. Stojanovic, Natasa Zdravkovic, Minja Mitrovic, Jasmina Stojanovic, Darko Laketic, Maja Vulovic, and Danijela Cvetkovic. The enigma of mammaglobin: redefining the biomarker paradigm in breast carcinoma. International Journal of Molecular Sciences, 24:13407, Aug 2023. URL: https://doi.org/10.3390/ijms241713407, doi:10.3390/ijms241713407. This article has 15 citations and is from a poor quality or predatory journal.
(milosevic2023theenigmaof pages 7-9): Bojan Milosevic, Bojan Stojanovic, Aleksandar Cvetkovic, Ivan Jovanovic, Marko Spasic, Milica Dimitrijevic Stojanovic, Vesna Stankovic, Marija Sekulic, Bojana S. Stojanovic, Natasa Zdravkovic, Minja Mitrovic, Jasmina Stojanovic, Darko Laketic, Maja Vulovic, and Danijela Cvetkovic. The enigma of mammaglobin: redefining the biomarker paradigm in breast carcinoma. International Journal of Molecular Sciences, 24:13407, Aug 2023. URL: https://doi.org/10.3390/ijms241713407, doi:10.3390/ijms241713407. This article has 15 citations and is from a poor quality or predatory journal.
(ghersevich2014mammaglobina pages 18-21): Sergio Ghersevich and María Paula Ceballos. Mammaglobin a. Advances in Clinical Chemistry, 64:241-268, Jan 2014. URL: https://doi.org/10.1016/b978-0-12-800263-6.00006-9, doi:10.1016/b978-0-12-800263-6.00006-9. This article has 24 citations and is from a peer-reviewed journal.
(milosevic2023theenigmaof pages 11-12): Bojan Milosevic, Bojan Stojanovic, Aleksandar Cvetkovic, Ivan Jovanovic, Marko Spasic, Milica Dimitrijevic Stojanovic, Vesna Stankovic, Marija Sekulic, Bojana S. Stojanovic, Natasa Zdravkovic, Minja Mitrovic, Jasmina Stojanovic, Darko Laketic, Maja Vulovic, and Danijela Cvetkovic. The enigma of mammaglobin: redefining the biomarker paradigm in breast carcinoma. International Journal of Molecular Sciences, 24:13407, Aug 2023. URL: https://doi.org/10.3390/ijms241713407, doi:10.3390/ijms241713407. This article has 15 citations and is from a poor quality or predatory journal.
id: Q13296
gene_symbol: SCGB2A2
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: SCGB2A2 (mammaglobin-A) is a small secreted secretoglobin (lipophilin subfamily)
that forms disulfide-linked complexes and is highly expressed in mammary gland tissue.
As a secreted secretoglobin, it is expected to bind hydrophobic ligands in extracellular
fluids, although specific ligands and direct biochemical activity remain poorly defined.
existing_annotations:
- term:
id: GO:0005615
label: extracellular space
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: SCGB2A2 is a secreted protein; extracellular space annotation is appropriate.
action: ACCEPT
reason: Secreted secretoglobins function in the extracellular milieu.
supported_by:
- reference_id: UniProt:Q13296
supporting_text: "SUBCELLULAR LOCATION: Secreted {ECO:0000305}."
- term:
id: GO:0030521
label: androgen receptor signaling pathway
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: No direct evidence links SCGB2A2 to androgen receptor signaling.
action: REMOVE
reason: Neither UniProt nor the deep research summary provides evidence for androgen receptor
pathway involvement; this appears to be an over-annotation for a secreted secretoglobin.
supported_by:
- reference_id: UniProt:Q13296
supporting_text: "Belongs to the secretoglobin family. Lipophilin subfamily."
- term:
id: GO:0005576
label: extracellular region
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: Secreted protein localized to the extracellular region.
action: ACCEPT
reason: Secreted localization is a core feature of mammaglobin-A.
supported_by:
- reference_id: UniProt:Q13296
supporting_text: "SUBCELLULAR LOCATION: Secreted {ECO:0000305}."
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25416956
review:
summary: High-throughput interactome study does not provide gene-specific evidence for SCGB2A2.
action: UNDECIDED
reason: The cached PMID:25416956 text is a global interactome map without SCGB2A2-specific
interaction evidence, so this annotation cannot be verified from the publication.
supported_by:
- reference_id: PMID:25416956
supporting_text: A proteome-scale map of the human interactome network.
- reference_id: UniProt:Q13296
supporting_text: "Q13296; P50552: VASP; NbExp=3; IntAct=EBI-9058786, EBI-748201;"
- term:
id: GO:0008289
label: lipid binding
evidence_type: IEA
review:
summary: Secretoglobin family members are reported to bind steroid-like ligands.
action: NEW
reason: Family-level evidence supports hydrophobic ligand binding as a molecular function.
supported_by:
- reference_id: file:human/SCGB2A2/SCGB2A2-deep-research-falcon.md
supporting_text: Member of the secretoglobin/uteroglobin superfamily; literature describes steroid-like ligand binding as a shared property in the family.
references:
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt.
findings: []
- id: PMID:25416956
title: A proteome-scale map of the human interactome network.
findings: []
- id: UniProt:Q13296
title: UniProt record for SCGB2A2 (Q13296)
findings: []
- id: file:human/SCGB2A2/SCGB2A2-deep-research-falcon.md
title: Deep research on SCGB2A2 function
findings: []
core_functions:
- description: Secreted secretoglobin that likely binds hydrophobic ligands in extracellular fluids.
molecular_function:
id: GO:0008289
label: lipid binding
locations:
- id: GO:0005576
label: extracellular region
supported_by:
- reference_id: file:human/SCGB2A2/SCGB2A2-deep-research-falcon.md
supporting_text: Member of the secretoglobin/uteroglobin superfamily; literature describes steroid-like ligand binding as a shared property in the family.
- reference_id: UniProt:Q13296
supporting_text: "SUBCELLULAR LOCATION: Secreted {ECO:0000305}."