SAMM50 encodes the human Sam50/SAM50 Omp85-family beta-barrel subunit of the mitochondrial sorting and assembly machinery (SAM) complex. It is an outer mitochondrial membrane insertase for beta-barrel proteins such as TOM40 and VDACs and also participates in SAM-MICOS/MIB contact sites that link outer-membrane beta-barrel biogenesis to cristae organization.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001401 SAM complex | IBA GO_REF:0000033 | ACCEPT | Summary: SAMM50 is the conserved core beta-barrel subunit of the mitochondrial SAM complex. Reason: SAM complex membership is a core cellular component annotation for SAMM50. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md The **Sorting and Assembly Machinery (SAM)** is the **mitochondrial outer-membrane insertase** required for insertion/assembly of **β-barrel proteins** into the OMM. Its core subunit **Sam50 (SAMM50 in humans)** is itself an Omp85-family β-barrel protein; yeast SAM includes additional subunits (e.g., Sam35/Sam37/Mdm10/Mco6), whereas in mammals the accessory subunits are functionally replaced by **metaxins**. (ganesan2024biogenesisofmitochondrial pages 1-2, ravi2025mitochondrialsortingand pages 1-3) |
| GO:0045040 protein insertion into mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: SAMM50/SAM inserts and assembles mitochondrial outer-membrane beta-barrel proteins such as TOM40 and VDAC. Reason: Protein insertion into the mitochondrial outer membrane captures the central biological process of SAMM50. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The **Sorting and Assembly Machinery (SAM)** is the **mitochondrial outer-membrane insertase** required for insertion/assembly of **β-barrel proteins** into the OMM. Its core subunit **Sam50 (SAMM50 in humans)** is itself an Omp85-family β-barrel protein; yeast SAM includes additional subunits (e.g., Sam35/Sam37/Mdm10/Mco6), whereas in mammals the accessory subunits are functionally replaced by **metaxins**. (ganesan2024biogenesisofmitochondrial pages 1-2, ravi2025mitochondrialsortingand pages 1-3) file:human/SAMM50/SAMM50-deep-research-falcon.md **Primary function:** SAMM50 is the core insertase/chaperone of the SAM complex that assembles **mitochondrial outer membrane β-barrel proteins** (including **Tom40** and **VDACs**) in an **energy-independent** manner. (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | TOO GENERAL | Summary: True but broad: entailed by MIB complex, SAM complex and mitochondrial outer membrane, kept in this review. Reason: GO's cytoplasm covers everything inside the plasma membrane except the nucleus, organelles and secretory compartments included, so MIB complex, SAM complex and mitochondrial outer membrane, kept in this review, entail this term and the claim is true. TOO_GENERAL rather than REMOVE. The objection is a reason not to annotate a narrower term such as cytosol, not to remove this one. Objection recorded at removal: The cytoplasm annotation conflicts with the curated outer mitochondrial membrane localization and likely reflects a broad or transferred location call. Summary at removal: SAMM50 is an outer mitochondrial membrane beta-barrel protein, not a cytoplasmic protein. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | MODIFY | Summary: SAMM50 is mitochondrial, but the literature supports the more specific outer mitochondrial membrane localization. Reason: Use mitochondrial outer membrane rather than the broad parent term mitochondrion. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: SAMM50 is an outer mitochondrial membrane Omp85-family beta-barrel protein. Reason: Outer mitochondrial membrane localization is central to SAMM50 topology and function. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0019867 outer membrane | IEA GO_REF:0000002 | MODIFY | Summary: SAMM50 is in an outer membrane, specifically the mitochondrial outer membrane. Reason: The taxon/gene-specific evidence supports mitochondrial outer membrane as the precise location. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: SAMM50 has many physical partners in SAM, TOM, MICOS/MIB, and contact-site assemblies, but generic protein binding is less informative than its insertase and complex annotations. Reason: Retain specific SAM complex, MIB/contact-site, and membrane insertase annotations rather than broad protein binding. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0005515 protein binding | IPI PMID:27059175 SAMM50 Affects Mitochondrial Morphology through the Associat... | MARK AS OVER ANNOTATED | Summary: SAMM50 has many physical partners in SAM, TOM, MICOS/MIB, and contact-site assemblies, but generic protein binding is less informative than its insertase and complex annotations. Reason: Retain specific SAM complex, MIB/contact-site, and membrane insertase annotations rather than broad protein binding. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: SAMM50 has many physical partners in SAM, TOM, MICOS/MIB, and contact-site assemblies, but generic protein binding is less informative than its insertase and complex annotations. Reason: Retain specific SAM complex, MIB/contact-site, and membrane insertase annotations rather than broad protein binding. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: SAMM50 has many physical partners in SAM, TOM, MICOS/MIB, and contact-site assemblies, but generic protein binding is less informative than its insertase and complex annotations. Reason: Retain specific SAM complex, MIB/contact-site, and membrane insertase annotations rather than broad protein binding. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | MODIFY | Summary: SAMM50 is mitochondrial, but the literature supports the more specific outer mitochondrial membrane localization. Reason: Use mitochondrial outer membrane rather than the broad parent term mitochondrion. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | TOO GENERAL | Summary: True but broad: entailed by MIB complex, SAM complex and mitochondrial outer membrane, kept in this review. Reason: GO's cytoplasm covers everything inside the plasma membrane except the nucleus, organelles and secretory compartments included, so MIB complex, SAM complex and mitochondrial outer membrane, kept in this review, entail this term and the claim is true. TOO_GENERAL rather than REMOVE. The objection is a reason not to annotate a narrower term such as cytosol, not to remove this one. Objection recorded at removal: The cytoplasm annotation conflicts with the curated outer mitochondrial membrane localization and likely reflects a broad or transferred location call. Summary at removal: SAMM50 is an outer mitochondrial membrane beta-barrel protein, not a cytoplasmic protein. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0001401 SAM complex | IPI PMID:17510655 Conserved roles of Sam50 and metaxins in VDAC biogenesis. | ACCEPT | Summary: SAMM50 is the conserved core beta-barrel subunit of the mitochondrial SAM complex. Reason: SAM complex membership is a core cellular component annotation for SAMM50. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md The **Sorting and Assembly Machinery (SAM)** is the **mitochondrial outer-membrane insertase** required for insertion/assembly of **β-barrel proteins** into the OMM. Its core subunit **Sam50 (SAMM50 in humans)** is itself an Omp85-family β-barrel protein; yeast SAM includes additional subunits (e.g., Sam35/Sam37/Mdm10/Mco6), whereas in mammals the accessory subunits are functionally replaced by **metaxins**. (ganesan2024biogenesisofmitochondrial pages 1-2, ravi2025mitochondrialsortingand pages 1-3) |
| GO:0005741 mitochondrial outer membrane | NAS PMID:31387448 Mitochondria-hubs for regulating cellular biochemistry: emer... | ACCEPT | Summary: SAMM50 is an outer mitochondrial membrane Omp85-family beta-barrel protein. Reason: Outer mitochondrial membrane localization is central to SAMM50 topology and function. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0045040 protein insertion into mitochondrial outer membrane | NAS PMID:31387448 Mitochondria-hubs for regulating cellular biochemistry: emer... | ACCEPT | Summary: SAMM50/SAM inserts and assembles mitochondrial outer-membrane beta-barrel proteins such as TOM40 and VDAC. Reason: Protein insertion into the mitochondrial outer membrane captures the central biological process of SAMM50. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The **Sorting and Assembly Machinery (SAM)** is the **mitochondrial outer-membrane insertase** required for insertion/assembly of **β-barrel proteins** into the OMM. Its core subunit **Sam50 (SAMM50 in humans)** is itself an Omp85-family β-barrel protein; yeast SAM includes additional subunits (e.g., Sam35/Sam37/Mdm10/Mco6), whereas in mammals the accessory subunits are functionally replaced by **metaxins**. (ganesan2024biogenesisofmitochondrial pages 1-2, ravi2025mitochondrialsortingand pages 1-3) file:human/SAMM50/SAMM50-deep-research-falcon.md **Primary function:** SAMM50 is the core insertase/chaperone of the SAM complex that assembles **mitochondrial outer membrane β-barrel proteins** (including **Tom40** and **VDACs**) in an **energy-independent** manner. (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0030150 protein import into mitochondrial matrix | IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | MODIFY | Summary: SAMM50 handles outer-membrane beta-barrel substrates after TOM translocation, not matrix-targeted presequence import through TIM23. Reason: The original Tom40 pathway evidence is better captured by protein insertion into mitochondrial outer membrane. Proposed replacements: protein insertion into mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The **Sorting and Assembly Machinery (SAM)** is the **mitochondrial outer-membrane insertase** required for insertion/assembly of **β-barrel proteins** into the OMM. Its core subunit **Sam50 (SAMM50 in humans)** is itself an Omp85-family β-barrel protein; yeast SAM includes additional subunits (e.g., Sam35/Sam37/Mdm10/Mco6), whereas in mammals the accessory subunits are functionally replaced by **metaxins**. (ganesan2024biogenesisofmitochondrial pages 1-2, ravi2025mitochondrialsortingand pages 1-3) file:human/SAMM50/SAMM50-deep-research-falcon.md **Primary function:** SAMM50 is the core insertase/chaperone of the SAM complex that assembles **mitochondrial outer membrane β-barrel proteins** (including **Tom40** and **VDACs**) in an **energy-independent** manner. (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MODIFY | Summary: SAMM50 is mitochondrial, but the literature supports the more specific outer mitochondrial membrane localization. Reason: Use mitochondrial outer membrane rather than the broad parent term mitochondrion. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005515 protein binding | IPI PMID:31644573 Armadillo repeat-containing protein 1 is a dual localization... | MARK AS OVER ANNOTATED | Summary: SAMM50 has many physical partners in SAM, TOM, MICOS/MIB, and contact-site assemblies, but generic protein binding is less informative than its insertase and complex annotations. Reason: Retain specific SAM complex, MIB/contact-site, and membrane insertase annotations rather than broad protein binding. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0001401 SAM complex | HDA PMID:26477565 Evolution and structural organization of the mitochondrial c... | ACCEPT | Summary: SAMM50 is the conserved core beta-barrel subunit of the mitochondrial SAM complex. Reason: SAM complex membership is a core cellular component annotation for SAMM50. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md The **Sorting and Assembly Machinery (SAM)** is the **mitochondrial outer-membrane insertase** required for insertion/assembly of **β-barrel proteins** into the OMM. Its core subunit **Sam50 (SAMM50 in humans)** is itself an Omp85-family β-barrel protein; yeast SAM includes additional subunits (e.g., Sam35/Sam37/Mdm10/Mco6), whereas in mammals the accessory subunits are functionally replaced by **metaxins**. (ganesan2024biogenesisofmitochondrial pages 1-2, ravi2025mitochondrialsortingand pages 1-3) |
| GO:0007007 inner mitochondrial membrane organization | IC PMID:26477565 Evolution and structural organization of the mitochondrial c... | KEEP AS NON CORE | Summary: SAMM50 contributes to inner-membrane/cristae architecture through SAM-MICOS/MIB contact sites, but this is secondary to its core SAM insertase role. Reason: The annotation is supported as a downstream organizational role of the MIB/SAM-MICOS axis rather than the primary evolved molecular function. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0140275 MIB complex | HDA PMID:26477565 Evolution and structural organization of the mitochondrial c... | KEEP AS NON CORE | Summary: SAMM50 participates in the mitochondrial intermembrane-space bridging (MIB) complex/contact-site axis with MICOS components. Reason: MIB complex association is supported but is treated as a contact-site/architecture role secondary to SAM beta-barrel insertion. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0005739 mitochondrion | IDA PMID:25781180 Detailed analysis of the human mitochondrial contact site co... | MODIFY | Summary: SAMM50 is mitochondrial, but the literature supports the more specific outer mitochondrial membrane localization. Reason: Use mitochondrial outer membrane rather than the broad parent term mitochondrion. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0042407 cristae formation | IMP PMID:22252321 Sam50 functions in mitochondrial intermembrane space bridgin... | KEEP AS NON CORE | Summary: SAMM50 perturbation affects cristae organization through SAM-MICOS/MIB contact sites. Reason: Cristae formation is a supported cellular architecture consequence, but the core SAMM50 function remains outer-membrane beta-barrel insertion. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0042407 cristae formation | IMP PMID:25781180 Detailed analysis of the human mitochondrial contact site co... | KEEP AS NON CORE | Summary: SAMM50 perturbation affects cristae organization through SAM-MICOS/MIB contact sites. Reason: Cristae formation is a supported cellular architecture consequence, but the core SAMM50 function remains outer-membrane beta-barrel insertion. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0005739 mitochondrion | HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated... | MODIFY | Summary: SAMM50 is mitochondrial, but the literature supports the more specific outer mitochondrial membrane localization. Reason: Use mitochondrial outer membrane rather than the broad parent term mitochondrion. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: The curated literature supports mitochondrial outer membrane localization and SAM complex function, not extracellular exosome localization. Reason: SAMM50 was detected in a large-scale proteomic study of urinary exosomes, so the row records a real observation. SAMM50 is a beta-barrel protein of the mitochondrial outer membrane, and mitochondrial proteins in exosome preparations may reflect co-isolated material; no targeted study shows SAMM50 as exosome cargo. The term over-reads a single proteomic hit; it has not been refuted, so it is marked as an over-annotation rather than removed. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0016020 membrane | IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | MODIFY | Summary: SAMM50 is a membrane protein, specifically a mitochondrial outer membrane beta-barrel protein. Reason: Use mitochondrial outer membrane rather than generic membrane. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005515 protein binding | IPI PMID:21081504 ChChd3, an inner mitochondrial membrane protein, is essentia... | MARK AS OVER ANNOTATED | Summary: SAMM50 has many physical partners in SAM, TOM, MICOS/MIB, and contact-site assemblies, but generic protein binding is less informative than its insertase and complex annotations. Reason: Retain specific SAM complex, MIB/contact-site, and membrane insertase annotations rather than broad protein binding. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md **SAM–MICOS contact site / MIB axis (cristae junction biology):** SAM is also described as an interaction hub forming a defined **outer–inner membrane contact** with **MICOS**, notably via interaction between Sam50 and MICOS subunits (e.g., Mic60/Mic19), thereby linking β-barrel biogenesis to **cristae organization** and mitochondrial architecture. (ravi2025mitochondrialsortingand pages 8-10, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
| GO:0001401 SAM complex | IMP PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | ACCEPT | Summary: SAMM50 is the conserved core beta-barrel subunit of the mitochondrial SAM complex. Reason: SAM complex membership is a core cellular component annotation for SAMM50. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md The **Sorting and Assembly Machinery (SAM)** is the **mitochondrial outer-membrane insertase** required for insertion/assembly of **β-barrel proteins** into the OMM. Its core subunit **Sam50 (SAMM50 in humans)** is itself an Omp85-family β-barrel protein; yeast SAM includes additional subunits (e.g., Sam35/Sam37/Mdm10/Mco6), whereas in mammals the accessory subunits are functionally replaced by **metaxins**. (ganesan2024biogenesisofmitochondrial pages 1-2, ravi2025mitochondrialsortingand pages 1-3) |
| GO:0005739 mitochondrion | IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | MODIFY | Summary: SAMM50 is mitochondrial, but the literature supports the more specific outer mitochondrial membrane localization. Reason: Use mitochondrial outer membrane rather than the broad parent term mitochondrion. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0005741 mitochondrial outer membrane | IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | ACCEPT | Summary: SAMM50 is an outer mitochondrial membrane Omp85-family beta-barrel protein. Reason: Outer mitochondrial membrane localization is central to SAMM50 topology and function. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The target in this report is **human SAMM50** (UniProt **Q9Y512**), annotated as **Sorting and assembly machinery component 50 homolog** (also called **SAM50**; synonym **TRG-3 / transformation-related gene 3**) and belonging to the **SAM50/Omp85** family that mediates mitochondrial outer-membrane β-barrel biogenesis. The literature summarized below consistently describes **Sam50/SAMM50** as the **core β-barrel subunit of the mitochondrial Sorting and Assembly Machinery (SAM) complex**, localized to the **mitochondrial outer membrane (OMM)** and functionally homologous to bacterial **BamA** (Omp85 family). (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50/Sam50 is an **outer mitochondrial membrane (OMM)** protein. It is described as a **16-stranded transmembrane β-barrel** with a single N-terminal **POTRA** domain. In mitochondria, the POTRA domain is positioned to participate in intermembrane-space (IMS) interactions and outer–inner membrane contacts (e.g., with MICOS). (ravi2025mitochondrialsortingand pages 20-24, ganesan2024biogenesisofmitochondrial pages 1-2) |
| GO:0032977 membrane insertase activity | NAS file:human/SAMM50/SAMM50-deep-research-falcon.md | NEW | Summary: SAMM50 is the core Sam50/SAM50 membrane insertase subunit that inserts and assembles mitochondrial outer-membrane beta-barrel proteins. Reason: The current GOA captures the biological process and complex but lacks the precise molecular function membrane insertase activity for SAMM50. Supporting Evidence: file:human/SAMM50/SAMM50-deep-research-falcon.md The **Sorting and Assembly Machinery (SAM)** is the **mitochondrial outer-membrane insertase** required for insertion/assembly of **β-barrel proteins** into the OMM. Its core subunit **Sam50 (SAMM50 in humans)** is itself an Omp85-family β-barrel protein; yeast SAM includes additional subunits (e.g., Sam35/Sam37/Mdm10/Mco6), whereas in mammals the accessory subunits are functionally replaced by **metaxins**. (ganesan2024biogenesisofmitochondrial pages 1-2, ravi2025mitochondrialsortingand pages 1-3) file:human/SAMM50/SAMM50-deep-research-falcon.md **Primary function:** SAMM50 is the core insertase/chaperone of the SAM complex that assembles **mitochondrial outer membrane β-barrel proteins** (including **Tom40** and **VDACs**) in an **energy-independent** manner. (ravi2025mitochondrialsortingand pages 1-3, ganesan2024biogenesisofmitochondrial pages 1-2) file:human/SAMM50/SAMM50-deep-research-falcon.md SAMM50 (UniProt Q9Y512; SAM50/TRG-3) is a **mitochondrial outer membrane Omp85-family β-barrel insertase** and the **core subunit of the SAM complex**. Its primary, experimentally grounded role is the **assembly/insertion of OMM β-barrel proteins** (e.g., Tom40 and VDAC) delivered through the TOM→IMS chaperone→SAM pathway and assembled via **β-signal recognition**, **lateral gating**, and **β-barrel switching**. SAMM50 also serves as an organizational hub by forming **TOM–SAM** supercomplexes and participating in **SAM–MICOS** contact sites that connect outer-membrane protein biogenesis to **cristae junction organization**. In human populations, common SAMM50 variants show reproducible associations with **NAFLD risk** in some cohorts, supporting a role for mitochondrial membrane architecture pathways in metabolic liver disease susceptibility. (ganesan2024biogenesisofmitochondrial pages 1-2, zhao2023samm50rs2073082rs738491and pages 1-2) |
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Download this section (compressed HTML)Q: Should human SAMM50 be annotated directly to membrane insertase activity in GOA, and should that annotation be made with a contributes_to qualifier for the SAM complex or as enabled by the Sam50 subunit itself?
Experiment: Reconstitute the human SAMM50-MTX SAM complex with purified human TOM40 or VDAC beta-barrel precursors and assay insertion intermediates, lateral-gate mutants, and beta-signal dependence.
Hypothesis: Human SAMM50 provides the core membrane insertase activity for outer-membrane beta-barrel substrate assembly.
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