PAM16 encodes MAGMAS/TIM16, a matrix-facing regulatory J-like cochaperone/adaptor subunit of the TIM23-associated PAM import motor. It forms a Pam18/Tim14 subcomplex, recruits and restrains Pam18 activity, and tunes mtHsp70-driven import of presequence-containing proteins into the mitochondrial matrix.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | IBA GO_REF:0000033 | MODIFY | Summary: PAM16 is functionally coupled to TIM23, but its complex membership is more precisely the PAM import motor rather than the TIM23 channel/core translocase. Reason: Use the PAM complex term for PAM16 complex membership; TIM23 is the coupled translocase. Proposed replacements: PAM complex, Tim23 associated import motor Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md The literature and database evidence summarized here consistently refers to **human PAM16** as **MAGMAS/TIM16/TIMM16**, a small mitochondrial protein (~125 aa; ~13 kDa) that is part of the **TIM23-associated presequence import motor (PAM complex)**. This matches the UniProt description for Q9Y3D7 (mitochondrial import inner membrane translocase subunit TIM16 / PAM16 family), including the hallmark **J-like domain** and functional role in mitochondrial protein import. (riva2018ajourneythrough pages 11-15, riva2018ajourneythrough pages 8-11, sinha2017thecomplexitiesofa pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md Most mitochondrial matrix proteins are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. The **TIM23 complex** (inner membrane presequence translocase) mediates import of presequence-containing proteins; for matrix translocation, TIM23 couples to the **PAM (presequence translocase-associated motor)**, which uses an **mtHsp70 ATPase cycle** to pull precursor polypeptides into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0030150 protein import into mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Correct and core. PAM16 regulates the PAM motor that powers TIM23-mediated matrix import. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md Most mitochondrial matrix proteins are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. The **TIM23 complex** (inner membrane presequence translocase) mediates import of presequence-containing proteins; for matrix translocation, TIM23 couples to the **PAM (presequence translocase-associated motor)**, which uses an **mtHsp70 ATPase cycle** to pull precursor polypeptides into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0001405 PAM complex, Tim23 associated import motor | IEA GO_REF:0000117 | ACCEPT | Summary: Correct and core. PAM16/MAGMAS is a regulatory subunit of the TIM23-associated PAM motor. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md The literature and database evidence summarized here consistently refers to **human PAM16** as **MAGMAS/TIM16/TIMM16**, a small mitochondrial protein (~125 aa; ~13 kDa) that is part of the **TIM23-associated presequence import motor (PAM complex)**. This matches the UniProt description for Q9Y3D7 (mitochondrial import inner membrane translocase subunit TIM16 / PAM16 family), including the hallmark **J-like domain** and functional role in mitochondrial protein import. (riva2018ajourneythrough pages 11-15, riva2018ajourneythrough pages 8-11, sinha2017thecomplexitiesofa pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct. PAM16 is a peripheral component associated with the matrix side of the mitochondrial inner membrane. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md PAM16/MAGMAS is localized to **mitochondria** and described as a **peripheral membrane protein** associated with the TIM23/PAM machinery at the **inner membrane, matrix-facing side**. One source explicitly notes that it does **not extend into the intermembrane space (IMS)**, consistent with a matrix-side role in regulating the mtHsp70 motor. (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | IEA GO_REF:0000002 | MODIFY | Summary: PAM16 is functionally coupled to TIM23, but its complex membership is more precisely the PAM import motor rather than the TIM23 channel/core translocase. Reason: Use the PAM complex term for PAM16 complex membership; TIM23 is the coupled translocase. Proposed replacements: PAM complex, Tim23 associated import motor Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md The literature and database evidence summarized here consistently refers to **human PAM16** as **MAGMAS/TIM16/TIMM16**, a small mitochondrial protein (~125 aa; ~13 kDa) that is part of the **TIM23-associated presequence import motor (PAM complex)**. This matches the UniProt description for Q9Y3D7 (mitochondrial import inner membrane translocase subunit TIM16 / PAM16 family), including the hallmark **J-like domain** and functional role in mitochondrial protein import. (riva2018ajourneythrough pages 11-15, riva2018ajourneythrough pages 8-11, sinha2017thecomplexitiesofa pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md Most mitochondrial matrix proteins are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. The **TIM23 complex** (inner membrane presequence translocase) mediates import of presequence-containing proteins; for matrix translocation, TIM23 couples to the **PAM (presequence translocase-associated motor)**, which uses an **mtHsp70 ATPase cycle** to pull precursor polypeptides into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0030150 protein import into mitochondrial matrix | IEA GO_REF:0000002 | ACCEPT | Summary: Correct and core. PAM16 regulates the PAM motor that powers TIM23-mediated matrix import. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md Most mitochondrial matrix proteins are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. The **TIM23 complex** (inner membrane presequence translocase) mediates import of presequence-containing proteins; for matrix translocation, TIM23 couples to the **PAM (presequence translocase-associated motor)**, which uses an **mtHsp70 ATPase cycle** to pull precursor polypeptides into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0005515 protein binding | IPI PMID:23263864 Methylation-controlled J-protein MCJ acts in the import of p... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PAM16. The informative role is a regulatory adaptor/cochaperone function within the Pam16-Pam18/PAM import motor. Reason: Replace generic protein-binding capture with PAM complex membership and adaptor/regulatory cochaperone activity where supported. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md **PAM16 is not an enzyme catalyzing a metabolic reaction nor a transporter substrate-binding channel.** Instead, it functions as a **regulatory cochaperone/adaptor** within the import motor. It is described as a **J-like** protein (Hsp40/J-domain superfamily-like) that regulates the activity and positioning of the true J-domain cochaperone **Pam18/Tim14** (metazoan functional ortholog often discussed as DNAJC19/Pam18 in the PAM motor context) which stimulates mtHsp70 ATPase activity. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5, riva2018ajourneythrough pages 11-15) file:human/PAM16/PAM16-deep-research-falcon.md | Mechanistic role | PAM16 is primarily a **regulatory cochaperone/adaptor**, not an enzyme or transporter substrate-binding transporter itself. It forms a stable subcomplex with Pam18 and **recruits/controls Pam18 at the import channel**, thereby **modulating Pam18-driven stimulation of mtHsp70 ATPase activity** and fine-tuning the ATP-dependent import motor. It is described as a **negative regulator/antagonist** of Pam18’s stimulatory effect on mtHsp70. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, jain2025investigatingmitochondrialpresequence pages 15-17, sinha2017thecomplexitiesof pages 4-5) | Riva 2018; Sinha 2017; Jain 2025 thesis, https://doi.org/10.53846/goediss-11596 | |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PAM16. The informative role is a regulatory adaptor/cochaperone function within the Pam16-Pam18/PAM import motor. Reason: Replace generic protein-binding capture with PAM complex membership and adaptor/regulatory cochaperone activity where supported. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md **PAM16 is not an enzyme catalyzing a metabolic reaction nor a transporter substrate-binding channel.** Instead, it functions as a **regulatory cochaperone/adaptor** within the import motor. It is described as a **J-like** protein (Hsp40/J-domain superfamily-like) that regulates the activity and positioning of the true J-domain cochaperone **Pam18/Tim14** (metazoan functional ortholog often discussed as DNAJC19/Pam18 in the PAM motor context) which stimulates mtHsp70 ATPase activity. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5, riva2018ajourneythrough pages 11-15) file:human/PAM16/PAM16-deep-research-falcon.md | Mechanistic role | PAM16 is primarily a **regulatory cochaperone/adaptor**, not an enzyme or transporter substrate-binding transporter itself. It forms a stable subcomplex with Pam18 and **recruits/controls Pam18 at the import channel**, thereby **modulating Pam18-driven stimulation of mtHsp70 ATPase activity** and fine-tuning the ATP-dependent import motor. It is described as a **negative regulator/antagonist** of Pam18’s stimulatory effect on mtHsp70. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, jain2025investigatingmitochondrialpresequence pages 15-17, sinha2017thecomplexitiesof pages 4-5) | Riva 2018; Sinha 2017; Jain 2025 thesis, https://doi.org/10.53846/goediss-11596 | |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PAM16. The informative role is a regulatory adaptor/cochaperone function within the Pam16-Pam18/PAM import motor. Reason: Replace generic protein-binding capture with PAM complex membership and adaptor/regulatory cochaperone activity where supported. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md **PAM16 is not an enzyme catalyzing a metabolic reaction nor a transporter substrate-binding channel.** Instead, it functions as a **regulatory cochaperone/adaptor** within the import motor. It is described as a **J-like** protein (Hsp40/J-domain superfamily-like) that regulates the activity and positioning of the true J-domain cochaperone **Pam18/Tim14** (metazoan functional ortholog often discussed as DNAJC19/Pam18 in the PAM motor context) which stimulates mtHsp70 ATPase activity. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5, riva2018ajourneythrough pages 11-15) file:human/PAM16/PAM16-deep-research-falcon.md | Mechanistic role | PAM16 is primarily a **regulatory cochaperone/adaptor**, not an enzyme or transporter substrate-binding transporter itself. It forms a stable subcomplex with Pam18 and **recruits/controls Pam18 at the import channel**, thereby **modulating Pam18-driven stimulation of mtHsp70 ATPase activity** and fine-tuning the ATP-dependent import motor. It is described as a **negative regulator/antagonist** of Pam18’s stimulatory effect on mtHsp70. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, jain2025investigatingmitochondrialpresequence pages 15-17, sinha2017thecomplexitiesof pages 4-5) | Riva 2018; Sinha 2017; Jain 2025 thesis, https://doi.org/10.53846/goediss-11596 | |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PAM16. The informative role is a regulatory adaptor/cochaperone function within the Pam16-Pam18/PAM import motor. Reason: Replace generic protein-binding capture with PAM complex membership and adaptor/regulatory cochaperone activity where supported. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md **PAM16 is not an enzyme catalyzing a metabolic reaction nor a transporter substrate-binding channel.** Instead, it functions as a **regulatory cochaperone/adaptor** within the import motor. It is described as a **J-like** protein (Hsp40/J-domain superfamily-like) that regulates the activity and positioning of the true J-domain cochaperone **Pam18/Tim14** (metazoan functional ortholog often discussed as DNAJC19/Pam18 in the PAM motor context) which stimulates mtHsp70 ATPase activity. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5, riva2018ajourneythrough pages 11-15) file:human/PAM16/PAM16-deep-research-falcon.md | Mechanistic role | PAM16 is primarily a **regulatory cochaperone/adaptor**, not an enzyme or transporter substrate-binding transporter itself. It forms a stable subcomplex with Pam18 and **recruits/controls Pam18 at the import channel**, thereby **modulating Pam18-driven stimulation of mtHsp70 ATPase activity** and fine-tuning the ATP-dependent import motor. It is described as a **negative regulator/antagonist** of Pam18’s stimulatory effect on mtHsp70. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, jain2025investigatingmitochondrialpresequence pages 15-17, sinha2017thecomplexitiesof pages 4-5) | Riva 2018; Sinha 2017; Jain 2025 thesis, https://doi.org/10.53846/goediss-11596 | |
| GO:0005743 mitochondrial inner membrane | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | ACCEPT | Summary: Correct. PAM16 is a peripheral component associated with the matrix side of the mitochondrial inner membrane. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md PAM16/MAGMAS is localized to **mitochondria** and described as a **peripheral membrane protein** associated with the TIM23/PAM machinery at the **inner membrane, matrix-facing side**. One source explicitly notes that it does **not extend into the intermembrane space (IMS)**, consistent with a matrix-side role in regulating the mtHsp70 motor. (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | MODIFY | Summary: PAM16 is functionally coupled to TIM23, but its complex membership is more precisely the PAM import motor rather than the TIM23 channel/core translocase. Reason: Use the PAM complex term for PAM16 complex membership; TIM23 is the coupled translocase. Proposed replacements: PAM complex, Tim23 associated import motor Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md The literature and database evidence summarized here consistently refers to **human PAM16** as **MAGMAS/TIM16/TIMM16**, a small mitochondrial protein (~125 aa; ~13 kDa) that is part of the **TIM23-associated presequence import motor (PAM complex)**. This matches the UniProt description for Q9Y3D7 (mitochondrial import inner membrane translocase subunit TIM16 / PAM16 family), including the hallmark **J-like domain** and functional role in mitochondrial protein import. (riva2018ajourneythrough pages 11-15, riva2018ajourneythrough pages 8-11, sinha2017thecomplexitiesofa pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md Most mitochondrial matrix proteins are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. The **TIM23 complex** (inner membrane presequence translocase) mediates import of presequence-containing proteins; for matrix translocation, TIM23 couples to the **PAM (presequence translocase-associated motor)**, which uses an **mtHsp70 ATPase cycle** to pull precursor polypeptides into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0006886 intracellular protein transport | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | MARK AS OVER ANNOTATED | Summary: Correct pathway family but too broad. PAM16 specifically supports TIM23/PAM-mediated mitochondrial matrix protein import. Reason: Prefer protein import into mitochondrial matrix and PAM complex terms over generic intracellular protein transport. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md Most mitochondrial matrix proteins are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. The **TIM23 complex** (inner membrane presequence translocase) mediates import of presequence-containing proteins; for matrix translocation, TIM23 couples to the **PAM (presequence translocase-associated motor)**, which uses an **mtHsp70 ATPase cycle** to pull precursor polypeptides into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: Correct but broad. PAM16 is specifically associated with the matrix-facing side of the mitochondrial inner membrane in the PAM import motor. Reason: Prefer matrix side of mitochondrial inner membrane and PAM complex annotations over generic mitochondrion. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md PAM16/MAGMAS is localized to **mitochondria** and described as a **peripheral membrane protein** associated with the TIM23/PAM machinery at the **inner membrane, matrix-facing side**. One source explicitly notes that it does **not extend into the intermembrane space (IMS)**, consistent with a matrix-side role in regulating the mtHsp70 motor. (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MARK AS OVER ANNOTATED | Summary: Correct but broad. PAM16 is specifically associated with the matrix-facing side of the mitochondrial inner membrane in the PAM import motor. Reason: Prefer matrix side of mitochondrial inner membrane and PAM complex annotations over generic mitochondrion. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md PAM16/MAGMAS is localized to **mitochondria** and described as a **peripheral membrane protein** associated with the TIM23/PAM machinery at the **inner membrane, matrix-facing side**. One source explicitly notes that it does **not extend into the intermembrane space (IMS)**, consistent with a matrix-side role in regulating the mtHsp70 motor. (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0099617 matrix side of mitochondrial inner membrane | IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | ACCEPT | Summary: Correct. PAM16 localizes to the matrix-facing side of the mitochondrial inner membrane. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md PAM16/MAGMAS is localized to **mitochondria** and described as a **peripheral membrane protein** associated with the TIM23/PAM machinery at the **inner membrane, matrix-facing side**. One source explicitly notes that it does **not extend into the intermembrane space (IMS)**, consistent with a matrix-side role in regulating the mtHsp70 motor. (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0001405 PAM complex, Tim23 associated import motor | ISS GO_REF:0000024 | ACCEPT | Summary: Correct and core. PAM16/MAGMAS is a regulatory subunit of the TIM23-associated PAM motor. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md The literature and database evidence summarized here consistently refers to **human PAM16** as **MAGMAS/TIM16/TIMM16**, a small mitochondrial protein (~125 aa; ~13 kDa) that is part of the **TIM23-associated presequence import motor (PAM complex)**. This matches the UniProt description for Q9Y3D7 (mitochondrial import inner membrane translocase subunit TIM16 / PAM16 family), including the hallmark **J-like domain** and functional role in mitochondrial protein import. (riva2018ajourneythrough pages 11-15, riva2018ajourneythrough pages 8-11, sinha2017thecomplexitiesofa pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0001503 ossification | IMP PMID:24786642 The impairment of MAGMAS function in human is responsible fo... | KEEP AS NON CORE | Summary: Keep as non-core. Human PAM16/MAGMAS disease data support a skeletal dysplasia/ossification phenotype, but the evolved core function is mitochondrial protein import motor regulation. Reason: Ossification is a downstream organismal phenotype of MAGMAS impairment, not the core molecular function of PAM16. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md | Disease/phenotype links | PAM16 has recognized disease links, including **autosomal recessive spondylometaphyseal dysplasia, Megarbane type** in disease databases. Literature summarized in retrieved sources also links **MAGMAS overexpression** to neoplasia, including **prostate cancer**, **pituitary adenomas**, and anti-apoptotic/chemoresistance phenotypes. Open Targets also lists associations to neurodegenerative disease/Parkinson disease, but these are weaker database associations than the skeletal dysplasia link. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesof pages 12-14, zhao2023mitochondrialskeletaldisorders pages 8-11, OpenTargets Search: -PAM16,TIMM16,MAGMAS) | Open Targets platform search context; Zhao 2023 dissertation; Riva 2018 | file:human/PAM16/PAM16-deep-research-falcon.md **PAM16 (Q9Y3D7; MAGMAS/TIM16/TIMM16)** is a mitochondrial, inner-membrane-associated (matrix-facing) **regulatory subunit of the TIM23 presequence import motor (PAM complex)**. Its defining molecular feature is a **degenerate J-like domain lacking the HPD motif**, consistent with a function in **forming a heterodimer with Pam18 and modulating Pam18’s stimulation of mtHsp70 ATPase activity**, thereby tuning ATP-dependent protein translocation into the mitochondrial matrix. Disease relevance includes database-supported association with **autosomal recessive spondylometaphyseal dysplasia (Megarbane type)** and literature-supported roles in tumor cell survival/chemoresistance with reported overexpression frequencies in prostate cancer and pituitary adenomas. (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5, OpenTargets Search: -PAM16,TIMM16,MAGMAS) |
| GO:0001405 PAM complex, Tim23 associated import motor | IGI PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | ACCEPT | Summary: Correct and core. PAM16/MAGMAS is a regulatory subunit of the TIM23-associated PAM motor. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md The literature and database evidence summarized here consistently refers to **human PAM16** as **MAGMAS/TIM16/TIMM16**, a small mitochondrial protein (~125 aa; ~13 kDa) that is part of the **TIM23-associated presequence import motor (PAM complex)**. This matches the UniProt description for Q9Y3D7 (mitochondrial import inner membrane translocase subunit TIM16 / PAM16 family), including the hallmark **J-like domain** and functional role in mitochondrial protein import. (riva2018ajourneythrough pages 11-15, riva2018ajourneythrough pages 8-11, sinha2017thecomplexitiesofa pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0005515 protein binding | IPI PMID:19564938 The mitochondrial protein translocation motor: structural co... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PAM16. The informative role is a regulatory adaptor/cochaperone function within the Pam16-Pam18/PAM import motor. Reason: Replace generic protein-binding capture with PAM complex membership and adaptor/regulatory cochaperone activity where supported. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md **PAM16 is not an enzyme catalyzing a metabolic reaction nor a transporter substrate-binding channel.** Instead, it functions as a **regulatory cochaperone/adaptor** within the import motor. It is described as a **J-like** protein (Hsp40/J-domain superfamily-like) that regulates the activity and positioning of the true J-domain cochaperone **Pam18/Tim14** (metazoan functional ortholog often discussed as DNAJC19/Pam18 in the PAM motor context) which stimulates mtHsp70 ATPase activity. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5, riva2018ajourneythrough pages 11-15) file:human/PAM16/PAM16-deep-research-falcon.md | Mechanistic role | PAM16 is primarily a **regulatory cochaperone/adaptor**, not an enzyme or transporter substrate-binding transporter itself. It forms a stable subcomplex with Pam18 and **recruits/controls Pam18 at the import channel**, thereby **modulating Pam18-driven stimulation of mtHsp70 ATPase activity** and fine-tuning the ATP-dependent import motor. It is described as a **negative regulator/antagonist** of Pam18’s stimulatory effect on mtHsp70. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, jain2025investigatingmitochondrialpresequence pages 15-17, sinha2017thecomplexitiesof pages 4-5) | Riva 2018; Sinha 2017; Jain 2025 thesis, https://doi.org/10.53846/goediss-11596 | |
| GO:0005515 protein binding | IPI PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PAM16. The informative role is a regulatory adaptor/cochaperone function within the Pam16-Pam18/PAM import motor. Reason: Replace generic protein-binding capture with PAM complex membership and adaptor/regulatory cochaperone activity where supported. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md **PAM16 is not an enzyme catalyzing a metabolic reaction nor a transporter substrate-binding channel.** Instead, it functions as a **regulatory cochaperone/adaptor** within the import motor. It is described as a **J-like** protein (Hsp40/J-domain superfamily-like) that regulates the activity and positioning of the true J-domain cochaperone **Pam18/Tim14** (metazoan functional ortholog often discussed as DNAJC19/Pam18 in the PAM motor context) which stimulates mtHsp70 ATPase activity. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5, riva2018ajourneythrough pages 11-15) file:human/PAM16/PAM16-deep-research-falcon.md | Mechanistic role | PAM16 is primarily a **regulatory cochaperone/adaptor**, not an enzyme or transporter substrate-binding transporter itself. It forms a stable subcomplex with Pam18 and **recruits/controls Pam18 at the import channel**, thereby **modulating Pam18-driven stimulation of mtHsp70 ATPase activity** and fine-tuning the ATP-dependent import motor. It is described as a **negative regulator/antagonist** of Pam18’s stimulatory effect on mtHsp70. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, jain2025investigatingmitochondrialpresequence pages 15-17, sinha2017thecomplexitiesof pages 4-5) | Riva 2018; Sinha 2017; Jain 2025 thesis, https://doi.org/10.53846/goediss-11596 | |
| GO:0005759 mitochondrial matrix | IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | ACCEPT | Summary: Correct. PAM16 acts at the matrix-facing side of the inner membrane and does not extend into the IMS. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md PAM16/MAGMAS is localized to **mitochondria** and described as a **peripheral membrane protein** associated with the TIM23/PAM machinery at the **inner membrane, matrix-facing side**. One source explicitly notes that it does **not extend into the intermembrane space (IMS)**, consistent with a matrix-side role in regulating the mtHsp70 motor. (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0030150 protein import into mitochondrial matrix | IGI PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | ACCEPT | Summary: Correct and core. PAM16 regulates the PAM motor that powers TIM23-mediated matrix import. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md Most mitochondrial matrix proteins are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. The **TIM23 complex** (inner membrane presequence translocase) mediates import of presequence-containing proteins; for matrix translocation, TIM23 couples to the **PAM (presequence translocase-associated motor)**, which uses an **mtHsp70 ATPase cycle** to pull precursor polypeptides into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0032780 negative regulation of ATP-dependent activity | IDA PMID:19564938 The mitochondrial protein translocation motor: structural co... | ACCEPT | Summary: Correct and mechanistically informative. PAM16 restrains Pam18-mediated stimulation of mtHsp70 ATPase activity in the import motor. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md A recurring mechanistic interpretation is that Pam16/MAGMAS functions antagonistically to Pam18: it is required for correct association of the motor with the translocon and **inhibits Pam18-mediated stimulation of mtHsp70 ATPase activity**, thus tuning the import motor’s activity. (riva2018ajourneythrough pages 11-15, jain2025investigatingmitochondrialpresequence pages 15-17) file:human/PAM16/PAM16-deep-research-falcon.md | Mechanistic role | PAM16 is primarily a **regulatory cochaperone/adaptor**, not an enzyme or transporter substrate-binding transporter itself. It forms a stable subcomplex with Pam18 and **recruits/controls Pam18 at the import channel**, thereby **modulating Pam18-driven stimulation of mtHsp70 ATPase activity** and fine-tuning the ATP-dependent import motor. It is described as a **negative regulator/antagonist** of Pam18’s stimulatory effect on mtHsp70. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, jain2025investigatingmitochondrialpresequence pages 15-17, sinha2017thecomplexitiesof pages 4-5) | Riva 2018; Sinha 2017; Jain 2025 thesis, https://doi.org/10.53846/goediss-11596 | |
| GO:0032780 negative regulation of ATP-dependent activity | IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | ACCEPT | Summary: Correct and mechanistically informative. PAM16 restrains Pam18-mediated stimulation of mtHsp70 ATPase activity in the import motor. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md A recurring mechanistic interpretation is that Pam16/MAGMAS functions antagonistically to Pam18: it is required for correct association of the motor with the translocon and **inhibits Pam18-mediated stimulation of mtHsp70 ATPase activity**, thus tuning the import motor’s activity. (riva2018ajourneythrough pages 11-15, jain2025investigatingmitochondrialpresequence pages 15-17) file:human/PAM16/PAM16-deep-research-falcon.md | Mechanistic role | PAM16 is primarily a **regulatory cochaperone/adaptor**, not an enzyme or transporter substrate-binding transporter itself. It forms a stable subcomplex with Pam18 and **recruits/controls Pam18 at the import channel**, thereby **modulating Pam18-driven stimulation of mtHsp70 ATPase activity** and fine-tuning the ATP-dependent import motor. It is described as a **negative regulator/antagonist** of Pam18’s stimulatory effect on mtHsp70. | (riva2018ajourneythrough pages 11-15, sinha2017thecomplexitiesofa pages 4-5, jain2025investigatingmitochondrialpresequence pages 15-17, sinha2017thecomplexitiesof pages 4-5) | Riva 2018; Sinha 2017; Jain 2025 thesis, https://doi.org/10.53846/goediss-11596 | |
| GO:0032991 protein-containing complex | IDA PMID:19564938 The mitochondrial protein translocation motor: structural co... | MARK AS OVER ANNOTATED | Summary: Correct but too generic. The specific protein-containing complex is the TIM23-associated PAM motor. Reason: Use PAM complex rather than the generic protein-containing complex term. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md The literature and database evidence summarized here consistently refers to **human PAM16** as **MAGMAS/TIM16/TIMM16**, a small mitochondrial protein (~125 aa; ~13 kDa) that is part of the **TIM23-associated presequence import motor (PAM complex)**. This matches the UniProt description for Q9Y3D7 (mitochondrial import inner membrane translocase subunit TIM16 / PAM16 family), including the hallmark **J-like domain** and functional role in mitochondrial protein import. (riva2018ajourneythrough pages 11-15, riva2018ajourneythrough pages 8-11, sinha2017thecomplexitiesofa pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0032991 protein-containing complex | IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | MARK AS OVER ANNOTATED | Summary: Correct but too generic. The specific protein-containing complex is the TIM23-associated PAM motor. Reason: Use PAM complex rather than the generic protein-containing complex term. Supporting Evidence: file:human/PAM16/PAM16-deep-research-falcon.md The literature and database evidence summarized here consistently refers to **human PAM16** as **MAGMAS/TIM16/TIMM16**, a small mitochondrial protein (~125 aa; ~13 kDa) that is part of the **TIM23-associated presequence import motor (PAM complex)**. This matches the UniProt description for Q9Y3D7 (mitochondrial import inner membrane translocase subunit TIM16 / PAM16 family), including the hallmark **J-like domain** and functional role in mitochondrial protein import. (riva2018ajourneythrough pages 11-15, riva2018ajourneythrough pages 8-11, sinha2017thecomplexitiesofa pages 4-5) file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | NEW | Summary: New annotation. PAM16 functions as a regulatory adaptor/cochaperone that forms a Magmas-DnaJC19/Pam18 subcomplex, tethers the J-protein component to the translocon, and restrains Pam18-stimulated mtHsp70 ATPase activity. Reason: PAM16 has a specific adaptor/cochaperone role in the PAM motor that is more informative than generic protein binding and is not present in GOA. Supporting Evidence: PMID:20053669 Moreover, Magmas interacts with yeast Pam18 as well as human DnaJC19 (ortholog of yeast Pam18) both in vivo and in vitro conditions to form a heterodimeric subcomplex. PMID:20053669 Our results are consistent with the existence of stable interaction between Magmas and DnaJC19 that plays a crucial role in tethering of DnaJC19 at the translocon and perhaps regulating human import motor activity. PMID:19564938 A similar effect was observed using human Tim16/Pam16s, which inhibited the increase in the ATPase activity of mtHsp70 (obtained due to the presence of yTim14/Pam18) by almost 50%. The latter result indicates that hTim16/Pam16s can replace its yeast Tim16/Pam18s homologue, in vitro, and can act as a negative regulator of yTim14/Pam18. file:human/PAM16/PAM16-deep-research-falcon.md PAM16 (MAGMAS/TIM16/TIMM16) is an essential subunit of the **TIM23-associated PAM motor**. Mechanistically, it forms a stable subcomplex with Pam18/Tim14 and is described as (i) **recruiting Pam18** to the import channel and (ii) **controlling Pam18 activity**, thereby indirectly regulating mtHsp70’s ATP-driven pulling activity during translocation into the matrix. (sinha2017thecomplexitiesofa pages 4-5, sinha2017thecomplexitiesof pages 4-5) |
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Download this section (compressed HTML)Q: Which human PAM16 surfaces are required for Pam18 recruitment versus inhibition of Pam18-stimulated mtHsp70 ATPase activity?
Q: How do skeletal dysplasia variants alter PAM16 stability, Pam18 binding, and matrix import flux in patient-relevant cells?
Experiment: Measure Pam18 binding, PAM/TIM23 association, mtHsp70 ATPase regulation, and matrix-import reporter flux after rescue of PAM16-null human cells with wild-type and disease-variant PAM16.
Hypothesis: PAM16 disease variants impair matrix import by destabilizing the Pam16-Pam18 regulatory subcomplex.
Experiment: Compare acute PAM16 knockdown or overexpression with Pam18-interface mutants for precursor import, mitochondrial proteostasis, apoptosis sensitivity, and respiratory function.
Hypothesis: PAM16 overexpression phenotypes in cancer models derive from altered PAM motor activity rather than a separate enzymatic function.
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