ATP1B4 encodes BetaM, a member of the Na,K-ATPase beta-subunit family that was co-opted for a new role in placental mammals. In fish, amphibians and birds, BetaM is a plasma-membrane Na,K-ATPase beta-subunit. Eutherian BetaM gained a long Glu-rich N-terminal domain, no longer assembles with Na,K-ATPase alpha-subunits, and instead resides in the inner nuclear membrane of skeletal and cardiac myocytes, peaking in late fetal and early postnatal life. There it binds the transcriptional coregulator SKIP (SNW1) and nuclear-envelope proteins such as LAP1 and Syne1. It modulates TGF-beta-responsive transcription and Smad7 expression, and, independently of SKIP, binds the MyoD distal regulatory region and recruits BRG1 to activate MyoD. Mice lacking BetaM are leaner, with higher energy expenditure and fat oxidation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:17592128 Evolution of Na,K-ATPase beta m-subunit into a coregulator o... | MODIFY | Summary: Protein binding (IPI) with mouse SKIP (SNW1), a transcriptional coregulator. BetaM binds SKIP through nucleoplasmic residues 72-98, and the two occupy the Smad7 promoter complex in vivo. Transcription coregulator binding is the informative term. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:17592128 "To demonstrate directly the presence of the authentic βm and SKIP in the Smad7 transcriptional complex in vivo , we performed a ChIP analysis."] [PMID:26939788 "Analysis of truncated forms of BetaM indicates that residues 72-98 adjacent to the membrane in nucleoplasmic domain are important for the interaction with SKIP."] Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:17592128 To demonstrate directly the presence of the authentic βm and SKIP in the Smad7 transcriptional complex in vivo , we performed a ChIP analysis. PMID:26939788 Analysis of truncated forms of BetaM indicates that residues 72-98 adjacent to the membrane in nucleoplasmic domain are important for the interaction with SKIP. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with TSPAN2, from the HuRI binary Y2H map. The partner has no established link to BetaM's nuclear-envelope transcriptional role. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with ASGR1, from the HuRI binary Y2H map. The partner has no established link to BetaM's nuclear-envelope transcriptional role. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with CXCL9, from the HuRI binary Y2H map. The partner has no established link to BetaM's nuclear-envelope transcriptional role. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with TTMP, from the HuRI binary Y2H map. The partner has no established link to BetaM's nuclear-envelope transcriptional role. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with ERMP1, from the HuRI binary Y2H map. The partner has no established link to BetaM's nuclear-envelope transcriptional role. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with CSGALNACT2, from the HuRI binary Y2H map. The partner has no established link to BetaM's nuclear-envelope transcriptional role. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with SMIM3, from the HuRI binary Y2H map. The partner has no established link to BetaM's nuclear-envelope transcriptional role. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | ACCEPT | Summary: Nucleus (IEA, mouse ortholog projection). Consistent with BetaM's inner-nuclear-membrane residence, detected in purified nuclei and nuclear membranes. Accepted. Reason: [PMID:14656723 "Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles."] Supporting Evidence: PMID:14656723 Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles. |
| GO:0005635 nuclear envelope | TAS Reactome:R-HSA-5252001 | ACCEPT | Summary: Nuclear envelope (TAS, Reactome ATP1B4:SNW1 binding). Consistent with BetaM's inner-nuclear-membrane residence, detected in purified nuclei and nuclear membranes. Accepted. Reason: [PMID:14656723 "Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles."] [file:reactome/R-HSA-5252001.md "display_name: ATP1B4 binds SNW1"] Supporting Evidence: PMID:14656723 Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles. file:reactome/R-HSA-5252001.md display_name: ATP1B4 binds SNW1 |
| GO:0005637 nuclear inner membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear inner membrane (IBA). Eutherian BetaM accumulates in the nuclear membrane of perinatal myocytes. It is enriched in purified myonuclear membranes, needs its transmembrane segment for nuclear-envelope targeting, and binds the inner-membrane proteins LAP1 and Syne1. Core location. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:14656723 "Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles."] [PMID:14656723 "On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm."] [PMID:26939788 "The inventory of identified BetaM interactors includes lamina-associated protein LAP-1, myocyte nuclear envelope protein Syne1, BetaM itself, heme oxidases HMOX1 and HMOX2; transcription factor LZIP/CREB3, ERGIC3, PHF3, reticulocalbin-3, and β-sarcoglycan."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002609208 SUPPORTS TRANSFER Eutherian BetaM node; human ATP1B4 (Q9UN42) is itself among the experimentally annotated members. Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:14656723 Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles. PMID:14656723 On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm. PMID:26939788 The inventory of identified BetaM interactors includes lamina-associated protein LAP-1, myocyte nuclear envelope protein Syne1, BetaM itself, heme oxidases HMOX1 and HMOX2; transcription factor LZIP/CREB3, ERGIC3, PHF3, reticulocalbin-3, and β-sarcoglycan. |
| GO:0005637 nuclear inner membrane | IDA PMID:17592128 Evolution of Na,K-ATPase beta m-subunit into a coregulator o... | ACCEPT | Summary: Nuclear inner membrane (IDA). Eutherian BetaM accumulates in the nuclear membrane of perinatal myocytes. It is enriched in purified myonuclear membranes, needs its transmembrane segment for nuclear-envelope targeting, and binds the inner-membrane proteins LAP1 and Syne1. Core location. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:14656723 "Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles."] [PMID:14656723 "On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm."] [PMID:26939788 "The inventory of identified BetaM interactors includes lamina-associated protein LAP-1, myocyte nuclear envelope protein Syne1, BetaM itself, heme oxidases HMOX1 and HMOX2; transcription factor LZIP/CREB3, ERGIC3, PHF3, reticulocalbin-3, and β-sarcoglycan."] Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:14656723 Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles. PMID:14656723 On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm. PMID:26939788 The inventory of identified BetaM interactors includes lamina-associated protein LAP-1, myocyte nuclear envelope protein Syne1, BetaM itself, heme oxidases HMOX1 and HMOX2; transcription factor LZIP/CREB3, ERGIC3, PHF3, reticulocalbin-3, and β-sarcoglycan. |
| GO:0005637 nuclear inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear inner membrane (IEA). Eutherian BetaM accumulates in the nuclear membrane of perinatal myocytes. It is enriched in purified myonuclear membranes, needs its transmembrane segment for nuclear-envelope targeting, and binds the inner-membrane proteins LAP1 and Syne1. Core location. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:14656723 "Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles."] [PMID:14656723 "On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm."] [PMID:26939788 "The inventory of identified BetaM interactors includes lamina-associated protein LAP-1, myocyte nuclear envelope protein Syne1, BetaM itself, heme oxidases HMOX1 and HMOX2; transcription factor LZIP/CREB3, ERGIC3, PHF3, reticulocalbin-3, and β-sarcoglycan."] Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:14656723 Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles. PMID:14656723 On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm. PMID:26939788 The inventory of identified BetaM interactors includes lamina-associated protein LAP-1, myocyte nuclear envelope protein Syne1, BetaM itself, heme oxidases HMOX1 and HMOX2; transcription factor LZIP/CREB3, ERGIC3, PHF3, reticulocalbin-3, and β-sarcoglycan. |
| GO:0005886 plasma membrane | TAS PMID:10456317 Identification of a novel gene of the X,K-ATPase beta-subuni... | REMOVE | Summary: Plasma membrane (TAS). This is the location predicted in 1999 by analogy to Na,K-ATPase beta-subunits. Plasma-membrane BetaM is the ancestral, non-eutherian state. Human and rodent BetaM localize to the nuclear envelope and intracellular membranes, and no plasma-membrane pool is reported for the eutherian protein. Contradicted; removed. Reason: [PMID:10456317 "The data obtained indicate the existence of hitherto unknown X,K-ATPase (most probably Na,K-ATPase) isozymes in muscle cells."] [PMID:17592128 "The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane."] [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:14656723 "On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm."] Supporting Evidence: PMID:10456317 The data obtained indicate the existence of hitherto unknown X,K-ATPase (most probably Na,K-ATPase) isozymes in muscle cells. PMID:17592128 The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane. PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:14656723 On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm. |
| GO:0005890 sodium:potassium-exchanging ATPase complex | IEA GO_REF:0000002 | REMOVE | Summary: Sodium:potassium-exchanging atpase complex (IEA, InterPro Na,K-ATPase beta-subunit family). The family mapping reflects the ancestral role kept by fish, amphibian and avian BetaM. In placental mammals BetaM does not assemble with any X,K-ATPase alpha-subunit and has lost the pump-subunit function; a curated NOT transmembrane transport IDA row records this. The electronic mapping is contradicted for the human protein. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:17592128 "Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 )."] [PMID:17592128 "In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12)."] [file:human/ATP1B4/ATP1B4-uniprot.txt "CC does not associate with known Na,K-ATPase alpha-subunits."] [PMID:17592128 "The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane."] Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:17592128 Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 ). PMID:17592128 In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12). PMID:17592128 The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane. file:human/ATP1B4/ATP1B4-uniprot.txt CC does not associate with known Na,K-ATPase alpha-subunits. |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of DNA-templated transcription (IBA). Through SKIP, BetaM modulates TGF-beta-responsive reporters and raises Smad7 mRNA, and it is present with SKIP in the Smad7 transcriptional complex. Independently of SKIP, it binds the MyoD distal regulatory region and recruits BRG1 to stimulate MyoD expression. Core process. Reason: [PMID:17592128 "Through interaction with SKIP, eutherian beta m acquired new functions as exemplified by regulation of TGF-beta-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-beta signaling."] [PMID:17592128 "To demonstrate directly the presence of the authentic βm and SKIP in the Smad7 transcriptional complex in vivo , we performed a ChIP analysis."] [PMID:36836771 "BetaM binds to the distal regulatory region (DRR) of MyoD, promotes epigenetic changes associated with activation of transcription, and recruits the SWI/SNF chromatin remodeling subunit, BRG1."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002609208 SUPPORTS TRANSFER Eutherian-specific node seeded by human ATP1B4 IDA (PMID:17592128); correctly placed after the co-option event. Supporting Evidence: PMID:17592128 Through interaction with SKIP, eutherian beta m acquired new functions as exemplified by regulation of TGF-beta-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-beta signaling. PMID:17592128 To demonstrate directly the presence of the authentic βm and SKIP in the Smad7 transcriptional complex in vivo , we performed a ChIP analysis. PMID:36836771 BetaM binds to the distal regulatory region (DRR) of MyoD, promotes epigenetic changes associated with activation of transcription, and recruits the SWI/SNF chromatin remodeling subunit, BRG1. |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:17592128 Evolution of Na,K-ATPase beta m-subunit into a coregulator o... | ACCEPT | Summary: Regulation of DNA-templated transcription (IDA). Through SKIP, BetaM modulates TGF-beta-responsive reporters and raises Smad7 mRNA, and it is present with SKIP in the Smad7 transcriptional complex. Independently of SKIP, it binds the MyoD distal regulatory region and recruits BRG1 to stimulate MyoD expression. Core process. Reason: [PMID:17592128 "Through interaction with SKIP, eutherian beta m acquired new functions as exemplified by regulation of TGF-beta-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-beta signaling."] [PMID:17592128 "To demonstrate directly the presence of the authentic βm and SKIP in the Smad7 transcriptional complex in vivo , we performed a ChIP analysis."] [PMID:36836771 "BetaM binds to the distal regulatory region (DRR) of MyoD, promotes epigenetic changes associated with activation of transcription, and recruits the SWI/SNF chromatin remodeling subunit, BRG1."] Supporting Evidence: PMID:17592128 Through interaction with SKIP, eutherian beta m acquired new functions as exemplified by regulation of TGF-beta-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-beta signaling. PMID:17592128 To demonstrate directly the presence of the authentic βm and SKIP in the Smad7 transcriptional complex in vivo , we performed a ChIP analysis. PMID:36836771 BetaM binds to the distal regulatory region (DRR) of MyoD, promotes epigenetic changes associated with activation of transcription, and recruits the SWI/SNF chromatin remodeling subunit, BRG1. |
| GO:0006813 potassium ion transport | IEA GO_REF:0000002 | REMOVE | Summary: Potassium ion transport (IEA, InterPro Na,K-ATPase beta-subunit family). The family mapping reflects the ancestral role kept by fish, amphibian and avian BetaM. In placental mammals BetaM does not assemble with any X,K-ATPase alpha-subunit and has lost the pump-subunit function; a curated NOT transmembrane transport IDA row records this. The electronic mapping is contradicted for the human protein. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:17592128 "Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 )."] [PMID:17592128 "In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12)."] [file:human/ATP1B4/ATP1B4-uniprot.txt "CC does not associate with known Na,K-ATPase alpha-subunits."] [PMID:17592128 "The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane."] Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:17592128 Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 ). PMID:17592128 In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12). PMID:17592128 The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane. file:human/ATP1B4/ATP1B4-uniprot.txt CC does not associate with known Na,K-ATPase alpha-subunits. |
| GO:0006814 sodium ion transport | IEA GO_REF:0000002 | REMOVE | Summary: Sodium ion transport (IEA, InterPro Na,K-ATPase beta-subunit family). The family mapping reflects the ancestral role kept by fish, amphibian and avian BetaM. In placental mammals BetaM does not assemble with any X,K-ATPase alpha-subunit and has lost the pump-subunit function; a curated NOT transmembrane transport IDA row records this. The electronic mapping is contradicted for the human protein. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:17592128 "Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 )."] [PMID:17592128 "In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12)."] [file:human/ATP1B4/ATP1B4-uniprot.txt "CC does not associate with known Na,K-ATPase alpha-subunits."] [PMID:17592128 "The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane."] Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:17592128 Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 ). PMID:17592128 In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12). PMID:17592128 The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane. file:human/ATP1B4/ATP1B4-uniprot.txt CC does not associate with known Na,K-ATPase alpha-subunits. |
| GO:0022857 transmembrane transporter activity | TAS PMID:10456317 Identification of a novel gene of the X,K-ATPase beta-subuni... | REMOVE | Summary: Transmembrane transporter activity (TAS). This follows the 1999 discovery paper, which inferred an Na,K-ATPase isozyme in muscle from sequence similarity alone. The same group later showed that eutherian BetaM does not assemble with any X,K-ATPase alpha-subunit and has lost the ancestral function. The original inference is superseded. Reason: [PMID:10456317 "The data obtained indicate the existence of hitherto unknown X,K-ATPase (most probably Na,K-ATPase) isozymes in muscle cells."] [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:17592128 "Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 )."] [PMID:17592128 "In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12)."] [file:human/ATP1B4/ATP1B4-uniprot.txt "CC does not associate with known Na,K-ATPase alpha-subunits."] Supporting Evidence: PMID:10456317 The data obtained indicate the existence of hitherto unknown X,K-ATPase (most probably Na,K-ATPase) isozymes in muscle cells. PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:17592128 Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 ). file:human/ATP1B4/ATP1B4-uniprot.txt CC does not associate with known Na,K-ATPase alpha-subunits. |
| GO:0055085 transmembrane transport | IDA NOT PMID:17592128 Evolution of Na,K-ATPase beta m-subunit into a coregulator o... | ACCEPT | Summary: NOT involved in transmembrane transport (IDA). Human BetaM does not coimmunoprecipitate with Na,K-ATPase alpha-subunits and does not assemble into X,K-ATPases. Eutherian BetaM has lost the ancestral beta-subunit function that its fish, amphibian and bird orthologs keep. Accepted as a negative statement. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:17592128 "Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 )."] [PMID:17592128 "In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12)."] [file:human/ATP1B4/ATP1B4-uniprot.txt "CC does not associate with known Na,K-ATPase alpha-subunits."] Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:17592128 Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 ). PMID:17592128 In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12). file:human/ATP1B4/ATP1B4-uniprot.txt CC does not associate with known Na,K-ATPase alpha-subunits. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000108 | REMOVE | Summary: Transmembrane transport (IEA, inferred from transporter activity). The family mapping reflects the ancestral role kept by fish, amphibian and avian BetaM. In placental mammals BetaM does not assemble with any X,K-ATPase alpha-subunit and has lost the pump-subunit function; a curated NOT transmembrane transport IDA row records this. The electronic mapping is contradicted for the human protein. Reason: [PMID:17592128 "In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP)."] [PMID:17592128 "Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 )."] [PMID:17592128 "In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12)."] [file:human/ATP1B4/ATP1B4-uniprot.txt "CC does not associate with known Na,K-ATPase alpha-subunits."] [PMID:17592128 "The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane."] Supporting Evidence: PMID:17592128 In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). PMID:17592128 Finally, βm does not assemble with any of the X,K-ATPase α-subunits, thus indicating that it does not function as a subunit of X,K-ATPase in placental mammals ( 8 , 9 ). PMID:17592128 In contrast to human Na,K-ATPase β1(hβ1) used as a control (lanes 13–18), hβm was not coimmunoprecipitated with an α-antibody (lanes 7–12). PMID:17592128 The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane. file:human/ATP1B4/ATP1B4-uniprot.txt CC does not associate with known Na,K-ATPase alpha-subunits. |
| GO:0003712 transcription coregulator activity | IDA PMID:36836771 Eutherian-Specific Functions of BetaM Acquired through Atp1b... | NEW | Summary: Transcription coregulator activity (NEW, IDA). The coregulator experiments used human BetaM (the constructs from PMID:17592128) expressed in mouse C2C12 cells, which lack endogenous BetaM. Chromatin occupancy was confirmed on endogenous rat neonatal-muscle BetaM. BetaM acts on transcription together with other factors. It sits with SKIP in the Smad7 transcriptional complex and modulates Smad7 and TGF-beta reporters. Independently of SKIP, it occupies the MyoD distal regulatory region, promotes activating chromatin marks and recruits BRG1, so it does part of the regulatory work. Comparator: its partner SNW1/SKIP carries coactivator and corepressor activity by IDA. The general coregulator term is used because BetaM acts in both directions (Smad7 up, TGF-beta reporters modulated). Reason: [PMID:36836771 "BetaM binds to the distal regulatory region (DRR) of MyoD, promotes epigenetic changes associated with activation of transcription, and recruits the SWI/SNF chromatin remodeling subunit, BRG1."] [PMID:17592128 "To demonstrate directly the presence of the authentic βm and SKIP in the Smad7 transcriptional complex in vivo , we performed a ChIP analysis."] [PMID:17592128 "Through interaction with SKIP, eutherian beta m acquired new functions as exemplified by regulation of TGF-beta-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-beta signaling."] Supporting Evidence: PMID:36836771 BetaM binds to the distal regulatory region (DRR) of MyoD, promotes epigenetic changes associated with activation of transcription, and recruits the SWI/SNF chromatin remodeling subunit, BRG1. PMID:17592128 To demonstrate directly the presence of the authentic βm and SKIP in the Smad7 transcriptional complex in vivo , we performed a ChIP analysis. PMID:17592128 Through interaction with SKIP, eutherian beta m acquired new functions as exemplified by regulation of TGF-beta-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-beta signaling. |
Loading supporting content…
Download this section (compressed HTML)Q: How does an inner-nuclear-membrane protein bind the MyoD distal regulatory region: through LAP1/lamina tethering of the locus, or through a nucleoplasmic pool?
Experiment: Map BetaM-associated chromatin genome-wide (CUT&RUN) in neonatal muscle, and test whether lamina tethering via LAP1 is required for MyoD activation and for the lean phenotype of Atp1b4-null mice.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)