SAR1B is a small GTPase of the SAR1/ARF family that starts the formation of COPII-coated transport carriers at endoplasmic reticulum exit sites. GDP-bound SAR1B is cytosolic; the ER-membrane guanine nucleotide exchange factor PREB/SEC12 loads it with GTP, and GTP-bound SAR1B inserts an N-terminal amphipathic helix into the ER membrane and recruits the SEC23-SEC24 inner coat, which captures cargo and recruits the SEC13-SEC31 outer coat. SEC23 then stimulates GTP hydrolysis, driving coat turnover. Compared with its close paralog SAR1A, SAR1B binds SEC23A more strongly and is specifically required, together with the cargo receptor SURF4, for ER export of large apolipoprotein B-containing lipoproteins: chylomicrons in enterocytes and VLDL in hepatocytes. Biallelic loss-of-function variants cause chylomicron retention disease (Anderson disease). Independently of its GTPase activity, SAR1B also binds leucine and, when leucine is scarce, associates with GATOR2 to inhibit mTORC1 signalling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002474 antigen processing and presentation of peptide antigen via MHC class I | TAS Reactome:R-HSA-983169 | MARK AS OVER ANNOTATED | Summary: Reactome places COPII-dependent ER export within its class I MHC antigen processing pathway. Reason: SAR1B is included because general COPII ER export is a step in MHC class I trafficking in the Reactome pathway. It has no specific role in antigen processing or presentation, and this inherits a pathway-level label onto a general secretory component. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. |
| GO:0003924 GTPase activity | EXP PMID:32358066 Small sequence variations between two mammalian paralogs of ... | ACCEPT | Summary: SAR1B is a small GTPase of the SAR1/ARF family; GTP hydrolysis drives COPII coat turnover (EXP). Reason: GTP binding and hydrolysis are the core enzymatic activity of SAR1B. Human SAR1B GTPase activity was measured directly (PMID:32358066; PMID:36369712, which reports a Vmax and crystal structures of SAR1B with GDP and GTP), and SEC23 acts as its GAP during coat cycling. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. PMID:36594468 SEC23 also functions as the GTPase-activating protein for SAR1 and stimulates SAR1 GTP hydrolysis. |
| GO:0003924 GTPase activity | EXP PMID:36369712 The alarmone ppGpp selectively inhibits the isoform A of the... | ACCEPT | Summary: SAR1B is a small GTPase of the SAR1/ARF family; GTP hydrolysis drives COPII coat turnover (EXP). Reason: GTP binding and hydrolysis are the core enzymatic activity of SAR1B. Human SAR1B GTPase activity was measured directly (PMID:32358066; PMID:36369712, which reports a Vmax and crystal structures of SAR1B with GDP and GTP), and SEC23 acts as its GAP during coat cycling. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. PMID:36594468 SEC23 also functions as the GTPase-activating protein for SAR1 and stimulates SAR1 GTP hydrolysis. |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | ACCEPT | Summary: SAR1B is a small GTPase of the SAR1/ARF family; GTP hydrolysis drives COPII coat turnover (IBA). Reason: GTP binding and hydrolysis are the core enzymatic activity of SAR1B. Human SAR1B GTPase activity was measured directly (PMID:32358066; PMID:36369712, which reports a Vmax and crystal structures of SAR1B with GDP and GTP), and SEC23 acts as its GAP during coat cycling. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. PMID:36594468 SEC23 also functions as the GTPase-activating protein for SAR1 and stimulates SAR1 GTP hydrolysis. |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: SAR1B is a small GTPase of the SAR1/ARF family; GTP hydrolysis drives COPII coat turnover (IEA, InterPro). Reason: GTP binding and hydrolysis are the core enzymatic activity of SAR1B. Human SAR1B GTPase activity was measured directly (PMID:32358066; PMID:36369712, which reports a Vmax and crystal structures of SAR1B with GDP and GTP), and SEC23 acts as its GAP during coat cycling. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. PMID:36594468 SEC23 also functions as the GTPase-activating protein for SAR1 and stimulates SAR1 GTP hydrolysis. |
| GO:0003924 GTPase activity | TAS Reactome:R-HSA-983422 | ACCEPT | Summary: SAR1B is a small GTPase of the SAR1/ARF family; GTP hydrolysis drives COPII coat turnover (TAS, Reactome). Reason: GTP binding and hydrolysis are the core enzymatic activity of SAR1B. Human SAR1B GTPase activity was measured directly (PMID:32358066; PMID:36369712, which reports a Vmax and crystal structures of SAR1B with GDP and GTP), and SEC23 acts as its GAP during coat cycling. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. PMID:36594468 SEC23 also functions as the GTPase-activating protein for SAR1 and stimulates SAR1 GTP hydrolysis. |
| GO:0003925 G protein activity | IDA PMID:32358066 Small sequence variations between two mammalian paralogs of ... | ACCEPT | Summary: SAR1B acts as a GTP-dependent molecular switch for COPII assembly (IDA). Reason: GO:0003925 G protein activity covers small monomeric GTPases that switch between GDP- and GTP-bound states; SAR1B-GTP recruits COPII and GTP hydrolysis releases it. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. |
| GO:0003925 G protein activity | IEA GO_REF:0000003 | ACCEPT | Summary: SAR1B acts as a GTP-dependent molecular switch (IEA, EC mapping). Reason: Consistent with the experimentally supported switch activity of SAR1B (PMID:32358066; PMID:36369712). Supporting Evidence: PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: High-throughput interactome detection of a SAR1B interaction (SAR1A (UniProtKB:Q9NR31)). Reason: This large-scale interaction screen reports an interaction with SAR1A (UniProtKB:Q9NR31); removal does not dispute the interaction, but GO:0005515 protein binding conveys no functional information. The informative SAR1B interactions (SEC23, PREB/SEC12, SURF4, MIOS/GATOR2) are captured by COPII coat, cargo loading and TORC1-regulation terms. Supporting Evidence: PMID:32358066 We found that the latter cluster confers to SAR1B a binding preference for SEC23A that is stronger than that of SAR1A for SEC23A. PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome detection of a SAR1B interaction (UniProtKB:Q9NUH8). Reason: This large-scale interaction screen reports an interaction with UniProtKB:Q9NUH8; removal does not dispute the interaction, but GO:0005515 protein binding conveys no functional information. The informative SAR1B interactions (SEC23, PREB/SEC12, SURF4, MIOS/GATOR2) are captured by COPII coat, cargo loading and TORC1-regulation terms. Supporting Evidence: PMID:32358066 We found that the latter cluster confers to SAR1B a binding preference for SEC23A that is stronger than that of SAR1A for SEC23A. PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome detection of a SAR1B interaction (CIDEB (UniProtKB:Q9UHD4)). Reason: This large-scale interaction screen reports an interaction with CIDEB (UniProtKB:Q9UHD4); removal does not dispute the interaction, but GO:0005515 protein binding conveys no functional information. The informative SAR1B interactions (SEC23, PREB/SEC12, SURF4, MIOS/GATOR2) are captured by COPII coat, cargo loading and TORC1-regulation terms. Supporting Evidence: PMID:32358066 We found that the latter cluster confers to SAR1B a binding preference for SEC23A that is stronger than that of SAR1A for SEC23A. PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interactome detection of a SAR1B interaction (SAR1A (UniProtKB:Q9NR31)). Reason: This large-scale interaction screen reports an interaction with SAR1A (UniProtKB:Q9NR31); removal does not dispute the interaction, but GO:0005515 protein binding conveys no functional information. The informative SAR1B interactions (SEC23, PREB/SEC12, SURF4, MIOS/GATOR2) are captured by COPII coat, cargo loading and TORC1-regulation terms. Supporting Evidence: PMID:32358066 We found that the latter cluster confers to SAR1B a binding preference for SEC23A that is stronger than that of SAR1A for SEC23A. PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: SAR1B binds GTP (IEA, InterPro). Reason: GTP binding is intrinsic to the SAR1B switch; crystal structures of SAR1B with GTP and GDP were solved (PMID:36369712). Supporting Evidence: PMID:36369712 the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. |
| GO:0005765 lysosomal membrane | IDA PMID:34290409 SAR1B senses leucine levels to regulate mTORC1 signalling. | ACCEPT | Summary: Upon leucine deprivation SAR1B associates with lysosomal membranes (IDA). Reason: Lysosomal-membrane association upon leucine deprivation is reported in the leucine-sensing study and is where SAR1B engages GATOR2 to repress mTORC1; it is the location of the leucine-sensor core function, distinct from the ER exit sites of its COPII function. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. file:human/SAR1B/SAR1B-uniprot.txt Lysosome membrane |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Lysosomal membrane localization (IEA, UniProt subcellular location mapping). Reason: Derived from the UniProt subcellular location based on PMID:34290409; the location of the leucine-sensing function. Supporting Evidence: file:human/SAR1B/SAR1B-uniprot.txt Lysosome membrane PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
| GO:0005783 endoplasmic reticulum | NAS PMID:36594468 Cargo selection in endoplasmic reticulum-to-Golgi transport ... | ACCEPT | Summary: SAR1B functions at the endoplasmic reticulum (NAS). Reason: Correct, though less specific than ER membrane and ER exit site. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:33186557 Receptor-Mediated ER Export of Lipoproteins Controls Lipid H... | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (EXP). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (IEA). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-203973 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-203977 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-203979 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-204008 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-2130731 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-2213243 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5694417 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5694522 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5694527 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-983424 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-983425 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-983426 | ACCEPT | Summary: GTP-bound SAR1B associates peripherally with the ER membrane (TAS, Reactome). Reason: UniProt records ER membrane localization for human SAR1B from PMID:33186557; GTP-bound SAR1 inserts its N-terminal amphipathic helix into the ER membrane at exit sites. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0005829 cytosol | IDA PMID:34290409 SAR1B senses leucine levels to regulate mTORC1 signalling. | ACCEPT | Summary: GDP-bound SAR1B is cytosolic (IDA). Reason: Like other ARF/SAR family GTPases, inactive GDP-bound SAR1B is soluble in the cytosol and is recruited to membranes on activation; cytosolic localization was also observed for human SAR1B in PMID:34290409. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: GDP-bound SAR1B is cytosolic (IEA). Reason: Like other ARF/SAR family GTPases, inactive GDP-bound SAR1B is soluble in the cytosol and is recruited to membranes on activation; cytosolic localization was also observed for human SAR1B in PMID:34290409. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-203973 | ACCEPT | Summary: GDP-bound SAR1B is cytosolic (TAS, Reactome). Reason: Like other ARF/SAR family GTPases, inactive GDP-bound SAR1B is soluble in the cytosol and is recruited to membranes on activation; cytosolic localization was also observed for human SAR1B in PMID:34290409. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-203977 | ACCEPT | Summary: GDP-bound SAR1B is cytosolic (TAS, Reactome). Reason: Like other ARF/SAR family GTPases, inactive GDP-bound SAR1B is soluble in the cytosol and is recruited to membranes on activation; cytosolic localization was also observed for human SAR1B in PMID:34290409. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5694527 | ACCEPT | Summary: GDP-bound SAR1B is cytosolic (TAS, Reactome). Reason: Like other ARF/SAR family GTPases, inactive GDP-bound SAR1B is soluble in the cytosol and is recruited to membranes on activation; cytosolic localization was also observed for human SAR1B in PMID:34290409. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983422 | ACCEPT | Summary: GDP-bound SAR1B is cytosolic (TAS, Reactome). Reason: Like other ARF/SAR family GTPases, inactive GDP-bound SAR1B is soluble in the cytosol and is recruited to membranes on activation; cytosolic localization was also observed for human SAR1B in PMID:34290409. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: SAR1B participates in intracellular protein transport (IEA, InterPro). Reason: Correct but general parent of ER to Golgi vesicle-mediated transport, which is the specific process. Supporting Evidence: PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: SAR1B initiates COPII vesicle formation for ER-to-Golgi transport (IBA). Reason: SAR1B-GTP nucleates the COPII coat at ER exit sites; depletion of SAR1A and SAR1B disrupts COPII assembly and classical ER-to-Golgi transfer, and SAR1B is selectively required for lipoprotein ER export. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IDA PMID:32358066 Small sequence variations between two mammalian paralogs of ... | ACCEPT | Summary: SAR1B initiates COPII vesicle formation for ER-to-Golgi transport (IDA). Reason: SAR1B-GTP nucleates the COPII coat at ER exit sites; depletion of SAR1A and SAR1B disrupts COPII assembly and classical ER-to-Golgi transfer, and SAR1B is selectively required for lipoprotein ER export. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IMP PMID:23433038 Silencing of mammalian Sar1 isoforms reveals COPII-independe... | ACCEPT | Summary: SAR1B initiates COPII vesicle formation for ER-to-Golgi transport (IMP). Reason: SAR1B-GTP nucleates the COPII coat at ER exit sites; depletion of SAR1A and SAR1B disrupts COPII assembly and classical ER-to-Golgi transfer, and SAR1B is selectively required for lipoprotein ER export. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | ISS GO_REF:0000024 | ACCEPT | Summary: SAR1B initiates COPII vesicle formation for ER-to-Golgi transport (ISS). Reason: SAR1B-GTP nucleates the COPII coat at ER exit sites; depletion of SAR1A and SAR1B disrupts COPII assembly and classical ER-to-Golgi transfer, and SAR1B is selectively required for lipoprotein ER export. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-983422 | ACCEPT | Summary: SAR1B is on the membrane of nascent COPII ER-to-Golgi carriers before uncoating (TAS, Reactome). Reason: SAR1 is part of the COPII coat on budding and budded ER-to-Golgi transport vesicles until GTP hydrolysis triggers uncoating. Supporting Evidence: PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. PMID:36594468 SEC23 also functions as the GTPase-activating protein for SAR1 and stimulates SAR1 GTP hydrolysis. |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-983424 | ACCEPT | Summary: SAR1B is on the membrane of nascent COPII ER-to-Golgi carriers before uncoating (TAS, Reactome). Reason: SAR1 is part of the COPII coat on budding and budded ER-to-Golgi transport vesicles until GTP hydrolysis triggers uncoating. Supporting Evidence: PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. PMID:36594468 SEC23 also functions as the GTPase-activating protein for SAR1 and stimulates SAR1 GTP hydrolysis. |
| GO:0016050 vesicle organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Vesicle organization (IBA). Reason: Correct but generic; the specific SAR1B processes are COPII vesicle coat assembly and ER to Golgi vesicle-mediated transport, which are annotated separately. Supporting Evidence: PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. |
| GO:0030127 COPII vesicle coat | IBA GO_REF:0000033 | ACCEPT | Summary: SAR1B is the GTPase component of the COPII coat (IBA). Reason: SAR1 is a constituent of the COPII coat: the GTP-bound form inserts into the ER membrane and recruits SEC23-SEC24, which then recruits SEC13-SEC31. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0030127 COPII vesicle coat | IDA PMID:32358066 Small sequence variations between two mammalian paralogs of ... | ACCEPT | Summary: SAR1B is the GTPase component of the COPII coat (IDA). Reason: SAR1 is a constituent of the COPII coat: the GTP-bound form inserts into the ER membrane and recruits SEC23-SEC24, which then recruits SEC13-SEC31. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0030127 COPII vesicle coat | IEA GO_REF:0000117 | ACCEPT | Summary: SAR1B is the GTPase component of the COPII coat (IEA, ARBA). Reason: SAR1 is a constituent of the COPII coat: the GTP-bound form inserts into the ER membrane and recruits SEC23-SEC24, which then recruits SEC13-SEC31. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0030127 COPII vesicle coat | NAS PMID:36594468 Cargo selection in endoplasmic reticulum-to-Golgi transport ... | ACCEPT | Summary: SAR1B is the GTPase component of the COPII coat (NAS). Reason: SAR1 is a constituent of the COPII coat: the GTP-bound form inserts into the ER membrane and recruits SEC23-SEC24, which then recruits SEC13-SEC31. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:36369712 The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0032368 regulation of lipid transport | IDA PMID:34015269 TMEM41B acts as an ER scramblase required for lipoprotein bi... | KEEP AS NON CORE | Summary: Regulation of lipid transport (IDA) from a study of the TMEM41B lipoprotein-export machinery. Reason: The cached abstract of PMID:34015269 concerns TMEM41B and does not mention SAR1B; the full text, not available here, presumably assayed SAR1B. SAR1B does control lipoprotein export from the ER, but this is direct participation in transport rather than regulation, so the term is kept as non-core. Supporting Evidence: PMID:34015269 Here, we show that TMEM41B, present in the lipoprotein export machinery, encodes a previously conceptualized ER lipid scramblase mediating trans-bilayer shuttling of bulk phospholipids. PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0032580 Golgi cisterna membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Golgi cisterna membrane (IEA, UniProt subcellular location, by similarity). Reason: The UniProt Golgi stack membrane entry is by similarity to the hamster protein. SAR1B is released from COPII carriers by GTP hydrolysis before or during fusion with the ER-Golgi intermediate compartment, and its functional site is the ER exit site. Supporting Evidence: PMID:36594468 SEC23 also functions as the GTPase-activating protein for SAR1 and stimulates SAR1 GTP hydrolysis. PMID:23433038 The Sar1 GTPase coordinates the assembly of coat protein complex-II (COPII) at specific sites of the endoplasmic reticulum (ER). |
| GO:0042953 lipoprotein transport | IDA PMID:32358066 Small sequence variations between two mammalian paralogs of ... | ACCEPT | Summary: SAR1B is required for ER export of apoB-containing lipoproteins (IDA). Reason: SAR1B knockdown abolishes lipoprotein secretion and only SAR1B (not SAR1A) restores it; biallelic SAR1B variants cause chylomicron retention disease, and hepatic Sar1b inactivation depletes plasma lipids. Supporting Evidence: PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. PMID:33186557 hepatic inactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis. PMID:12692552 Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell. |
| GO:0042953 lipoprotein transport | IDA PMID:34015269 TMEM41B acts as an ER scramblase required for lipoprotein bi... | ACCEPT | Summary: Lipoprotein transport (IDA) from the TMEM41B lipoprotein-export study. Reason: The cached abstract of PMID:34015269 concerns TMEM41B and does not mention SAR1B; deferring to the curator who read the full text. The function is independently well established for SAR1B (PMID:32358066; PMID:33186557). Supporting Evidence: PMID:34015269 Here, we show that TMEM41B, present in the lipoprotein export machinery, encodes a previously conceptualized ER lipid scramblase mediating trans-bilayer shuttling of bulk phospholipids. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. |
| GO:0042953 lipoprotein transport | IEA GO_REF:0000107 | ACCEPT | Summary: SAR1B is required for ER export of apoB-containing lipoproteins (IEA, Ensembl Compara). Reason: SAR1B knockdown abolishes lipoprotein secretion and only SAR1B (not SAR1A) restores it; biallelic SAR1B variants cause chylomicron retention disease, and hepatic Sar1b inactivation depletes plasma lipids. Supporting Evidence: PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. PMID:33186557 hepatic inactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis. PMID:12692552 Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell. |
| GO:0042953 lipoprotein transport | ISS GO_REF:0000024 | ACCEPT | Summary: SAR1B is required for ER export of apoB-containing lipoproteins (ISS). Reason: SAR1B knockdown abolishes lipoprotein secretion and only SAR1B (not SAR1A) restores it; biallelic SAR1B variants cause chylomicron retention disease, and hepatic Sar1b inactivation depletes plasma lipids. Supporting Evidence: PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. PMID:33186557 hepatic inactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis. PMID:12692552 Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell. |
| GO:0048208 COPII vesicle coat assembly | IDA PMID:32358066 Small sequence variations between two mammalian paralogs of ... | ACCEPT | Summary: SAR1B-GTP initiates COPII coat assembly (IDA). Reason: SAR1-GTP recruits SEC23-SEC24 to the ER membrane, the first step of COPII coat assembly; depletion of SAR1 isoforms disrupts COPII assembly. SAR1B has a stronger SEC23A binding preference than SAR1A. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:32358066 We found that the latter cluster confers to SAR1B a binding preference for SEC23A that is stronger than that of SAR1A for SEC23A. PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. |
| GO:0048208 COPII vesicle coat assembly | IEA GO_REF:0000117 | ACCEPT | Summary: SAR1B-GTP initiates COPII coat assembly (IEA, ARBA). Reason: SAR1-GTP recruits SEC23-SEC24 to the ER membrane, the first step of COPII coat assembly; depletion of SAR1 isoforms disrupts COPII assembly. SAR1B has a stronger SEC23A binding preference than SAR1A. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:32358066 We found that the latter cluster confers to SAR1B a binding preference for SEC23A that is stronger than that of SAR1A for SEC23A. PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. |
| GO:0048208 COPII vesicle coat assembly | IMP PMID:23433038 Silencing of mammalian Sar1 isoforms reveals COPII-independe... | ACCEPT | Summary: SAR1B-GTP initiates COPII coat assembly (IMP). Reason: SAR1-GTP recruits SEC23-SEC24 to the ER membrane, the first step of COPII coat assembly; depletion of SAR1 isoforms disrupts COPII assembly. SAR1B has a stronger SEC23A binding preference than SAR1A. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:32358066 We found that the latter cluster confers to SAR1B a binding preference for SEC23A that is stronger than that of SAR1A for SEC23A. PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. |
| GO:0055088 lipid homeostasis | IDA PMID:34015269 TMEM41B acts as an ER scramblase required for lipoprotein bi... | KEEP AS NON CORE | Summary: Lipid homeostasis (IDA) from the TMEM41B lipoprotein-export study. Reason: Hepatic Sar1b inactivation depletes plasma lipids, so SAR1B affects organismal lipid homeostasis through lipoprotein export. This is a downstream systemic consequence rather than the core activity. The cited abstract does not mention SAR1B; deferring to the curator. Supporting Evidence: PMID:33186557 hepatic inactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis. PMID:34015269 Here, we show that TMEM41B, present in the lipoprotein export machinery, encodes a previously conceptualized ER lipid scramblase mediating trans-bilayer shuttling of bulk phospholipids. |
| GO:0061024 membrane organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Membrane organization (IBA). Reason: Generic; SAR1-GTP insertion of its amphipathic helix contributes to membrane deformation during budding, but the informative term is COPII vesicle coat assembly. Supporting Evidence: PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0070971 endoplasmic reticulum exit site | IBA GO_REF:0000033 | ACCEPT | Summary: SAR1B acts at ER exit sites (IBA). Reason: ER exit sites are where SAR1-GTP inserts into the membrane and nucleates the COPII coat. Supporting Evidence: PMID:23433038 The Sar1 GTPase coordinates the assembly of coat protein complex-II (COPII) at specific sites of the endoplasmic reticulum (ER). PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0070971 endoplasmic reticulum exit site | IDA PMID:33186557 Receptor-Mediated ER Export of Lipoproteins Controls Lipid H... | ACCEPT | Summary: SAR1B acts at ER exit sites (IDA). Reason: ER exit sites are where SAR1-GTP inserts into the membrane and nucleates the COPII coat. Supporting Evidence: PMID:23433038 The Sar1 GTPase coordinates the assembly of coat protein complex-II (COPII) at specific sites of the endoplasmic reticulum (ER). PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0070971 endoplasmic reticulum exit site | IEA GO_REF:0000117 | ACCEPT | Summary: SAR1B acts at ER exit sites (IEA, ARBA). Reason: ER exit sites are where SAR1-GTP inserts into the membrane and nucleates the COPII coat. Supporting Evidence: PMID:23433038 The Sar1 GTPase coordinates the assembly of coat protein complex-II (COPII) at specific sites of the endoplasmic reticulum (ER). PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0070971 endoplasmic reticulum exit site | IMP PMID:23433038 Silencing of mammalian Sar1 isoforms reveals COPII-independe... | ACCEPT | Summary: SAR1B acts at ER exit sites (IMP). Reason: ER exit sites are where SAR1-GTP inserts into the membrane and nucleates the COPII coat. Supporting Evidence: PMID:23433038 The Sar1 GTPase coordinates the assembly of coat protein complex-II (COPII) at specific sites of the endoplasmic reticulum (ER). PMID:36594468 GTP-bound SAR1 inserts its hydrophobic N-terminus into the ER membrane and recruits SEC23-SEC24 heterodimers to the ER exit site |
| GO:0090110 COPII-coated vesicle cargo loading | IDA PMID:32358066 Small sequence variations between two mammalian paralogs of ... | ACCEPT | Summary: SAR1B-initiated COPII assembly loads cargo, with a SAR1B-specific role in lipoprotein cargo export via SURF4 (IDA). Reason: COPII assembly initiated by SAR1B captures cargo into budding carriers; SAR1B pairs with the cargo receptor SURF4 to quantitatively govern ER export of lipoproteins, and SAR1B is required for chylomicron export. Supporting Evidence: PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. PMID:12692552 Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell. |
| GO:0090110 COPII-coated vesicle cargo loading | IDA PMID:33186557 Receptor-Mediated ER Export of Lipoproteins Controls Lipid H... | ACCEPT | Summary: SAR1B-initiated COPII assembly loads cargo, with a SAR1B-specific role in lipoprotein cargo export via SURF4 (IDA). Reason: COPII assembly initiated by SAR1B captures cargo into budding carriers; SAR1B pairs with the cargo receptor SURF4 to quantitatively govern ER export of lipoproteins, and SAR1B is required for chylomicron export. Supporting Evidence: PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. PMID:12692552 Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell. |
| GO:0090110 COPII-coated vesicle cargo loading | IEA GO_REF:0000117 | ACCEPT | Summary: SAR1B-initiated COPII assembly loads cargo, with a SAR1B-specific role in lipoprotein cargo export via SURF4 (IEA, ARBA). Reason: COPII assembly initiated by SAR1B captures cargo into budding carriers; SAR1B pairs with the cargo receptor SURF4 to quantitatively govern ER export of lipoproteins, and SAR1B is required for chylomicron export. Supporting Evidence: PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. PMID:12692552 Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell. |
| GO:0090110 COPII-coated vesicle cargo loading | IMP PMID:23433038 Silencing of mammalian Sar1 isoforms reveals COPII-independe... | ACCEPT | Summary: SAR1B-initiated COPII assembly loads cargo, with a SAR1B-specific role in lipoprotein cargo export via SURF4 (IMP). Reason: COPII assembly initiated by SAR1B captures cargo into budding carriers; SAR1B pairs with the cargo receptor SURF4 to quantitatively govern ER export of lipoproteins, and SAR1B is required for chylomicron export. Supporting Evidence: PMID:33186557 Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. PMID:12692552 Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell. |
| GO:0140353 lipid export from cell | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lipid export from cell (IEA, Ensembl Compara). Reason: SAR1B is needed for secretion of lipids as lipoproteins because it forms the COPII carriers that export apoB lipoproteins from the ER. Its own step is ER export, so this whole-cell secretion term is kept as non-core. Supporting Evidence: PMID:28982670 SAR1B deletion resulted in significantly decreased secretion of triglycerides (≈40%), apolipoprotein B-48 (≈57%), and chylomicron (≈34.5%). PMID:32358066 SAR1B knockdown caused loss of lipoprotein secretion, overexpression of SAR1B but not of SAR1A could restore secretion, and a divergent cluster adjacent to the SEC31/SEC23-binding site was critical for this SAR1B function. |
| GO:0140785 amino acid sensor activity | IDA PMID:34290409 SAR1B senses leucine levels to regulate mTORC1 signalling. | ACCEPT | Summary: SAR1B binds leucine and acts as a leucine sensor upstream of mTORC1 (IDA). Reason: Leucine binding causes a conformational change in SAR1B that releases GATOR2, matching GO:0140785 amino acid sensor activity. Supporting Evidence: PMID:34290409 In conditions of leucine sufficiency, SAR1B binds to leucine, undergoes a conformational change and dissociates from GATOR2, which results in mTORC1 activation. PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
| GO:0140785 amino acid sensor activity | IEA GO_REF:0000117 | ACCEPT | Summary: SAR1B binds leucine and acts as a leucine sensor upstream of mTORC1 (IEA, ARBA). Reason: Leucine binding causes a conformational change in SAR1B that releases GATOR2, matching GO:0140785 amino acid sensor activity. Supporting Evidence: PMID:34290409 In conditions of leucine sufficiency, SAR1B binds to leucine, undergoes a conformational change and dissociates from GATOR2, which results in mTORC1 activation. PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
| GO:1902953 positive regulation of ER to Golgi vesicle-mediated transport | NAS PMID:36594468 Cargo selection in endoplasmic reticulum-to-Golgi transport ... | MARK AS OVER ANNOTATED | Summary: Positive regulation of ER to Golgi vesicle-mediated transport (NAS). Reason: SAR1B performs ER-to-Golgi transport as a COPII component rather than regulating it from outside, so the core process term GO:0006888 (already annotated) is the appropriate one; describing a core component as a positive regulator is an over-annotation. Supporting Evidence: PMID:32358066 Secretion-associated Ras-related GTPase 1 (SAR1) is a small GTPase that is part of COPII and, upon GTP binding, recruits the other COPII proteins to the endoplasmic reticulum membrane. PMID:23433038 We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. |
| GO:1903432 regulation of TORC1 signaling | IDA PMID:34290409 SAR1B senses leucine levels to regulate mTORC1 signalling. | ACCEPT | Summary: SAR1B restrains mTORC1 under leucine deprivation by binding GATOR2 (IDA). Reason: SAR1B is a leucine sensor: in leucine deficiency it binds GATOR2 (via MIOS) and inhibits mTORC1; leucine binding releases GATOR2. This function is independent of its GTPase activity and is a distinct, well-supported second role. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:34290409 In conditions of leucine sufficiency, SAR1B binds to leucine, undergoes a conformational change and dissociates from GATOR2, which results in mTORC1 activation. |
| GO:1904262 negative regulation of TORC1 signaling | IEA GO_REF:0000117 | ACCEPT | Summary: SAR1B restrains mTORC1 under leucine deprivation by binding GATOR2 (IEA, ARBA). Reason: SAR1B is a leucine sensor: in leucine deficiency it binds GATOR2 (via MIOS) and inhibits mTORC1; leucine binding releases GATOR2. This function is independent of its GTPase activity and is a distinct, well-supported second role. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:34290409 In conditions of leucine sufficiency, SAR1B binds to leucine, undergoes a conformational change and dissociates from GATOR2, which results in mTORC1 activation. |
| GO:1904262 negative regulation of TORC1 signaling | IMP PMID:34290409 SAR1B senses leucine levels to regulate mTORC1 signalling. | ACCEPT | Summary: SAR1B restrains mTORC1 under leucine deprivation by binding GATOR2 (IMP). Reason: SAR1B is a leucine sensor: in leucine deficiency it binds GATOR2 (via MIOS) and inhibits mTORC1; leucine binding releases GATOR2. This function is independent of its GTPase activity and is a distinct, well-supported second role. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. PMID:34290409 In conditions of leucine sufficiency, SAR1B binds to leucine, undergoes a conformational change and dissociates from GATOR2, which results in mTORC1 activation. |
| GO:1990253 cellular response to leucine starvation | IEA GO_REF:0000117 | ACCEPT | Summary: SAR1B mediates mTORC1 inhibition in response to leucine starvation (IEA, ARBA). Reason: Under leucine deficiency SAR1B binds GATOR2 to inhibit mTORC1; loss of SAR1B blunts this response. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
| GO:1990253 cellular response to leucine starvation | IMP PMID:34290409 SAR1B senses leucine levels to regulate mTORC1 signalling. | ACCEPT | Summary: SAR1B mediates mTORC1 inhibition in response to leucine starvation (IMP). Reason: Under leucine deficiency SAR1B binds GATOR2 to inhibit mTORC1; loss of SAR1B blunts this response. Supporting Evidence: PMID:34290409 Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. |
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Download this section (compressed HTML)Q: How does SAR1B, together with SURF4 and other export factors, generate carriers large enough for pre-chylomicrons and VLDL, given that these particles far exceed the size of a typical COPII vesicle?
Q: Are the COPII and leucine-sensing roles of SAR1B separable in enterocytes and hepatocytes, and does leucine availability affect lipoprotein export?
Q: Does the leucine-sensing role replicate independently of PMID:34290409? That single study is the source of the GO:0140785 IDA, of the ARBA IEA derived from it, and of the lysosomal-membrane location, so the whole second core function currently rests on one paper. Direct leucine binding by purified human SAR1B, the GATOR2/MIOS interaction, and mTORC1 repression on leucine withdrawal would each benefit from replication in a second laboratory and in a cell type where the COPII role is also measurable, which would also show whether the two activities compete for the same protein pool.
Q: What sets the partial redundancy between SAR1A and SAR1B in intestinal chylomicron export, and why does upregulation of SAR1A in patient duodenum fail to compensate?
Experiment: Reconstitute SEC12-dependent SAR1B and SAR1A loading and SEC23A recruitment on liposomes with matched patient missense alleles (e.g. D137N, S179R, G185V), measuring nucleotide exchange, GTP hydrolysis, SEC23 binding and membrane insertion.
Hypothesis: Chylomicron retention disease missense alleles disrupt distinct steps of the SAR1B GTPase cycle or its SEC23 interaction.
Type: in vitro biochemical reconstitution
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