SHR3 encodes an ER membrane-localized packaging chaperone specifically required for the proper folding and ER exit of amino acid permeases. Shr3p functions as a permease-specific adaptor that assists the folding of these polytopic membrane proteins in the ER and facilitates their incorporation into COPII-coated vesicles for transport to the cell surface. It acts in conjunction with the Sec62/Sec63 translocon complex. In the absence of Shr3p, amino acid permeases are retained in the ER in a misfolded state and are eventually degraded, resulting in pleiotropic amino acid uptake defects. Shr3p enables yeast cells to rapidly modulate the spectrum of permeases expressed at the plasma membrane in response to changing nutrient conditions. No direct human ortholog has been identified, though the functional principle of substrate-specific ER chaperones is conserved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005789
endoplasmic reticulum membrane
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Manual review: endoplasmic reticulum membrane is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0006888
endoplasmic reticulum to Golgi vesicle-mediated transport
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Manual review: endoplasmic reticulum to Golgi vesicle-mediated transport is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0051082
unfolded protein binding
|
IBA
GO_REF:0000033 |
MODIFY |
Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for SHR3.
Reason: Modified to align with current curation guidance and improve term specificity.
Proposed replacements:
protein folding chaperone
|
|
GO:0005789
endoplasmic reticulum membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Manual review: endoplasmic reticulum membrane is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0015031
protein transport
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: Manual review: protein transport is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0005515
protein binding
|
IPI
PMID:10688190 A comprehensive analysis of protein-protein interactions in ... |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for SHR3.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005515
protein binding
|
IPI
PMID:16093310 Large-scale identification of yeast integral membrane protei... |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for SHR3.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005515
protein binding
|
IPI
PMID:18467557 An in vivo map of the yeast protein interactome. |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for SHR3.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005515
protein binding
|
IPI
PMID:27107014 An inter-species protein-protein interaction network across ... |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for SHR3.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005515
protein binding
|
IPI
PMID:37968396 The social and structural architecture of the yeast protein ... |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for SHR3.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005789
endoplasmic reticulum membrane
|
IDA
PMID:1423607 SHR3: a novel component of the secretory pathway specificall... |
ACCEPT |
Summary: Manual review: endoplasmic reticulum membrane is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0005789
endoplasmic reticulum membrane
|
IDA
PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... |
ACCEPT |
Summary: Manual review: endoplasmic reticulum membrane is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0090114
COPII-coated vesicle budding
|
IGI
PMID:10564255 Shr3p mediates specific COPII coatomer-cargo interactions re... |
ACCEPT |
Summary: Manual review: COPII-coated vesicle budding is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0005783
endoplasmic reticulum
|
HDA
PMID:26928762 One library to make them all: streamlining the creation of y... |
ACCEPT |
Summary: Manual review: endoplasmic reticulum is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0043332
mating projection tip
|
HDA
PMID:19053807 Systematic definition of protein constituents along the majo... |
KEEP AS NON CORE |
Summary: Manual review: mating projection tip may be context-dependent or peripheral for SHR3.
Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
|
|
GO:0006457
protein folding
|
IMP
PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... |
ACCEPT |
Summary: Manual review: protein folding is consistent with known biology of SHR3.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0051082
unfolded protein binding
|
IMP
PMID:10564255 Shr3p mediates specific COPII coatomer-cargo interactions re... |
MODIFY |
Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for SHR3.
Reason: Modified to align with current curation guidance and improve term specificity.
Proposed replacements:
protein folding chaperone
|
|
GO:0051082
unfolded protein binding
|
IMP
PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... |
MODIFY |
Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for SHR3.
Reason: Modified to align with current curation guidance and improve term specificity.
Proposed replacements:
protein folding chaperone
|
id: Q02774
gene_symbol: SHR3
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:559292
label: Saccharomyces cerevisiae
description: >-
SHR3 encodes an ER membrane-localized packaging chaperone specifically
required for the proper folding and ER exit of amino acid permeases. Shr3p
functions as a permease-specific adaptor that assists the folding of these
polytopic membrane proteins in the ER and facilitates their incorporation
into COPII-coated vesicles for transport to the cell surface. It acts in
conjunction with the Sec62/Sec63 translocon complex. In the absence of
Shr3p, amino acid permeases are retained in the ER in a misfolded state and
are eventually degraded, resulting in pleiotropic amino acid uptake defects.
Shr3p enables yeast cells to rapidly modulate the spectrum of permeases
expressed at the plasma membrane in response to changing nutrient conditions.
No direct human ortholog has been identified, though the functional
principle of substrate-specific ER chaperones is conserved.
existing_annotations:
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: endoplasmic reticulum membrane is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0006888
label: endoplasmic reticulum to Golgi vesicle-mediated transport
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: endoplasmic reticulum to Golgi vesicle-mediated transport is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0051082
label: unfolded protein binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: unfolded protein binding is better represented by a more specific replacement term for SHR3.'
action: MODIFY
reason: Modified to align with current curation guidance and improve term specificity.
proposed_replacement_terms:
- id: GO:0044183
label: protein folding chaperone
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: 'Manual review: endoplasmic reticulum membrane is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0015031
label: protein transport
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: 'Manual review: protein transport is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:10688190
review:
summary: 'Manual review: protein binding is too generic or over-extended for SHR3.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16093310
review:
summary: 'Manual review: protein binding is too generic or over-extended for SHR3.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18467557
review:
summary: 'Manual review: protein binding is too generic or over-extended for SHR3.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27107014
review:
summary: 'Manual review: protein binding is too generic or over-extended for SHR3.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:37968396
review:
summary: 'Manual review: protein binding is too generic or over-extended for SHR3.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: IDA
original_reference_id: PMID:1423607
review:
summary: 'Manual review: endoplasmic reticulum membrane is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: IDA
original_reference_id: PMID:15623581
review:
summary: 'Manual review: endoplasmic reticulum membrane is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0090114
label: COPII-coated vesicle budding
evidence_type: IGI
original_reference_id: PMID:10564255
review:
summary: 'Manual review: COPII-coated vesicle budding is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: HDA
original_reference_id: PMID:26928762
review:
summary: 'Manual review: endoplasmic reticulum is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0043332
label: mating projection tip
evidence_type: HDA
original_reference_id: PMID:19053807
review:
summary: 'Manual review: mating projection tip may be context-dependent or peripheral for SHR3.'
action: KEEP_AS_NON_CORE
reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
id: GO:0006457
label: protein folding
evidence_type: IMP
original_reference_id: PMID:15623581
review:
summary: 'Manual review: protein folding is consistent with known biology of SHR3.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0051082
label: unfolded protein binding
evidence_type: IMP
original_reference_id: PMID:10564255
review:
summary: 'Manual review: unfolded protein binding is better represented by a more specific replacement term for SHR3.'
action: MODIFY
reason: Modified to align with current curation guidance and improve term specificity.
proposed_replacement_terms:
- id: GO:0044183
label: protein folding chaperone
- term:
id: GO:0051082
label: unfolded protein binding
evidence_type: IMP
original_reference_id: PMID:15623581
review:
summary: 'Manual review: unfolded protein binding is better represented by a more specific replacement term for SHR3.'
action: MODIFY
reason: Modified to align with current curation guidance and improve term specificity.
proposed_replacement_terms:
- id: GO:0044183
label: protein folding chaperone
references:
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: PMID:10564255
title: Shr3p mediates specific COPII coatomer-cargo interactions required for the packaging of amino acid permeases into ER-derived transport vesicles.
findings: []
- id: PMID:10688190
title: A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.
findings: []
- id: PMID:1423607
title: 'SHR3: a novel component of the secretory pathway specifically required for localization of amino acid permeases in yeast.'
findings: []
- id: PMID:15623581
title: Specialized membrane-localized chaperones prevent aggregation of polytopic proteins in the ER.
findings: []
- id: PMID:16093310
title: Large-scale identification of yeast integral membrane protein interactions.
findings: []
- id: PMID:18467557
title: An in vivo map of the yeast protein interactome.
findings: []
- id: PMID:19053807
title: Systematic definition of protein constituents along the major polarization axis reveals an adaptive reuse of the polarization machinery in pheromone-treated budding yeast.
findings: []
- id: PMID:26928762
title: 'One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy.'
findings: []
- id: PMID:27107014
title: An inter-species protein-protein interaction network across vast evolutionary distance.
findings: []
- id: PMID:37968396
title: The social and structural architecture of the yeast protein interactome.
findings: []