E1BL04

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001725 stress fiber	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: XIRP2 colocalizes with stress fibers based on phylogenetic inference from human (A4UGR9) and mouse (Q702N8) orthologs. Human XIRP2 has been shown to colocalize with stress fibers in non-muscle cell overexpression assays, consistent with its actin-binding activity mediated by Xin repeats. The qualifier colocalizes_with is appropriate as XIRP2 is not an integral component of stress fibers but rather associates with them. Reason: Stress fiber colocalization is likely observed in experimental overexpression contexts rather than being a primary physiological localization for this muscle-specific protein. The core localizations are the Z disc and intercalated disc in cardiac and skeletal muscle.
GO:0005925 focal adhesion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: XIRP2 colocalizes with focal adhesions based on phylogenetic inference from human and mouse orthologs. In muscle cells, the analogous structures to focal adhesions are costameres and myotendinous junctions, where XIRP2 has been reported to localize. The colocalizes_with qualifier is appropriate. Reason: Focal adhesion colocalization is consistent with XIRP2 biology but represents a non-muscle cell context or the muscle-equivalent structure. The core localization is at the Z disc and intercalated disc.
GO:0007015 actin filament organization	IBA GO_REF:0000033	ACCEPT	Summary: XIRP2 is involved in actin filament organization based on phylogenetic inference from mouse Xirp2 (Q702N8). This is consistent with the protein's multiple Xin repeats that bind F-actin and its known role in maintaining sarcomeric actin architecture. Mouse Xirp2 knockout studies demonstrate disrupted actin organization in the heart. Reason: Actin filament organization is a well-supported core biological process for XIRP2, given its domain architecture (26 Xin repeats binding F-actin) and the phenotypic consequences of loss-of-function in mouse.
GO:0051015 actin filament binding	IBA GO_REF:0000033	ACCEPT	Summary: XIRP2 binds actin filaments through its 26 Xin repeats, as supported by phylogenetic inference from both human (A4UGR9) and mouse (Q702N8) orthologs. The Xin repeat domain is a well-characterized actin-binding module, and the bovine protein contains the same domain architecture (18 Pfam Xin domains, 26 PROSITE Xin repeats). This is the most specific and informative molecular function annotation for the protein. Reason: Actin filament binding is the core molecular function of XIRP2, directly mediated by its characteristic Xin repeat domains. This is more specific than the generic actin binding term. Supporting Evidence: file:BOVIN/E1BL04/E1BL04-uniprot.txt Xin repeats bind F-actin
GO:0003779 actin binding	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Actin binding is assigned via combined automated methods (InterPro IPR012510 Xin repeat and IPR030072 XIRP1/XIRP2 family). This is a parent term of the more specific GO:0051015 (actin filament binding) which is also annotated via IBA. Both are technically correct, but the more specific term is preferred. Reason: GO:0003779 (actin binding) is subsumed by the more specific GO:0051015 (actin filament binding) already present in the annotation set. The Xin repeats specifically bind F-actin (filamentous actin), making the filament-specific term more informative. Supporting Evidence: file:BOVIN/E1BL04/E1BL04-uniprot.txt Xin repeats bind F-actin
GO:0030036 actin cytoskeleton organization	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Actin cytoskeleton organization is assigned via InterPro domain mapping (IPR012510, IPR030072). This is a parent term of the more specific GO:0007015 (actin filament organization) already annotated via IBA. Both are correct, but the more specific term is preferred. Reason: GO:0030036 is a broader parent of GO:0007015 (actin filament organization) which is already annotated. The more specific term better captures XIRP2's role in organizing actin filaments within the sarcomere.
GO:0030054 cell junction	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Cell junction localization is assigned via InterPro (IPR012510). XIRP2 localizes to intercalated discs in cardiomyocytes, which are specialized cell junctions. The term is correct but very general; the more specific GO:0005911 (cell-cell junction) is also annotated. Reason: GO:0030054 is a broad parent term. The more specific GO:0005911 (cell-cell junction) already present in the annotation set, and even more specific terms such as intercalated disc (GO:0014704) would better capture the known localization.
GO:0070161 anchoring junction	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Anchoring junction localization is assigned from UniProt subcellular location vocabulary mapping. The UniProt entry lists cell junction as the subcellular location. Intercalated discs contain adherens junctions (a type of anchoring junction), so this is biologically consistent with XIRP2 localization at intercalated discs and myotendinous junctions. Reason: The annotation is consistent with XIRP2 biology. Intercalated discs contain adherens junctions (anchoring junctions), and XIRP2 is found at these structures. However, this is a broad localization term and not as informative as Z disc or intercalated disc.
GO:0001725 stress fiber	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Duplicate of the IBA annotation above, transferred from human XIRP2 (A4UGR9) via Ensembl Compara orthology. The same biological reasoning applies: stress fiber colocalization is observed but not the primary physiological localization. Reason: Redundant with the IBA annotation for the same term and qualifier. Stress fiber colocalization is not a core localization for this muscle-specific protein.
GO:0005911 cell-cell junction	IEA GO_REF:0000107	ACCEPT	Summary: Cell-cell junction localization is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. XIRP2 localizes to intercalated discs, which are specialized cell-cell junctions in cardiac muscle. This is a reasonable annotation, though intercalated disc (GO:0014704) would be more precise. Reason: XIRP2 is well-established at intercalated discs, which are specialized cell-cell junctions. This annotation correctly captures an important aspect of XIRP2 localization in cardiac tissue.
GO:0005925 focal adhesion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Duplicate of the IBA annotation above, transferred from human XIRP2 (A4UGR9) via Ensembl Compara. Same reasoning applies as for the IBA version. Reason: Redundant with the IBA annotation for the same term and qualifier. Focal adhesion colocalization represents a non-muscle context or the muscle-equivalent costamere.
GO:0030018 Z disc	IEA GO_REF:0000107	ACCEPT	Summary: Z disc localization is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. XIRP2 is well-established as a Z disc component in striated muscle, where it interacts with alpha-actinin and maintains sarcomeric structure. This is one of the most important and well-characterized localizations for XIRP2. Reason: Z disc localization is a core aspect of XIRP2 biology. The protein interacts with alpha-actinin at the Z disc and is essential for sarcomeric integrity in both cardiac and skeletal muscle.
GO:0051015 actin filament binding	IEA GO_REF:0000107	ACCEPT	Summary: Duplicate of the IBA annotation above, transferred from human XIRP2 (A4UGR9) via Ensembl Compara. Same reasoning applies: actin filament binding is the core molecular function mediated by Xin repeats. Reason: Actin filament binding is the defining molecular function of XIRP2. This Ensembl Compara annotation reinforces the IBA annotation from the same source ortholog. Supporting Evidence: file:BOVIN/E1BL04/E1BL04-uniprot.txt Xin repeats bind F-actin
GO:0051393 alpha-actinin binding	IEA GO_REF:0000107	ACCEPT	Summary: Alpha-actinin binding is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. XIRP2 has been shown to interact with alpha-actinin at the Z disc in mouse cardiomyocytes, which is important for its role in sarcomeric integrity. This interaction is distinct from and complementary to its actin filament binding activity. Reason: Alpha-actinin binding is a well-characterized molecular function of XIRP2 that is important for its localization to the Z disc and its role in sarcomeric maintenance.
GO:0110053 regulation of actin filament organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Regulation of actin filament organization is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. This is consistent with XIRP2's role in maintaining sarcomeric actin architecture, though it is somewhat redundant with GO:0007015 (actin filament organization) already annotated via IBA. Reason: While XIRP2 does regulate actin filament organization, the direct involvement in actin filament organization (GO:0007015) is a more fundamental annotation. The regulatory aspect is secondary to the structural role.
GO:1903829 positive regulation of protein localization	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Positive regulation of protein localization is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. This is a very broad term. XIRP2 may promote the localization of specific proteins (such as alpha-actinin or other sarcomeric components) to the Z disc, but the term lacks specificity about which proteins or which localization context. Reason: The term is too broad to be informative. Without specifying which protein's localization is being regulated, this annotation provides limited biological insight. A more specific term would be preferred if the regulated protein can be identified.

GO Term

Evidence

Action

Reason

IBA
GO_REF:0000033

KEEP AS NON CORE

Summary: XIRP2 colocalizes with stress fibers based on phylogenetic inference from human (A4UGR9) and mouse (Q702N8) orthologs. Human XIRP2 has been shown to colocalize with stress fibers in non-muscle cell overexpression assays, consistent with its actin-binding activity mediated by Xin repeats. The qualifier colocalizes_with is appropriate as XIRP2 is not an integral component of stress fibers but rather associates with them.

Reason: Stress fiber colocalization is likely observed in experimental overexpression contexts rather than being a primary physiological localization for this muscle-specific protein. The core localizations are the Z disc and intercalated disc in cardiac and skeletal muscle.

GO:0005925 focal adhesion

IBA
GO_REF:0000033

KEEP AS NON CORE

Summary: XIRP2 colocalizes with focal adhesions based on phylogenetic inference from human and mouse orthologs. In muscle cells, the analogous structures to focal adhesions are costameres and myotendinous junctions, where XIRP2 has been reported to localize. The colocalizes_with qualifier is appropriate.

Reason: Focal adhesion colocalization is consistent with XIRP2 biology but represents a non-muscle cell context or the muscle-equivalent structure. The core localization is at the Z disc and intercalated disc.

GO:0007015 actin filament organization

IBA
GO_REF:0000033

Summary: XIRP2 is involved in actin filament organization based on phylogenetic inference from mouse Xirp2 (Q702N8). This is consistent with the protein's multiple Xin repeats that bind F-actin and its known role in maintaining sarcomeric actin architecture. Mouse Xirp2 knockout studies demonstrate disrupted actin organization in the heart.

Reason: Actin filament organization is a well-supported core biological process for XIRP2, given its domain architecture (26 Xin repeats binding F-actin) and the phenotypic consequences of loss-of-function in mouse.

GO:0051015 actin filament binding

IBA
GO_REF:0000033

Summary: XIRP2 binds actin filaments through its 26 Xin repeats, as supported by phylogenetic inference from both human (A4UGR9) and mouse (Q702N8) orthologs. The Xin repeat domain is a well-characterized actin-binding module, and the bovine protein contains the same domain architecture (18 Pfam Xin domains, 26 PROSITE Xin repeats). This is the most specific and informative molecular function annotation for the protein.

Reason: Actin filament binding is the core molecular function of XIRP2, directly mediated by its characteristic Xin repeat domains. This is more specific than the generic actin binding term.

Supporting Evidence:

file:BOVIN/E1BL04/E1BL04-uniprot.txt

Xin repeats bind F-actin

GO:0003779 actin binding

IEA
GO_REF:0000120

MARK AS OVER ANNOTATED

Summary: Actin binding is assigned via combined automated methods (InterPro IPR012510 Xin repeat and IPR030072 XIRP1/XIRP2 family). This is a parent term of the more specific GO:0051015 (actin filament binding) which is also annotated via IBA. Both are technically correct, but the more specific term is preferred.

Reason: GO:0003779 (actin binding) is subsumed by the more specific GO:0051015 (actin filament binding) already present in the annotation set. The Xin repeats specifically bind F-actin (filamentous actin), making the filament-specific term more informative.

Supporting Evidence:

file:BOVIN/E1BL04/E1BL04-uniprot.txt

Xin repeats bind F-actin

GO:0030036 actin cytoskeleton organization

IEA
GO_REF:0000002

MARK AS OVER ANNOTATED

Summary: Actin cytoskeleton organization is assigned via InterPro domain mapping (IPR012510, IPR030072). This is a parent term of the more specific GO:0007015 (actin filament organization) already annotated via IBA. Both are correct, but the more specific term is preferred.

Reason: GO:0030036 is a broader parent of GO:0007015 (actin filament organization) which is already annotated. The more specific term better captures XIRP2's role in organizing actin filaments within the sarcomere.

GO:0030054 cell junction

IEA
GO_REF:0000002

MARK AS OVER ANNOTATED

Summary: Cell junction localization is assigned via InterPro (IPR012510). XIRP2 localizes to intercalated discs in cardiomyocytes, which are specialized cell junctions. The term is correct but very general; the more specific GO:0005911 (cell-cell junction) is also annotated.

Reason: GO:0030054 is a broad parent term. The more specific GO:0005911 (cell-cell junction) already present in the annotation set, and even more specific terms such as intercalated disc (GO:0014704) would better capture the known localization.

GO:0070161 anchoring junction

IEA
GO_REF:0000044

KEEP AS NON CORE

Summary: Anchoring junction localization is assigned from UniProt subcellular location vocabulary mapping. The UniProt entry lists cell junction as the subcellular location. Intercalated discs contain adherens junctions (a type of anchoring junction), so this is biologically consistent with XIRP2 localization at intercalated discs and myotendinous junctions.

Reason: The annotation is consistent with XIRP2 biology. Intercalated discs contain adherens junctions (anchoring junctions), and XIRP2 is found at these structures. However, this is a broad localization term and not as informative as Z disc or intercalated disc.

GO:0001725 stress fiber

IEA
GO_REF:0000107

KEEP AS NON CORE

Summary: Duplicate of the IBA annotation above, transferred from human XIRP2 (A4UGR9) via Ensembl Compara orthology. The same biological reasoning applies: stress fiber colocalization is observed but not the primary physiological localization.

Reason: Redundant with the IBA annotation for the same term and qualifier. Stress fiber colocalization is not a core localization for this muscle-specific protein.

GO:0005911 cell-cell junction

IEA
GO_REF:0000107

Summary: Cell-cell junction localization is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. XIRP2 localizes to intercalated discs, which are specialized cell-cell junctions in cardiac muscle. This is a reasonable annotation, though intercalated disc (GO:0014704) would be more precise.

Reason: XIRP2 is well-established at intercalated discs, which are specialized cell-cell junctions. This annotation correctly captures an important aspect of XIRP2 localization in cardiac tissue.

GO:0005925 focal adhesion

IEA
GO_REF:0000107

KEEP AS NON CORE

Summary: Duplicate of the IBA annotation above, transferred from human XIRP2 (A4UGR9) via Ensembl Compara. Same reasoning applies as for the IBA version.

Reason: Redundant with the IBA annotation for the same term and qualifier. Focal adhesion colocalization represents a non-muscle context or the muscle-equivalent costamere.

GO:0030018 Z disc

IEA
GO_REF:0000107

Summary: Z disc localization is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. XIRP2 is well-established as a Z disc component in striated muscle, where it interacts with alpha-actinin and maintains sarcomeric structure. This is one of the most important and well-characterized localizations for XIRP2.

Reason: Z disc localization is a core aspect of XIRP2 biology. The protein interacts with alpha-actinin at the Z disc and is essential for sarcomeric integrity in both cardiac and skeletal muscle.

GO:0051015 actin filament binding

IEA
GO_REF:0000107

Summary: Duplicate of the IBA annotation above, transferred from human XIRP2 (A4UGR9) via Ensembl Compara. Same reasoning applies: actin filament binding is the core molecular function mediated by Xin repeats.

Reason: Actin filament binding is the defining molecular function of XIRP2. This Ensembl Compara annotation reinforces the IBA annotation from the same source ortholog.

Supporting Evidence:

file:BOVIN/E1BL04/E1BL04-uniprot.txt

Xin repeats bind F-actin

GO:0051393 alpha-actinin binding

IEA
GO_REF:0000107

Summary: Alpha-actinin binding is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. XIRP2 has been shown to interact with alpha-actinin at the Z disc in mouse cardiomyocytes, which is important for its role in sarcomeric integrity. This interaction is distinct from and complementary to its actin filament binding activity.

Reason: Alpha-actinin binding is a well-characterized molecular function of XIRP2 that is important for its localization to the Z disc and its role in sarcomeric maintenance.

GO:0110053 regulation of actin filament organization

IEA
GO_REF:0000107

KEEP AS NON CORE

Summary: Regulation of actin filament organization is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. This is consistent with XIRP2's role in maintaining sarcomeric actin architecture, though it is somewhat redundant with GO:0007015 (actin filament organization) already annotated via IBA.

Reason: While XIRP2 does regulate actin filament organization, the direct involvement in actin filament organization (GO:0007015) is a more fundamental annotation. The regulatory aspect is secondary to the structural role.

GO:1903829 positive regulation of protein localization

IEA
GO_REF:0000107

MARK AS OVER ANNOTATED

Summary: Positive regulation of protein localization is transferred from mouse Xirp2 (Q4U4S6) via Ensembl Compara. This is a very broad term. XIRP2 may promote the localization of specific proteins (such as alpha-actinin or other sarcomeric components) to the Z disc, but the term lacks specificity about which proteins or which localization context.

Reason: The term is too broad to be informative. Without specifying which protein's localization is being regulated, this annotation provides limited biological insight. A more specific term would be preferred if the regulated protein can be identified.

Core Functions

XIRP2 binds F-actin filaments through its multiple Xin repeat domains (26 repeats), providing the molecular basis for its structural role at the Z disc and intercalated disc in striated muscle.

Molecular Function:

actin filament binding

Directly Involved In:

actin filament organization

Cellular Locations:

Z disc

Supporting Evidence:

file:BOVIN/E1BL04/E1BL04-uniprot.txt
Xin repeats bind F-actin

XIRP2 binds alpha-actinin at the Z disc, contributing to the structural integrity of the sarcomere and proper organization of the actin cytoskeleton in cardiac and skeletal muscle.

Molecular Function:

alpha-actinin binding

Cellular Locations:

Z disc

Supporting Evidence:

file:BOVIN/E1BL04/E1BL04-uniprot.txt
Belongs to the Xin family

ProtNLM2 External predictions

View prediction review YAML · E1BL04-protnlm-predictions-review.yaml · Review status: COMPLETE

The three broad predictions agree with the actin-associated function of XIRP2 and are less specific than existing annotations.

Source documents: genes/BOVIN/E1BL04/E1BL04-uniprot.txt · genes/BOVIN/E1BL04/E1BL04-goa.tsv · publications/PMID_15454575.md

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0030036 actin cytoskeleton organization GO_BP

LSP — Less precise than existing annotation Review score: 2/2

Prediction method: ProtNLM2 · Version: UniProt 2024_06 pilot

Review rationale: The target has Xin actin-binding repeats and an XIRP2 subfamily assignment. Experiments on Xin repeats, including human XIRP2 repeats, demonstrate actin binding and stabilization of the actin cytoskeleton (PMID:15454575), supporting transfer of the broad process to bovine XIRP2. The cached IBA annotation actin filament organization is more specific than actin cytoskeleton organization. The prediction is therefore supported but less precise.

Supporting Evidence:

file:BOVIN/E1BL04/E1BL04-uniprot.txt: "ID E1BL04_BOVIN Unreviewed; 3561 AA. ... DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central. ... DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central. ... DR InterPro; IPR012510; Actin-binding_Xin_repeat. ... DR PANTHER; PTHR22591:SF1; XIN ACTIN-BINDING REPEAT-CONTAINING PROTEIN 2; 1."
PMID:15454575: "Human XIRP2 contains 28 Xin repeats with properties identical to those of Xin"

GO:0030054 cell junction GO_CC

LSP — Less precise than existing annotation Review score: 2/2

Prediction method: ProtNLM2 · Version: UniProt 2024_06 pilot

Review rationale: The target is a Xin-repeat protein in the XIRP2 subfamily. Xin-family localization at muscle attachment sites and the repeat-mediated actin interactions provide a biological basis for junction association (PMID:15454575), consistent with the target focal-adhesion IBA. The cached annotations include focal adhesion and cell-cell junction, which specify junction types beyond the predicted cell junction. The broad prediction is supported but less precise.

Supporting Evidence:

file:BOVIN/E1BL04/E1BL04-uniprot.txt: "ID E1BL04_BOVIN Unreviewed; 3561 AA. ... DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central. ... DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central. ... DR InterPro; IPR012510; Actin-binding_Xin_repeat. ... DR PANTHER; PTHR22591:SF1; XIN ACTIN-BINDING REPEAT-CONTAINING PROTEIN 2; 1."
PMID:15454575: "Human XIRP2 contains 28 Xin repeats with properties identical to those of Xin"

GO:0003779 actin binding GO_MF

LSP — Less precise than existing annotation Review score: 2/2

Prediction method: ProtNLM2 · Version: UniProt 2024_06 pilot

Review rationale: Xin repeats are experimentally established actin-binding modules, and human XIRP2 repeats share this activity (PMID:15454575). The bovine target contains these repeats and has a curated IBA for actin filament binding. Actin binding is a broader molecular function than that existing annotation. It is biologically correct but adds no specificity.

Supporting Evidence:

file:BOVIN/E1BL04/E1BL04-uniprot.txt: "ID E1BL04_BOVIN Unreviewed; 3561 AA. ... DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central. ... DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central. ... DR InterPro; IPR012510; Actin-binding_Xin_repeat. ... DR PANTHER; PTHR22591:SF1; XIN ACTIN-BINDING REPEAT-CONTAINING PROTEIN 2; 1."
PMID:15454575: "Human XIRP2 contains 28 Xin repeats with properties identical to those of Xin"

Gene Description

Existing Annotations Review

Core Functions

XIRP2 binds F-actin filaments through its multiple Xin repeat domains (26 repeats), providing the molecular basis for its structural role at the Z disc and intercalated disc in striated muscle.

XIRP2 binds alpha-actinin at the Z disc, contributing to the structural integrity of the sarcomere and proper organization of the actin cytoskeleton in cardiac and skeletal muscle.

References

Suggested Questions for Experts

Suggested Experiments

External Prediction Reviews

ProtNLM2 External predictions

Deep Research

Falcon

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