CNNM4

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation placing CNNM4 as active in the plasma membrane, based on ortholog data from mouse and human CNNM family members as well as C. elegans and Drosophila orthologs. CNNM4 is a multi-pass transmembrane protein with four transmembrane helices in the CNNM domain (residues 178-358). The UniProt record confirms cell membrane localization. Human CNNM4 localizes to the basolateral plasma membrane of intestinal epithelial cells. Reason: Plasma membrane localization is well established for CNNM4 orthologs. The protein has a signal peptide and four transmembrane helices, consistent with an integral plasma membrane protein. The IBA annotation is supported by multiple ortholog sources including mouse and human CNNM4.
GO:0010960 magnesium ion homeostasis	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation for involvement in magnesium ion homeostasis, based on orthologs including mouse Cnnm4 and human CNNM4. CNNM4 is a magnesium efflux transporter, and its role in Mg2+ homeostasis is well established. Loss-of-function mutations in human CNNM4 cause Jalili syndrome with hypomagnesemia as a feature, demonstrating the protein's critical role in systemic magnesium homeostasis. Reason: Magnesium ion homeostasis is a core biological process for CNNM4. The protein directly mediates Mg2+ efflux, and its dysfunction leads to magnesium imbalance. This annotation is well supported by ortholog data.
GO:0015081 sodium ion transmembrane transporter activity	IBA GO_REF:0000033	UNDECIDED	Summary: Phylogenetic annotation for sodium ion transmembrane transporter activity based on mouse Cnnm4 ortholog data. Some studies have suggested that CNNM family members can mediate Na+ transport or that Mg2+ extrusion by CNNM proteins is coupled to Na+ influx. However, the primary and best-characterized transport activity of CNNM4 is magnesium transport. The sodium transport activity may reflect a coupled or secondary activity rather than an independent transport function. Reason: The sodium ion transport activity of CNNM4 is less well established than its magnesium transport function. While some evidence supports Na+-coupled Mg2+ transport by CNNM family members, the mechanistic details remain debated and the sodium transport may be secondary to the primary Mg2+ efflux function. Without access to the primary experimental literature on this specific activity, marking as UNDECIDED is appropriate.
GO:0015095 magnesium ion transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation for magnesium ion transmembrane transporter activity based on mouse Cnnm4 ortholog data. This is the primary characterized molecular function of CNNM4. The protein mediates Mg2+ efflux across the plasma membrane, and this activity is essential for intestinal magnesium absorption in mammals. Reason: Magnesium ion transmembrane transporter activity is the core molecular function of CNNM4. This is well supported by experimental evidence in orthologs showing that CNNM4 mediates cellular Mg2+ extrusion. The IBA annotation correctly captures the primary function of this protein.
GO:0015693 magnesium ion transport	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation for involvement in magnesium ion transport, based on mouse Cnnm4 ortholog data. CNNM4 directly mediates Mg2+ efflux, so involvement in magnesium ion transport is a direct consequence of its transporter activity. Reason: Magnesium ion transport is a core biological process for CNNM4, directly reflecting its molecular function as a Mg2+ transporter. Well supported by ortholog evidence.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for plasma membrane localization based on human ortholog Q6P4Q7 (CNNM4) via Ensembl, UniProt SubCell mapping, and PANTHER. Consistent with the IBA annotation above and the protein's domain architecture (signal peptide plus four transmembrane helices). Reason: Plasma membrane localization is well established for CNNM4. This IEA annotation is consistent with the IBA annotation and the protein's structural features as a multi-pass transmembrane protein with a signal peptide.
GO:0010960 magnesium ion homeostasis	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for magnesium ion homeostasis based on InterPro ACDP family (IPR045095) and PANTHER. This is consistent with the IBA annotation for the same term and reflects the well-established role of CNNM4 in Mg2+ homeostasis. Reason: Consistent with the IBA annotation and the known biology of CNNM4 as a magnesium efflux transporter critical for Mg2+ homeostasis. The InterPro ACDP family classification correctly predicts this function.
GO:0015693 magnesium ion transport	IEA GO_REF:0000118	ACCEPT	Summary: TreeGrafter-generated annotation for magnesium ion transport. Consistent with the IBA annotation for the same term and the core function of CNNM4 as a magnesium transporter. Reason: This TreeGrafter annotation is consistent with the IBA annotation and accurately reflects the core biological process of CNNM4. Magnesium ion transport is the primary physiological function of this protein.
GO:0016020 membrane	IEA GO_REF:0000104	ACCEPT	Summary: UniRule-based annotation for membrane localization. This is an extremely broad cellular component term. CNNM4 is indeed an integral membrane protein with four transmembrane helices, but more specific CC terms (plasma membrane, basolateral plasma membrane) are already annotated. Reason: While very broad, this annotation is not incorrect. CNNM4 is an integral membrane protein. More specific CC terms are already present (GO:0005886 plasma membrane, GO:0016323 basolateral plasma membrane).
GO:0022857 transmembrane transporter activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Combined IEA annotation for transmembrane transporter activity based on PANTHER and UniRule. This is a broad parent term of the more specific magnesium and sodium ion transmembrane transporter activities. CNNM4 is a transmembrane transporter, so this is accurate but uninformative given the more specific MF annotations. Reason: This is a valid but very general molecular function term. The more specific GO:0015095 (magnesium ion transmembrane transporter activity) better captures the core function. This broad term adds no information beyond what the specific terms already provide.
GO:0035725 sodium ion transmembrane transport	IEA GO_REF:0000108	UNDECIDED	Summary: Logical inference (IC) annotation for sodium ion transmembrane transport, derived from the sodium ion transmembrane transporter activity annotation (GO:0015081). This is a downstream inference -- if the protein enables sodium ion transmembrane transporter activity, it is logically involved in sodium ion transmembrane transport. Reason: This annotation is logically derived from GO:0015081 (sodium ion transmembrane transporter activity). Since the sodium transporter activity annotation itself is UNDECIDED due to limited evidence for CNNM4 sodium transport, this derived annotation inherits the same uncertainty.
GO:0055085 transmembrane transport	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Logical inference annotation for transmembrane transport, derived from the transmembrane transporter activity annotation (GO:0022857). This is a very broad biological process term. Reason: This is a valid but extremely general annotation logically derived from the transmembrane transporter activity MF annotation. The more specific magnesium ion transport annotation better captures the core process.
GO:1903830 magnesium ion transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: Logical inference annotation for magnesium ion transmembrane transport, derived from the magnesium ion transmembrane transporter activity annotation (GO:0015095). This is the specific biological process corresponding to the core molecular function of CNNM4. Reason: This annotation is logically derived from GO:0015095 (magnesium ion transmembrane transporter activity) which is well supported. Magnesium ion transmembrane transport is a core biological process for CNNM4 and this inference is correct.
GO:0015081 sodium ion transmembrane transporter activity	IEA GO_REF:0000120	UNDECIDED	Summary: Combined IEA annotation for sodium ion transmembrane transporter activity based on mouse ortholog Q69ZF7 (Cnnm4) via Ensembl and PANTHER. This is a duplicate source for the same function annotated by IBA. As with the IBA annotation, the sodium transport activity of CNNM4 is less well established than its magnesium transport function. Reason: Same uncertainty as the IBA annotation for this term. The sodium transport activity of CNNM4 remains debated and may reflect a coupled mechanism rather than an independent transport function. Without deep research literature access, marking as UNDECIDED is appropriate.
GO:0015095 magnesium ion transmembrane transporter activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for magnesium ion transmembrane transporter activity based on mouse ortholog Q69ZF7 (Cnnm4) via Ensembl and PANTHER. This is a duplicate source for the same function annotated by IBA. Reason: Consistent with the IBA annotation and the well-established core function of CNNM4 as a magnesium efflux transporter.
GO:0016323 basolateral plasma membrane	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara ortholog transfer annotation for basolateral plasma membrane localization, based on mouse ortholog Q69ZF7 (Cnnm4). Human and mouse CNNM4 localizes specifically to the basolateral plasma membrane of intestinal epithelial cells, where it mediates Mg2+ efflux into the interstitial space. This is the most specific and informative CC annotation for CNNM4. Reason: Basolateral plasma membrane localization is well established for mammalian CNNM4. The protein mediates vectorial Mg2+ transport from the apical to basolateral side of intestinal epithelial cells, and its basolateral localization is essential for this function. This is the most informative cellular component annotation and represents the primary site of CNNM4 activity.
GO:0030003 intracellular monoatomic cation homeostasis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara annotation for intracellular monoatomic cation homeostasis, based on human ortholog Q6P4Q7. CNNM4 mediates Mg2+ efflux and thereby contributes to intracellular cation homeostasis. This is a broader parent term of magnesium ion homeostasis. Reason: This is a valid but broad biological process annotation. CNNM4 contributes to intracellular cation homeostasis primarily through its Mg2+ efflux activity. The more specific GO:0010960 (magnesium ion homeostasis) better captures the core function.
GO:0032991 protein-containing complex	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara annotation indicating CNNM4 is part of a protein-containing complex, based on human ortholog Q6P4Q7. CNNM family members are known to form oligomeric complexes (likely dimers or trimers) and to interact with phosphatases of regenerating liver (PRL/PTP4A) family members. However, the term protein-containing complex is extremely broad and uninformative. Reason: While CNNM4 does form oligomeric complexes and interacts with PRL phosphatases, the term protein-containing complex is too broad to be informative. A more specific complex term would be needed to capture the meaningful biology. Keeping as non-core rather than removing since the protein does indeed participate in complexes.

GO Term

Evidence

Action

Reason

GO:0005886 plasma membrane

IBA
GO_REF:0000033

Summary: Phylogenetic annotation placing CNNM4 as active in the plasma membrane, based on ortholog data from mouse and human CNNM family members as well as C. elegans and Drosophila orthologs. CNNM4 is a multi-pass transmembrane protein with four transmembrane helices in the CNNM domain (residues 178-358). The UniProt record confirms cell membrane localization. Human CNNM4 localizes to the basolateral plasma membrane of intestinal epithelial cells.

Reason: Plasma membrane localization is well established for CNNM4 orthologs. The protein has a signal peptide and four transmembrane helices, consistent with an integral plasma membrane protein. The IBA annotation is supported by multiple ortholog sources including mouse and human CNNM4.

GO:0010960 magnesium ion homeostasis

IBA
GO_REF:0000033

Summary: Phylogenetic annotation for involvement in magnesium ion homeostasis, based on orthologs including mouse Cnnm4 and human CNNM4. CNNM4 is a magnesium efflux transporter, and its role in Mg2+ homeostasis is well established. Loss-of-function mutations in human CNNM4 cause Jalili syndrome with hypomagnesemia as a feature, demonstrating the protein's critical role in systemic magnesium homeostasis.

Reason: Magnesium ion homeostasis is a core biological process for CNNM4. The protein directly mediates Mg2+ efflux, and its dysfunction leads to magnesium imbalance. This annotation is well supported by ortholog data.

GO:0015081 sodium ion transmembrane transporter activity

IBA
GO_REF:0000033

UNDECIDED

Summary: Phylogenetic annotation for sodium ion transmembrane transporter activity based on mouse Cnnm4 ortholog data. Some studies have suggested that CNNM family members can mediate Na+ transport or that Mg2+ extrusion by CNNM proteins is coupled to Na+ influx. However, the primary and best-characterized transport activity of CNNM4 is magnesium transport. The sodium transport activity may reflect a coupled or secondary activity rather than an independent transport function.

Reason: The sodium ion transport activity of CNNM4 is less well established than its magnesium transport function. While some evidence supports Na+-coupled Mg2+ transport by CNNM family members, the mechanistic details remain debated and the sodium transport may be secondary to the primary Mg2+ efflux function. Without access to the primary experimental literature on this specific activity, marking as UNDECIDED is appropriate.

GO:0015095 magnesium ion transmembrane transporter activity

IBA
GO_REF:0000033

Summary: Phylogenetic annotation for magnesium ion transmembrane transporter activity based on mouse Cnnm4 ortholog data. This is the primary characterized molecular function of CNNM4. The protein mediates Mg2+ efflux across the plasma membrane, and this activity is essential for intestinal magnesium absorption in mammals.

Reason: Magnesium ion transmembrane transporter activity is the core molecular function of CNNM4. This is well supported by experimental evidence in orthologs showing that CNNM4 mediates cellular Mg2+ extrusion. The IBA annotation correctly captures the primary function of this protein.

GO:0015693 magnesium ion transport

IBA
GO_REF:0000033

Summary: Phylogenetic annotation for involvement in magnesium ion transport, based on mouse Cnnm4 ortholog data. CNNM4 directly mediates Mg2+ efflux, so involvement in magnesium ion transport is a direct consequence of its transporter activity.

Reason: Magnesium ion transport is a core biological process for CNNM4, directly reflecting its molecular function as a Mg2+ transporter. Well supported by ortholog evidence.

GO:0005886 plasma membrane

IEA
GO_REF:0000120

Summary: Combined IEA annotation for plasma membrane localization based on human ortholog Q6P4Q7 (CNNM4) via Ensembl, UniProt SubCell mapping, and PANTHER. Consistent with the IBA annotation above and the protein's domain architecture (signal peptide plus four transmembrane helices).

Reason: Plasma membrane localization is well established for CNNM4. This IEA annotation is consistent with the IBA annotation and the protein's structural features as a multi-pass transmembrane protein with a signal peptide.

GO:0010960 magnesium ion homeostasis

IEA
GO_REF:0000120

Summary: Combined IEA annotation for magnesium ion homeostasis based on InterPro ACDP family (IPR045095) and PANTHER. This is consistent with the IBA annotation for the same term and reflects the well-established role of CNNM4 in Mg2+ homeostasis.

Reason: Consistent with the IBA annotation and the known biology of CNNM4 as a magnesium efflux transporter critical for Mg2+ homeostasis. The InterPro ACDP family classification correctly predicts this function.

GO:0015693 magnesium ion transport

IEA
GO_REF:0000118

Summary: TreeGrafter-generated annotation for magnesium ion transport. Consistent with the IBA annotation for the same term and the core function of CNNM4 as a magnesium transporter.

Reason: This TreeGrafter annotation is consistent with the IBA annotation and accurately reflects the core biological process of CNNM4. Magnesium ion transport is the primary physiological function of this protein.

GO:0016020 membrane

IEA
GO_REF:0000104

Summary: UniRule-based annotation for membrane localization. This is an extremely broad cellular component term. CNNM4 is indeed an integral membrane protein with four transmembrane helices, but more specific CC terms (plasma membrane, basolateral plasma membrane) are already annotated.

Reason: While very broad, this annotation is not incorrect. CNNM4 is an integral membrane protein. More specific CC terms are already present (GO:0005886 plasma membrane, GO:0016323 basolateral plasma membrane).

GO:0022857 transmembrane transporter activity

IEA
GO_REF:0000120

KEEP AS NON CORE

Summary: Combined IEA annotation for transmembrane transporter activity based on PANTHER and UniRule. This is a broad parent term of the more specific magnesium and sodium ion transmembrane transporter activities. CNNM4 is a transmembrane transporter, so this is accurate but uninformative given the more specific MF annotations.

Reason: This is a valid but very general molecular function term. The more specific GO:0015095 (magnesium ion transmembrane transporter activity) better captures the core function. This broad term adds no information beyond what the specific terms already provide.

GO:0035725 sodium ion transmembrane transport

IEA
GO_REF:0000108

UNDECIDED

Summary: Logical inference (IC) annotation for sodium ion transmembrane transport, derived from the sodium ion transmembrane transporter activity annotation (GO:0015081). This is a downstream inference -- if the protein enables sodium ion transmembrane transporter activity, it is logically involved in sodium ion transmembrane transport.

Reason: This annotation is logically derived from GO:0015081 (sodium ion transmembrane transporter activity). Since the sodium transporter activity annotation itself is UNDECIDED due to limited evidence for CNNM4 sodium transport, this derived annotation inherits the same uncertainty.

GO:0055085 transmembrane transport

IEA
GO_REF:0000108

KEEP AS NON CORE

Summary: Logical inference annotation for transmembrane transport, derived from the transmembrane transporter activity annotation (GO:0022857). This is a very broad biological process term.

Reason: This is a valid but extremely general annotation logically derived from the transmembrane transporter activity MF annotation. The more specific magnesium ion transport annotation better captures the core process.

GO:1903830 magnesium ion transmembrane transport

IEA
GO_REF:0000108

Summary: Logical inference annotation for magnesium ion transmembrane transport, derived from the magnesium ion transmembrane transporter activity annotation (GO:0015095). This is the specific biological process corresponding to the core molecular function of CNNM4.

Reason: This annotation is logically derived from GO:0015095 (magnesium ion transmembrane transporter activity) which is well supported. Magnesium ion transmembrane transport is a core biological process for CNNM4 and this inference is correct.

GO:0015081 sodium ion transmembrane transporter activity

IEA
GO_REF:0000120

UNDECIDED

Summary: Combined IEA annotation for sodium ion transmembrane transporter activity based on mouse ortholog Q69ZF7 (Cnnm4) via Ensembl and PANTHER. This is a duplicate source for the same function annotated by IBA. As with the IBA annotation, the sodium transport activity of CNNM4 is less well established than its magnesium transport function.

Reason: Same uncertainty as the IBA annotation for this term. The sodium transport activity of CNNM4 remains debated and may reflect a coupled mechanism rather than an independent transport function. Without deep research literature access, marking as UNDECIDED is appropriate.

GO:0015095 magnesium ion transmembrane transporter activity

IEA
GO_REF:0000120

Summary: Combined IEA annotation for magnesium ion transmembrane transporter activity based on mouse ortholog Q69ZF7 (Cnnm4) via Ensembl and PANTHER. This is a duplicate source for the same function annotated by IBA.

Reason: Consistent with the IBA annotation and the well-established core function of CNNM4 as a magnesium efflux transporter.

GO:0016323 basolateral plasma membrane

IEA
GO_REF:0000107

Summary: Ensembl Compara ortholog transfer annotation for basolateral plasma membrane localization, based on mouse ortholog Q69ZF7 (Cnnm4). Human and mouse CNNM4 localizes specifically to the basolateral plasma membrane of intestinal epithelial cells, where it mediates Mg2+ efflux into the interstitial space. This is the most specific and informative CC annotation for CNNM4.

Reason: Basolateral plasma membrane localization is well established for mammalian CNNM4. The protein mediates vectorial Mg2+ transport from the apical to basolateral side of intestinal epithelial cells, and its basolateral localization is essential for this function. This is the most informative cellular component annotation and represents the primary site of CNNM4 activity.

GO:0030003 intracellular monoatomic cation homeostasis

IEA
GO_REF:0000107

KEEP AS NON CORE

Summary: Ensembl Compara annotation for intracellular monoatomic cation homeostasis, based on human ortholog Q6P4Q7. CNNM4 mediates Mg2+ efflux and thereby contributes to intracellular cation homeostasis. This is a broader parent term of magnesium ion homeostasis.

Reason: This is a valid but broad biological process annotation. CNNM4 contributes to intracellular cation homeostasis primarily through its Mg2+ efflux activity. The more specific GO:0010960 (magnesium ion homeostasis) better captures the core function.

GO:0032991 protein-containing complex

IEA
GO_REF:0000107

KEEP AS NON CORE

Summary: Ensembl Compara annotation indicating CNNM4 is part of a protein-containing complex, based on human ortholog Q6P4Q7. CNNM family members are known to form oligomeric complexes (likely dimers or trimers) and to interact with phosphatases of regenerating liver (PRL/PTP4A) family members. However, the term protein-containing complex is extremely broad and uninformative.

Reason: While CNNM4 does form oligomeric complexes and interacts with PRL phosphatases, the term protein-containing complex is too broad to be informative. A more specific complex term would be needed to capture the meaningful biology. Keeping as non-core rather than removing since the protein does indeed participate in complexes.

Core Functions

CNNM4 is a magnesium efflux transporter that mediates Mg2+ extrusion across the basolateral plasma membrane of epithelial cells. The protein contains a CNNM transmembrane domain with four transmembrane helices that forms the transport pathway, and a cytoplasmic CBS domain pair that binds Mg2+-ATP to regulate transport activity. CNNM4 localizes to the basolateral membrane where it functions in transcellular magnesium absorption, particularly in intestinal epithelium. Loss of function causes Jalili syndrome (cone-rod dystrophy with amelogenesis imperfecta) in humans, highlighting its essential role in magnesium homeostasis for eye and tooth development. CNNM4 forms oligomeric complexes and interacts with PRL (PTP4A) family phosphatases which regulate its activity.

Molecular Function:

magnesium ion transmembrane transporter activity

Directly Involved In:

magnesium ion transmembrane transport magnesium ion homeostasis

Cellular Locations:

basolateral plasma membrane

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · A0A8I3PI07-protnlm-predictions-review.yaml · Review status: COMPLETE

The CNNM4-family assignment supports membrane-associated ion transport. All three predictions are broader than existing localization or transport annotations.

Source documents: genes/CANLF/A0A8I3PI07/A0A8I3PI07-uniprot.txt · genes/CANLF/A0A8I3PI07/A0A8I3PI07-goa.tsv · publications/PMID_24339795.md

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

GO:0005886 plasma membrane 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 assigned to the CNNM4 subfamily and contains the CNNM transmembrane region and CBS domain. Mouse CNNM4 experiments show basolateral localization in transporting epithelia (PMID:24339795), supporting the conserved membrane localization inference for the canine protein. Plasma membrane is already annotated, and basolateral plasma membrane is an existing, more specific localization. The prediction is supported but less precise.

Supporting Evidence:

file:CANLF/A0A8I3PI07/A0A8I3PI07-uniprot.txt: "ID A0A8I3PI07_CANLF Unreviewed; 796 AA. ... DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. ... DR GO; GO:0015095; F:magnesium ion transmembrane transporter activity; IBA:GO_Central. ... DR GO; GO:0015081; F:sodium ion transmembrane transporter activity; IBA:GO_Central. ... DR GO; GO:0010960; P:magnesium ion homeostasis; IBA:GO_Central. ... DR GO; GO:0015693; P:magnesium ion transport; IBA:GO_Central. ... DR InterPro; IPR002550; CNNM. ... DR PANTHER; PTHR12064:SF26; METAL TRANSPORTER CNNM4; 1. ... FT SIGNAL 1..37 ... FT TRANSMEM 182..206 ... FT TRANSMEM 240..261 ... FT TRANSMEM 267..286 ... FT TRANSMEM 298..318 ... FT DOMAIN 178..358 ... FT /note="CNNM transmembrane" ... FT DOMAIN 445..511 ... FT /note="CBS""
PMID:24339795: "CNNM4 localizes to the basolateral membrane"

GO:0022857 transmembrane transporter activity GO_MF

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

Prediction method: ProtNLM2 · Version: UniProt 2024_06 pilot

Review rationale: The CNNM4 subfamily and membrane-spanning architecture support ion transport rather than an arbitrary membrane role. Mouse CNNM4 expression and knockout experiments establish a role in magnesium extrusion and epithelial magnesium transport (PMID:24339795). The target already has curated IBA magnesium ion transmembrane transporter activity, which is more specific than the predicted generic transmembrane transporter activity. The broad prediction is supported without resolving the detailed transport mechanism.

Supporting Evidence:

file:CANLF/A0A8I3PI07/A0A8I3PI07-uniprot.txt: "ID A0A8I3PI07_CANLF Unreviewed; 796 AA. ... DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. ... DR GO; GO:0015095; F:magnesium ion transmembrane transporter activity; IBA:GO_Central. ... DR GO; GO:0015081; F:sodium ion transmembrane transporter activity; IBA:GO_Central. ... DR GO; GO:0010960; P:magnesium ion homeostasis; IBA:GO_Central. ... DR GO; GO:0015693; P:magnesium ion transport; IBA:GO_Central. ... DR InterPro; IPR002550; CNNM. ... DR PANTHER; PTHR12064:SF26; METAL TRANSPORTER CNNM4; 1. ... FT SIGNAL 1..37 ... FT TRANSMEM 182..206 ... FT TRANSMEM 240..261 ... FT TRANSMEM 267..286 ... FT TRANSMEM 298..318 ... FT DOMAIN 178..358 ... FT /note="CNNM transmembrane" ... FT DOMAIN 445..511 ... FT /note="CBS""
PMID:24339795: "CNNM4 localizes to the basolateral membrane"

GO:0006811 monoatomic ion transport GO_BP

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

Prediction method: ProtNLM2 · Version: UniProt 2024_06 pilot

Review rationale: CNNM4-dependent magnesium transport is supported by mouse epithelial experiments (PMID:24339795) and by the target CNNM4 subfamily and membrane architecture. The target has a curated IBA annotation for magnesium ion transport. Ion transport is a broader process that discards the established ion specificity. The prediction is therefore supported but less precise.

Supporting Evidence:

file:CANLF/A0A8I3PI07/A0A8I3PI07-uniprot.txt: "ID A0A8I3PI07_CANLF Unreviewed; 796 AA. ... DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. ... DR GO; GO:0015095; F:magnesium ion transmembrane transporter activity; IBA:GO_Central. ... DR GO; GO:0015081; F:sodium ion transmembrane transporter activity; IBA:GO_Central. ... DR GO; GO:0010960; P:magnesium ion homeostasis; IBA:GO_Central. ... DR GO; GO:0015693; P:magnesium ion transport; IBA:GO_Central. ... DR InterPro; IPR002550; CNNM. ... DR PANTHER; PTHR12064:SF26; METAL TRANSPORTER CNNM4; 1. ... FT SIGNAL 1..37 ... FT TRANSMEM 182..206 ... FT TRANSMEM 240..261 ... FT TRANSMEM 267..286 ... FT TRANSMEM 298..318 ... FT DOMAIN 178..358 ... FT /note="CNNM transmembrane" ... FT DOMAIN 445..511 ... FT /note="CBS""
PMID:24339795: "CNNM4 localizes to the basolateral membrane"

Gene Description

Existing Annotations Review

Core Functions

References

External Prediction Reviews

ProtNLM2 External predictions

Deep Research

Falcon

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