SLC35A1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000139 Golgi membrane	IBA GO_REF:0000033	ACCEPT	Summary: Golgi membrane is the correct site of action for this multipass Golgi nucleotide-sugar transporter. The phylogenetic (IBA) call is consistent with the experimentally verified Golgi localization and with the UniProt subcellular location. Reason: SLC35A1 is a multipass integral Golgi-membrane protein; the antiport activity is active in the Golgi membrane. Supported by UniProt SUBCELLULAR LOCATION and by experimental IF. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0005456 CMP-N-acetylneuraminate transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: This is the core molecular function of SLC35A1. The phylogenetic (IBA) transporter activity call matches the experimentally established CMP-sialic acid transport activity. Reason: CMP-N-acetylneuraminate (CMP-sialic acid) transmembrane transporter activity is the defining, experimentally supported function of the gene. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt Transports CMP-sialic acid from the cytosol into the Golgi
GO:0015782 CMP-N-acetylneuraminate transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Correct core biological-process term describing the transport process this protein carries out; consistent with the IDA annotation from PMID:15576474. Reason: The gene mediates CMP-N-acetylneuraminate transmembrane transport into the Golgi; supported experimentally. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt Transports CMP-sialic acid from the cytosol into the Golgi
GO:0000139 Golgi membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (combined IEA) Golgi membrane localization, redundant with and consistent with the experimentally supported location. Reason: Correct localization for an integral Golgi-membrane transporter. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	ACCEPT	Summary: Electronic Subcellular-Location mapping to Golgi apparatus; consistent with the experimental Golgi localization but less specific than Golgi membrane. Reason: The protein resides in the Golgi apparatus; correct though a compartment-level (rather than membrane-level) term. Supporting Evidence: PMID:23873973 normal Golgi localization
GO:0006864 pyrimidine nucleotide transport	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Over-general inter-ontology inference. SLC35A1 does transport CMP (a pyrimidine nucleotide) as the antiport counter-substrate, so the term is not wrong, but it is a broad parent of the specific CMP-sialic acid transport function and adds little. Reason: True at a high level (CMP is the exported counter-ion) but far more general than the specific, experimentally supported CMP-N-acetylneuraminate transport; represents automated over-propagation rather than the gene's characterized role.
GO:0015165 pyrimidine nucleotide-sugar transmembrane transporter activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Family-level InterPro-to-GO inference. CMP-sialic acid is a pyrimidine nucleotide-sugar, so the parent term is technically consistent, but the specific child term GO:0005456 is the appropriate annotation. Reason: Correct superclass of the specific function but less informative; automated InterPro family assignment. The specific CMP-N-acetylneuraminate transporter term is preferred.
GO:0015748 organophosphate ester transport	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Very broad ARBA electronic inference. Nucleotide sugars are organophosphate esters, so the term is a distant, uninformative parent of the actual function. Reason: Over-general machine-learning (ARBA) annotation; not wrong in the broadest sense but uninformative relative to the specific CMP-sialic acid transport function.
GO:0015931 nucleobase-containing compound transport	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Broad ARBA electronic inference; a high-level parent of the CMP/CMP-sialic acid transport function. Reason: Over-general automated annotation; the specific CMP-N-acetylneuraminate transport term is the appropriate level.
GO:0016020 membrane	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Generic membrane localization from combined IEA methods; correct but far less specific than the Golgi-membrane annotation. Reason: Uninformative root-level cellular-component term superseded by the specific Golgi membrane annotation.
GO:0090481 pyrimidine nucleotide-sugar transmembrane transport	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro family-level process inference. CMP-sialic acid is a pyrimidine nucleotide-sugar, so this is a correct parent of the specific transport process, but less informative. Reason: Correct superclass but over-general; the specific CMP-N-acetylneuraminate transmembrane transport term is preferred.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a single high-throughput binary interactome screen (HuRI, Luck et al. 2020), the source of 35 IntAct IPI calls to a heterogeneous set of membrane proteins. These systematic Y2H interactors have no established functional relationship to CMP-sialic acid transport and the term is uninformative. Reason: Uninformative bare protein-binding term derived from a proteome-scale binary interactome map; no specific, functionally meaningful partner is established. Retained per policy (IPI not removed) but flagged as over-annotation. Supporting Evidence: PMID:32296183 we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'
GO:0005456 CMP-N-acetylneuraminate transmembrane transporter activity	IEA GO_REF:0000107	ACCEPT	Summary: Electronic transfer (Ensembl Compara) of the mouse ortholog's experimentally verified CMP-sialic acid transporter activity; consistent with the core function. Reason: Correct core molecular function, supported by orthology and by direct human experimental evidence. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt Transports CMP-sialic acid from the cytosol into the Golgi
GO:0015297 antiporter activity	IEA GO_REF:0000107	ACCEPT	Summary: SLC35A1 is a CMP-sialic-acid/CMP antiporter; this electronic transfer of antiporter activity from the mouse ortholog is consistent with the UniProt-described exchange mechanism. Reason: The protein exchanges CMP-sialic acid for CMP (also AMP/UMP), i.e. it is an antiporter. Supported experimentally. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt functioning as an antiporter that exchanges CMP-sialic acid for CMP
GO:0015782 CMP-N-acetylneuraminate transmembrane transport	IEA GO_REF:0000107	ACCEPT	Summary: Electronic transfer of the core CMP-sialic acid transport process from the mouse ortholog; consistent with the human IDA annotation. Reason: Correct core biological process; redundant with experimentally supported annotations. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt Transports CMP-sialic acid from the cytosol into the Golgi
GO:0006493 protein O-linked glycosylation	TAS Reactome:R-HSA-8931838	KEEP AS NON CORE	Summary: Reactome (DAG1 glycosylations pathway) links SLC35A1 to O-linked glycosylation because the transporter supplies CMP-sialic acid (and CDP-ribitol) needed to build O-mannosyl/matriglycan structures. SLC35A1 is a transporter, not a glycosyltransferase, so this is a downstream process it supports rather than a direct activity. Reason: SLC35A1 enables protein O-linked glycosylation indirectly by providing the sugar-nucleotide donor; it is a valid pathway participation but not the gene's core (transport) function.
GO:0015218 pyrimidine nucleotide transmembrane transporter activity	TAS Reactome:R-HSA-9940804	KEEP AS NON CORE	Summary: Reactome annotates this term for the reaction "SLC35A1,4 import CDP-ribitol", reflecting the By-similarity CDP-ribitol/CDP exchange activity that contributes CDP-ribitol for matriglycan synthesis. CDP-ribitol/CDP are pyrimidine nucleotides, so the term fits this secondary activity. Reason: Captures a real secondary (CDP-ribitol import) activity via a general pyrimidine-nucleotide transporter term; a genuine but non-core function relative to CMP-sialic acid transport. Supporting Evidence: Reactome:R-HSA-9940804 transport CDP-ribitol from cytosol into the Golgi, in exchange for one molecule of CDP
GO:0000139 Golgi membrane	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer (from mouse Q61420) of Golgi-membrane localization; consistent with experimental data. Reason: Correct localization for the integral Golgi-membrane transporter. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0005794 Golgi apparatus	EXP PMID:23873973 Intellectual disability and bleeding diathesis due to defici...	ACCEPT	Summary: Experimental (functional analysis of the p.Q101H CDG2F variant) confirming normal Golgi localization of SLC35A1. Directly supports Golgi apparatus localization. Reason: Experimentally demonstrated Golgi localization; the disease variant retained Golgi localization while losing transport activity. Supporting Evidence: PMID:23873973 Functional analysis of mutant SLC35A1 showed normal Golgi localization
GO:0015782 CMP-N-acetylneuraminate transmembrane transport	IDA PMID:15576474 Genetic complementation reveals a novel human congenital dis...	ACCEPT	Summary: Direct experimental evidence (genetic complementation of Lec2 CHO cells) that SLC35A1 mediates CMP-sialic acid transport into the Golgi; the core biological process, and the basis for defining CDG2F. Reason: IDA supporting the central transport process; wild-type transcript restored the sialylated phenotype in transporter-deficient cells. Supporting Evidence: PMID:15576474 full restoration of the sialylated phenotype was obtained in the Lec2 cells transfected with the corresponding human wild-type transcript
GO:0005456 CMP-N-acetylneuraminate transmembrane transporter activity	TAS Reactome:R-HSA-5651942	ACCEPT	Summary: Reactome ("Defective SLC35A1 does not exchange CMP-Neu5Ac for CMP") asserts the core CMP-sialic acid transporter activity in the disease context. Consistent with the core function. Reason: Correct core molecular function; TAS from Reactome. Supporting Evidence: Reactome:R-HSA-5651942 SLC35A1 encodes the CMP-sialic acid transporter which mediates the antiport of CMP-sialic acid (CMP-Neu5Ac) into the Golgi lumen in exchange for CMP
GO:0005456 CMP-N-acetylneuraminate transmembrane transporter activity	TAS Reactome:R-HSA-727807	ACCEPT	Summary: Reactome ("SLC35A1 exchanges CMP-Neu5Ac for CMP") asserts the core CMP-sialic acid transporter activity. Consistent with the core function. Reason: Correct core molecular function; TAS from Reactome. Supporting Evidence: Reactome:R-HSA-727807 SLC35A1 encodes the CMP-sialic acid transporter which mediates the antiport of CMP-sialic acid (CMP-Neu5Ac) into the Golgi lumen in exchange for CMP
GO:0005456 CMP-N-acetylneuraminate transmembrane transporter activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the core CMP-sialic acid transporter activity from the mouse ortholog; consistent with human experimental data. Reason: Correct core molecular function. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt Transports CMP-sialic acid from the cytosol into the Golgi
GO:0015297 antiporter activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of antiporter activity; consistent with the CMP-sialic acid/CMP exchange mechanism described in UniProt. Reason: The protein is an antiporter (CMP-sialic acid for CMP/AMP/UMP); supported experimentally. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt functioning as an antiporter that exchanges CMP-sialic acid for CMP
GO:0015782 CMP-N-acetylneuraminate transmembrane transport	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the core transport process; consistent with the human IDA annotation. Reason: Correct core biological process. Supporting Evidence: file:human/SLC35A1/SLC35A1-uniprot.txt Transports CMP-sialic acid from the cytosol into the Golgi
GO:0016020 membrane	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Generic membrane localization by sequence similarity; correct but superseded by the specific Golgi-membrane annotation. Reason: Root-level cellular-component term; uninformative given the specific Golgi membrane localization.
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-5651942	ACCEPT	Summary: Reactome Golgi-membrane localization in the CDG2F disease-reaction context; consistent with the experimentally supported location. Reason: Correct localization for this integral Golgi-membrane transporter. Supporting Evidence: Reactome:R-HSA-5651942 into the Golgi lumen in exchange for CMP
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-727807	ACCEPT	Summary: Reactome Golgi-membrane localization for the CMP-Neu5Ac/CMP exchange reaction; consistent with the experimentally supported location. Reason: Correct localization for this integral Golgi-membrane transporter. Supporting Evidence: Reactome:R-HSA-727807 into the Golgi lumen in exchange for CMP
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-9940804	ACCEPT	Summary: Reactome Golgi-membrane localization for the CDP-ribitol import reaction; consistent with the Golgi location. Reason: Correct localization; the CDP-ribitol import reaction likewise occurs at the Golgi membrane. Supporting Evidence: Reactome:R-HSA-9940804 transport CDP-ribitol from cytosol into the Golgi
GO:0005456 CMP-N-acetylneuraminate transmembrane transporter activity	TAS PMID:9644260 Functional expression of human golgi CMP-sialic acid transpo...	ACCEPT	Summary: Legacy TAS (ProtInc) from the 1998 functional-expression paper that established hCST as the human CMP-sialic acid transporter by correcting the Lec2 CHO transporter-deficient phenotype. Supports the core molecular function. Reason: Correct core molecular function; the paper demonstrated recovery of CMP-sialic acid transporting ability by microsomes from transformants. Supporting Evidence: PMID:9644260 recovery of CMP-sialic acid transporting ability by microsomal vesicles prepared from them
GO:0005794 Golgi apparatus	TAS PMID:9644260 Functional expression of human golgi CMP-sialic acid transpo...	ACCEPT	Summary: TAS Golgi localization from the 1998 paper, which demonstrated Golgi-membrane localization of hCST by immunofluorescence. Consistent with experimental data. Reason: Correct Golgi localization; demonstrated by immunofluorescence microscopy. Supporting Evidence: PMID:9644260 subcellular localization of the hCST protein in the Golgi membrane was demonstrated by immunofluorescence
GO:0005886 plasma membrane	TAS PMID:9644260 Functional expression of human golgi CMP-sialic acid transpo...	MARK AS OVER ANNOTATED	Summary: This legacy ProtInc TAS assigns plasma-membrane localization, but the cited 1998 paper actually localizes hCST to the Golgi membrane (it only uses plasma-membrane-selective permeabilization as a technique to show the C-terminus faces the cytosol). SLC35A1 is a Golgi transporter, not a plasma-membrane protein; UniProt lists only Golgi. This is not supported. Reason: The plasma-membrane call is unsupported by the cited paper (which shows Golgi localization) and inconsistent with UniProt; likely a mis-annotation, but retained per TAS policy rather than removed. Best treated as an over-annotation to be dropped. Supporting Evidence: PMID:9644260 subcellular localization of the hCST protein in the Golgi membrane was demonstrated by immunofluorescence
GO:0005975 carbohydrate metabolic process	TAS PMID:9644260 Functional expression of human golgi CMP-sialic acid transpo...	KEEP AS NON CORE	Summary: Broad legacy TAS process term. SLC35A1 participates in glycan biosynthesis only by supplying the sialic-acid donor; the term is a very general, non-core process description. Reason: The gene contributes to carbohydrate/glycan metabolism as a substrate supplier, but this broad term is not the core (transport) function.
GO:0015782 CMP-N-acetylneuraminate transmembrane transport	TAS PMID:9644260 Functional expression of human golgi CMP-sialic acid transpo...	ACCEPT	Summary: Legacy TAS for the core CMP-sialic acid transport process, from the paper that established hCST function. Consistent with the IDA/IBA annotations. Reason: Correct core biological process; well supported. Supporting Evidence: PMID:9644260 recovery of CMP-sialic acid transporting ability by microsomal vesicles prepared from them
GO:0036211 protein modification process	TAS PMID:9644260 Functional expression of human golgi CMP-sialic acid transpo...	KEEP AS NON CORE	Summary: Very broad legacy TAS term. SLC35A1 enables protein glycosylation (a protein modification) only indirectly by supplying CMP-sialic acid; it is not itself a protein-modifying enzyme. Reason: Downstream, indirect participation via substrate supply; broad and non-core relative to the transport function.

Gene Description

Existing Annotations Review

Core Functions

CMP-sialic acid (CMP-N-acetylneuraminate) / CMP antiporter that imports CMP-sialic acid from the cytosol into the Golgi lumen in exchange for CMP, supplying the activated sialic-acid donor for Golgi sialyltransferases.

Acts mechanistically as an antiporter (solute:solute exchanger), coupling import of CMP-sialic acid to export of CMP (and, less efficiently, AMP or UMP) across the Golgi membrane.

References

📚 Additional Documentation

Notes

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