SLC35B2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	MODIFY	Summary: SLC35B2 is a Golgi-membrane transporter, not an ER protein. This IBA location was over-propagated across the nucleotide-sugar-transporter family tree, some members of which reside in the ER. The experimentally established compartment for SLC35B2 is the Golgi apparatus membrane. Reason: Wrong compartment for this gene; direct experimental evidence (PMID:12716889, PMID:35325049) and UniProt place SLC35B2 at the Golgi membrane. Replace the ER membrane term with the Golgi membrane term. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Proposed replacements: Golgi membrane Supporting Evidence: file:human/SLC35B2/SLC35B2-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0055085 transmembrane transport	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: A correct but very general parent process. SLC35B2 is a transmembrane transporter, so this is not wrong, but it is subsumed by the specific PAPS transport terms that capture the actual function. Reason: True but generic; retained as background rather than a core function, since the specific PAPS (transmembrane) transport terms are the informative annotations.
GO:0046963 3'-phosphoadenosine 5'-phosphosulfate transport	IBA GO_REF:0000033	ACCEPT	Summary: Correct core biological process. SLC35B2 mediates PAPS transport across the Golgi membrane, consistent with the original functional characterization. Supporting Evidence: PMID:12716889 significantly increased the transport of PAPS
GO:0000139 Golgi membrane	IBA GO_REF:0000033	ACCEPT	Summary: Correct core cellular component. SLC35B2 is an integral Golgi-membrane protein, confirmed experimentally. Supporting Evidence: file:human/SLC35B2/SLC35B2-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0046964 3'-phosphoadenosine 5'-phosphosulfate transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Correct core molecular function. This is the defining activity of SLC35B2: it moves PAPS across the Golgi membrane, functioning as a PAPS:PAP antiporter. Supporting Evidence: file:human/SLC35B2/SLC35B2-uniprot.txt 3'-phosphoadenylyl sulfate:adenosine
GO:0000139 Golgi membrane	IEA GO_REF:0000044	ACCEPT	Summary: Correct core cellular component, derived from the UniProt Subcellular Location vocabulary mapping. This is the gene's own correct location, not an over-annotation. Supporting Evidence: file:human/SLC35B2/SLC35B2-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0055085 transmembrane transport	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct but generic InterPro-derived process, redundant with the specific PAPS transmembrane transport annotations. Reason: True generic parent; the specific PAPS transport terms carry the informative function.
GO:1902559 3'-phospho-5'-adenylyl sulfate transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: Correct specific core biological process. "3'-phospho-5'-adenylyl sulfate" is a synonym of PAPS, so this precisely captures the PAPS transmembrane transport mediated by SLC35B2. Supporting Evidence: PMID:12716889 significantly increased the transport of PAPS
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 large-scale reference-interactome (HuRI) screen. The recorded partners (e.g. GOLM1, AQP6, CREB3L1, ERGIC3, TMEM248) do not define a specific molecular function for SLC35B2 and no adapter/scaffold role is established. Reason: Uninformative generic MF from a high-throughput interactome; provides no specific functional insight beyond the transporter activity.
GO:0005515 protein binding	IPI PMID:40355756 The solute carrier superfamily interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from the large-scale SLC-superfamily AP-MS interactome, mapping the SLC35B2-GOLM1 interaction. As above, this generic term adds no specific molecular-function information. Reason: Uninformative generic MF from a high-throughput interactome; no specific function established.
GO:1902558 5'-adenylyl sulfate transmembrane transport	TAS Reactome:R-HSA-741449	MODIFY	Summary: This term is the wrong metabolite. GO:1902558 is transport of 5'-adenylyl sulfate (adenosine 5'-phosphosulfate, APS), which is the biosynthetic PRECURSOR of PAPS (APS + ATP -> PAPS), not the substrate of this Golgi antiporter. SLC35B2 transports PAPS, and the cited Reactome reaction itself describes PAPS:PAP exchange. The annotation should use the PAPS transmembrane transport term. Reason: APS (5'-adenylyl sulfate) is not the SLC35B2 substrate; PAPS is. Replace with the PAPS transmembrane transport term, which is what the Reactome reaction actually describes. Proposed replacements: 3'-phospho-5'-adenylyl sulfate transmembrane transport Supporting Evidence: Reactome:R-HSA-741449 Both proteins can transport PAPS from the cytosol to the Golgi lumen, simultaneously antiporting PAP back to cytosol
GO:0000139 Golgi membrane	EXP PMID:35325049 Biallelic variants in SLC35B2 cause a novel chondrodysplasia...	ACCEPT	Summary: Correct core cellular component, experimentally supported. Guasto et al. confirmed Golgi localization of SLC35B2 and showed the HLD26 variant causes partial mislocalization away from the Golgi. Supporting Evidence: file:human/SLC35B2/SLC35B2-uniprot.txt only partial
GO:0005794 Golgi apparatus	IDA PMID:35325049 Biallelic variants in SLC35B2 cause a novel chondrodysplasia...	ACCEPT	Summary: Correct core cellular component (Golgi apparatus), experimentally supported by immunolocalization in patient/control fibroblasts. Supporting Evidence: file:human/SLC35B2/SLC35B2-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0050650 chondroitin sulfate proteoglycan biosynthetic process	IMP PMID:35325049 Biallelic variants in SLC35B2 cause a novel chondrodysplasia...	KEEP AS NON CORE	Summary: A genuine downstream biological role: by importing PAPS into the Golgi, SLC35B2 supplies the sulfonate donor for proteoglycan sulfotransferases, and loss of function impairs chondroitin-sulfate/proteoglycan sulfation in patient fibroblasts. This is an indirect, downstream consequence of the transporter activity rather than the direct core molecular function, so it is retained as non-core. Reason: Experimentally supported (IMP) and biologically real, but downstream of the core PAPS-transport function; SLC35B2 does not itself catalyze proteoglycan biosynthesis. Supporting Evidence: PMID:35325049 we detected proteoglycan sulphation impairment in SLC35B2 patient
GO:0000139 Golgi membrane	IDA PMID:12716889 Molecular cloning and identification of 3'-phosphoadenosine ...	ACCEPT	Summary: Correct core cellular component, from the original characterization: transiently expressed PAPST1 localized to the Golgi membrane in SW480 cells. Supporting Evidence: PMID:12716889 The transient expression of PAPST1 in SW480 cells showed
GO:0046964 3'-phosphoadenosine 5'-phosphosulfate transmembrane transporter activity	TAS Reactome:R-HSA-741449	ACCEPT	Summary: Correct core molecular function, curated by Reactome, matching the experimentally demonstrated PAPS transporter activity. Supporting Evidence: Reactome:R-HSA-741449 Both proteins can transport PAPS from the cytosol to the Golgi lumen, simultaneously antiporting PAP back to cytosol
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-741449	ACCEPT	Summary: Correct core cellular component, curated by Reactome, consistent with all other evidence for Golgi-membrane localization. Supporting Evidence: file:human/SLC35B2/SLC35B2-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	HMP PMID:12761501 Large-scale identification and characterization of human gen...	MARK AS OVER ANNOTATED	Summary: This annotation derives from a large-scale overexpression cDNA reporter screen in HEK293 cells that flagged this clone as an NF-kappaB/MAPK activator (the origin of UniProt's legacy "Putative MAPK-activating protein PM15" / "Putative NF-kappa-B-activating protein 48" names). The evidence is high-throughput (HMP) forced overexpression, not a demonstrated physiological role, and is mechanistically unrelated to the well-established Golgi PAPS-transporter function. It is best treated as an over-annotation / screen artifact. Reason: Result of a high-throughput overexpression screen with no established mechanistic link to SLC35B2's transporter function; likely an artifact of forced overexpression. Supporting Evidence: PMID:12761501 we identified 299
GO:0005794 Golgi apparatus	IDA PMID:12716889 Molecular cloning and identification of 3'-phosphoadenosine ...	ACCEPT	Summary: Correct core cellular component (Golgi apparatus), from the original localization of transiently expressed PAPST1. Supporting Evidence: PMID:12716889 The transient expression of PAPST1 in SW480 cells showed
GO:0016020 membrane	NAS PMID:12716889 Molecular cloning and identification of 3'-phosphoadenosine ...	MARK AS OVER ANNOTATED	Summary: "membrane" is an uninformative, high-level cellular component subsumed by the specific Golgi-membrane annotation. It adds no localization information beyond what GO:0000139 already provides. Reason: Overly general CC; the specific Golgi membrane term is the appropriate annotation.
GO:0016020 membrane	IDA PMID:12716889 Molecular cloning and identification of 3'-phosphoadenosine ...	MARK AS OVER ANNOTATED	Summary: Same uninformative high-level "membrane" component as above (here with IDA evidence). It is not incorrect but is fully subsumed by the specific Golgi-membrane annotation and provides no additional information. Reason: Overly general CC subsumed by GO:0000139 (Golgi membrane); redundant/uninformative.
GO:0046963 3'-phosphoadenosine 5'-phosphosulfate transport	IDA PMID:12716889 Molecular cloning and identification of 3'-phosphoadenosine ...	ACCEPT	Summary: Correct core biological process, experimentally demonstrated: expression of PAPST1 significantly increased transport of PAPS into the Golgi membrane fraction. Supporting Evidence: PMID:12716889 significantly increased the transport of PAPS
GO:0046964 3'-phosphoadenosine 5'-phosphosulfate transmembrane transporter activity	IDA PMID:12716889 Molecular cloning and identification of 3'-phosphoadenosine ...	ACCEPT	Summary: Correct core molecular function, directly demonstrated. This is the primary experimental basis for SLC35B2 as the Golgi PAPS transporter, with measured PAPS transport activity (KM = 0.8 uM for PAPS). Supporting Evidence: PMID:12716889 significantly increased the transport of PAPS file:human/SLC35B2/SLC35B2-uniprot.txt KM=0.8 uM for 3'-phosphoadenylyl sulfate

Gene Description

Existing Annotations Review

Core Functions

Golgi-membrane PAPS:PAP antiporter that imports cytosolic 3'-phosphoadenosine 5'-phosphosulfate (PAPS) into the Golgi lumen in exchange for the product adenosine 3',5'-bisphosphate (PAP), supplying the sulfonate donor for Golgi sulfation.

References

📚 Additional Documentation

Notes

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