{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"J9VHN6","uniProtkbId":"X325_CRYN9","entryAudit":{"firstPublicDate":"2020-04-22","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2012-11-28","entryVersion":49,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Cryptococcus neoformans (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487)","commonName":"Cryptococcus neoformans var. grubii serotype A","taxonId":235443,"lineage":["Eukaryota","Fungi","Dikarya","Basidiomycota","Agaricomycotina","Tremellomycetes","Tremellales","Cryptococcaceae","Cryptococcus","Cryptococcus neoformans species complex"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31932719"}],"value":"Copper acquisition factor BIM1"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31932719"}],"value":"BCS-inducible membrane protein 1"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"35737716"}],"value":"Copper binding and release protein 1"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31932719"}],"value":"Lytic polysaccharide monooxygenase-like protein BIM1"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31932719"}],"value":"LPMO-like protein BIM1"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31932718"}],"value":"X325 family protein BIM1"}}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31932719"}],"value":"BIM1"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"35737716"}],"value":"CBI1"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31932718"}],"value":"X325"}],"orfNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31932719"}],"value":"CNAG_02775"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932719"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35737716"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"31932718"}],"value":"Lytic polysaccharide monooxygenase-like protein that has diverged to biological functions other than polysaccharide degradation since it does not perform oxidative cleavage of polysaccharides (Probable). Cell surface-bound protein that functions in the copper-accumulation pathway shared by the CUF1-dependent copper transporter CTR1 (PubMed:31932719, PubMed:35737716). Involved in maintaining cell wall integrity during copper deficiency (PubMed:35737716). Binds Cu(2+) with an estimated 1:1 stoichiometry and might serve as an extracellular copper ligand (PubMed:31932719). FRE4 and FRE7 metalloreductases probably function together with CTR1 and BIM1 to liberate the Cu(2+) bound to the BIM1 copper-binding site for subsequent import of Cu(+) into the cell by CTR1, via the reduction of BIM1-bound Cu(2+) to Cu(+) to reduce binding affinity for BIM1 but increase affinity for CTR1 (PubMed:31932719). Facilitates copper acquisition in the brain of mammalian hosts and acts as a copper-dependent virulence trait in fungal meningitis (PubMed:31932719). While BIM1 plays a critical role in cryptococcal meningitis, at least in part through its role in copper acquisition, it could play additional roles during copper limitation or as a means to invade and colonize host tissues in the brain, by compromising host carbohydrate integrity via its lytic polysaccharide monooxygenase (LPMO) activity, which has still to be determined (PubMed:31932719)"}],"commentType":"FUNCTION"},{"commentType":"COFACTOR","cofactors":[{"name":"Cu(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932719"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29036"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932719"}],"value":"Binds 1 copper ion per subunit."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932719"}],"value":"Interacts with the CUF1-dependent copper transporter CTR1"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"31932718"}],"value":"Proteins attached to a GPI anchor via their C terminus are found in the outer leaflet of the lipid bilayer facing the extracellular environment. GPI anchors can also be considered as predetermined breaking points, which allow the release of proteins into the extracellular environment upon enzymatic cleavage"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Lipid-anchor, GPI-anchor","id":"SL-9902"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932719"}],"value":"Expression is highly induced in response to copper limitation by the copper-specific chelator bathocuproine disulfonic acid (BCS) (PubMed:31932719). The BIM1 promoter harbors three conserved Cu-responsive elements (CuRE), which are critical for CUF1 binding and activation under copper-limiting conditions, beginning at positions -239, -268 and -516 (PubMed:31932719). Consistent with their presence, binding of the CUF1 copper-sensing transcription factor to the BIM1 promoter is strongly induced under copper-limiting conditions and expression of BIM1 under these conditions is CUF1-dependent (PubMed:31932719)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932719"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35737716"}],"value":"Exhibits growth defect on copper-deficient medium ot in the presence of the copper-specific chelator bathocuproine disulfonic acid (BCS) (PubMed:31932719). Shows a reduction in cell-associated copper, in the enzymatic activity of Cu/Zn superoxide dismutase, in laccase-dependent melanin production and in the accumulation of cellular iron, a well-established copper-dependent process (PubMed:31932719). Shows a distinct cell wall electron density pattern, which is not due to overall difference in cell associated copper levels or copper adsorption ability (PubMed:35737716). Leads to a reduction in the inner cell wall chito-oligomer layer when exposed to copper-deficiency (PubMed:35737716). Does not affect virulence in an A/J mouse pulmonary infection model (PubMed:31932719)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the X325 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":19,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":20,"modifier":"EXACT"},"end":{"value":190,"modifier":"EXACT"}},"description":"Copper acquisition factor BIM1","featureId":"PRO_5003829135"},{"type":"Propeptide","location":{"start":{"value":191,"modifier":"EXACT"},"end":{"value":218,"modifier":"EXACT"}},"description":"Removed in mature form","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":"PRO_0000449516"},{"type":"Region","location":{"start":{"value":160,"modifier":"EXACT"},"end":{"value":194,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":165,"modifier":"EXACT"},"end":{"value":194,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Binding site","location":{"start":{"value":20,"modifier":"EXACT"},"end":{"value":20,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29036"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A0A4P9I8G4"}],"ligand":{"name":"Cu(2+)","id":"ChEBI:CHEBI:29036"}},{"type":"Binding site","location":{"start":{"value":65,"modifier":"EXACT"},"end":{"value":65,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29036"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A0A4P9I8G4"}],"ligand":{"name":"Cu(2+)","id":"ChEBI:CHEBI:29036"}},{"type":"Binding site","location":{"start":{"value":138,"modifier":"EXACT"},"end":{"value":138,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29036"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A0A4P9I8G4"}],"ligand":{"name":"Cu(2+)","id":"ChEBI:CHEBI:29036"}},{"type":"Lipidation","location":{"start":{"value":190,"modifier":"EXACT"},"end":{"value":190,"modifier":"EXACT"}},"description":"GPI-anchor amidated serine","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Glycosylation","location":{"start":{"value":87,"modifier":"EXACT"},"end":{"value":87,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":91,"modifier":"EXACT"},"end":{"value":91,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":124,"modifier":"EXACT"},"end":{"value":124,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":158,"modifier":"EXACT"},"end":{"value":158,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":170,"modifier":"EXACT"},"end":{"value":170,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00498"}],"featureId":""},{"type":"Mutagenesis","location":{"start":{"value":20,"modifier":"EXACT"},"end":{"value":20,"modifier":"EXACT"}},"description":"Leads to a hypomelanization phenotype and growth defect on copper-deficient conditions.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932719"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":64,"modifier":"EXACT"},"end":{"value":64,"modifier":"EXACT"}},"description":"Leads to a hypomelanization phenotype and growth defect on copper-deficient conditions; 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