BIM1_CRYNH
ID BIM1_CRYNH Reviewed; 218 AA.
AC J9VHN6;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Copper acquisition factor BIM1 {ECO:0000303|PubMed:31932719};
DE AltName: Full=BCS-inducible membrane protein 1 {ECO:0000303|PubMed:31932719};
DE AltName: Full=Lytic polysaccharide monooxygenase-like protein BIM1 {ECO:0000303|PubMed:31932719};
DE Short=LPMO-like protein BIM1 {ECO:0000303|PubMed:31932719};
DE EC=1.14.99.- {ECO:0000305|PubMed:31932719};
DE Flags: Precursor;
GN Name=BIM; ORFNames=CNAG_02775 {ECO:0000303|PubMed:31932719};
OS Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 /
OS CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=235443;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=24743168; DOI=10.1371/journal.pgen.1004261;
RA Janbon G., Ormerod K.L., Paulet D., Byrnes E.J. III, Yadav V.,
RA Chatterjee G., Mullapudi N., Hon C.-C., Billmyre R.B., Brunel F.,
RA Bahn Y.-S., Chen W., Chen Y., Chow E.W.L., Coppee J.-Y., Floyd-Averette A.,
RA Gaillardin C., Gerik K.J., Goldberg J., Gonzalez-Hilarion S., Gujja S.,
RA Hamlin J.L., Hsueh Y.-P., Ianiri G., Jones S., Kodira C.D., Kozubowski L.,
RA Lam W., Marra M., Mesner L.D., Mieczkowski P.A., Moyrand F., Nielsen K.,
RA Proux C., Rossignol T., Schein J.E., Sun S., Wollschlaeger C., Wood I.A.,
RA Zeng Q., Neuveglise C., Newlon C.S., Perfect J.R., Lodge J.K., Idnurm A.,
RA Stajich J.E., Kronstad J.W., Sanyal K., Heitman J., Fraser J.A.,
RA Cuomo C.A., Dietrich F.S.;
RT "Analysis of the genome and transcriptome of Cryptococcus neoformans var.
RT grubii reveals complex RNA expression and microevolution leading to
RT virulence attenuation.";
RL PLoS Genet. 10:E1004261-E1004261(2014).
RN [2]
RP FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, INTERACTION WITH CTR1,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-20; HIS-64; HIS-65 AND
RP ASP-138.
RX PubMed=31932719; DOI=10.1038/s41589-019-0437-9;
RA Garcia-Santamarina S., Probst C., Festa R.A., Ding C., Smith A.D.,
RA Conklin S.E., Brander S., Kinch L.N., Grishin N.V., Franz K.J.,
RA Riggs-Gelasco P., Lo Leggio L., Johansen K.S., Thiele D.J.;
RT "A lytic polysaccharide monooxygenase-like protein functions in fungal
RT copper import and meningitis.";
RL Nat. Chem. Biol. 16:337-344(2020).
CC -!- FUNCTION: Cell surface-bound protein that functions in the copper-
CC accumulation pathway shared by the CUF1-dependent copper transporter
CC CTR1 (PubMed:31932719). Binds Cu(2+) with an estimated 1:1
CC stoichiometry and might serve as an extracellular copper ligand
CC (PubMed:31932719). FRE4 and FRE7 metalloreductases probably function
CC together with CTR1 and BIM1 to liberate the Cu(2+) bound to the BIM1
CC copper-binding site for subsequent import of Cu(+) into the cell by
CC CTR1, via the reduction of BIM1-bound Cu(2+) to Cu(+) to reduce binding
CC affinity for BIM1 but increase affinity for CTR1 (Probable).
CC Facilitates copper acquisition in the brain of mammalian hosts and acts
CC as a copper-dependent virulence trait in fungal meningitis
CC (PubMed:31932719). While BIM1 plays a critical role in cryptococcal
CC meningitis, at least in part through its role in copper acquisition, it
CC could play additional roles during copper limitation or as a means to
CC invade and colonize host tissues in the brain, by compromising host
CC carbohydrate integrity via its lytic polysaccharide monooxygenase
CC (LPMO) activity, which has still to be determined (Probable).
CC {ECO:0000269|PubMed:31932719, ECO:0000305|PubMed:31932719}.
CC -!- SUBUNIT: Interacts with the CUF1-dependent copper transporter CTR1.
CC {ECO:0000269|PubMed:31932719}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31932719};
CC Lipid-anchor, GPI-anchor {ECO:0000255}.
CC -!- INDUCTION: Expression is highly induced in response to copper
CC limitation by the copper-specific chelator bathocuproine disulfonic
CC acid (BCS) (PubMed:31932719). The BIM1 promoter harbors three conserved
CC Cu-responsive elements (CuRE), which are critical for CUF1 binding and
CC activation under copper-limiting conditions, beginning at positions
CC -239, -268 and -516 (PubMed:31932719). Consistent with their presence,
CC binding of the CUF1 copper-sensing transcription factor to the BIM1
CC promoter is strongly induced under copper-limiting conditions and
CC expression of BIM1 under these conditions is CUF1-dependent
CC (PubMed:31932719). {ECO:0000269|PubMed:31932719}.
CC -!- DISRUPTION PHENOTYPE: Exhibits growth defect on copper-deficient medium
CC ot in the presence of the copper-specific chelator bathocuproine
CC disulfonic acid (BCS) (PubMed:31932719). Shows a reduction in cell-
CC associated copper, in the enzymatic activity of Cu/Zn superoxide
CC dismutase, in laccase-dependent melanin production and in the
CC accumulation of cellular iron, a well-established copper-dependent
CC process (PubMed:31932719). Does not affect virulence in an A/J mouse
CC pulmonary infection model (PubMed:31932719).
CC {ECO:0000269|PubMed:31932719}.
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DR EMBL; CP003822; AFR93917.1; -; Genomic_DNA.
DR RefSeq; XP_012048123.1; XM_012192733.1.
DR AlphaFoldDB; J9VHN6; -.
DR SMR; J9VHN6; -.
DR EnsemblFungi; AFR93917; AFR93917; CNAG_02775.
DR GeneID; 23886334; -.
DR VEuPathDB; FungiDB:CNAG_02775; -.
DR HOGENOM; CLU_070647_3_1_1; -.
DR Proteomes; UP000010091; Chromosome 3.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Cell membrane; Copper; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Metal-binding; Monooxygenase; Oxidoreductase; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..190
FT /note="Copper acquisition factor BIM1"
FT /id="PRO_5003829135"
FT PROPEP 191..218
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000449516"
FT REGION 160..194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 20
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000305|PubMed:31932719"
FT BINDING 65
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000305|PubMed:31932719"
FT BINDING 138
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000305|PubMed:31932719"
FT LIPID 190
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 20
FT /note="H->A: Leads to a hypomelanization phenotype and
FT growth defect on copper-deficient conditions."
FT /evidence="ECO:0000269|PubMed:31932719"
FT MUTAGEN 64
FT /note="H->A: Leads to a hypomelanization phenotype and
FT growth defect on copper-deficient conditions; when
FT associated with A-65."
FT /evidence="ECO:0000269|PubMed:31932719"
FT MUTAGEN 65
FT /note="H->A: Leads to a hypomelanization phenotype and
FT growth defect on copper-deficient conditions; when
FT associated with A-64."
FT /evidence="ECO:0000269|PubMed:31932719"
FT MUTAGEN 138
FT /note="D->A,S: Leads to a hypomelanization phenotype and
FT growth defect on copper-deficient conditions."
FT /evidence="ECO:0000269|PubMed:31932719"
SQ SEQUENCE 218 AA; 22460 MW; 0436973FA833B8B2 CRC64;
MFALKSILVT SLITSTALAH FTLDYPQSRG FVDDTENQFC GGFNTVEARQ PFPLGSGPVH
IDSHHALATI VAFISTSSNP TSFDDFNTTS NGTAIPLASS IFQVPQGEKC FNIDLQSLNV
GLTNGSEVTL QIQYDGGDGN LYQCSDLVLI EGYEVPSNET CTNDASKASN ATSTSSGSAT
ATSAAATSSS SGTSGAIKEV VGFGALSLAL GIAGLIIL
