CMT2_CRYNH
ID CMT2_CRYNH Reviewed; 183 AA.
AC J9VL95;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 2.
DT 25-MAY-2022, entry version 31.
DE RecName: Full=Copper metallothionein 2 {ECO:0000303|PubMed:21819456};
DE Short=Cu-MT 2 {ECO:0000303|PubMed:21819456};
DE Short=Cu-metallothionein 2 {ECO:0000303|PubMed:21819456};
DE AltName: Full=Copper chelatin 2 {ECO:0000305};
DE AltName: Full=Copper thionein 2 {ECO:0000305};
GN Name=CMT2 {ECO:0000303|PubMed:23498952}; ORFNames=CNAG_00306;
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, AND INDUCTION.
RX PubMed=21819456; DOI=10.1111/j.1365-2958.2011.07794.x;
RA Ding C., Yin J., Tovar E.M., Fitzpatrick D.A., Higgins D.G., Thiele D.J.;
RT "The copper regulon of the human fungal pathogen Cryptococcus neoformans
RT H99.";
RL Mol. Microbiol. 81:1560-1576(2011).
RN [3]
RP FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, DOMAIN, COPPER-BINDING, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23498952; DOI=10.1016/j.chom.2013.02.002;
RA Ding C., Festa R.A., Chen Y.L., Espart A., Palacios O., Espin J.,
RA Capdevila M., Atrian S., Heitman J., Thiele D.J.;
RT "Cryptococcus neoformans copper detoxification machinery is critical for
RT fungal virulence.";
RL Cell Host Microbe 13:265-276(2013).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31694529; DOI=10.1186/s12866-019-1606-4;
RA Dbouk N.H., Covington M.B., Nguyen K., Chandrasekaran S.;
RT "Increase of reactive oxygen species contributes to growth inhibition by
RT fluconazole in Cryptococcus neoformans.";
RL BMC Microbiol. 19:243-243(2019).
CC -!- FUNCTION: Copper metallothionein that protects the cell against copper
CC toxicity by tightly chelating copper ions (PubMed:21819456,
CC PubMed:23498952). Required for antioxidant-mediated growth rescue in
CC the presence of fluconazole (PubMed:31694529). Acts as a critical
CC factors for lung colonization and virulence (PubMed:23498952).
CC {ECO:0000269|PubMed:21819456, ECO:0000269|PubMed:23498952,
CC ECO:0000269|PubMed:31694529}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:23498952}.
CC -!- INDUCTION: Expression is induced in a dose-dependent manner in response
CC to high concentrations of copper and basal transcription is repressed
CC in the presence of the copper chelator bathocuproin sulphonate (BCS)
CC (PubMed:21819456). Expression is regulated by the CUF1 copper-dependent
CC transcription factor (PubMed:21819456). Highly induced during mice
CC pulmonary infection (PubMed:23498952). {ECO:0000269|PubMed:21819456,
CC ECO:0000269|PubMed:23498952}.
CC -!- DOMAIN: Divided into 5 Cys-rich domains by 4 spacer sequences termed
CC B1-B4 (PubMed:23498952). Each cystein-rich domain contains the
CC conserved copper-binding motif Cys-X-Cys-X6-Cys-X-Cys-X4-Cys-X-Cys-X2-
CC Cys (PubMed:23498952). The copper-binding domains together are able to
CC chelate up to 24 copper ions (PubMed:23498952).
CC {ECO:0000269|PubMed:23498952}.
CC -!- DISRUPTION PHENOTYPE: Fungi lacking both CMT1 and CMT2 whow attenuated
CC virulence and reduced pulmonary colonization in mice (PubMed:23498952).
CC Impairs growth rescue by antioxidants when cells are treated with
CC fluconazole (PubMed:31694529). {ECO:0000269|PubMed:23498952,
CC ECO:0000269|PubMed:31694529}.
CC -!- SIMILARITY: Belongs to the metallothionein superfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP003820; AFR92440.2; -; Genomic_DNA.
DR RefSeq; XP_012046252.1; XM_012190862.1.
DR AlphaFoldDB; J9VL95; -.
DR EnsemblFungi; AFR92440; AFR92440; CNAG_00306.
DR GeneID; 23884125; -.
DR VEuPathDB; FungiDB:CNAG_00306; -.
DR HOGENOM; CLU_146153_0_0_1; -.
DR Proteomes; UP000010091; Chromosome 1.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Copper; Cytoplasm; Metal-binding; Metal-thiolate cluster; Repeat.
FT CHAIN 1..183
FT /note="Copper metallothionein 2"
FT /id="PRO_0000449497"
FT REGION 1..35
FT /note="Cys-rich copper-binding 1"
FT /evidence="ECO:0000305|PubMed:23498952"
FT REGION 36..45
FT /note="Spacer B1"
FT /evidence="ECO:0000305|PubMed:23498952"
FT REGION 46..79
FT /note="Cys-rich copper-binding 2"
FT /evidence="ECO:0000305|PubMed:23498952"
FT REGION 80..88
FT /note="Spacer B2"
FT /evidence="ECO:0000305|PubMed:23498952"
FT REGION 89..110
FT /note="Cys-rich copper-binding 3"
FT /evidence="ECO:0000305|PubMed:23498952"
FT REGION 111..120
FT /note="Spacer B3"
FT /evidence="ECO:0000305|PubMed:23498952"
FT REGION 121..142
FT /note="Cys-rich copper-binding 4"
FT /evidence="ECO:0000305|PubMed:23498952"
FT REGION 143..156
FT /note="Spacer B4"
FT /evidence="ECO:0000305|PubMed:23498952"
FT REGION 157..183
FT /note="Cys-rich copper-binding 5"
FT /evidence="ECO:0000305|PubMed:23498952"
SQ SEQUENCE 183 AA; 17832 MW; 0A35A1804EABDF34 CRC64;
MAFNPNPEKT TSCCSTSKAQ DKCTCPKGKC ECETCPKSTK TPGSGPCNCG VKEKVSTCGC
NGSGAACTCP PGQCACDSCP RKAKSVSTCG CGGSAAACSC PPGKCACDSC PKQAQEKVSS
CACNGSGGAC TCPPGKCSCS GCPAQAKENP ADQPTTCGCQ GVGVACTCPP GQCACDGCPA
KAK
