ID SOD5_CANAL Reviewed; 228 AA.
AC Q5AD07; A0A1D8PG56;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 13-SEP-2023, entry version 127.
DE RecName: Full=Cell surface Cu-only superoxide dismutase 5;
DE EC=1.15.1.1;
DE AltName: Full=Predicted GPI-anchored protein 3;
DE Flags: Precursor;
GN Name=SOD5; Synonyms=PGA3, SOD31; OrderedLocusNames=CAALFM_C200680CA;
GN ORFNames=CaO19.2060, CaO19.9607;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP PREDICTION OF GPI-ANCHOR.
RX PubMed=12845604; DOI=10.1002/yea.1007;
RA De Groot P.W., Hellingwerf K.J., Klis F.M.;
RT "Genome-wide identification of fungal GPI proteins.";
RL Yeast 20:781-796(2003).
RN [5]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14617819; DOI=10.1091/mbc.e03-03-0179;
RA Martchenko M., Alarco A.M., Harcus D., Whiteway M.;
RT "Superoxide dismutases in Candida albicans: transcriptional regulation and
RT functional characterization of the hyphal-induced SOD5 gene.";
RL Mol. Biol. Cell 15:456-467(2004).
RN [6]
RP INDUCTION.
RX PubMed=15814840; DOI=10.1091/mbc.e05-01-0073;
RA Kadosh D., Johnson A.D.;
RT "Induction of the Candida albicans filamentous growth program by relief of
RT transcriptional repression: a genome-wide analysis.";
RL Mol. Biol. Cell 16:2903-2912(2005).
RN [7]
RP INDUCTION.
RX PubMed=15813733; DOI=10.1111/j.1365-2958.2005.04557.x;
RA Fradin C., De Groot P., MacCallum D., Schaller M., Klis F., Odds F.C.,
RA Hube B.;
RT "Granulocytes govern the transcriptional response, morphology and
RT proliferation of Candida albicans in human blood.";
RL Mol. Microbiol. 56:397-415(2005).
RN [8]
RP FUNCTION.
RX PubMed=19019164; DOI=10.1111/j.1365-2958.2008.06528.x;
RA Frohner I.E., Bourgeois C., Yatsyk K., Majer O., Kuchler K.;
RT "Candida albicans cell surface superoxide dismutases degrade host-derived
RT reactive oxygen species to escape innate immune surveillance.";
RL Mol. Microbiol. 71:240-252(2009).
RN [9]
RP FUNCTION.
RX PubMed=21746956; DOI=10.1128/aac.00280-11;
RA Bink A., Vandenbosch D., Coenye T., Nelis H., Cammue B.P., Thevissen K.;
RT "Superoxide dismutases are involved in Candida albicans biofilm persistence
RT against miconazole.";
RL Antimicrob. Agents Chemother. 55:4033-4037(2011).
RN [10]
RP INDUCTION.
RX PubMed=23123467; DOI=10.1248/bpb.b12-00338;
RA Miao H., Zhao L., Li C., Shang Q., Lu H., Fu Z., Wang L., Jiang Y., Cao Y.;
RT "Inhibitory effect of Shikonin on Candida albicans growth.";
RL Biol. Pharm. Bull. 35:1956-1963(2012).
RN [11]
RP INDUCTION.
RX PubMed=23285201; DOI=10.1371/journal.pone.0052850;
RA Miramon P., Dunker C., Windecker H., Bohovych I.M., Brown A.J., Kurzai O.,
RA Hube B.;
RT "Cellular responses of Candida albicans to phagocytosis and the
RT extracellular activities of neutrophils are critical to counteract
RT carbohydrate starvation, oxidative and nitrosative stress.";
RL PLoS ONE 7:E52850-E52850(2012).
RN [12]
RP INDUCTION.
RX PubMed=23125349; DOI=10.1128/ec.00236-12;
RA Pierce J.V., Dignard D., Whiteway M., Kumamoto C.A.;
RT "Normal adaptation of Candida albicans to the murine gastrointestinal tract
RT requires Efg1p-dependent regulation of metabolic and host defense genes.";
RL Eukaryot. Cell 12:37-49(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INDUCTION.
RX PubMed=23948566; DOI=10.1016/j.jprot.2013.07.031;
RA Aoki W., Tatsukami Y., Kitahara N., Matsui K., Morisaka H., Kuroda K.,
RA Ueda M.;
RT "Elucidation of potentially virulent factors of Candida albicans during
RT serum adaptation by using quantitative time-course proteomics.";
RL J. Proteomics 91:417-429(2013).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=23136884; DOI=10.1111/mmi.12087;
RA Rohm M., Lindemann E., Hiller E., Ermert D., Lemuth K., Trkulja D.,
RA Sogukpinar O., Brunner H., Rupp S., Urban C.F., Sohn K.;
RT "A family of secreted pathogenesis-related proteins in Candida albicans.";
RL Mol. Microbiol. 87:132-151(2013).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 27-181, COFACTOR, DISULFIDE BOND,
RP SUBUNIT, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=24711423; DOI=10.1073/pnas.1400137111;
RA Gleason J.E., Galaleldeen A., Peterson R.L., Taylor A.B., Holloway S.P.,
RA Waninger-Saroni J., Cormack B.P., Cabelli D.E., Hart P.J., Culotta V.C.;
RT "Candida albicans SOD5 represents the prototype of an unprecedented class
RT of Cu-only superoxide dismutases required for pathogen defense.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:5866-5871(2014).
CC -!- FUNCTION: Superoxide dismutases serve to convert damaging superoxide
CC radicals, a key form of ROS, to less damaging hydrogen peroxide that
CC can be converted into water by catalase action. Degrades host-derived
CC reactive oxygen species to escape innate immune surveillance. Involved
CC in the occurrence of miconazole-tolerant persisters in biofilms.
CC Persisters are cells that survive high doses of an antimicrobial agent.
CC The unusual attributes of SOD5-like fungal proteins, including the
CC absence of zinc and an open active site that readily captures
CC extracellular copper, make these SODs well suited to meet challenges in
CC zinc and copper availability at the host-pathogen interface.
CC {ECO:0000269|PubMed:14617819, ECO:0000269|PubMed:19019164,
CC ECO:0000269|PubMed:21746956, ECO:0000269|PubMed:24711423}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:18421; EC=1.15.1.1;
CC Evidence={ECO:0000269|PubMed:24711423};
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000269|PubMed:24711423};
CC Note=Binds 1 copper ion per subunit. {ECO:0000269|PubMed:24711423};
CC -!- ACTIVITY REGULATION: Secreted in a disulfide-oxidized form and apo-
CC pools of secreted SOD5 can readily capture extracellular copper for
CC rapid induction of enzyme activity. {ECO:0000269|PubMed:24711423}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:24711423}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:23136884}. Membrane {ECO:0000250}; Lipid-anchor,
CC GPI-anchor {ECO:0000250}. Note=Covalently-linked GPI-modified cell wall
CC protein (GPI-CWP). {ECO:0000250}.
CC -!- INDUCTION: Induced during yeast-to-hyphal transition and by osmotic and
CC oxidative stresses. Expression is also increased when cells were grown
CC on nonfermentable substrates as the only carbon source, in serum, and
CC in the presence of neutrophils. Down-regulated by shikonin. Expression
CC is controlled by EFG1, NRG1 and RIM101. {ECO:0000269|PubMed:14617819,
CC ECO:0000269|PubMed:15813733, ECO:0000269|PubMed:15814840,
CC ECO:0000269|PubMed:23123467, ECO:0000269|PubMed:23125349,
CC ECO:0000269|PubMed:23136884, ECO:0000269|PubMed:23285201,
CC ECO:0000269|PubMed:23948566}.
CC -!- PTM: The GPI-anchor is attached to the protein in the endoplasmic
CC reticulum and serves to target the protein to the cell surface. There,
CC the glucosamine-inositol phospholipid moiety is cleaved off and the
CC GPI-modified mannoprotein is covalently attached via its lipidless GPI
CC glycan remnant to the 1,6-beta-glucan of the outer cell wall layer (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Leads to sensitivity to hydrogen peroxide when
CC cells were grown in nutrient-limited conditions.
CC {ECO:0000269|PubMed:14617819}.
CC -!- SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family.
CC {ECO:0000305}.
CC -!- CAUTION: Although the beta-barrel of Cu/Zn SODs is largely preserved,
CC SOD5 is a monomeric copper protein that lacks a zinc-binding site and
CC is missing the electrostatic loop element proposed to promote catalysis
CC through superoxide guidance. Without an electrostatic loop, the copper
CC site of SOD5 is not recessed and is readily accessible to bulk solvent
CC (PubMed:24711423). {ECO:0000305|PubMed:24711423}.
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; CP017624; AOW27120.1; -; Genomic_DNA.
DR RefSeq; XP_719507.1; XM_714414.1.
DR PDB; 4N3T; X-ray; 1.40 A; A=27-181.
DR PDB; 4N3U; X-ray; 1.75 A; A=27-181.
DR PDB; 5CU9; X-ray; 1.48 A; A=27-181.
DR PDB; 5KBK; X-ray; 1.41 A; A=27-181.
DR PDB; 5KBL; X-ray; 1.41 A; A=27-181.
DR PDB; 5KBM; X-ray; 1.42 A; A=27-181.
DR PDBsum; 4N3T; -.
DR PDBsum; 4N3U; -.
DR PDBsum; 5CU9; -.
DR PDBsum; 5KBK; -.
DR PDBsum; 5KBL; -.
DR PDBsum; 5KBM; -.
DR AlphaFoldDB; Q5AD07; -.
DR SMR; Q5AD07; -.
DR STRING; 237561.Q5AD07; -.
DR GlyCosmos; Q5AD07; 8 sites, No reported glycans.
DR EnsemblFungi; C2_00680C_A-T; C2_00680C_A-T-p1; C2_00680C_A.
DR GeneID; 3638886; -.
DR KEGG; cal:CAALFM_C200680CA; -.
DR CGD; CAL0000188676; SOD5.
DR VEuPathDB; FungiDB:C2_00680C_A; -.
DR eggNOG; ENOG502S5NX; Eukaryota.
DR HOGENOM; CLU_063073_1_1_1; -.
DR InParanoid; Q5AD07; -.
DR OrthoDB; 3040041at2759; -.
DR PHI-base; PHI:383; -.
DR PHI-base; PHI:8749; -.
DR PRO; PR:Q5AD07; -.
DR Proteomes; UP000000559; Chromosome 2.
DR GO; GO:0009986; C:cell surface; IDA:CGD.
DR GO; GO:0005576; C:extracellular region; IDA:CGD.
DR GO; GO:0009277; C:fungal-type cell wall; IDA:CGD.
DR GO; GO:0030446; C:hyphal cell wall; IDA:CGD.
DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005507; F:copper ion binding; IDA:CGD.
DR GO; GO:0004784; F:superoxide dismutase activity; IDA:CGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:CGD.
DR GO; GO:0071451; P:cellular response to superoxide; IDA:CGD.
DR GO; GO:0042783; P:evasion of host immune response; IMP:CGD.
DR GO; GO:0019430; P:removal of superoxide radicals; IBA:GO_Central.
DR GO; GO:0006801; P:superoxide metabolic process; IDA:CGD.
DR GO; GO:0052164; P:symbiont defense to host-produced reactive oxygen species; IMP:CGD.
DR Gene3D; 2.60.40.200; Superoxide dismutase, copper/zinc binding domain; 1.
DR InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR InterPro; IPR036423; SOD-like_Cu/Zn_dom_sf.
DR InterPro; IPR024134; SOD_Cu/Zn_/chaperone.
DR InterPro; IPR001424; SOD_Cu_Zn_dom.
DR PANTHER; PTHR10003:SF37; CELL SURFACE SUPEROXIDE DISMUTASE [CU-ZN] 4; 1.
DR PANTHER; PTHR10003; SUPEROXIDE DISMUTASE CU-ZN -RELATED; 1.
DR Pfam; PF00080; Sod_Cu; 1.
DR SUPFAM; SSF49329; Cu,Zn superoxide dismutase-like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antioxidant; Cell wall; Copper; Disulfide bond; Glycoprotein;
KW GPI-anchor; Lipoprotein; Membrane; Metal-binding; Oxidoreductase;
KW Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..205
FT /note="Cell surface Cu-only superoxide dismutase 5"
FT /id="PRO_0000424636"
FT PROPEP 206..228
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000424637"
FT REGION 176..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 176..203
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 75
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_note="catalytic"
FT BINDING 77
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_note="catalytic"
FT BINDING 93
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_note="catalytic"
FT BINDING 153
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_note="catalytic"
FT LIPID 205
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..162
FT /evidence="ECO:0000269|PubMed:24711423"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:4N3T"
FT STRAND 43..51
FT /evidence="ECO:0007829|PDB:4N3T"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:4N3T"
FT STRAND 55..63
FT /evidence="ECO:0007829|PDB:4N3T"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:4N3T"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:4N3T"
FT HELIX 87..90
FT /evidence="ECO:0007829|PDB:4N3T"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:5CU9"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:4N3T"
FT HELIX 114..118
FT /evidence="ECO:0007829|PDB:4N3T"
FT STRAND 123..136
FT /evidence="ECO:0007829|PDB:4N3T"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:4N3T"
FT STRAND 159..168
FT /evidence="ECO:0007829|PDB:4N3T"
SQ SEQUENCE 228 AA; 23589 MW; 2724BF2E7B9FAC91 CRC64;
MKYLSIFLLA TFALAGDAPI STDSKGSPSL IAKFEKTSKS NIEGTIKFTP ANNGTVSVSV
DLKGLPSDIG PFPYHVHEKP VPASKNCSAT ENHFNPYNGT VRAATPAAHE VGDLAGKHGN
IMGESYKTEY DDSYISLNEK SRSYIGGLSI VIHANNGTRL NCANITLLDE GHGNANTTMS
NSSSSSSQSA VNTSSSMAST APQGNGAERA VVNGLLAAGV VGVIAALI
//
