COTH2_RHIO9
ID COTH2_RHIO9 Reviewed; 594 AA.
AC I1C4E4;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 25-MAY-2022, entry version 31.
DE RecName: Full=Invasin CotH2 {ECO:0000303|PubMed:24355926};
DE AltName: Full=Spore coat protein homolog 2 {ECO:0000303|PubMed:24355926};
DE Flags: Precursor;
GN Name=CotH2 {ECO:0000303|PubMed:24355926};
GN ORFNames=RO3G_08029 {ECO:0000312|EMBL:EIE83324.1};
OS Rhizopus delemar (strain RA 99-880 / ATCC MYA-4621 / FGSC 9543 / NRRL
OS 43880) (Mucormycosis agent) (Rhizopus arrhizus var. delemar).
OC Eukaryota; Fungi; Fungi incertae sedis; Mucoromycota; Mucoromycotina;
OC Mucoromycetes; Mucorales; Mucorineae; Rhizopodaceae; Rhizopus.
OX NCBI_TaxID=246409 {ECO:0000312|Proteomes:UP000009138};
RN [1] {ECO:0000312|Proteomes:UP000009138}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=RA 99-880 / ATCC MYA-4621 / FGSC 9543 / NRRL 43880
RC {ECO:0000312|Proteomes:UP000009138};
RX PubMed=19578406; DOI=10.1371/journal.pgen.1000549;
RA Ma L.-J., Ibrahim A.S., Skory C., Grabherr M.G., Burger G., Butler M.,
RA Elias M., Idnurm A., Lang B.F., Sone T., Abe A., Calvo S.E.,
RA Corrochano L.M., Engels R., Fu J., Hansberg W., Kim J.-M., Kodira C.D.,
RA Koehrsen M.J., Liu B., Miranda-Saavedra D., O'Leary S.,
RA Ortiz-Castellanos L., Poulter R., Rodriguez-Romero J., Ruiz-Herrera J.,
RA Shen Y.-Q., Zeng Q., Galagan J., Birren B.W., Cuomo C.A., Wickes B.L.;
RT "Genomic analysis of the basal lineage fungus Rhizopus oryzae reveals a
RT whole-genome duplication.";
RL PLoS Genet. 5:E1000549-E1000549(2009).
RN [2] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HOST HSPA5/BIP, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, INDUCTION, DISRUPTION PHENOTYPE, AND BIOTECHNOLOGY.
RX PubMed=24355926; DOI=10.1172/jci71349;
RA Gebremariam T., Liu M., Luo G., Bruno V., Phan Q.T., Waring A.J.,
RA Edwards J.E. Jr., Filler S.G., Yeaman M.R., Ibrahim A.S.;
RT "CotH3 mediates fungal invasion of host cells during mucormycosis.";
RL J. Clin. Invest. 124:237-250(2014).
RN [3] {ECO:0000305}
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27159390; DOI=10.1172/jci82744;
RA Gebremariam T., Lin L., Liu M., Kontoyiannis D.P., French S.,
RA Edwards J.E. Jr., Filler S.G., Ibrahim A.S.;
RT "Bicarbonate correction of ketoacidosis alters host-pathogen interactions
RT and alleviates mucormycosis.";
RL J. Clin. Invest. 126:2280-2294(2016).
RN [4] {ECO:0000305}
RP BIOTECHNOLOGY.
RX PubMed=31206021; DOI=10.1126/sciadv.aaw1327;
RA Gebremariam T., Alkhazraji S., Soliman S.S.M., Gu Y., Jeon H.H., Zhang L.,
RA French S.W., Stevens D.A., Edwards J.E. Jr., Filler S.G., Uppuluri P.,
RA Ibrahim A.S.;
RT "Anti-CotH3 antibodies protect mice from mucormycosis by prevention of
RT invasion and augmenting opsonophagocytosis.";
RL Sci. Adv. 5:eaaw1327-eaaw1327(2019).
CC -!- FUNCTION: Promotes invasion of host epithelial cells by adhering to
CC receptors on the host cell surface to facilitate endocytosis of the
CC pathogen into host cells (PubMed:24355926). Binds HSPA5/BiP protein on
CC the cell surface of host epithelial cells (PubMed:24355926).
CC {ECO:0000269|PubMed:24355926}.
CC -!- SUBUNIT: Interacts with host epithelial cell surface HSPA5/BiP protein.
CC {ECO:0000269|PubMed:24355926}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24355926};
CC Lipid-anchor, GPI-anchor {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Expressed in spores.
CC {ECO:0000269|PubMed:24355926}.
CC -!- INDUCTION: Expressed during growth in host lung and brain, and during
CC growth in presence of epithelial cells (PubMed:24355926). Induced in
CC presence of high free iron (at protein level) (PubMed:27159390).
CC Induced during growth in high glucose (at protein level)
CC (PubMed:27159390). Induced in presence of 3-hydroxybutyric acid (BHB)
CC (at protein level) (PubMed:27159390). {ECO:0000269|PubMed:24355926,
CC ECO:0000269|PubMed:27159390}.
CC -!- DISRUPTION PHENOTYPE: Simultaneous RNAi-mediated knockdown of CotH2 and
CC CotH3 decreases invasion of host epithelial cells (PubMed:24355926).
CC Simultaneous RNAi-mediated knockdown of CotH2 and CotH3 decreases
CC virulence in a mouse model of ketoacidosis (PubMed:24355926,
CC PubMed:27159390). Simultaneous RNAi-mediated knockdown of CotH2 and
CC CotH3 does not lead to sensitivity to cell wall stress (induced by
CC Congo Red, Calcofluor White, hydrogen peroxide, sodium dodecyl sulfate,
CC or Triton X-100) (PubMed:24355926). {ECO:0000269|PubMed:24355926,
CC ECO:0000269|PubMed:27159390}.
CC -!- BIOTECHNOLOGY: Antibodies against CotH2 protects mice from
CC mucormycosis, and thus could potentially be used to treat the disease.
CC {ECO:0000305|PubMed:24355926, ECO:0000305|PubMed:31206021}.
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DR EMBL; CH476737; EIE83324.1; -; Genomic_DNA.
DR SMR; I1C4E4; -.
DR EnsemblFungi; EIE83324; EIE83324; RO3G_08029.
DR VEuPathDB; FungiDB:RO3G_08029; -.
DR eggNOG; ENOG502SKY8; Eukaryota.
DR InParanoid; I1C4E4; -.
DR OMA; EWFDINT; -.
DR OrthoDB; 405193at2759; -.
DR PHI-base; PHI:4142; -.
DR Proteomes; UP000009138; Unassembled WGS sequence.
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:0046789; F:host cell surface receptor binding; IDA:UniProtKB.
DR GO; GO:0044652; P:adhesion of symbiont to host endothelial cell; IDA:UniProtKB.
DR GO; GO:0044409; P:entry into host; IMP:UniProtKB.
DR InterPro; IPR014867; Spore_coat_CotH_CotH2/3/7.
DR Pfam; PF08757; CotH; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Reference proteome; Signal; Virulence.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..594
FT /note="Invasin CotH2"
FT /evidence="ECO:0000255"
FT /id="PRO_5003637889"
FT PROPEP 572..594
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000453693"
FT REGION 528..565
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 531..565
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 571
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 519
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 533
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 594 AA; 65254 MW; 08DB8CEA6938BAF4 CRC64;
MKLSLTIVSS SFLVAIAHAA SVQFNLIAPS ATDVKVSVNG QQVALTASDP NVPYFTGSAE
VGGTEESFER SLAGITNSTF NDFYNRPVTY ANLPQLPWPI ENDPQWTRKG KKAEIFDDNY
IPSVFFHGDD SQVQDLVKNV PKDKVTGTLT FIGSNYVHSF ANVSFGIHGA GKKHNNAKQS
WKWTLSGTDT MGNRNHFKLR HMEEDPTQIR ERLYADILHA MGTYANETTM VRLFINGQGF
GTFNMLDDIT EFSYINAMFY GGNPPATLGP LFDGASGADF IYHPGNLDGY SSWKPNKDNA
NGEGYEAFDP LCKAWNETDY TDNTAIANFE KMFDTEHFLR FMVIEYLTAH WDGYWMGQTN
DGAYRDPSDN NKWYFLDQDF DATFGVNLDV PENKDFISVS YKDFPSRYPA GVMANGLLQN
ADKKAKFEQY LTETVRVLFN NVTLTNRVLA IHNFLSPDLE WDRSIVQQSP GTNFGWTFEQ
TSQNLWQGVS APNNNGGGAE WGLVEYIAAK SQAMAKEFNI TIVSEPVGPP AANGTATSTN
DGGNTHTAAG ESKPASSSES SGSKIASQSV SGASRSAVST VLLGVTALVA TAIF
