COTH3_RHIO9
ID COTH3_RHIO9 Reviewed; 601 AA.
AC I1CFE1;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 25-MAY-2022, entry version 34.
DE RecName: Full=Invasin CotH3 {ECO:0000303|PubMed:24355926};
DE AltName: Full=Spore coat protein homolog 3 {ECO:0000303|PubMed:24355926};
DE Flags: Precursor;
GN Name=CotH3 {ECO:0000303|PubMed:24355926};
GN ORFNames=RO3G_11882 {ECO:0000312|EMBL:EIE87171.1};
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).
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HOST HSPA5/BIP, DISRUPTION PHENOTYPE, AND
RP BIOTECHNOLOGY.
RX PubMed=32487760; DOI=10.1128/mbio.01087-20;
RA Alqarihi A., Gebremariam T., Gu Y., Swidergall M., Alkhazraji S.,
RA Soliman S.S.M., Bruno V.M., Edwards J.E. Jr., Filler S.G., Uppuluri P.,
RA Ibrahim A.S.;
RT "GRP78 and Integrins Play Different Roles in Host Cell Invasion during
RT Mucormycosis.";
RL MBio 11:e01087-e01087(2020).
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, PubMed:32487760). Binds
CC HSPA5/BiP protein on the cell surface of host nasal epithelial cells
CC (PubMed:24355926). {ECO:0000269|PubMed:24355926,
CC ECO:0000269|PubMed:32487760}.
CC -!- SUBUNIT: Interacts with HSPA5/BiP on the cell surface of host nasal
CC epithelial cells. {ECO:0000269|PubMed:24355926,
CC ECO:0000305|PubMed:32487760}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24355926};
CC Lipid-anchor, GPI-anchor {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Expressed in spores (PubMed:24355926). Expressed
CC in germlings (PubMed:24355926). {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 (PubMed:27159390). Induced during growth in
CC high glucose (PubMed:27159390). Induced in presence of 3-hydroxybutyric
CC acid (BHB) (PubMed:27159390). {ECO:0000269|PubMed:24355926,
CC ECO:0000269|PubMed:27159390}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown decreases invasion of
CC human nasal epithelial cells by R.delemar (PubMed:32487760).
CC Simultaneous RNAi-mediated knockdown of CotH2 and CotH3 decreases
CC invasion of human epithelial cells (PubMed:24355926). Simultaneous
CC RNAi-mediated knockdown of CotH2 and CotH3 decreases virulence in a
CC mouse model of ketoacidosis (PubMed:24355926, PubMed:27159390).
CC Simultaneous RNAi-mediated knockdown of CotH2 and CotH3 does not lead
CC to sensitivity to cell wall stress (induced by Congo Red, Calcofluor
CC White, hydrogen peroxide, sodium dodecyl sulfate, or Triton X-100) or
CC alter resistance to killing by phagocytes (PubMed:24355926).
CC {ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:27159390,
CC ECO:0000269|PubMed:32487760}.
CC -!- BIOTECHNOLOGY: Antibodies against the protein protects a diabetic
CC ketoacidotic (DKA) mouse model and a neutropenic mouse model from
CC mucormycosis infection, and nasal epithelial cells from invasion by
CC R.delemar, and thus could potentially be used to treat the disease.
CC {ECO:0000305|PubMed:24355926, ECO:0000305|PubMed:31206021,
CC ECO:0000305|PubMed:32487760}.
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DR EMBL; CH476740; EIE87171.1; -; Genomic_DNA.
DR SMR; I1CFE1; -.
DR EnsemblFungi; EIE87171; EIE87171; RO3G_11882.
DR VEuPathDB; FungiDB:RO3G_11882; -.
DR eggNOG; ENOG502SKY8; Eukaryota.
DR InParanoid; I1CFE1; -.
DR OMA; HEFLLPD; -.
DR OrthoDB; 405193at2759; -.
DR PHI-base; PHI:4143; -.
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:0044651; P:adhesion of symbiont to host epithelial cell; IDA:UniProtKB.
DR GO; GO:0044409; P:entry into host; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
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..17
FT /evidence="ECO:0000255"
FT CHAIN 18..601
FT /note="Invasin CotH3"
FT /evidence="ECO:0000255"
FT /id="PRO_5003638081"
FT PROPEP 580..601
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000453694"
FT REGION 539..581
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 555..581
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 579
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 85
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 CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 527
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 541
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 554
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 571
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 601 AA; 65759 MW; DCCA6BBD264A4DB2 CRC64;
MKLSIISAAF LVAITHAASI KFNVIAPNAT DVKVSVNGQQ VTLTASDANV PYFTGSAEVG
ASKTYKYVAG GTEESFDRSL DGITNSTLND FYNRPVTYAN LPQLPWPIEK DPQWTRSGSK
ADIFDDNYIP SVFFHGDDSQ VQNVVKNVPA DRISGTLTFI GSNYVYSFQN VSFGIHGAGK
KHNNAKQSWN WILSGSDTMG NRNFFKLRHM EEDPTQIRER LYSDILHAMG TYANDATMVR
LFINNQGFGT FNMLDDITQF SYINAKFYNG KPPATLGPLY DGASGADFLY HPGNLDGYSS
WVANTANPNG EAYEALDPLC KAWNETTYTD NTAIANFEKM FDLDRFMRFM VIEYLTADWD
GYWMGQTNDG AYRDPTDNNK WYFLDQDFDG TFGVNLAAPE GNAFLDVSYK DFPSRYPGAV
MINNLLQNAD KKATFEKYLT ETVRVLFNNV TLTNRVLALH NFLLPDLEWD RSIVQQSPGI
NFGWTFDQVT QNLWQGVTAP NNNGGGAAFG LVEYIAAKAQ AVAKEFNISI VSQPVGPPSA
NGTTAAAPAP AAGNSTGKGG NQSISSSASS NKTSAQSTSG ASRSKTAPIV LAISALALLV
F
