HETS_PODAS
ID HETS_PODAS Reviewed; 289 AA.
AC Q03689; Q01531;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Heterokaryon incompatibility protein s;
DE AltName: Full=Small s protein;
DE AltName: Full=Vegetative incompatibility protein s;
GN Name=het-s; Synonyms=small s;
OS Podospora anserina (Pleurage anserina).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Podosporaceae; Podospora.
OX NCBI_TaxID=2587412;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=s / FGSC 6710;
RX PubMed=1886611; DOI=10.1007/bf00282475;
RA Turcq B., Deleu C., Denayrolles M., Begueret J.;
RT "Two allelic genes responsible for vegetative incompatibility in the fungus
RT Podospora anserina are not essential for cell viability.";
RL Mol. Gen. Genet. 228:265-269(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF ASP-23 AND
RP PRO-33.
RC STRAIN=A, C, s / FGSC 6710, and V;
RX PubMed=8224826; DOI=10.1093/genetics/135.1.45;
RA Deleu C., Clave C., Begueret J.;
RT "A single amino acid difference is sufficient to elicit vegetative
RT incompatibility in the fungus Podospora anserina.";
RL Genetics 135:45-52(1993).
RN [3]
RP PRION IDENTIFICATION, FUNCTION, AND INTERACTION WITH HET-S.
RX PubMed=9275200; DOI=10.1073/pnas.94.18.9773;
RA Coustou V., Deleu C., Saupe S., Begueret J.;
RT "The protein product of the het-s heterokaryon incompatibility gene of the
RT fungus Podospora anserina behaves as a prion analog.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:9773-9778(1997).
RN [4]
RP PRION FORMATION.
RX PubMed=12032295; DOI=10.1073/pnas.072199199;
RA Maddelein M.L., Dos Reis S., Duvezin-Caubet S., Coulary-Salin B.,
RA Saupe S.J.;
RT "Amyloid aggregates of the HET-s prion protein are infectious.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7402-7407(2002).
RN [5]
RP PRION FORMATION, AND DOMAIN.
RX PubMed=12727874; DOI=10.1093/emboj/cdg213;
RA Balguerie A., Dos Reis S., Ritter C., Chaignepain S., Coulary-Salin B.,
RA Forge V., Bathany K., Lascu I., Schmitter J.M., Riek R., Saupe S.J.;
RT "Domain organization and structure-function relationship of the HET-s prion
RT protein of Podospora anserina.";
RL EMBO J. 22:2071-2081(2003).
RN [6]
RP PRION FORMATION, AND DOMAIN.
RX PubMed=15159455; DOI=10.1242/jcs.01116;
RA Balguerie A., Dos Reis S., Coulary-Salin B., Chaignepain S., Sabourin M.,
RA Schmitter J.M., Saupe S.J.;
RT "The sequences appended to the amyloid core region of the HET-s prion
RT protein determine higher-order aggregate organization in vivo.";
RL J. Cell Sci. 117:2599-2610(2004).
RN [7]
RP STRUCTURE BY NMR OF 218-289.
RX PubMed=18339938; DOI=10.1126/science.1151839;
RA Wasmer C., Lange A., Van Melckebeke H., Siemer A.B., Riek R., Meier B.H.;
RT "Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a
RT triangular hydrophobic core.";
RL Science 319:1523-1526(2008).
RN [8]
RP STRUCTURE BY NMR OF 218-289.
RX PubMed=20828131; DOI=10.1021/ja104213j;
RA Van Melckebeke H., Wasmer C., Lange A., Ab E., Loquet A., Bockmann A.,
RA Meier B.H.;
RT "Atomic-resolution three-dimensional structure of HET-s(218-289) amyloid
RT fibrils by solid-state NMR spectroscopy.";
RL J. Am. Chem. Soc. 132:13765-13775(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 13-221, PRION FORMATION, AND
RP DOMAIN.
RX PubMed=20620958; DOI=10.1016/j.molcel.2010.05.019;
RA Greenwald J., Buhtz C., Ritter C., Kwiatkowski W., Choe S., Maddelein M.L.,
RA Ness F., Cescau S., Soragni A., Leitz D., Saupe S.J., Riek R.;
RT "The mechanism of prion inhibition by HET-S.";
RL Mol. Cell 38:889-899(2010).
RN [10]
RP STRUCTURE BY NMR OF 218-289.
RX PubMed=21591034; DOI=10.1002/anie.201008276;
RA Schutz A.K., Soragni A., Hornemann S., Aguzzi A., Ernst M., Bockmann A.,
RA Meier B.H.;
RT "The amyloid-Congo red interface at atomic resolution.";
RL Angew. Chem. Int. Ed. 50:5956-5960(2011).
CC -!- FUNCTION: Responsible for heterokaryon incompatibility, a process that
CC ensures that during spontaneous, vegetative cell fusion only compatible
CC cells from the same colony survive (non-self-recognition). Forms a
CC prion for the non-Mendelian trait [het-s]. Interacts with het-S from
CC incompatible cells to trigger a lethal reaction that prevents the
CC formation of viable heterokaryons. It is unknown if the native, soluble
CC protein has a cellular function. {ECO:0000269|PubMed:1886611,
CC ECO:0000269|PubMed:8224826, ECO:0000269|PubMed:9275200}.
CC -!- SUBUNIT: Homodimer. Forms heterodimers with het-S.
CC -!- INTERACTION:
CC Q03689; Q03689: het-s; NbExp=3; IntAct=EBI-15800884, EBI-15800884;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- DOMAIN: The globular domain is dispensable for prion formation and
CC incompatibility function. However, the het-S globular domain, but not
CC the het-s globular domain, is essential for programmed cell death.
CC -!- DOMAIN: The prion domain (PrD) is unstructured in its native, soluble
CC form, and forms a form a beta solenoid with a hydrophobic core in its
CC amyloid form. It is both necessary and sufficient for amyloid formation
CC and prion propagation.
CC -!- MISCELLANEOUS: [Het-s] is the prion form of het-s (PubMed:9275200).
CC [Het-s] is the result of a conformational change of the cellular het-s
CC protein that becomes self-propagating and infectious. This
CC conformational change generates a form of het-S that assembles into
CC amyloid fibrils (PubMed:12032295). [Het-s] is transmitted as a non-
CC Mendelian cytoplasmic element. On vegetative cell fusion with neutral
CC [Het-s*] strains, the prion spreads throughout the cellular network and
CC converts the non-prion form of het-s to a prion state, making the
CC strains acquire the [het-s] phenotype (PubMed:9275200). Interacts with
CC het-S to trigger incompatibility (PubMed:12032295). The protein present
CC in [Het-s] strains is more resistant to proteinase K than that present
CC in [Het-s*] mycelium (PubMed:9275200). {ECO:0000305|PubMed:12032295,
CC ECO:0000305|PubMed:9275200}.
CC -!- MISCELLANEOUS: In P.anserina, the het-s locus exists as 2 incompatible
CC alleles, het-s and het-S. Strains of het-s genotype (e.g. A, C, s, and
CC V) can display 2 distinct phenoypes, the neutral (prion-free) [Het-s*],
CC which is compatible with het-S strains (e.g. D, S, U, and X), and the
CC reactive [Het-s] phenotype, which causes rapid cell death in het-S
CC strains. Although the two alleles het-s and het-S differ from each
CC other by 14 amino acids, vegetative incompatibility between s and S
CC strains can be attributed to a single amino acid difference in the
CC proteins encoded by the het-s locus (PubMed:8224826). A sequence for
CC the het-S allele can be found in strain S (AC B2ACC7).
CC {ECO:0000305|PubMed:8224826}.
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DR EMBL; M38529; AAB94631.1; -; Genomic_DNA.
DR PIR; S16556; S16556.
DR PIR; S16557; S16557.
DR PDB; 2KJ3; NMR; -; A/B/C=218-289.
DR PDB; 2LBU; NMR; -; A/B/C/D/E=218-289.
DR PDB; 2MUS; NMR; -; A/B/C/D/E=218-289.
DR PDB; 2RNM; NMR; -; A/B/C/D/E=218-289.
DR PDB; 2WVN; X-ray; 2.62 A; A=1-227.
DR PDB; 2WVQ; X-ray; 2.00 A; A/B=13-221.
DR PDBsum; 2KJ3; -.
DR PDBsum; 2LBU; -.
DR PDBsum; 2MUS; -.
DR PDBsum; 2RNM; -.
DR PDBsum; 2WVN; -.
DR PDBsum; 2WVQ; -.
DR AlphaFoldDB; Q03689; -.
DR BMRB; Q03689; -.
DR SMR; Q03689; -.
DR DIP; DIP-58535N; -.
DR IntAct; Q03689; 1.
DR TCDB; 1.C.104.1.1; the heterokaryon incompatibility prion/amyloid protein (het-s) family.
DR VEuPathDB; FungiDB:PODANS_3_620; -.
DR EvolutionaryTrace; Q03689; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR DisProt; DP02317; -.
DR Gene3D; 1.20.120.1020; -; 1.
DR InterPro; IPR029498; HeLo_dom.
DR InterPro; IPR038305; HeLo_sf.
DR InterPro; IPR021084; Het-s_prion_dom.
DR Pfam; PF14479; HeLo; 1.
DR Pfam; PF11558; HET-s_218-289; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyloid; Cytoplasm; Prion.
FT CHAIN 1..289
FT /note="Heterokaryon incompatibility protein s"
FT /id="PRO_0000417569"
FT REGION 1..227
FT /note="Globular domain"
FT REGION 218..289
FT /note="Prion domain (PrD)"
FT MUTAGEN 23
FT /note="D->A: Converts its specificity to [Het-S]; when
FT associated with H-33."
FT /evidence="ECO:0000269|PubMed:8224826"
FT MUTAGEN 33
FT /note="P->H: Converts its specificity to [Het-S]; when
FT associated with A-23."
FT /evidence="ECO:0000269|PubMed:8224826"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:2WVQ"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 32..37
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 38..58
FT /evidence="ECO:0007829|PDB:2WVQ"
FT TURN 59..63
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 65..68
FT /evidence="ECO:0007829|PDB:2WVQ"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:2WVN"
FT HELIX 75..104
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 107..110
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 120..136
FT /evidence="ECO:0007829|PDB:2WVQ"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 153..172
FT /evidence="ECO:0007829|PDB:2WVQ"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 177..187
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 194..203
FT /evidence="ECO:0007829|PDB:2WVQ"
FT TURN 204..207
FT /evidence="ECO:0007829|PDB:2WVQ"
FT HELIX 209..220
FT /evidence="ECO:0007829|PDB:2WVQ"
FT STRAND 226..236
FT /evidence="ECO:0007829|PDB:2KJ3"
FT STRAND 238..245
FT /evidence="ECO:0007829|PDB:2KJ3"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:2KJ3"
FT STRAND 261..272
FT /evidence="ECO:0007829|PDB:2KJ3"
FT STRAND 274..283
FT /evidence="ECO:0007829|PDB:2KJ3"
SQ SEQUENCE 289 AA; 31978 MW; D37468804C3DC793 CRC64;
MSEPFGIVAG ALNVAGLFNN CVDCFEYVQL GRPFGRDYER CQLRLDIAKA RLSRWGEAVK
INDDPRFHSD APTDKSVQLA KSIVEEILLL FESAQKTSKR YELVADQQDL VVFEDKDMKP
IGRALHRRLN DLVSRRQKQT SLAKKTAWAL YDGKSLEKIV DQVARFVDEL EKAFPIEAVC
HKLAEIEIEE VEDEASLTIL KDAAGGIDAA MSDAAAQKID AIVGRNSAKD IRTEERARVQ
LGNVVTAAAL HGGIRISDQT TNSVETVVGK GESRVLIGNE YGGKGFWDN
