Q03689 (HETS_PODAS) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Heterokaryon incompatibility protein s

Alternative name(s):
Small s protein
Vegetative incompatibility protein s

Gene names

Name:	het-s
Synonyms:	small s

Organism

Podospora anserina (Pleurage anserina)

Taxonomic identifier

5145 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Pezizomycotina › leotiomyceta › sordariomyceta › Sordariomycetes › Sordariomycetidae › Sordariales › Lasiosphaeriaceae › Podospora

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Responsible for heterokaryon incompatibility, a process that ensures that during spontaneous, vegetative cell fusion only compatible cells from the same colony survive (non-self-recognition). Forms a prion for the non-Mendelian trait [het-s]. Interacts with het-S from incompatible cells to trigger a lethal reaction that prevents the formation of viable heterokaryons. It is unknown if the native, soluble protein has a cellular function. Ref.1 Ref.2 Ref.3
Subunit structure	Homodimer. Forms heterodimers with het-S.
Subcellular location	Cytoplasm.
Domain	The globular domain is dispensable for prion formation and incompatibility function. However, the het-S globular domain, but not the het-s globular domain, is essential for programmed cell death. Ref.5 Ref.6 Ref.9 The prion domain (PrD) is unstructured in its native, soluble form, and forms a form a beta solenoid with a hydrophobic core in its amyloid form. It is both necessary and sufficient for amyloid formation and prion propagation. Ref.5 Ref.6 Ref.9
Miscellaneous	[Het-s] is the prion form of het-s (Ref.3). [Het-s] is the result of a conformational change of the cellular het-s protein that becomes self-propagating and infectious. This conformational change generates a form of het-S that assembles into amyloid fibrils (Ref.4). [Het-s] is transmitted as a non-Mendelian cytplasmic element. On vegetative cell fusion with neutral [Het-s*] strains, the prion spreads throuhout the cellular network and converts the non-prion form of het-s to a prion state, making the strains acquire the [het-s] phenotype (Ref.3). Interacts with het-S to trigger incompatibility (Ref.4). The protein present in [Het-s] strains is more resistant to proteinase K than that present in [Het-s*] mycelium (Ref.3). In P.anserina, the het-s locus exists as 2 incompatible alleles, het-s and het-S. Strains of het-s genotype (e.g. A, C, s, and V) can display 2 distinct phenoypes, the neutral (prion-free) [Het-s*], which is compatible with het-S strains (e.g. D, S, U, and X), and the reactive [Het-s] phenotype, which causes rapid cell death in het-S strains. Although the two alleles het-s and het-S differ from each other by 14 amino acids, vegetative incompatibility between s and S strains can be attributed to a single amino acid difference in the proteins encoded by the het-s locus (Ref.2). A sequence for the het-S allele can be found in strain S (AC B2ACC7).

Ontologies

Keywords
Cellular component	Amyloid Cytoplasm
Molecular function	Prion
Technical term	3D-structure
Gene Ontology (GO)
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 289

289

Heterokaryon incompatibility protein s

PRO_0000417569

Regions

Region

1 – 227

227

Globular domain

Region

218 – 289

72

Prion domain (PrD)

Experimental info

Mutagenesis

23

1

D → A: Converts its specificity to [Het-S]; when associated with H-33. Ref.2

Mutagenesis

33

1

P → H: Converts its specificity to [Het-S]; when associated with A-23. Ref.2

Secondary structure

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289

Helix Strand Turn

Details...

Helix

14 – 24

11

Helix

25 – 27

3

Beta strand

28 – 31

4

Helix

32 – 37

6

Helix

38 – 58

21

Turn

59 – 63

5

Helix

65 – 68

4

Beta strand

69 – 71

3

Helix

75 – 104

30

Helix

107 – 110

4

Helix

115 – 117

3

Helix

120 – 136

17

Beta strand

148 – 150

3

Helix

153 – 172

20

Turn

173 – 175

3

Helix

177 – 187

11

Helix

194 – 203

10

Turn

204 – 207

4

Helix

209 – 220

12

Beta strand

226 – 236

11

Beta strand

238 – 245

8

Turn

247 – 249

3

Beta strand

261 – 272

12

Beta strand

274 – 283

10

Sequences

	Sequence		Length	Mass (Da)
	Q03689 [UniParc]. Last modified July 5, 2004. Version 3. Checksum: D37468804C3DC793	FASTA	289	31,978
	10 20 30 40 50 60 MSEPFGIVAG ALNVAGLFNN CVDCFEYVQL GRPFGRDYER CQLRLDIAKA RLSRWGEAVK 70 80 90 100 110 120 INDDPRFHSD APTDKSVQLA KSIVEEILLL FESAQKTSKR YELVADQQDL VVFEDKDMKP 130 140 150 160 170 180 IGRALHRRLN DLVSRRQKQT SLAKKTAWAL YDGKSLEKIV DQVARFVDEL EKAFPIEAVC 190 200 210 220 230 240 HKLAEIEIEE VEDEASLTIL KDAAGGIDAA MSDAAAQKID AIVGRNSAKD IRTEERARVQ 250 260 270 280 LGNVVTAAAL HGGIRISDQT TNSVETVVGK GESRVLIGNE YGGKGFWDN

References

[1]	"Two allelic genes responsible for vegetative incompatibility in the fungus Podospora anserina are not essential for cell viability." Turcq B., Deleu C., Denayrolles M., Begueret J. Mol. Gen. Genet. 228:265-269(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION. Strain: s / FGSC 6710.
[2]	"A single amino acid difference is sufficient to elicit vegetative incompatibility in the fungus Podospora anserina." Deleu C., Clave C., Begueret J. Genetics 135:45-52(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, MUTAGENESIS OF ASP-23 AND PRO-33. Strain: A, C, s / FGSC 6710 and V.
[3]	"The protein product of the het-s heterokaryon incompatibility gene of the fungus Podospora anserina behaves as a prion analog." Coustou V., Deleu C., Saupe S., Begueret J. Proc. Natl. Acad. Sci. U.S.A. 94:9773-9778(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PRION IDENTIFICATION, FUNCTION, INTERACTION WITH HET-S.
[4]	"Amyloid aggregates of the HET-s prion protein are infectious." Maddelein M.L., Dos Reis S., Duvezin-Caubet S., Coulary-Salin B., Saupe S.J. Proc. Natl. Acad. Sci. U.S.A. 99:7402-7407(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PRION FORMATION.
[5]	"Domain organization and structure-function relationship of the HET-s prion protein of Podospora anserina." Balguerie A., Dos Reis S., Ritter C., Chaignepain S., Coulary-Salin B., Forge V., Bathany K., Lascu I., Schmitter J.M., Riek R., Saupe S.J. EMBO J. 22:2071-2081(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PRION FORMATION, DOMAIN.
[6]	"The sequences appended to the amyloid core region of the HET-s prion protein determine higher-order aggregate organization in vivo." Balguerie A., Dos Reis S., Coulary-Salin B., Chaignepain S., Sabourin M., Schmitter J.M., Saupe S.J. J. Cell Sci. 117:2599-2610(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PRION FORMATION, DOMAIN.
[7]	"Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a triangular hydrophobic core." Wasmer C., Lange A., Van Melckebeke H., Siemer A.B., Riek R., Meier B.H. Science 319:1523-1526(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 218-289.
[8]	"Atomic-resolution three-dimensional structure of HET-s(218-289) amyloid fibrils by solid-state NMR spectroscopy." Van Melckebeke H., Wasmer C., Lange A., Ab E., Loquet A., Bockmann A., Meier B.H. J. Am. Chem. Soc. 132:13765-13775(2010) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 218-289.
[9]	"The mechanism of prion inhibition by HET-S." Greenwald J., Buhtz C., Ritter C., Kwiatkowski W., Choe S., Maddelein M.L., Ness F., Cescau S., Soragni A., Leitz D., Saupe S.J., Riek R. Mol. Cell 38:889-899(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 13-221, PRION FORMATION, DOMAIN.
[10]	"The amyloid-Congo red interface at atomic resolution." Schutz A.K., Soragni A., Hornemann S., Aguzzi A., Ernst M., Bockmann A., Meier B.H. Angew. Chem. Int. Ed. 50:5956-5960(2011) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 218-289.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M38529 Genomic DNA. Translation: AAB94631.1.

PIR

S16556.
S16557.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KJ3	NMR	-	A/B/C	218-289	[»]
2LBU	NMR	-	A/B/C/D/E	218-289	[»]
2RNM	NMR	-	A/B/C/D/E	218-289	[»]
2WVN	X-ray	2.62	A	1-227	[»]
2WVQ	X-ray	2.00	A/B	13-221	[»]

ProteinModelPortal

Q03689.

SMR

Q03689. Positions 218-289.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-58535N.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR021084. HET-s_C.
[Graphical view]

Pfam

PF11558. HET-s_218-289. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q03689.

Entry information

Entry name

HETS_PODAS

Accession

Primary (citable) accession number: Q03689
Secondary accession number(s): Q01531

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 13, 2012
Last sequence update:	July 5, 2004
Last modified:	April 3, 2013
This is version 45 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program