HNM1/YGL077C Summary

Standard Name	HNM1 1 (see Nomenclature conflict Note)
Systematic Name	YGL077C
Alias	CTR1 2
Feature Type	ORF, Verified
Description	Choline/ethanolamine transporter; involved in the uptake of nitrogen mustard and the uptake of glycine betaine during hypersaline stress; co-regulated with phospholipid biosynthetic genes and negatively regulated by choline and myo-inositol (1, 3, 4, 5, 6 and see Summary Paragraph)
Name Description	Hyper-resistance to Nitrogen Mustard 7

Chromosomal Location	ChrVII:363916 to 362225 \| ORF Map \| GBrowse
	Note: this feature is encoded on the Crick strand.

Gene Ontology Annotations All HNM1 GO evidence and references

	View Computational GO annotations for HNM1
Molecular Function
Manually curated	choline transmembrane transporter activity (IGI, IMP) ethanolamine transmembrane transporter activity (IGI)
Biological Process
Manually curated	choline transport (IGI, IMP) ethanolamine transport (IGI) glycine betaine transport (IMP)
Cellular Component
Manually curated	plasma membrane (ISS)
High-throughput	integral to membrane (ISM)

Mutant phenotypes All HNM1 Phenotype evidence and references

Classical genetics
null	dessication resistance: decreased hyperosmotic stress resistance: decreased nutrient uptake: absent nutrient uptake: decreased resistance to choline analog G25: increased small molecule transport: decreased viable
overexpression	resistance to mechlorethamine: decreased
unspecified	resistance to 2-hydroxyethylhydrazine: increased resistance to mechlorethamine: increased
Large-scale survey
null	competitive fitness: increased haploproficient resistance to cycloheximide: decreased resistance to tirapazamine: increased resistance to amitrole: decreased vacuolar morphology: abnormal viable
overexpression	vegetative growth: decreased
Resources	PROPHECY \| SCMD \| ScreenTroll \| Yeast Fitness Database

interactions All HNM1 Interaction evidence and references

	103 total interaction(s) for 93 unique genes/features.
Physical Interactions	Affinity Capture-MS: 2 PCA: 56 Protein-RNA: 1 Reconstituted Complex: 1
Genetic Interactions	Dosage Growth Defect: 2 Dosage Lethality: 2 Negative Genetic: 25 Phenotypic Enhancement: 1 Positive Genetic: 10 Synthetic Growth Defect: 1 Synthetic Lethality: 1 Synthetic Rescue: 1
Resources	BioGRID \| BOND \| BioPIXIE \| CYC2008 (complexes) \| Complexome \| DIP \| DRYGIN \| GeneMANIA \| InterologFinder

Expression Summary


Resources	Expression Summary \| Cell cycle and metabolic oscillation \| Cell cycle transcript profile \| Cyclebase \| Genevestigator \| GermOnline \| SPELL \| YMGV \| YeastFunc

Protein Information All HNM1 Protein evidence and references

Localization	YeastRC \| YPL+ \| YeastGFP
Phosphorylation	PhosphoGRID \| PhosphoPep Database
Structure	GPMDB \| SCOP \| YeastRC
Homologs	Ashbya (AGD) \| AspGD Homologs \| CGD Homologs \| CandidaDB Homologs \| Fungal Orthogroups Repository \| P-POD \| PDB Homologs \| PhylomeDB \| YGOB \| YOGY

sequence information

ChrVII:363916 to 362225 | |

Note: this feature is encoded on the Crick strand.

Last Update

Coordinates: 2011-02-03 | Sequence: 1996-07-31

Subfeature details

	Relative Coordinates	Chromosomal Coordinates	Most Recent Updates
	Relative Coordinates	Chromosomal Coordinates	Coordinates	Sequence
CDS	1..1692	363916..362225	2011-02-03	1996-07-31

Retrieve sequences

Analyze Sequence

S288C only	BLASTP \| ATCC/WashU Clones \| BLASTN \| Design Primers \| Restriction Fragment Map \| Restriction Fragment Sizes \| Six-Frame Translation
S288C vs. other species	Fungal Alignment \| BLASTN vs. fungi \| BLASTP at NCBI \| BLASTP vs. fungi \| Synteny Viewer
S288C vs. other strains	Strain Alignment

Resources

External Links	All Associated Seq \| Entrez Gene \| Entrez RefSeq Protein \| MIPS \| Search all NCBI (Entrez) \| TCDB \| UniProtKB

Primary SGDID	S000003045

NOMENCLATURE CONFLICT NOTE

Name	Relevance	Description
CTR1	Nomenclature conflict	Both CTR1/YPR124W and HNM1/YGL077C have been referred to as CTR1.

SUMMARY PARAGRAPH for HNM1

HNM1 encodes a high affinity permease involved in the active transport of choline and ethanolamine, which are used as precursors for the biosynthesis of phosphatidylcholine and phosphatidylethanolamine, respectively (8, 5, 4). During hypersaline stress, Hnm1p is involved in the uptake of glycine betaine as well as choline. When cells are exposed to high-salt stress, phosphatidylcholine turnover increases and choline is used for the biosynthesis of two methylamine osmoprotectants, glycerophosphocholine and glycine betaine (6). In HNM1 deletion mutants grown on high salt-containing medium, the transport of choline and glycine betaine is almost eliminated, as is the choline- and glycine betaine-mediated growth enhancement observed in wild-type cultures (6). Based on both functional and phylogenetic criteria, Hnm1p has been classified as a member of the amino acid/choline transporter (ACT) subfamily, TC 2.A.3.4, (9, 10), and by sequence similarity is most closely related to Uga4p, the yeast gamma-aminobutyrate (GABA) transporter (11).

In addition to its role in the transport of phospholipid biosynthetic precursors and osmoprotectants, HNM1 has been identified as a target of the toxic effects of the DNA alkylating agents nitrogen mustard (HN2) and nitrogen half-mustard, such that these compounds competitively inhibit choline transport (7, 12). Mutant strains defective in choline transport are nitrogen mustard hyper-resistant, while HNM1 overexpression results in HN2 hyper-sensitivity that is dependent upon the concentration of choline and inositol in the growth medium, and the cellular capacity to repair HN2-induced DNA damage (7, 1, 12).

Expression of HNM1 is co-regulated along with genes involved in phospholipid biosynthesis (3). HNM1 transcription is strongly repressed by the phospholipid precursors myo-inositol and choline, with myo-inositol alone having a weak repressive effect (4, 3). Two promoter regions contribute to this regulation, a UAS-INO element that is responsive to transcriptional activators, Ino2p and Ino4p, as well as the transcriptional corepressor, Opi1p and a second region that responds to Ino4p, but not Ino2p (3).

Last updated: 2008-02-28

References cited on this page View Complete Literature Guide for HNM1

1)	Li ZY, et al. (1991) Hyper-resistance to nitrogen mustard in Saccharomyces cerevisiae is caused by defective choline transport. Curr Genet 19(6):423-7
2)	Matsushita M and Nikawa J (1995) Isolation and characterization of a SCT1 gene which can suppress a choline-transport mutant of Saccharomyces cerevisiae. J Biochem 117(2):447-51
3)	Li Z and Brendel M (1993) Co-regulation with genes of phospholipid biosynthesis of the CTR/HNM1-encoded choline/nitrogen mustard permease in Saccharomyces cerevisiae. Mol Gen Genet 241(5-6):680-4
4)	Nikawa J, et al. (1990) Primary structure of the yeast choline transport gene and regulation of its expression. J Biol Chem 265(26):15996-6003
5)	Nikawa J, et al. (1986) Cloning of a gene encoding choline transport in Saccharomyces cerevisiae. J Bacteriol 166(1):328-30
6)	Kiewietdejonge A, et al. (2006) Hypersaline stress induces the turnover of phosphatidylcholine and results in the synthesis of the renal osmoprotectant glycerophosphocholine in Saccharomyces cerevisiae. FEMS Yeast Res 6(2):205-17
7)	Haase E and Brendel M (1990) A recessive mutant allele of the HNM1 gene of Saccharomyces cerevisiae is responsible for hyper-resistance to nitrogen mustard. Curr Genet 18(3):187-92
8)	Mondoux MA and Zakian VA (2007) Subtelomeric Elements Influence But Do Not Determine Silencing Levels at Saccharomyces cerevisiae Telomeres. Genetics 177(4):2541-6
9)	Saier MH Jr (2000) A functional-phylogenetic classification system for transmembrane solute transporters. Microbiol Mol Biol Rev 64(2):354-411
10)	De Hertogh B, et al. (2002) Phylogenetic classification of transporters and other membrane proteins from Saccharomyces cerevisiae. Funct Integr Genomics 2(4-5):154-70
11)	Andre B, et al. (1993) Cloning and expression of the UGA4 gene coding for the inducible GABA-specific transport protein of Saccharomyces cerevisiae. Mol Gen Genet 237(1-2):17-25
12)	Li Z and Brendel M (1994) Sensitivity to nitrogen mustard in Saccharomyces cerevisiae is independently determined by regulated choline permease and DNA repair. Mutat Res 315(2):139-45