HNM1/YGL077C Summary Help

Standard Name HNM1 1
Systematic Name YGL077C
Alias CTR1 2
Feature Type ORF, Verified
Description Plasma membrane transporter for choline, ethanolamine, and carnitine; 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, 7 and see Summary Paragraph)
Name Description Hyper-resistance to Nitrogen Mustard 8
Chromosomal Location
ChrVII:363916 to 362225 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All HNM1 GO evidence and references
  View Computational GO annotations for HNM1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 3 genes
Resources
Classical genetics
null
overexpression
unspecified
Large-scale survey
null
overexpression
Resources
106 total interaction(s) for 93 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-Western: 1
  • 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
Expression Summary
histogram
Resources
Length (a.a.) 563
Molecular Weight (Da) 62,055
Isoelectric Point (pI) 6.83
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:363916 to 362225 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1692 363916..362225 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000003045
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 (9, 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, (10, 11), and by sequence similarity is most closely related to Uga4p, the yeast gamma-aminobutyrate (GABA) transporter (12).

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 (8, 13). 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 (8, 1, 13).

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 Contact SGD

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 (Tokyo) 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) Aouida M, et al.  (2013) Agp2, a member of the yeast amino Acid permease family, positively regulates polyamine transport at the transcriptional level. PLoS One 8(6):e65717
8) 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
9) Mondoux MA and Zakian VA  (2007) Subtelomeric Elements Influence But Do Not Determine Silencing Levels at Saccharomyces cerevisiae Telomeres. Genetics 177(4):2541-6
10) Saier MH Jr  (2000) A functional-phylogenetic classification system for transmembrane solute transporters. Microbiol Mol Biol Rev 64(2):354-411
11) 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
12) 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
13) 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