YHC3/YJL059W Summary Help

Standard Name YHC3 1
Systematic Name YJL059W
Alias BTN1 2
Feature Type ORF, Verified
Description Protein required for the ATP-dependent transport of arginine; vacuolar membrane protein; involved in the ATP-dependent transport of arginine into the vacuole and possibly in balancing ion homeostasis; homolog of human CLN3 involved in Batten disease (juvenile onset neuronal ceroid lipofuscinosis) (1, 2, 3, 4, 5 and see Summary Paragraph)
Name Description Yeast Homolog of human Cln3 1
Chromosomal Location
ChrX:324964 to 326190 | ORF Map | GBrowse
Gene Ontology Annotations All YHC3 GO evidence and references
  View Computational GO annotations for YHC3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Classical genetics
Large-scale survey
27 total interaction(s) for 22 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 1
  • PCA: 2

Genetic Interactions
  • Dosage Growth Defect: 4
  • Negative Genetic: 6
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 2
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 2
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 408
Molecular Weight (Da) 46,383
Isoelectric Point (pI) 7.15
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrX:324964 to 326190 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1227 324964..326190 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003595

Yhc3p is a vacuolar protein required for the ATP-dependent transport of arginine into the yeast vacuole, a process that also requires a functional vacuolar H+-ATPase (V-ATPase) complex (3, 6, 4). Yhc3p is also involved in vacuolar pH maintenance as deletion strains display abnormally acidic vacuolar pH during the early phases of growth (6). As a result the activity of the V-ATPase is down-regulated in deletion strains to compensate for the vacuolar pH imbalance (7). The altered ability to maintain pH homeostasis in the deletion strain results in an elevated rate of medium acidification during early growth that correlates with increased plasma membrane H+-ATPase activity, encoded by the Pma1p and Pma2p isozymes (8). The elevated acidification results in increased resistance to D-(-)-threo-2-amino-1-[p-nitrophenyl]-1,3-propanediol (ANP), a product derived from chloramphenicol (9, 10). Several phenotypes associated with deletion of YHC3 are altered by addition of chloroquine to the growth medium including elevation of vacuolar pH, reversal of ANP resistance, decreased acidification of the growth medium, and decreased activity of the plasma membrane H+-ATPase (11).

Expression of HSP30 and BTN2 are specifically induced in the YHC3 deletion stain to compensate for the elevated vacuolar pH (6). Deletion of either HSP30 or BTN2 does not alter vacuolar pH, but does increase the activity of the V-ATPase in late growth phase (12). Hsp30p, a plasma membrane localized heat shock protein, may also act to down regulate the activity of the plasma membrane H+-ATPase (13). Btn2p is also known to be required for the correct localization of Rhb1p, a negative regulator of the Can1p plasma membrane arginine transporter, thereby modulating cellular arginine levels in the YHC3 deletion strain (14).

YHC3 has a high degree of functional and sequence similarity with the human CLN3 gene, mutations in which cause the progressive neurodegenerative Batten disease, also known as juvenile neuronal ceroid-lipofuscinoses (JNCL, OMIM), characterized by a decline in mental abilities, loss of motor skills, blindness, epileptic seizures and premature death (2, 1). Lysosomes (equivalent to the yeast vacuole) isolated from cell lines established from individuals with Batten disease display defective arginine transport which can be reversed by expression of CLN3 (15). In addition, cells derived from individuals with juvenile Batten disease are depleted for arginine and CLN3 antibodies block lysosomal arginine transport in normal lymphoblasts (15). Heterologous expression of human CLN3 in yeast complements the ANP resistance phenotype of YHC3 deletion strains, as well as the arginine transport defect further emphasizing the functional conservation associated with these orthologs (10, 9, 4).

Last updated: 2006-10-11 Contact SGD

References cited on this page View Complete Literature Guide for YHC3
1) Mitchison HM, et al.  (1997) Structure of the CLN3 gene and predicted structure, location and function of CLN3 protein. Neuropediatrics 28(1):12-4
2) Pearce DA and Sherman F  (1997) BTN1, a yeast gene corresponding to the human gene responsible for Batten's disease, is not essential for viability, mitochondrial function, or degradation of mitochondrial ATP synthase. Yeast 13(8):691-7
3) Croopnick JB, et al.  (1998) The subcellular location of the yeast Saccharomyces cerevisiae homologue of the protein defective in the juvenile form of Batten disease. Biochem Biophys Res Commun 250(2):335-41
4) Kim Y, et al.  (2003) A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the protein defective in Batten disease. Proc Natl Acad Sci U S A 100(26):15458-62
5) Kim Y, et al.  (2005) Interaction among Btn1p, Btn2p, and Ist2p reveals potential interplay among the vacuole, amino acid levels, and ion homeostasis in the yeast Saccharomyces cerevisiae. Eukaryot Cell 4(2):281-8
6) Pearce DA, et al.  (1999) Action of BTN1, the yeast orthologue of the gene mutated in Batten disease. Nat Genet 22(1):55-8
7) Padilla-Lopez S and Pearce DA  (2006) Saccharomyces cerevisiae lacking Btn1p modulate vacuolar ATPase activity to regulate pH imbalance in the vacuole. J Biol Chem 281(15):10273-80
8) Pearce DA, et al.  (1999) Studies of pH regulation by Btn1p, the yeast homolog of human Cln3p. Mol Genet Metab 66(4):320-3
9) Pearce DA and Sherman F  (1999) Investigation of Batten disease with the yeast Saccharomyces cerevisiae. Mol Genet Metab 66(4):314-9
10) Pearce DA and Sherman F  (1998) A yeast model for the study of Batten disease. Proc Natl Acad Sci U S A 95(12):6915-8
11) Pearce DA, et al.  (1999) Phenotypic reversal of the btn1 defects in yeast by chloroquine: a yeast model for Batten disease. Proc Natl Acad Sci U S A 96(20):11341-5
12) Chattopadhyay S, et al.  (2000) The yeast model for batten disease: mutations in BTN1, BTN2, and HSP30 alter pH homeostasis. J Bacteriol 182(22):6418-23
13) Piper PW, et al.  (1997) Hsp30, the integral plasma membrane heat shock protein of Saccharomyces cerevisiae, is a stress-inducible regulator of plasma membrane H(+)-ATPase. Cell Stress Chaperones 2(1):12-24
14) Chattopadhyay S and Pearce DA  (2002) Interaction with Btn2p is required for localization of Rsglp: Btn2p-mediated changes in arginine uptake in Saccharomyces cerevisiae. Eukaryot Cell 1(4):606-12
15) Ramirez-Montealegre D and Pearce DA  (2005) Defective lysosomal arginine transport in juvenile Batten disease. Hum Mol Genet 14(23):3759-73