DRS2/YAL026C Summary Help

Standard Name DRS2 1
Systematic Name YAL026C
Alias FUN38 , SWA3
Feature Type ORF, Verified
Description Trans-golgi network aminophospholipid translocase (flippase); maintains membrane lipid asymmetry in post-Golgi secretory vesicles; contributes to clathrin-coated vesicle formation and endocytosis; subject to auto-inhibition by its C-terminal tail; mutations in human homolog ATP8B1 result in liver disease (2, 3, 4, 5, 6, 7, 8 and see Summary Paragraph)
Name Description Deficiency of Ribosomal Subunits 1
Chromosomal Location
ChrI:99697 to 95630 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All DRS2 GO evidence and references
  View Computational GO annotations for DRS2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 3 genes
Resources
Classical genetics
conditional
null
Large-scale survey
null
Resources
332 total interaction(s) for 190 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 23
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 12
  • Co-fractionation: 1
  • PCA: 7
  • Two-hybrid: 8

Genetic Interactions
  • Dosage Rescue: 3
  • Negative Genetic: 158
  • Phenotypic Enhancement: 14
  • Phenotypic Suppression: 16
  • Positive Genetic: 41
  • Synthetic Growth Defect: 21
  • Synthetic Lethality: 24
  • Synthetic Rescue: 3

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,355
Molecular Weight (Da) 153,764
Isoelectric Point (pI) 5.14
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrI:99697 to 95630 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 2011-02-03
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..4068 99697..95630 2011-02-03 2011-02-03
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000000024
SUMMARY PARAGRAPH for DRS2

S. cerevisiae has five genes encoding type 4 P-type ATPases: NEO1, DRS2, DNF1, DNF2, and DNF3. The "P-type" designation indicates that these integral membrane proteins form a covalent aspartyl-phosphate catalytic intermediate during ATP hydrolysis (9 and references therein). Most P-type ATPases mediate the transport of small cations across biological membranes. However, members of the "type 4" subfamily are aminophospholipid translocases (flippases), rather than cation transporters, and move phospholipids from one side of a membrane bilayer to the other (reviewed in 10). Of the five S. cerevisiae type 4 P-type ATPases, only NEO1 is essential. Although the four other genes appear to have substantial functional overlap (any single DRS2/DNF gene confers cell viability) (9), they are distinct in their localization, specificity, and cofactor association.

Drs2p localizes to the trans-Golgi network and it is proposed that phospholipid translocation in Golgi vessicles helps create aminophospholipid asymmetry in membranes en route to the cell surface (6 and references therein). Drs2p phospholipid translocation contributes to endocytosis (4, 11), intracellular protein transport (9), and other post-Golgi vesicle-mediated transport (2). Drs2p is associated with the non-catalytic subunit Cdc50p (12), and is specific for phosphatidylserine (5, 6).

The P-type ATPase superfamily is evolutionarily conserved, but the type 4 subfamily is found only in eukaryotes. Fourteen type 4 P-type ATPases have been characterized in humans (10 and references therein), including the DRS2 homolog, ATP8A1 (aka ATPase II) (5) and the DNF1/DNF2 homolog ATP8B1 (aka FIC1) (9). Mutations in ATP8B1 result in progressive familial intrahepatic cholestasis (Byler disease), benign recurrent intrahepatic cholestasis (BRIC), and intrahepatic cholestasis of pregnancy (ICP).

Last updated: 2007-03-01 Contact SGD

References cited on this page View Complete Literature Guide for DRS2
1) Ripmaster TL, et al.  (1993) DRS1 to DRS7, novel genes required for ribosome assembly and function in Saccharomyces cerevisiae. Mol Cell Biol 13(12):7901-12
2) Chen CY, et al.  (1999) Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. J Cell Biol 147(6):1223-36
3) Gall WE, et al.  (2002) Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo. Curr Biol 12(18):1623-7
4) Pomorski T, et al.  (2003) Drs2p-related P-type ATPases Dnf1p and Dnf2p are required for phospholipid translocation across the yeast plasma membrane and serve a role in endocytosis. Mol Biol Cell 14(3):1240-54
5) Natarajan P, et al.  (2004) Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to in vivo function. Proc Natl Acad Sci U S A 101(29):10614-9
6) Alder-Baerens N, et al.  (2006) Loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles. Mol Biol Cell 17(4):1632-42
7) Bull LN, et al.  (1998) A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet 18(3):219-24
8) Zhou X, et al.  (2013) Auto-inhibition of Drs2p, a Yeast Phospholipid Flippase, by Its Carboxyl-terminal Tail. J Biol Chem 288(44):31807-15
9) Hua Z, et al.  (2002) An essential subfamily of Drs2p-related P-type ATPases is required for protein trafficking between Golgi complex and endosomal/vacuolar system. Mol Biol Cell 13(9):3162-77
10) Paulusma CC and Oude Elferink RP  (2005) The type 4 subfamily of P-type ATPases, putative aminophospholipid translocases with a role in human disease. Biochim Biophys Acta 1741(1-2):11-24
11) Kishimoto T, et al.  (2005) Defects in structural integrity of ergosterol and the Cdc50p-Drs2p putative phospholipid translocase cause accumulation of endocytic membranes, onto which actin patches are assembled in yeast. Mol Biol Cell 16(12):5592-609
12) Saito K, et al.  (2004) Cdc50p, a protein required for polarized growth, associates with the Drs2p P-type ATPase implicated in phospholipid translocation in Saccharomyces cerevisiae. Mol Biol Cell 15(7):3418-32