DNF2/YDR093W Summary Help

Standard Name DNF2 1
Systematic Name YDR093W
Feature Type ORF, Verified
Description Aminophospholipid translocase (flippase); localizes primarily to the plasma membrane; contributes to endocytosis, protein transport and cell polarity; type 4 P-type ATPase; DNF2 has a paralog, DNF1, that arose from the whole genome duplication (1, 2, 3, 4, 5 and see Summary Paragraph)
Name Description Drs2 Neo1 Family 1
Chromosomal Location
ChrIV:631282 to 636120 | ORF Map | GBrowse
Gene Ontology Annotations All DNF2 GO evidence and references
  View Computational GO annotations for DNF2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 4 genes
Classical genetics
Large-scale survey
48 total interaction(s) for 32 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 8
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 3
  • Biochemical Activity: 1
  • Co-fractionation: 2
  • PCA: 5

Genetic Interactions
  • Negative Genetic: 13
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 1
  • Positive Genetic: 4
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 1
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 1,612
Molecular Weight (Da) 182,617
Isoelectric Point (pI) 6.07
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIV:631282 to 636120 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..4839 631282..636120 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 | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000002500

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 (1 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 6). 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) (1), they are distinct in their localization, specificity, and cofactor association.

Dnf1p and Dnf2p localize primarily to the plasma membrane where they maintain aminophospholipid asymmetry (2 and references therein) and play roles in endocytosis (2) and cell polarity (3). Both proteins are relatively non-specific and are capable of translocating phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine (2). The non-catalytic subunit Lem3p associates with both Dnf1p and Dnf2p, but this interaction has been best characterized with Dnf1p (7).

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 (6 and references therein), including the DRS2 homolog, ATP8A1 (aka ATPase II) (8) and the DNF1/DNF2 homolog ATP8B1 (aka FIC1) (1). 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 DNF2
1) 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
2) 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
3) Iwamoto K, et al.  (2004) Local exposure of phosphatidylethanolamine on the yeast plasma membrane is implicated in cell polarity. Genes Cells 9(10):891-903
4) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
5) Catty P, et al.  (1997) The complete inventory of the yeast Saccharomyces cerevisiae P-type transport ATPases. FEBS Lett 409(3):325-32
6) 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
7) Noji T, et al.  (2006) Mutational analysis of the Lem3p-Dnf1p putative phospholipid-translocating P-type ATPase reveals novel regulatory roles for Lem3p and a carboxyl-terminal region of Dnf1p independent of the phospholipid-translocating activity of Dnf1p in yeast. Biochem Biophys Res Commun 344(1):323-31
8) 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