P39524

EV
Gene name
DRS2 (SWA3, YAL026C, FUN38)
Protein name
Phospholipid-transporting ATPase DRS2
Names
Species
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
KEGG Pathway
sce:YAL026C
EC number
7.6.2.1: Linked to the hydrolysis of a nucleoside triphosphate
Protein Class
PROBABLE PHOSPHOLIPID-TRANSPORTING ATPASE (PTHR24092)

Descriptions

The heterodimeric eukaryotic Drs2p-Cdc50p complex is a lipid flippase that maintains cell membrane asymmetry by driving the transport of phospholipids directed to the cytoplasmic leaflet.
The enzyme complex exists in an autoinhibited form in the absence of an activator and is specifically activated by phosphatidylinositol-4-phosphate (PI4P). Drs2p belongs to a large family of Type IV P-type ATPases (P4 ATPases), having an actuator (A) domain, a nucleotide-binding (N) domain, a phosphorylation (P) domain, and a transmembrane domain (TMD) of 10 transmembrane helices (TMs). The N-terminal (N-tail) and C-terminal peptides (C-tail) of Drs2p inhibit the enzyme activity. The Drs2p C-tail inhibits the Drs2p activity by interacting extensively with the A, N, and P domains of Drs2p and occupying the ATP-binding pocket. Upon PI4P binding, the inhibitory C-tail of Drs2p is fully released from the extended horizontal groove in the regulatory A, N, and P domains of Drs2p and becomes disordered, and the putative substrate-translocating path becomes more open, especially in the cytosolic side. The N-terminal peptide of Drs2p is also known to be inhibitory, although its effect is much less severe than that of the C-tail. This N-tail engages in two hydrophobic interactions with the A domain.

Autoinhibitory domains (AIDs)

1231-1355 (C-terminal tail) EV

Target domain

282-427 (A-domain); 526-989 (N-, P-domains)

Relief mechanism

Ligand binding

Assay

Structural analysis, Deletion assay, Mutagenesis experiment

1-104 (N-terminal tail) EV

Target domain

282-427 (A-domain)

Relief mechanism

Ligand binding

Assay

Deletion assay, Structural analysis

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

11 structures for P39524

Entry ID Method Resolution Chain Position Source
6PSX EM 330 A A 1-1355 PDB
6PSY EM 280 A A 1-1355 PDB
6ROH EM 280 A A 1-1355 PDB
6ROI EM 370 A A 1-1355 PDB
6ROJ EM 290 A A 1-1355 PDB
7OH4 EM 300 A A 1-1355 PDB
7OH5 EM 290 A A 1-1355 PDB
7OH6 EM 300 A A 1-1355 PDB
7OH7 EM 380 A A 1-1355 PDB
7PEM EM 310 A A 1-1355 PDB
AF-P39524-F1 Predicted AlphaFoldDB

19 variants for P39524

Variant ID(s) Position Change Description Diseaes Association Provenance
s01-99611 30 S>T No SGRP
s01-99607 31 H>L No SGRP
s01-99575 42 H>Y No SGRP
s01-99472 76 L>P No SGRP
s01-99349 117 N>S No SGRP
s01-99149 184 V>I No SGRP
s01-99112 196 F>S No SGRP
s01-98903 266 C>G No SGRP
s01-98420 427 L>M No SGRP
s01-98122 526 G>A No SGRP
s01-97927 591 T>M No SGRP
s01-97892 603 R>G No SGRP
s01-97847 618 E>K No SGRP
s01-96674 1009 S>T No SGRP
s01-96599 1034 A>S No SGRP
s01-95884 1272 Q>P No SGRP
s01-95749 1317 G>V No SGRP
s01-95728 1324 E>G No SGRP
s01-95689 1337 G>D No SGRP

No associated diseases with P39524

No regional properties for P39524

Type Name Position InterPro Accession
No domain, repeats, and functional sites for P39524

Functions

Description
EC Number 7.6.2.1 Linked to the hydrolysis of a nucleoside triphosphate
Subcellular Localization
  • Golgi apparatus, trans-Golgi network membrane ; Multi-pass membrane protein
  • Endosome membrane ; Multi-pass membrane protein
PANTHER Family PTHR24092 PROBABLE PHOSPHOLIPID-TRANSPORTING ATPASE
PANTHER Subfamily PTHR24092:SF214 PHOSPHOLIPID-TRANSPORTING ATPASE
PANTHER Protein Class primary active transporter
transporter
PANTHER Pathway Category No pathway information available

6 GO annotations of cellular component

Name Definition
Cdc50p-Drs2p complex A protein complex that functions as a phospholipid-translocating P-Type ATPase. In budding yeast, this complex consists of Cdc50p and Drs2p proteins, and is involved in the trafficking of transport vesicles between the late Golgi and the early endosome.
endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
endosome membrane The lipid bilayer surrounding an endosome.
phospholipid-translocating ATPase complex A protein complex that functions as a phospholipid-translocating P-Type ATPase.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
trans-Golgi network The network of interconnected tubular and cisternal structures located within the Golgi apparatus on the side distal to the endoplasmic reticulum, from which secretory vesicles emerge. The trans-Golgi network is important in the later stages of protein secretion where it is thought to play a key role in the sorting and targeting of secreted proteins to the correct destination.

9 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
ATP hydrolysis activity Catalysis of the reaction
ATPase-coupled intramembrane lipid transporter activity Catalysis of the movement of lipids from one membrane leaflet to the other, driven by ATP hydrolysis. This includes flippases and floppases.
magnesium ion binding Binding to a magnesium (Mg) ion.
phosphatidylcholine flippase activity Catalysis of the movement of phosphatidylcholine from the exoplasmic to the cytosolic leaftlet of a membrane, using energy from the hydrolysis of ATP.
phosphatidylethanolamine flippase activity Catalysis of the movement of phosphatidylethanolamine from the exoplasmic to the cytosolic leaftlet of a membrane, using energy from the hydrolysis of ATP.
phosphatidylinositol-4-phosphate binding Binding to phosphatidylinositol-4-phosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 4' position.
phosphatidylserine flippase activity Catalysis of the movement of phosphatidylserine from the exoplasmic to the cytosolic leaftlet of a membrane, using energy from the hydrolysis of ATP.
phosphatidylserine floppase activity Catalysis of the movement of phosphatidylserine from the cytosolic to the exoplasmic leaftlet of a membrane, using energy from the hydrolysis of ATP.

5 GO annotations of biological process

Name Definition
endocytic recycling The directed movement of membrane-bounded vesicles from endosomes back to the plasma membrane, a trafficking pathway that promotes the recycling of internalized transmembrane proteins.
endocytosis A vesicle-mediated transport process in which cells take up external materials or membrane constituents by the invagination of a part of the plasma membrane to form a new membrane-bounded vesicle.
intracellular protein transport The directed movement of proteins in a cell, including the movement of proteins between specific compartments or structures within a cell, such as organelles of a eukaryotic cell.
phospholipid translocation The movement of a phospholipid molecule from one leaflet of a membrane bilayer to the opposite leaflet.
post-Golgi vesicle-mediated transport The directed movement of substances from the Golgi to other parts of the cell, including organelles and the plasma membrane, mediated by small transport vesicles.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P40527 NEO1 Probable phospholipid-transporting ATPase NEO1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
P32660 DNF1 Phospholipid-transporting ATPase DNF1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
Q9Y2Q0 ATP8A1 Phospholipid-transporting ATPase IA Homo sapiens (Human) PR
P70704 Atp8a1 Phospholipid-transporting ATPase IA Mus musculus (Mouse) PR
Q9U280 tat-1 Phospholipid-transporting ATPase tat-1 Caenorhabditis elegans PR
10 20 30 40 50 60
MNDDRETPPK RKPGEDDTLF DIDFLDDTTS HSGSRSKVTN SHANANYIPP SHVLPEETID
70 80 90 100 110 120
LDADDDNIEN DVHENLFMSN NHDDQTSWNA NRFDSDAYQP QSLRAVKPPG LFARFGNGLK
130 140 150 160 170 180
NAFTFKRKKG PESFEMNHYN AVTNNELDDN YLDSRNKFNI KILFNRYILR KNVGDAEGNG
190 200 210 220 230 240
EPRVIHINDS LANSSFGYSD NHISTTKYNF ATFLPKFLFQ EFSKYANLFF LCTSAIQQVP
250 260 270 280 290 300
HVSPTNRYTT IGTLLVVLIV SAMKECIEDI KRANSDKELN NSTAEIFSEA HDDFVEKRWI
310 320 330 340 350 360
DIRVGDIIRV KSEEPIPADT IILSSSEPEG LCYIETANLD GETNLKIKQS RVETAKFIDV
370 380 390 400 410 420
KTLKNMNGKV VSEQPNSSLY TYEGTMTLND RQIPLSPDQM ILRGATLRNT AWIFGLVIFT
430 440 450 460 470 480
GHETKLLRNA TATPIKRTAV EKIINRQIIA LFTVLIVLIL ISSIGNVIMS TADAKHLSYL
490 500 510 520 530 540
YLEGTNKAGL FFKDFLTFWI LFSNLVPISL FVTVELIKYY QAFMIGSDLD LYYEKTDTPT
550 560 570 580 590 600
VVRTSSLVEE LGQIEYIFSD KTGTLTRNIM EFKSCSIAGH CYIDKIPEDK TATVEDGIEV
610 620 630 640 650 660
GYRKFDDLKK KLNDPSDEDS PIINDFLTLL ATCHTVIPEF QSDGSIKYQA ASPDEGALVQ
670 680 690 700 710 720
GGADLGYKFI IRKPNSVTVL LEETGEEKEY QLLNICEFNS TRKRMSAIFR FPDGSIKLFC
730 740 750 760 770 780
KGADTVILER LDDEANQYVE ATMRHLEDYA SEGLRTLCLA MRDISEGEYE EWNSIYNEAA
790 800 810 820 830 840
TTLDNRAEKL DEAANLIEKN LILIGATAIE DKLQDGVPET IHTLQEAGIK IWVLTGDRQE
850 860 870 880 890 900
TAINIGMSCR LLSEDMNLLI INEETRDDTE RNLLEKINAL NEHQLSTHDM NTLALVIDGK
910 920 930 940 950 960
SLGFALEPEL EDYLLTVAKL CKAVICCRVS PLQKALVVKM VKRKSSSLLL AIGDGANDVS
970 980 990 1000 1010 1020
MIQAAHVGVG ISGMEGMQAA RSADIAVGQF KFLKKLLLVH GSWSYQRISV AILYSFYKNT
1030 1040 1050 1060 1070 1080
ALYMTQFWYV FANAFSGQSI MESWTMSFYN LFFTVWPPFV IGVFDQFVSS RLLERYPQLY
1090 1100 1110 1120 1130 1140
KLGQKGQFFS VYIFWGWIIN GFFHSAIVFI GTILIYRYGF ALNMHGELAD HWSWGVTVYT
1150 1160 1170 1180 1190 1200
TSVIIVLGKA ALVTNQWTKF TLIAIPGSLL FWLIFFPIYA SIFPHANISR EYYGVVKHTY
1210 1220 1230 1240 1250 1260
GSGVFWLTLI VLPIFALVRD FLWKYYKRMY EPETYHVIQE MQKYNISDSR PHVQQFQNAI
1270 1280 1290 1300 1310 1320
RKVRQVQRMK KQRGFAFSQA EEGGQEKIVR MYDTTQKRGK YGELQDASAN PFNDNNGLGS
1330 1340 1350
NDFESAEPFI ENPFADGNQN SNRFSSSRDD ISFDI