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Protein

Phosphatidylcholine translocator ABCB4

Gene

Abcb4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi between hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:8106172, PubMed:7912658, PubMed:7592705, PubMed:7814632, PubMed:8725158, PubMed:9366571). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (By similarity). Required for proper phospholipid bile formation (PubMed:8106172). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:7814632, PubMed:8725158). May promote biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:9366571). In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390). Does not confer multidrug resistance (PubMed:1990275).By similarity8 Publications

Catalytic activityi

ATP + H2O + xenobiotic(In) = ADP + phosphate + xenobiotic(Out).

Enzyme regulationi

Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:7912658). Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:7592705).2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi426 – 433ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1066 – 1073ATP 2PROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid transport, Transport

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-382556. ABC-family proteins mediated transport.

Chemistry databases

SwissLipidsiSLP:000000362.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylcholine translocator ABCB4Curated
Alternative name(s):
ATP-binding cassette sub-family B member 4Imported
Multidrug resistance protein 21 Publication
Multidrug resistance protein 3By similarity (EC:3.6.3.44)
P-glycoprotein 2By similarity
P-glycoprotein 3By similarity
Gene namesi
Name:Abcb4Imported
Synonyms:Mdr21 Publication, Pgy-2, Pgy2By similarity
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:97569. Abcb4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 47CytoplasmicBy similarityAdd BLAST47
Transmembranei48 – 70HelicalPROSITE-ProRule annotationAdd BLAST23
Topological domaini71 – 115ExtracellularBy similarityAdd BLAST45
Transmembranei116 – 136HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini137 – 185CytoplasmicBy similarityAdd BLAST49
Transmembranei186 – 207HelicalPROSITE-ProRule annotationAdd BLAST22
Topological domaini208 – 212ExtracellularBy similarity5
Transmembranei213 – 235HelicalPROSITE-ProRule annotationAdd BLAST23
Topological domaini236 – 293CytoplasmicBy similarityAdd BLAST58
Transmembranei294 – 315HelicalPROSITE-ProRule annotationAdd BLAST22
Topological domaini316 – 329ExtracellularBy similarityAdd BLAST14
Transmembranei330 – 351HelicalPROSITE-ProRule annotationAdd BLAST22
Topological domaini352 – 708CytoplasmicBy similarityAdd BLAST357
Transmembranei709 – 729HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini730 – 752ExtracellularBy similarityAdd BLAST23
Transmembranei753 – 773HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini774 – 828CytoplasmicBy similarityAdd BLAST55
Transmembranei829 – 849HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini850ExtracellularBy similarity1
Transmembranei851 – 870HelicalPROSITE-ProRule annotationAdd BLAST20
Topological domaini871 – 930CytoplasmicBy similarityAdd BLAST60
Transmembranei931 – 953HelicalPROSITE-ProRule annotationAdd BLAST23
Topological domaini954 – 969ExtracellularBy similarityAdd BLAST16
Transmembranei970 – 991HelicalPROSITE-ProRule annotationAdd BLAST22
Topological domaini992 – 1276CytoplasmicBy similarityAdd BLAST285

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • clathrin-coated vesicle Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: MGI
  • integral component of membrane Source: GO_Central
  • intercellular canaliculus Source: MGI
  • membrane Source: MGI
  • membrane raft Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice show severe necrotic damage of hepatocytes, strong portal inflammation, proliferation and destruction of the canalicular and small bile ductular tracts (PubMed:8106172). Display almost complete reduction of biliary phospholipid secretion, although bile salt secretion is normal (PubMed:8106172, PubMed:7814632, PubMed:8725158, PubMed:9366571). Show also reduced cholesterol secretion (PubMed:8106172, PubMed:9366571). Knockout mice lacking both ABCB4 and ATP8B1 show lower hepatic damage compared with the single ABCB4 knockout mice (PubMed:21820390). Display equivalent reduction of biliary phosphatidylcholine (PC) secretion as the single ABCB4 knockout mice (PubMed:21820390). Biliary cholesterol secretion is higher compared to the single ABCB4 knockout mice (PubMed:21820390). Bile salt secretion is normal in both single ABCB4 knockout mice and double ABCB4 and ATP8B1 knockout mice (PubMed:21820390). Biliary excretion of canalicular ectoenzymes, aminopeptidase N and alkaline phosphatase is strongly reduced compared to single ATP8B1 knockout mice (PubMed:21820390).5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000933371 – 1276Phosphatidylcholine translocator ABCB4Add BLAST1276

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24PhosphoserineCombined sources1
Glycosylationi88N-linked (GlcNAc...)Sequence analysis1
Glycosylationi94N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Phosphorylated. Phosphorylation is required for PC efflux activity. Phosphorylation occurs on serine and threonine residues in a protein kinase A- or C-dependent manner. May be phosphorylated on Thr-41 and Ser-46.By similarity
Glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP21440.
PaxDbiP21440.
PeptideAtlasiP21440.
PRIDEiP21440.

PTM databases

iPTMnetiP21440.
PhosphoSitePlusiP21440.

Expressioni

Tissue specificityi

Expressed in the liver (PubMed:1381362, PubMed:8615769) (at protein level). Expressed in adrenal, liver, muscle, spleen and heart (PubMed:2471060). Expressed in multidrug-resistant cell lines (PubMed:1969609).4 Publications

Inductioni

Up-regulated by compounds that cause peroxisome proliferation, such as ciprofibrate and clofibrate (at protein level) (PubMed:8615769). Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate, ciprofibrate, clofibrate, bezafibrate and gemfibrozil (PubMed:8615769, PubMed:12381268).2 Publications

Gene expression databases

BgeeiENSMUSG00000042476.
ExpressionAtlasiP21440. baseline and differential.
GenevisibleiP21440. MM.

Interactioni

Subunit structurei

May interact with RACK1. Interacts with HAX1.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000003717.

Structurei

3D structure databases

ProteinModelPortaliP21440.
SMRiP21440.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 356ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST303
Domaini391 – 627ABC transporter 1PROSITE-ProRule annotationAdd BLAST237
Domaini708 – 996ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST289
Domaini1031 – 1269ABC transporter 2PROSITE-ProRule annotationAdd BLAST239

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni622 – 646Interaction with HAX1By similarityAdd BLAST25

Sequence similaritiesi

Contains 2 ABC transmembrane type-1 domains.PROSITE-ProRule annotation
Contains 2 ABC transporter domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0055. Eukaryota.
COG1132. LUCA.
GeneTreeiENSGT00530000062896.
HOVERGENiHBG080809.
InParanoidiP21440.
KOiK05659.
OMAiPDIDACC.
OrthoDBiEOG091G0HVA.
TreeFamiTF105193.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view]
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
PROSITEiPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P21440-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLEAARNGT ARRLDGDFEL GSISNQGREK KKKVNLIGLL TLFRYSDWQD
60 70 80 90 100
KLFMFLGTLM AIAHGSGLPL MMIVFGEMTD KFVDNTGNFS LPVNFSLSML
110 120 130 140 150
NPGRILEEEM TRYAYYYSGL GGGVLVAAYI QVSFWTLAAG RQIKKIRQKF
160 170 180 190 200
FHAILRQEMG WFDIKGTTEL NTRLTDDVSK ISEGIGDKVG MFFQAIATFF
210 220 230 240 250
AGFIVGFIRG WKLTLVIMAI SPILGLSTAV WAKILSTFSD KELAAYAKAG
260 270 280 290 300
AVAEEALGAI RTVIAFGGQN KELERYQKHL ENAKKIGIKK AISANISMGI
310 320 330 340 350
AFLLIYASYA LAFWYGSTLV ISKEYTIGNA MTVFFSILIG AFSVGQAAPC
360 370 380 390 400
IDAFANARGA AYVIFDIIDN NPKIDSFSER GHKPDNIKGN LEFSDVHFSY
410 420 430 440 450
PSRANIKILK GLNLKVKSGQ TVALVGNSGC GKSTTVQLLQ RLYDPTEGKI
460 470 480 490 500
SIDGQDIRNF NVRCLREIIG VVSQEPVLFS TTIAENIRYG RGNVTMDEIE
510 520 530 540 550
KAVKEANAYD FIMKLPQKFD TLVGDRGAQL SGGQKQRIAI ARALVRNPKI
560 570 580 590 600
LLLDEATSAL DTESEAEVQA ALDKAREGRT TIVIAHRLST IRNADVIAGF
610 620 630 640 650
EDGVIVEQGS HSELMKKEGI YFRLVNMQTA GSQILSEEFE VELSDEKAAG
660 670 680 690 700
DVAPNGWKAR IFRNSTKKSL KSPHQNRLDE ETNELDANVP PVSFLKVLKL
710 720 730 740 750
NKTEWPYFVV GTVCAIANGA LQPAFSIILS EMIAIFGPGD DAVKQQKCNM
760 770 780 790 800
FSLVFLGLGV LSFFTFFLQG FTFGKAGEIL TTRLRSMAFK AMLRQDMSWF
810 820 830 840 850
DDHKNSTGAL STRLATDAAQ VQGATGTRLA LIAQNTANLG TGIIISFIYG
860 870 880 890 900
WQLTLLLLSV VPFIAVAGIV EMKMLAGNAK RDKKEMEAAG KIATEAIENI
910 920 930 940 950
RTVVSLTQER KFESMYVEKL HGPYRNSVRK AHIYGITFSI SQAFMYFSYA
960 970 980 990 1000
GCFRFGSYLI VNGHMRFKDV ILVFSAIVLG AVALGHASSF APDYAKAKLS
1010 1020 1030 1040 1050
AAYLFSLFER QPLIDSYSGE GLWPDKFEGS VTFNEVVFNY PTRANVPVLQ
1060 1070 1080 1090 1100
GLSLEVKKGQ TLALVGSSGC GKSTVVQLLE RFYDPMAGSV LLDGQEAKKL
1110 1120 1130 1140 1150
NVQWLRAQLG IVSQEPILFD CSIAENIAYG DNSRVVPHDE IVRAAKEANI
1160 1170 1180 1190 1200
HPFIETLPQK YNTRVGDKGT QLSGGQKQRI AIARALIRQP RVLLLDEATS
1210 1220 1230 1240 1250
ALDTESEKVV QEALDKAREG RTCIVIAHRL STIQNADLIV VIENGKVKEH
1260 1270
GTHQQLLAQK GIYFSMVNIQ AGTQNL
Length:1,276
Mass (Da):140,377
Last modified:June 28, 2011 - v2
Checksum:i30BC72EDDFA4388C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti257L → P in AAA39516 (PubMed:3405218).Curated1
Sequence conflicti828R → K in AAA39516 (PubMed:3405218).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03398 mRNA. Translation: AAA39516.1.
CH466600 Genomic DNA. Translation: EDL14681.1.
BC150687 mRNA. Translation: AAI50688.1.
M74151 Genomic DNA. Translation: AAA39515.1.
U46839 Genomic DNA. Translation: AAC52722.1.
CCDSiCCDS19086.1.
PIRiA30409. DVMS2.
RefSeqiNP_032856.2. NM_008830.2.
UniGeneiMm.297825.

Genome annotation databases

EnsembliENSMUST00000003717; ENSMUSP00000003717; ENSMUSG00000042476.
GeneIDi18670.
KEGGimmu:18670.
UCSCiuc008wkr.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03398 mRNA. Translation: AAA39516.1.
CH466600 Genomic DNA. Translation: EDL14681.1.
BC150687 mRNA. Translation: AAI50688.1.
M74151 Genomic DNA. Translation: AAA39515.1.
U46839 Genomic DNA. Translation: AAC52722.1.
CCDSiCCDS19086.1.
PIRiA30409. DVMS2.
RefSeqiNP_032856.2. NM_008830.2.
UniGeneiMm.297825.

3D structure databases

ProteinModelPortaliP21440.
SMRiP21440.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000003717.

Chemistry databases

SwissLipidsiSLP:000000362.

PTM databases

iPTMnetiP21440.
PhosphoSitePlusiP21440.

Proteomic databases

MaxQBiP21440.
PaxDbiP21440.
PeptideAtlasiP21440.
PRIDEiP21440.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003717; ENSMUSP00000003717; ENSMUSG00000042476.
GeneIDi18670.
KEGGimmu:18670.
UCSCiuc008wkr.2. mouse.

Organism-specific databases

CTDi5244.
MGIiMGI:97569. Abcb4.

Phylogenomic databases

eggNOGiKOG0055. Eukaryota.
COG1132. LUCA.
GeneTreeiENSGT00530000062896.
HOVERGENiHBG080809.
InParanoidiP21440.
KOiK05659.
OMAiPDIDACC.
OrthoDBiEOG091G0HVA.
TreeFamiTF105193.

Enzyme and pathway databases

ReactomeiR-MMU-382556. ABC-family proteins mediated transport.

Miscellaneous databases

PROiP21440.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000042476.
ExpressionAtlasiP21440. baseline and differential.
GenevisibleiP21440. MM.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view]
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
PROSITEiPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMDR3_MOUSE
AccessioniPrimary (citable) accession number: P21440
Secondary accession number(s): B9EK77, Q6LCL9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: June 28, 2011
Last modified: November 2, 2016
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.