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Protein

Phosphatidylcholine translocator ABCB4

Gene

Abcb4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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(Side 1) = ADP + phosphate + xenobiotic(Side 2).

Activity 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

Keywordsi

Molecular functionTranslocase
Biological processLipid transport, Transport
LigandATP-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:7.6.2.2)
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:97569 Abcb4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Glycosylationi94N-linked (GlcNAc...) asparagineSequence 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 Expressed in 197 organ(s), highest expression level in left lobe of liver
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

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0055 Eukaryota
COG1132 LUCA
GeneTreeiENSGT00530000062896
HOVERGENiHBG080809
InParanoidiP21440
KOiK05659
OMAiAFYMQRT
OrthoDBiEOG091G0HVA
TreeFamiTF105193

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR011527 ABC1_TM_dom
IPR036640 ABC1_TM_sf
IPR003439 ABC_transporter-like
IPR017871 ABC_transporter_CS
IPR030275 MDR3
IPR027417 P-loop_NTPase
IPR039421 Type_I_exporter
PANTHERiPTHR24221 PTHR24221, 1 hit
PTHR24221:SF241 PTHR24221:SF241, 1 hit
PfamiView protein in Pfam
PF00664 ABC_membrane, 2 hits
PF00005 ABC_tran, 2 hits
SMARTiView protein in SMART
SM00382 AAA, 2 hits
SUPFAMiSSF52540 SSF52540, 2 hits
SSF90123 SSF90123, 2 hits
PROSITEiView protein in PROSITE
PS50929 ABC_TM1F, 2 hits
PS00211 ABC_TRANSPORTER_1, 2 hits
PS50893 ABC_TRANSPORTER_2, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2JDM4A0A0G2JDM4_MOUSE
Phosphatidylcholine translocator AB...
Abcb4
882Annotation score:

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

Similar proteinsi

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
OMAiAFYMQRT
OrthoDBiEOG091G0HVA
TreeFamiTF105193

Enzyme and pathway databases

ReactomeiR-MMU-382556 ABC-family proteins mediated transport

Miscellaneous databases

PROiPR:P21440
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000042476 Expressed in 197 organ(s), highest expression level in left lobe of liver
ExpressionAtlasiP21440 baseline and differential
GenevisibleiP21440 MM

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR011527 ABC1_TM_dom
IPR036640 ABC1_TM_sf
IPR003439 ABC_transporter-like
IPR017871 ABC_transporter_CS
IPR030275 MDR3
IPR027417 P-loop_NTPase
IPR039421 Type_I_exporter
PANTHERiPTHR24221 PTHR24221, 1 hit
PTHR24221:SF241 PTHR24221:SF241, 1 hit
PfamiView protein in Pfam
PF00664 ABC_membrane, 2 hits
PF00005 ABC_tran, 2 hits
SMARTiView protein in SMART
SM00382 AAA, 2 hits
SUPFAMiSSF52540 SSF52540, 2 hits
SSF90123 SSF90123, 2 hits
PROSITEiView protein in PROSITE
PS50929 ABC_TM1F, 2 hits
PS00211 ABC_TRANSPORTER_1, 2 hits
PS50893 ABC_TRANSPORTER_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiMDR3_MOUSE
AccessioniPrimary (citable) accession number: P21440
Secondary accession number(s): B9EK77, Q6LCL9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: June 28, 2011
Last modified: November 7, 2018
This is version 154 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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