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Protein

Phosphatidylcholine translocator ABCB4

Gene

Abcb4

Organism
Rattus norvegicus (Rat)
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 of 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. 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. Required for proper phospholipid bile formation. Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner. May promote biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane. In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts. Does not confer multidrug resistance.By similarity

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. Translocation activity is enhanced by the addition of the bile salt taurocholate.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi426 – 4338ATP 1PROSITE-ProRule annotation
Nucleotide bindingi1068 – 10758ATP 2PROSITE-ProRule annotation

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

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylcholine translocator ABCB4
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 21 Publication
P-glycoprotein 31 Publication
Gene namesi
Name:Abcb4Imported
Synonyms:Mdr21 Publication, Pgp31 Publication, Pgy21 Publication
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620248. Abcb4.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein PROSITE-ProRule annotation
  • Apical cell membrane By similarity; Multi-pass membrane protein PROSITE-ProRule annotation
  • Membrane raft By similarity
  • Cytoplasm By similarity
  • Cytoplasmic vesicleclathrin-coated vesicle 1 Publication

  • Note: Localized at the apical canalicular membrane of the epithelial cells lining the lumen of the bile canaliculi and biliary ductules. Localized preferentially in lipid nonraft domains of canalicular plasma membranes. Transported from the Golgi to the apical bile canalicular membrane in a RACK1-dependent manner. Redistributed into pseudocanaliculi formed between cells in a bezafibrate- or PPARA-dependent manner.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4747CytoplasmicBy similarityAdd
BLAST
Transmembranei48 – 7023HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini71 – 11545ExtracellularBy similarityAdd
BLAST
Transmembranei116 – 13621HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini137 – 18549CytoplasmicBy similarityAdd
BLAST
Transmembranei186 – 20722HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini208 – 2147ExtracellularBy similarity
Transmembranei215 – 23521HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini236 – 29358CytoplasmicBy similarityAdd
BLAST
Transmembranei294 – 31522HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini316 – 32914ExtracellularBy similarityAdd
BLAST
Transmembranei330 – 35122HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini352 – 710359CytoplasmicBy similarityAdd
BLAST
Transmembranei711 – 73121HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini732 – 75423ExtracellularBy similarityAdd
BLAST
Transmembranei755 – 77521HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini776 – 83055CytoplasmicBy similarityAdd
BLAST
Transmembranei831 – 85121HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini852 – 8521ExtracellularBy similarity
Transmembranei853 – 87220HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini873 – 93260CytoplasmicBy similarityAdd
BLAST
Transmembranei933 – 95523HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini956 – 97116ExtracellularBy similarityAdd
BLAST
Transmembranei972 – 99322HelicalPROSITE-ProRule annotationAdd
BLAST
Topological domaini994 – 1278285CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • apical plasma membrane Source: RGD
  • clathrin-coated vesicle Source: UniProtKB-SubCell
  • Golgi membrane Source: RGD
  • integral component of membrane Source: GO_Central
  • membrane raft Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2073706.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12781278Phosphatidylcholine translocator ABCB4PRO_0000093338Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei24 – 241PhosphoserineBy similarity
Glycosylationi88 – 881N-linked (GlcNAc...)Sequence analysis
Glycosylationi94 – 941N-linked (GlcNAc...)Sequence analysis

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

PaxDbiQ08201.
PRIDEiQ08201.

PTM databases

PhosphoSiteiQ08201.

Expressioni

Tissue specificityi

Expressed in the liver (PubMed:15159385). Expressed in hepatocytes (PubMed:7948020, PubMed:10067174).3 Publications

Interactioni

Subunit structurei

Interacts with HAX1 (PubMed:15159385). May interact with RACK1 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Hax1Q7TSE93EBI-929988,EBI-930005

Protein-protein interaction databases

IntActiQ08201. 1 interaction.
STRINGi10116.ENSRNOP00000042556.

Structurei

3D structure databases

ProteinModelPortaliQ08201.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 356303ABC transmembrane type-1 1PROSITE-ProRule annotationAdd
BLAST
Domaini391 – 627237ABC transporter 1PROSITE-ProRule annotationAdd
BLAST
Domaini710 – 998289ABC transmembrane type-1 2PROSITE-ProRule annotationAdd
BLAST
Domaini1033 – 1271239ABC transporter 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni622 – 64625Interaction with HAX1Add
BLAST

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.
HOVERGENiHBG080809.
InParanoidiQ08201.
KOiK05659.
PhylomeDBiQ08201.

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.

Q08201-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLEAARNGT ARRLDGDFEL GSISNQSREK KKKVNLIGPL TLFRYSDWQD
60 70 80 90 100
KLFMLLGTAM AIAHGSGLPL MMIVFGEMTD KFVDNAGNFS LPVNFSLSML
110 120 130 140 150
NPGRILEEEM TRYAYYYSGL GGGVLLAAYI QVSFWTLAAG RQIRKIRQKF
160 170 180 190 200
FHAILRQEMG WFDIKGTTEL NTRLTDDISK ISEGIGDKVG MFFQAIATFF
210 220 230 240 250
AGFIVGFIRG WKLTLVIMAI TAILGLSTAV 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
IDAFPNARGA AYVIFDIIDN NPKIDSFSER GHKPDSIKGN LEFSDVHFSY
410 420 430 440 450
PSRANIKILK GLNLKVKSGQ TVALVGNSGC GKSTTVQLLQ RLYDPTEGTI
460 470 480 490 500
SIDGQDIRNF NVRCLREFIG VVSQEPVLFS TTIAENIRYG RGNVTMDEIK
510 520 530 540 550
KAVKEANAYD FIMKLPQKFD TLVGDRGAQL SGGQKQRIAI ARALVRNPKI
560 570 580 590 600
LLLDEATSAL DTESEAEVQA ALDKAREGRT TIVIAHRLST VRNADVIAGF
610 620 630 640 650
EDGVIVEQGS HSELIKKEGI YFRLVNMQTS GSQILSEEFE VELSDEKAAG
660 670 680 690 700
GVAPNGWKAR IFRNSTKKSL KSSRAHQNRL DVETNELDAN VPPVSFLKVL
710 720 730 740 750
RLNKTEWPYF VVGTLCAIAN GALQPAFSII LSEMIAIFGP GDDTVKQQKC
760 770 780 790 800
NMFSLVFLGL GVHSFFTFFL QGFTFGKAGE ILTTRLRSMA FKAMLRQDMS
810 820 830 840 850
WFDDHKNSTG ALSTRLATDA AQVQGATGTR LALIAQNTAN LGTGIIISFI
860 870 880 890 900
YGWQLTLLLL SVVPFIAVAG IVEMKMLAGN AKRDKKEMEA AGKIATEAIE
910 920 930 940 950
NIRTVVSLTQ ERKFESMYVE KLHGPYRNSV RKAHIYGITF SISQAFMYFS
960 970 980 990 1000
YAGCFRFGSY LIVNGHMRFK DVILVFSAIV LGAVALGHAS SFAPDYAKAK
1010 1020 1030 1040 1050
LSAAYLFSLF ERQPLIDSYS REGMWPDKFE GSVTFNEVVF NYPTRANVPV
1060 1070 1080 1090 1100
LQGLSLEVKK GQTLALVGSS GCGKSTVVQL LERFYDPMAG TVLLDGQEAK
1110 1120 1130 1140 1150
KLNVQWLRAQ LGIVSQEPIL FDCSIAKNIA YGDNSRVVSQ DEIVRAAKEA
1160 1170 1180 1190 1200
NIHPFIETLP QKYETRVGDK GTQLSGGQKQ RIAIARALIR QPRVLLLDEA
1210 1220 1230 1240 1250
TSALDTESEK VVQEALDKAR EGRTCIVIAH RLSTIQNADL IVVIDNGKVK
1260 1270
EHGTHQQLLA QKGIYFSMVN IQAGTQNL
Length:1,278
Mass (Da):140,655
Last modified:November 1, 1995 - v1
Checksum:iD4FB6BE745AF73BF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L15079 mRNA. Translation: AAA02937.1.
X61105 Genomic DNA. Translation: CAA43417.1.
PIRiS41646.
RefSeqiNP_036822.1. NM_012690.2.
UniGeneiRn.82691.

Genome annotation databases

GeneIDi24891.
KEGGirno:24891.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L15079 mRNA. Translation: AAA02937.1.
X61105 Genomic DNA. Translation: CAA43417.1.
PIRiS41646.
RefSeqiNP_036822.1. NM_012690.2.
UniGeneiRn.82691.

3D structure databases

ProteinModelPortaliQ08201.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ08201. 1 interaction.
STRINGi10116.ENSRNOP00000042556.

Chemistry

ChEMBLiCHEMBL2073706.

PTM databases

PhosphoSiteiQ08201.

Proteomic databases

PaxDbiQ08201.
PRIDEiQ08201.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24891.
KEGGirno:24891.

Organism-specific databases

CTDi5244.
RGDi620248. Abcb4.

Phylogenomic databases

eggNOGiKOG0055. Eukaryota.
COG1132. LUCA.
HOVERGENiHBG080809.
InParanoidiQ08201.
KOiK05659.
PhylomeDBiQ08201.

Miscellaneous databases

PROiQ08201.

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...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Fischer.
  2. "Identification of distinct P-glycoprotein gene sequences in rat."
    Deuchars K.L., Duthie M., Ling V.
    Biochim. Biophys. Acta 1130:157-165(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1211-1278.
    Strain: Sprague-Dawley.
    Tissue: Liver.
  3. "Isolation of rat pgp3 cDNA: evidence for gender and zonal regulation of expression in the liver."
    Furuya K.N., Gebhardt R., Schuetz E.G., Schuetz J.D.
    Biochim. Biophys. Acta 1219:636-644(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "Mapping of the genes for rat P-glycoprotein 1, 2, and 3 (Pgy1, Pgy2, and Pgy3) to chromosome 4."
    Moralejo D.H., Wei K., Wei S., Ogino T., Yamada T., Sogawa K., Hamakawa H., Szpirer C., Carbone C., Matsumoto K.
    Exp. Anim. 47:283-284(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "Identification of HAX-1 as a protein that binds bile salt export protein and regulates its abundance in the apical membrane of Madin-Darby canine kidney cells."
    Ortiz D.F., Moseley J., Calderon G., Swift A.L., Li S., Arias I.M.
    J. Biol. Chem. 279:32761-32770(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HAX1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiMDR3_RAT
AccessioniPrimary (citable) accession number: Q08201
Secondary accession number(s): Q78E07
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 6, 2016
This is version 122 of the entry and version 1 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. 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.