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Protein

Phosphatidylcholine translocator ABCB4

Gene

ABCB4

Organism
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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(Side 1) = ADP + phosphate + xenobiotic(Side 2).

Activity 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)DescriptionActionsGraphical viewLength
Nucleotide bindingi429 – 436ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1071 – 1078ATP 2PROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTranslocase
Biological processLipid transport, Transport
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylcholine translocator ABCB4
Alternative name(s):
ATP-binding cassette sub-family B member 4
Multidrug resistance protein 3By similarity (EC:7.6.2.2)
P-glycoprotein 3By similarity
Gene namesi
Name:ABCB4
Synonyms:PGP3By similarity, PGY3
OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifieri10029 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaCricetidaeCricetinaeCricetulus

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 – 50CytoplasmicBy similarityAdd BLAST50
Transmembranei51 – 73HelicalPROSITE-ProRule annotationAdd BLAST23
Topological domaini74 – 118ExtracellularBy similarityAdd BLAST45
Transmembranei119 – 139HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini140 – 188CytoplasmicBy similarityAdd BLAST49
Transmembranei189 – 210HelicalPROSITE-ProRule annotationAdd BLAST22
Topological domaini211 – 217ExtracellularBy similarity7
Transmembranei218 – 238HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini239 – 296CytoplasmicBy similarityAdd BLAST58
Transmembranei297 – 318HelicalPROSITE-ProRule annotationAdd BLAST22
Topological domaini319 – 332ExtracellularBy similarityAdd BLAST14
Transmembranei333 – 354HelicalPROSITE-ProRule annotationAdd BLAST22
Topological domaini355 – 713CytoplasmicBy similarityAdd BLAST359
Transmembranei714 – 734HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini735 – 757ExtracellularBy similarityAdd BLAST23
Transmembranei758 – 778HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini779 – 833CytoplasmicBy similarityAdd BLAST55
Transmembranei834 – 854HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini855ExtracellularBy similarity1
Transmembranei856 – 875HelicalPROSITE-ProRule annotationAdd BLAST20
Topological domaini876 – 937CytoplasmicBy similarityAdd BLAST62
Transmembranei938 – 958HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini959 – 974ExtracellularBy similarityAdd BLAST16
Transmembranei975 – 996HelicalPROSITE-ProRule annotationAdd BLAST22
Topological domaini997 – 1281CytoplasmicBy similarityAdd BLAST285

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000933411 – 1281Phosphatidylcholine translocator ABCB4Add BLAST1281

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei27PhosphoserineBy similarity1
Glycosylationi91N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi97N-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-44 and Ser-49.By similarity
Glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiP23174

Interactioni

Subunit structurei

Interacts with HAX1. May interact with RACK1.By similarity

Structurei

3D structure databases

ProteinModelPortaliP23174
SMRiP23174
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini57 – 359ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST303
Domaini394 – 630ABC transporter 1PROSITE-ProRule annotationAdd BLAST237
Domaini713 – 1001ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST289
Domaini1036 – 1274ABC transporter 2PROSITE-ProRule annotationAdd BLAST239

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni625 – 649Interaction with HAX1By similarityAdd BLAST25

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG080809
KOiK05659

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, 1 hit
PS50893 ABC_TRANSPORTER_2, 2 hits

Sequencei

Sequence statusi: Complete.

P23174-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDLEAARNGT ARRPGTVEGD FELGSISNQG RNKKKKVNLI GPLTLFRYSD
60 70 80 90 100
WQDKLFMLLG TIMAIAHGSG LPLMMIVFGE MTDKFVNNAG NFSLPVNFSL
110 120 130 140 150
SMINPGRILE EEMTRYAYYY SGLGGGVLVA AYIQVSFWTL AAGRQIKKIR
160 170 180 190 200
QNFFHAILRQ EMGWFDIKGT TELNTRLTDD ISKISEGIGD KVGMFFQAVA
210 220 230 240 250
TFFAGFIVGF IRGWKLTLVI MAISPILGLS AAVWAKILST FSDKELAAYA
260 270 280 290 300
KAGAVAEEAL GAIRTVIAFG GQNKELERYQ KHLENAKKIG IKKAISANIS
310 320 330 340 350
MGIAFLLIYA SYALAFWYGS TLVISKEYTI GNAMTVFFSI LIGAFSVGQA
360 370 380 390 400
APCIDAFANA RGAAYVIFDI IDNNPKIDSF SERGHKPDSI KGNLDFSDVH
410 420 430 440 450
FSYPSRANIK ILKGLNLKVQ SGQTVALVGN SGCGKTTTLQ LLQRLYDPTE
460 470 480 490 500
GTISIDGQDI RNFNVRYLRE IIGVVSQEPV LFSTTIAENI RYGRGNVTME
510 520 530 540 550
EIKKAVKEAN AYEFIMKLPQ KFDTLVGERG AQLSGGQKQR IAIARALVRN
560 570 580 590 600
PKILLLDEAT SALDTESEAE VQAALDKARE GRTTIVIAHR LSTVRNADVI
610 620 630 640 650
AGFEDGVIVE QGSHSELMQK EGVYFKLVNM QTSGSQILSQ EFEVELSEEK
660 670 680 690 700
AADGMTPNGW KSHIFRNSTK KSLKSSRAHH HRLDVDADEL DANVPPVSFL
710 720 730 740 750
KVLKLNKTEW PYFVVGTVCA IVNGALQPAI SIILSEMIAI FGPGDDAVKQ
760 770 780 790 800
QKCNLFSLVF LGLGVLSFFT FFLQGFTFGK AGEILTTRLR SMAFKAMLRQ
810 820 830 840 850
DMSWFDDYKN STGALSTRLA TDRAQVQGAT GTRLALIAQN TANLGTGIII
860 870 880 890 900
SFIYGWQLTL LLLSVVPFIA VSGIVEMKML AGNAKRDKKA LEAAGKIATE
910 920 930 940 950
AIENIRTVVS LTQERKFESM YVEKLHEPYR NSVQMAHIYG ITFSISQAFM
960 970 980 990 1000
YFSYAGCFRF GAYLIVNGHM RFRDVILVFS AIVFGAVALG HASSFAPDYA
1010 1020 1030 1040 1050
KAKLSAAHLF SLFERQPLID SYSGEGLWPD KFEGSVTFNE VVFNYPTRAN
1060 1070 1080 1090 1100
MPVLQGLSLE VKKGQTLALV GSSGCGKSTV VQLLERFYDP MAGTVLLDGQ
1110 1120 1130 1140 1150
EAKKLNIQWL RAQLGIVSQE PVLFDCSIAE NIAYGDNSRV VSQDEIVRAA
1160 1170 1180 1190 1200
KAANIHPFIE TLPQKYKTRV GDKGTQLSGG QKQRLAIRRA LIRQPRVLLL
1210 1220 1230 1240 1250
DEATSALDTE SEKVVQEALD KAREGRTCIV IAHRLSTIQN ADLIVVIQNG
1260 1270 1280
KVKEHGTHQQ LLAQKGIYFS MVNIQAGAQN S
Length:1,281
Mass (Da):140,866
Last modified:November 1, 1991 - v1
Checksum:i2203EF61EBB29602
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60042 mRNA Translation: AAA68885.1
PIRiI48120
I48123
RefSeqiNP_001230916.1, NM_001243987.1

Genome annotation databases

GeneIDi100682535
KEGGicge:100682535

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60042 mRNA Translation: AAA68885.1
PIRiI48120
I48123
RefSeqiNP_001230916.1, NM_001243987.1

3D structure databases

ProteinModelPortaliP23174
SMRiP23174
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiP23174

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100682535
KEGGicge:100682535

Organism-specific databases

CTDi5244

Phylogenomic databases

HOVERGENiHBG080809
KOiK05659

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, 1 hit
PS50893 ABC_TRANSPORTER_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiMDR3_CRIGR
AccessioniPrimary (citable) accession number: P23174
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: November 7, 2018
This is version 110 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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