ABCB4

Protein identityUniProt · HPA

UniProt accession

P21439

Gene

ABCB4

Ensembl

ENSG00000005471

Chromosome

7

Canonical length

1286 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Nucleoplasm,Plasma membrane,Focal adhesion sites,Cytosol

OverviewNCBI Gene

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1286 residues, UniProt reviewed canonical sequence.

>P21439|ABCB4
     1  MDLEAAKNGT AWRPTSAEGD FELGISSKQK RKKTKTVKMI GVLTLFRYSD WQDKLFMSLG
    61  TIMAIAHGSG LPLMMIVFGE MTDKFVDTAG NFSFPVNFSL SLLNPGKILE EEMTRYAYYY
   121  SGLGAGVLVA AYIQVSFWTL AAGRQIRKIR QKFFHAILRQ EIGWFDINDT TELNTRLTDD
   181  ISKISEGIGD KVGMFFQAVA TFFAGFIVGF IRGWKLTLVI MAISPILGLS AAVWAKILSA
   241  FSDKELAAYA KAGAVAEEAL GAIRTVIAFG GQNKELERYQ KHLENAKEIG IKKAISANIS
   301  MGIAFLLIYA SYALAFWYGS TLVISKEYTI GNAMTVFFSI LIGAFSVGQA APCIDAFANA
   361  RGAAYVIFDI IDNNPKIDSF SERGHKPDSI KGNLEFNDVH FSYPSRANVK ILKGLNLKVQ
   421  SGQTVALVGS SGCGKSTTVQ LIQRLYDPDE GTINIDGQDI RNFNVNYLRE IIGVVSQEPV
   481  LFSTTIAENI CYGRGNVTMD EIKKAVKEAN AYEFIMKLPQ KFDTLVGERG AQLSGGQKQR
   541  IAIARALVRN PKILLLDEAT SALDTESEAE VQAALDKARE GRTTIVIAHR LSTVRNADVI
   601  AGFEDGVIVE QGSHSELMKK EGVYFKLVNM QTSGSQIQSE EFELNDEKAA TRMAPNGWKS
   661  RLFRHSTQKN LKNSQMCQKS LDVETDGLEA NVPPVSFLKV LKLNKTEWPY FVVGTVCAIA
   721  NGGLQPAFSV IFSEIIAIFG PGDDAVKQQK CNIFSLIFLF LGIISFFTFF LQGFTFGKAG
   781  EILTRRLRSM AFKAMLRQDM SWFDDHKNST GALSTRLATD AAQVQGATGT RLALIAQNIA
   841  NLGTGIIISF IYGWQLTLLL LAVVPIIAVS GIVEMKLLAG NAKRDKKELE AAGKIATEAI
   901  ENIRTVVSLT QERKFESMYV EKLYGPYRNS VQKAHIYGIT FSISQAFMYF SYAGCFRFGA
   961  YLIVNGHMRF RDVILVFSAI VFGAVALGHA SSFAPDYAKA KLSAAHLFML FERQPLIDSY
  1021  SEEGLKPDKF EGNITFNEVV FNYPTRANVP VLQGLSLEVK KGQTLALVGS SGCGKSTVVQ
  1081  LLERFYDPLA GTVFVDFGFQ LLDGQEAKKL NVQWLRAQLG IVSQEPILFD CSIAENIAYG
  1141  DNSRVVSQDE IVSAAKAANI HPFIETLPHK YETRVGDKGT QLSGGQKQRI AIARALIRQP
  1201  QILLLDEATS ALDTESEKVV QEALDKAREG RTCIVIAHRL STIQNADLIV VFQNGRVKEH
  1261  GTHQQLLAQK GIYFSMVSVQ AGTQNL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ABCB4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

12

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

115 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ABCB4.

Disease | AllUniProt

Conditions ABCB4 is implicated in, by any mechanism.

• Cholestasis, progressive familial intrahepatic, 3 (PFIC3) MIM:602347
• Cholestasis of pregnancy, intrahepatic 3 (ICP3) MIM:614972
• Gallbladder disease 1 (GBD1) MIM:600803

Disease | GeneticClinVar

253 pathogenic / likely-pathogenic of 1,490 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial intrahepatic cholestasis
• Low phospholipid associated cholelithiasis
• Progressive familial intrahepatic cholestasis type 3
• Cholestasis, intrahepatic, of pregnancy, 3
• ABCB4-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.51

gnomAD pLI

0

gnomAD missense Z

1.97

DepMap mean gene effect

-0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bile acid secretion
• cellular response to bile acid
• lipid homeostasis
• lipid metabolic process
• phospholipid translocation
• positive regulation of cholesterol transport
• positive regulation of phospholipid translocation
• positive regulation of phospholipid transport
• response to fenofibrate
• transmembrane transport

Molecular functions

• ABC-type transporter activity
• ATP binding
• ATP hydrolysis activity
• ATPase-coupled transmembrane transporter activity
• phosphatidylcholine floppase activity
• phospholipid transporter activity

Cellular components

• apical plasma membrane
• clathrin-coated vesicle
• cytoplasm
• cytosol
• extracellular exosome
• focal adhesion
• intercellular canaliculus
• membrane
• membrane raft
• nucleoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• ABC transporter-like, ATP-binding domain
• AAA+ ATPase domain
• ABC transporter type 1, transmembrane domain
• ABC transporter-like, conserved site
• P-loop containing nucleoside triphosphate hydrolase
• ABC transporter type 1, transmembrane domain superfamily
• Type 1 protein exporter
• ABC transporter
• ABC transporter transmembrane region

KeywordsUniProt

• ATP-binding
• Cell membrane
• Cytoplasm
• Cytoplasmic vesicle
• Glycoprotein
• Intrahepatic cholestasis
• Lipid transport
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Translocase
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ABCB4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HAX1