ABCC8

Protein identityUniProt · HPA

UniProt accession

Q09428

Gene

ABCC8

Ensembl

ENSG00000006071

Chromosome

11

Canonical length

1581 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted membrane proteins, Transporters

Subcellular location

Nucleoli,Golgi apparatus,Cytosol,Principal piece

Quaternary structure

Homotetramer

OverviewNCBI Gene

The 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 MRP subfamily which is involved in multi-drug resistance. This protein functions as a modulator of ATP-sensitive potassium channels and insulin release. Mutations in the ABCC8 gene and deficiencies in the encoded protein have been observed in patients with hyperinsulinemic hypoglycemia of infancy, an autosomal recessive disorder of unregulated and high insulin secretion. Mutations have also been associated with non-insulin-dependent diabetes mellitus type II, an autosomal dominant disease of defective insulin secretion. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2020]

Canonical amino-acid sequenceUniProt

1581 residues, UniProt reviewed canonical sequence.

>Q09428|ABCC8
     1  MPLAFCGSEN HSAAYRVDQG VLNNGCFVDA LNVVPHVFLL FITFPILFIG WGSQSSKVHI
    61  HHSTWLHFPG HNLRWILTFM LLFVLVCEIA EGILSDGVTE SHHLHLYMPA GMAFMAAVTS
   121  VVYYHNIETS NFPKLLIALL VYWTLAFITK TIKFVKFLDH AIGFSQLRFC LTGLLVILYG
   181  MLLLVEVNVI RVRRYIFFKT PREVKPPEDL QDLGVRFLQP FVNLLSKGTY WWMNAFIKTA
   241  HKKPIDLRAI GKLPIAMRAL TNYQRLCEAF DAQVRKDIQG TQGARAIWQA LSHAFGRRLV
   301  LSSTFRILAD LLGFAGPLCI FGIVDHLGKE NDVFQPKTQF LGVYFVSSQE FLANAYVLAV
   361  LLFLALLLQR TFLQASYYVA IETGINLRGA IQTKIYNKIM HLSTSNLSMG EMTAGQICNL
   421  VAIDTNQLMW FFFLCPNLWA MPVQIIVGVI LLYYILGVSA LIGAAVIILL APVQYFVATK
   481  LSQAQRSTLE YSNERLKQTN EMLRGIKLLK LYAWENIFRT RVETTRRKEM TSLRAFAIYT
   541  SISIFMNTAI PIAAVLITFV GHVSFFKEAD FSPSVAFASL SLFHILVTPL FLLSSVVRST
   601  VKALVSVQKL SEFLSSAEIR EEQCAPHEPT PQGPASKYQA VPLRVVNRKR PAREDCRGLT
   661  GPLQSLVPSA DGDADNCCVQ IMGGYFTWTP DGIPTLSNIT IRIPRGQLTM IVGQVGCGKS
   721  SLLLAALGEM QKVSGAVFWS SLPDSEIGED PSPERETATD LDIRKRGPVA YASQKPWLLN
   781  ATVEENIIFE SPFNKQRYKM VIEACSLQPD IDILPHGDQT QIGERGINLS GGQRQRISVA
   841  RALYQHANVV FLDDPFSALD IHLSDHLMQA GILELLRDDK RTVVLVTHKL QYLPHADWII
   901  AMKDGTIQRE GTLKDFQRSE CQLFEHWKTL MNRQDQELEK ETVTERKATE PPQGLSRAMS
   961  SRDGLLQDEE EEEEEAAESE EDDNLSSMLH QRAEIPWRAC AKYLSSAGIL LLSLLVFSQL
  1021  LKHMVLVAID YWLAKWTDSA LTLTPAARNC SLSQECTLDQ TVYAMVFTVL CSLGIVLCLV
  1081  TSVTVEWTGL KVAKRLHRSL LNRIILAPMR FFETTPLGSI LNRFSSDCNT IDQHIPSTLE
  1141  CLSRSTLLCV SALAVISYVT PVFLVALLPL AIVCYFIQKY FRVASRDLQQ LDDTTQLPLL
  1201  SHFAETVEGL TTIRAFRYEA RFQQKLLEYT DSNNIASLFL TAANRWLEVR MEYIGACVVL
  1261  IAAVTSISNS LHRELSAGLV GLGLTYALMV SNYLNWMVRN LADMELQLGA VKRIHGLLKT
  1321  EAESYEGLLA PSLIPKNWPD QGKIQIQNLS VRYDSSLKPV LKHVNALIAP GQKIGICGRT
  1381  GSGKSSFSLA FFRMVDTFEG HIIIDGIDIA KLPLHTLRSR LSIILQDPVL FSGTIRFNLD
  1441  PERKCSDSTL WEALEIAQLK LVVKALPGGL DAIITEGGEN FSQGQRQLFC LARAFVRKTS
  1501  IFIMDEATAS IDMATENILQ KVVMTAFADR TVVTIAHRVH TILSADLVIV LKRGAILEFD
  1561  KPEKLLSRKD SVFASFVRAD K

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ABCC8 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

17

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

23 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ABCC8.

Disease | AllUniProt

Conditions ABCC8 is implicated in, by any mechanism.

• Leucine-induced hypoglycemia (LIH) MIM:240800
• Hyperinsulinemic hypoglycemia, familial, 1 (HHF1) MIM:256450
• Diabetes mellitus, permanent neonatal, 3 (PNDM3) MIM:618857
• Transient neonatal diabetes mellitus 2 (TNDM2) MIM:610374
• Maturity-onset diabetes of the young 12 (MODY12) MIM:621196

Disease | GeneticClinVar

481 pathogenic / likely-pathogenic of 2,963 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hyperinsulinemic hypoglycemia, familial, 1
• Type 2 diabetes mellitus
• Hereditary hyperinsulinism
• Diabetes mellitus, permanent neonatal 3
• Diabetes mellitus, transient neonatal, 2

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)

0.77

gnomAD pLI

0

gnomAD missense Z

1.91

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• action potential
• cellular response to nutrient levels
• female pregnancy
• glutamate secretion, neurotransmission
• inorganic cation transmembrane transport
• intracellular glucose homeostasis
• memory
• negative regulation of angiogenesis
• negative regulation of blood-brain barrier permeability
• negative regulation of glial cell proliferation
• negative regulation of insulin secretion
• negative regulation of low-density lipoprotein particle clearance
• neuromuscular process
• positive regulation of insulin secretion involved in cellular response to glucose stimulus
• positive regulation of potassium ion transport
• positive regulation of tight junction disassembly
• positive regulation of tumor necrosis factor production
• potassium ion import across plasma membrane
• potassium ion transmembrane transport
• potassium ion transport
• regulation of insulin secretion
• response to insulin
• response to lipopolysaccharide
• response to pH
• response to xenobiotic stimulus
• response to zinc ion
• transmembrane transport
• visual learning
• negative regulation of neuroblast migration
• positive regulation of uterine smooth muscle relaxation

Molecular functions

• ABC-type transporter activity
• ADP binding
• ATP binding
• ATP hydrolysis activity
• ATP-activated inward rectifier potassium channel activity
• ATPase-coupled monoatomic cation transmembrane transporter activity
• metal ion binding
• potassium channel activity
• sulfonylurea receptor activity
• transmembrane transporter binding

Cellular components

• inward rectifying potassium channel
• plasma membrane
• potassium ion-transporting ATPase complex
• presynaptic membrane
• sarcolemma
• synaptic vesicle membrane

Protein domainsUniProt · Pfam · InterPro

• ATP-binding cassette sub-family C member 8/9
• 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
• ATP-binding cassette transporter C-like
• ABC transporter
• ABC transporter transmembrane region
• ATP-binding cassette subfamily C member 8

KeywordsUniProt

• ATP-binding
• Cell membrane
• Diabetes mellitus
• Disulfide bond
• Glycoprotein
• Magnesium
• Membrane
• Metal-binding
• Nucleotide-binding
• Receptor
• Repeat
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ABCC8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ENSA