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3.A.1.208.13
Cyclic nucleotide (cAMP and cGMP) efflux pump, MRP8 (ABCC11); also exports other nucleoside and nucleotide analogues, and confers resistance to fluoropyrimidines and the anti-AIDS drug, 2',3'-dideoxycytidine (Guo et al., 2003). Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. A SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. Cells with allele A show a lower excretory activity for cGMP than those with allele G. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait (Yoshiura et al., 2006).  Binding sites in ABCC11 for cGMP (cyclic guanosine monophosphate) and 5FdUMP (5-fluoro-2'-deoxyuridine-5'-monophosphate), the active metabolite of the anticancer drug 5-fluoro-uracil, have been identified (Honorat et al. 2013).  MRP8 generally exports a variety of anionic lipophilic compounds including antiviral and anticancer agents (Arlanov et al. 2015). Inhibition of cAMP efflux can stimulate leukemia cell differentiation, cell growth arrest, and apoptosis (Perez et al. 2020).

Accession Number:Q96J66
Protein Name:ATP-binding cassette sub-family C member 11
Length:1382
Molecular Weight:154301.00
Species: [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate cyclic nucleotide, nucleoside analogue, dinucleotide analogue, zalcitabine, coenzyme Q10

Cross database links:

RefSeq: NP_115972.2    NP_149163.2    NP_660187.1   
Entrez Gene ID: 85320   
Pfam: PF00664    PF00005   
OMIM: 117800  phenotype
607040  gene
KEGG: hsa:85320   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005524 F:ATP binding
GO:0042626 F:ATPase activity, coupled to transmembrane m...
GO:0055085 P:transmembrane transport

References (6)

[1] “Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12.”  Tammur J.et.al.   11483364
[2] “Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12.”  Yabuuchi H.et.al.   11688999
[3] “MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer.”  Bera T.K.et.al.   11591886
[4] “MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine.”  Guo Y.et.al.   12764137
[5] “Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11).”  Chen Z.S.et.al.   15537867
[6] “A SNP in the ABCC11 gene is the determinant of human earwax type.”  Yoshiura K.et.al.   16444273

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FASTA formatted sequence 
1:	MTRKRTYWVP NSSGGLVNRG IDIGDDMVSG LIYKTYTLQD GPWSQQERNP EAPGRAAVPP 
61:	WGKYDAALRT MIPFRPKPRF PAPQPLDNAG LFSYLTVSWL TPLMIQSLRS RLDENTIPPL 
121:	SVHDASDKNV QRLHRLWEEE VSRRGIEKAS VLLVMLRFQR TRLIFDALLG ICFCIASVLG 
181:	PILIIPKILE YSEEQLGNVV HGVGLCFALF LSECVKSLSF SSSWIINQRT AIRFRAAVSS 
241:	FAFEKLIQFK SVIHITSGEA ISFFTGDVNY LFEGVCYGPL VLITCASLVI CSISSYFIIG 
301:	YTAFIAILCY LLVFPLAVFM TRMAVKAQHH TSEVSDQRIR VTSEVLTCIK LIKMYTWEKP 
361:	FAKIIEDLRR KERKLLEKCG LVQSLTSITL FIIPTVATAV WVLIHTSLKL KLTASMAFSM 
421:	LASLNLLRLS VFFVPIAVKG LTNSKSAVMR FKKFFLQESP VFYVQTLQDP SKALVFEEAT 
481:	LSWQQTCPGI VNGALELERN GHASEGMTRP RDALGPEEEG NSLGPELHKI NLVVSKGMML 
541:	GVCGNTGSGK SSLLSAILEE MHLLEGSVGV QGSLAYVPQQ AWIVSGNIRE NILMGGAYDK 
601:	ARYLQVLHCC SLNRDLELLP FGDMTEIGER GLNLSGGQKQ RISLARAVYS DRQIYLLDDP 
661:	LSAVDAHVGK HIFEECIKKT LRGKTVVLVT HQLQYLEFCG QIILLENGKI CENGTHSELM 
721:	QKKGKYAQLI QKMHKEATSD MLQDTAKIAE KPKVESQALA TSLEESLNGN AVPEHQLTQE 
781:	EEMEEGSLSW RVYHHYIQAA GGYMVSCIIF FFVVLIVFLT IFSFWWLSYW LEQGSGTNSS 
841:	RESNGTMADL GNIADNPQLS FYQLVYGLNA LLLICVGVCS SGIFTKVTRK ASTALHNKLF 
901:	NKVFRCPMSF FDTIPIGRLL NCFAGDLEQL DQLLPIFSEQ FLVLSLMVIA VLLIVSVLSP 
961:	YILLMGAIIM VICFIYYMMF KKAIGVFKRL ENYSRSPLFS HILNSLQGLS SIHVYGKTED 
1021:	FISQFKRLTD AQNNYLLLFL SSTRWMALRL EIMTNLVTLA VALFVAFGIS STPYSFKVMA 
1081:	VNIVLQLASS FQATARIGLE TEAQFTAVER ILQYMKMCVS EAPLHMEGTS CPQGWPQHGE 
1141:	IIFQDYHMKY RDNTPTVLHG INLTIRGHEV VGIVGRTGSG KSSLGMALFR LVEPMAGRIL 
1201:	IDGVDICSIG LEDLRSKLSV IPQDPVLLSG TIRFNLDPFD RHTDQQIWDA LERTFLTKAI 
1261:	SKFPKKLHTD VVENGGNFSV GERQLLCIAR AVLRNSKIIL IDEATASIDM ETDTLIQRTI 
1321:	REAFQGCTVL VIAHRVTTVL NCDHILVMGN GKVVEFDRPE VLRKKPGSLF AALMATATSS 
1381:	LR