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Protein

ATP-binding cassette sub-family C member 11

Gene

ABCC11

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Participates in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides (PubMed:12764137, PubMed:15537867). Enhances the cellular extrusion of cAMP and cGMP (PubMed:12764137, PubMed:15537867). Stimulates the ATP-dependent uptake of a range of physiological and synthetic lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E217betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate (PubMed:15537867, PubMed:25896536). Probably functions to secrete earwax (PubMed:16444273, PubMed:19383836). Required for the secretion of components contributing to axillary odor formation (PubMed:19710689).6 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi544 – 551ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1175 – 1182ATP 2PROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

  • organic anion transport Source: UniProtKB
  • purine nucleotide transport Source: UniProtKB
  • transmembrane transport Source: Reactome

Keywordsi

Biological processTransport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-382556. ABC-family proteins mediated transport.

Protein family/group databases

TCDBi3.A.1.208.13. the atp-binding cassette (abc) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-binding cassette sub-family C member 11
Alternative name(s):
Multidrug resistance-associated protein 8
Gene namesi
Name:ABCC11
Synonyms:MRP8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:14639. ABCC11.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 163CytoplasmicSequence analysisAdd BLAST163
Transmembranei164 – 184HelicalPROSITE-ProRule annotationAdd BLAST21
Transmembranei195 – 215HelicalPROSITE-ProRule annotationAdd BLAST21
Transmembranei271 – 291HelicalPROSITE-ProRule annotationAdd BLAST21
Transmembranei297 – 317HelicalPROSITE-ProRule annotationAdd BLAST21
Transmembranei384 – 404HelicalPROSITE-ProRule annotationAdd BLAST21
Transmembranei418 – 438HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini439 – 806CytoplasmicSequence analysisAdd BLAST368
Transmembranei807 – 827HelicalPROSITE-ProRule annotationAdd BLAST21
Transmembranei864 – 884HelicalPROSITE-ProRule annotationAdd BLAST21
Transmembranei931 – 951HelicalPROSITE-ProRule annotationAdd BLAST21
Transmembranei1050 – 1070HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini1071 – 1382CytoplasmicSequence analysisAdd BLAST312

GO - Cellular componenti

  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
  • vacuolar membrane Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane, Vacuole

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi180G → A or P: Does not affect N-glycosylation. 1 Publication1
Mutagenesisi180G → L, H, D or E: Loss of N-glycosylation. 1 Publication1
Mutagenesisi838N → Q: Loss of N-glycosylation. 1 Publication1
Mutagenesisi844N → Q: Loss of N-glycosylation. 1 Publication1

Organism-specific databases

DisGeNETi85320.
MIMi117800. phenotype.
OpenTargetsiENSG00000121270.
PharmGKBiPA24393.

Chemistry databases

ChEMBLiCHEMBL2073702.
DrugBankiDB00286. Conjugated Equine Estrogens.
DB02527. Cyclic Adenosine Monophosphate.
DB00158. Folic Acid.
DB00328. Indomethacin.
DB00563. Methotrexate.
DB01032. Probenecid.
DB04348. Taurocholic Acid.

Polymorphism and mutation databases

BioMutaiABCC11.
DMDMi74762666.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002255941 – 1382ATP-binding cassette sub-family C member 11Add BLAST1382

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi838N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Glycosylationi844N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Glycosylationi992N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ96J66.
PaxDbiQ96J66.
PeptideAtlasiQ96J66.
PRIDEiQ96J66.

PTM databases

iPTMnetiQ96J66.
PhosphoSitePlusiQ96J66.

Expressioni

Tissue specificityi

Expressed in ceruminous apocrine gland (at protein level) (PubMed:19383836, PubMed:19710689). Expressed in many tissues. Not expressed in kidney, spleen and colon. Highly expressed in breast cancer. Expressed at moderate levels in normal breast and testis and at very low levels in liver, brain and placenta.4 Publications

Gene expression databases

BgeeiENSG00000121270.
CleanExiHS_ABCC11.
ExpressionAtlasiQ96J66. baseline and differential.
GenevisibleiQ96J66. HS.

Organism-specific databases

HPAiCAB032513.
HPA031980.
HPA031981.
HPA031982.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000349017.

Structurei

3D structure databases

ProteinModelPortaliQ96J66.
SMRiQ96J66.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini163 – 443ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST281
Domaini508 – 732ABC transporter 1PROSITE-ProRule annotationAdd BLAST225
Domaini806 – 1105ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST300
Domaini1141 – 1375ABC transporter 2PROSITE-ProRule annotationAdd BLAST235

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0054. Eukaryota.
COG1132. LUCA.
GeneTreeiENSGT00880000137856.
HOVERGENiHBG108314.
InParanoidiQ96J66.
KOiK05671.
OMAiKYRDNTP.
OrthoDBiEOG091G01TC.
PhylomeDBiQ96J66.
TreeFamiTF352085.

Family and domain databases

InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR030251. ABCC11.
IPR027417. P-loop_NTPase.
PANTHERiPTHR24223:SF308. PTHR24223:SF308. 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. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96J66-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTRKRTYWVP NSSGGLVNRG IDIGDDMVSG LIYKTYTLQD GPWSQQERNP
60 70 80 90 100
EAPGRAAVPP WGKYDAALRT MIPFRPKPRF PAPQPLDNAG LFSYLTVSWL
110 120 130 140 150
TPLMIQSLRS RLDENTIPPL SVHDASDKNV QRLHRLWEEE VSRRGIEKAS
160 170 180 190 200
VLLVMLRFQR TRLIFDALLG ICFCIASVLG PILIIPKILE YSEEQLGNVV
210 220 230 240 250
HGVGLCFALF LSECVKSLSF SSSWIINQRT AIRFRAAVSS FAFEKLIQFK
260 270 280 290 300
SVIHITSGEA ISFFTGDVNY LFEGVCYGPL VLITCASLVI CSISSYFIIG
310 320 330 340 350
YTAFIAILCY LLVFPLAVFM TRMAVKAQHH TSEVSDQRIR VTSEVLTCIK
360 370 380 390 400
LIKMYTWEKP FAKIIEDLRR KERKLLEKCG LVQSLTSITL FIIPTVATAV
410 420 430 440 450
WVLIHTSLKL KLTASMAFSM LASLNLLRLS VFFVPIAVKG LTNSKSAVMR
460 470 480 490 500
FKKFFLQESP VFYVQTLQDP SKALVFEEAT LSWQQTCPGI VNGALELERN
510 520 530 540 550
GHASEGMTRP RDALGPEEEG NSLGPELHKI NLVVSKGMML GVCGNTGSGK
560 570 580 590 600
SSLLSAILEE MHLLEGSVGV QGSLAYVPQQ AWIVSGNIRE NILMGGAYDK
610 620 630 640 650
ARYLQVLHCC SLNRDLELLP FGDMTEIGER GLNLSGGQKQ RISLARAVYS
660 670 680 690 700
DRQIYLLDDP LSAVDAHVGK HIFEECIKKT LRGKTVVLVT HQLQYLEFCG
710 720 730 740 750
QIILLENGKI CENGTHSELM QKKGKYAQLI QKMHKEATSD MLQDTAKIAE
760 770 780 790 800
KPKVESQALA TSLEESLNGN AVPEHQLTQE EEMEEGSLSW RVYHHYIQAA
810 820 830 840 850
GGYMVSCIIF FFVVLIVFLT IFSFWWLSYW LEQGSGTNSS RESNGTMADL
860 870 880 890 900
GNIADNPQLS FYQLVYGLNA LLLICVGVCS SGIFTKVTRK ASTALHNKLF
910 920 930 940 950
NKVFRCPMSF FDTIPIGRLL NCFAGDLEQL DQLLPIFSEQ FLVLSLMVIA
960 970 980 990 1000
VLLIVSVLSP YILLMGAIIM VICFIYYMMF KKAIGVFKRL ENYSRSPLFS
1010 1020 1030 1040 1050
HILNSLQGLS SIHVYGKTED FISQFKRLTD AQNNYLLLFL SSTRWMALRL
1060 1070 1080 1090 1100
EIMTNLVTLA VALFVAFGIS STPYSFKVMA VNIVLQLASS FQATARIGLE
1110 1120 1130 1140 1150
TEAQFTAVER ILQYMKMCVS EAPLHMEGTS CPQGWPQHGE IIFQDYHMKY
1160 1170 1180 1190 1200
RDNTPTVLHG INLTIRGHEV VGIVGRTGSG KSSLGMALFR LVEPMAGRIL
1210 1220 1230 1240 1250
IDGVDICSIG LEDLRSKLSV IPQDPVLLSG TIRFNLDPFD RHTDQQIWDA
1260 1270 1280 1290 1300
LERTFLTKAI SKFPKKLHTD VVENGGNFSV GERQLLCIAR AVLRNSKIIL
1310 1320 1330 1340 1350
IDEATASIDM ETDTLIQRTI REAFQGCTVL VIAHRVTTVL NCDHILVMGN
1360 1370 1380
GKVVEFDRPE VLRKKPGSLF AALMATATSS LR
Length:1,382
Mass (Da):154,301
Last modified:December 1, 2001 - v1
Checksum:i0F3C17DC69AE97F4
GO
Isoform 2 (identifier: Q96J66-2) [UniParc]FASTAAdd to basket
Also known as: Isoform A

The sequence of this isoform differs from the canonical sequence as follows:
     1261-1298: Missing.

Show »
Length:1,344
Mass (Da):150,093
Checksum:i4859DCC95569B2C7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti199V → A in AAK58869 (PubMed:11688999).Curated1
Sequence conflicti199V → A in AAL99902 (PubMed:11688999).Curated1
Sequence conflicti311L → P in AAK19755 (PubMed:11591886).Curated1
Sequence conflicti363K → E in AAK58869 (PubMed:11688999).Curated1
Sequence conflicti363K → E in AAL99902 (PubMed:11688999).Curated1
Sequence conflicti395T → A in AAK19755 (PubMed:11591886).Curated1
Sequence conflicti632L → P in AAK19755 (PubMed:11591886).Curated1
Sequence conflicti688L → Q in AAK19755 (PubMed:11591886).Curated1
Sequence conflicti702I → V in AAK19755 (PubMed:11591886).Curated1
Sequence conflicti982K → E in AAK19755 (PubMed:11591886).Curated1

Polymorphismi

Polymorphism in ABCC11 is associated with variation in apocrine gland secretion [MIMi:117800]. This determines different ear wax phenotypes, presence or absence of axillary odor, and variation in colostrum secretion. Characteristic of earwax and strength of axillary odor are most likely interconnected. Human earwax is a Mendelian trait consisting of wet and dry types. The wet earwax is brownish and sticky, whereas the dry type lacks cerumen. The wet cerumen phenotype is completely dominant. The dry type is seen frequently (80-95%) among East Asians, but uncommon (0-3%) in populations of European and African origins. Intermediate frequencies (30-50%) of the dry type are seen in populations of Southern Asia, the Pacific Islands, Central Asia and Asia Minor, as well as among the Native North American and Inuit of Asian ancestry. The allele with Arg-180 is responsible for the dry earwax phenotype and lack of axillary odor.3 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02543719R → H No effect on glycosylation; no effect on transport activity; no effect on plasma membrane localization. 2 PublicationsCorresponds to variant dbSNP:rs16945988Ensembl.1
Natural variantiVAR_025438180G → R in dry earwax and lack of axillary odor phenotype; loss of N-glycosylation; strongly reduced plasma membrane localization; reduced transport activity; decreased protein concentration in axillary sweat. 4 PublicationsCorresponds to variant dbSNP:rs17822931Ensembl.1
Natural variantiVAR_048144317A → E No effect on glycoslylation; no effect on transport activity; no effect on plasma membrane localization. 3 PublicationsCorresponds to variant dbSNP:rs11863236Ensembl.1
Natural variantiVAR_048145546T → M Reduced transport activity; no effect on glycoslylation; no effect on plasma membrane localization. 2 PublicationsCorresponds to variant dbSNP:rs17822471Ensembl.1
Natural variantiVAR_077575630R → W No effect on glycoslylation. 1 PublicationCorresponds to variant dbSNP:rs41282045Ensembl.1
Natural variantiVAR_048146648V → I No effect on glycoslylation; no effect on transport activity; no effect on plasma membrane localization. 2 PublicationsCorresponds to variant dbSNP:rs16945930Ensembl.1
Natural variantiVAR_048147687V → I No effect on glycoslylation. 1 PublicationCorresponds to variant dbSNP:rs16945928Ensembl.1
Natural variantiVAR_048148735K → R No effect on glycoslylation. 1 PublicationCorresponds to variant dbSNP:rs16945926Ensembl.1
Natural variantiVAR_077576970M → V No effect on glycoslylation. 1 PublicationCorresponds to variant dbSNP:rs41280943Ensembl.1
Natural variantiVAR_0481491344H → R No effect on glycoslylation; no effect on transport activity; no effect on plasma membrane localization. 3 PublicationsCorresponds to variant dbSNP:rs16945916Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0173511261 – 1298Missing in isoform 2. 1 PublicationAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY040219 mRNA. Translation: AAK76739.1.
AF367202 mRNA. Translation: AAK58869.1.
AF411579 mRNA. Translation: AAL99902.1.
AF352582 mRNA. Translation: AAK19755.1.
CCDSiCCDS10732.1. [Q96J66-1]
CCDS10733.1. [Q96J66-2]
RefSeqiNP_115972.2. NM_032583.3. [Q96J66-1]
NP_149163.2. NM_033151.3. [Q96J66-1]
NP_660187.1. NM_145186.2. [Q96J66-2]
XP_016879284.1. XM_017023795.1. [Q96J66-1]
XP_016879285.1. XM_017023796.1. [Q96J66-1]
XP_016879286.1. XM_017023797.1. [Q96J66-1]
XP_016879287.1. XM_017023798.1. [Q96J66-1]
XP_016879288.1. XM_017023799.1. [Q96J66-1]
XP_016879289.1. XM_017023800.1. [Q96J66-1]
UniGeneiHs.652267.

Genome annotation databases

EnsembliENST00000353782; ENSP00000311326; ENSG00000121270. [Q96J66-2]
ENST00000356608; ENSP00000349017; ENSG00000121270. [Q96J66-1]
ENST00000394747; ENSP00000378230; ENSG00000121270. [Q96J66-1]
ENST00000394748; ENSP00000378231; ENSG00000121270. [Q96J66-1]
GeneIDi85320.
KEGGihsa:85320.
UCSCiuc002eff.1. human. [Q96J66-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.

Entry informationi

Entry nameiABCCB_HUMAN
AccessioniPrimary (citable) accession number: Q96J66
Secondary accession number(s): Q8TDJ0, Q96JA6, Q9BX80
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: December 1, 2001
Last modified: June 7, 2017
This is version 133 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  6. SIMILARITY comments
    Index of protein domains and families