AT8B1_RAT
ID AT8B1_RAT Reviewed; 1251 AA.
AC D4AA47;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 2.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Phospholipid-transporting ATPase IC {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000269|PubMed:19027009};
DE AltName: Full=ATPase class I type 8B member 1;
DE AltName: Full=P4-ATPase flippase complex alpha subunit ATP8B1;
GN Name=Atp8b1 {ECO:0000312|RGD:1308488};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19027009; DOI=10.1053/j.gastro.2008.10.025;
RA Cai S.Y., Gautam S., Nguyen T., Soroka C.J., Rahner C., Boyer J.L.;
RT "ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure
RT in hepatocytes, but FXR expression and activity are maintained.";
RL Gastroenterology 136:1060-1069(2009).
RN [3] {ECO:0007744|PubMed:22673903}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalytic component of a P4-ATPase flippase complex which
CC catalyzes the hydrolysis of ATP coupled to the transport of
CC phospholipids, in particular phosphatidylcholines (PC), from the outer
CC to the inner leaflet of the plasma membrane (PubMed:19027009) (By
CC similarity). May participate in the establishment of the canalicular
CC membrane integrity by ensuring asymmetric distribution of phospholipids
CC in the canicular membrane. Thus may have a role in the regulation of
CC bile acids transport into the canaliculus, uptake of bile acids from
CC intestinal contents into intestinal mucosa or both and protect
CC hepatocytes from bile salts (PubMed:19027009). Involved in the
CC microvillus formation in polarized epithelial cells; the function seems
CC to be independent from its flippase activity. Participates in correct
CC apical membrane localization of CDC42, CFTR and SLC10A2 (By
CC similarity). Enables CDC42 clustering at the apical membrane during
CC enterocyte polarization through the interaction between CDC42 polybasic
CC region and negatively charged membrane lipids provided by ATP8B1 (By
CC similarity). Together with TMEM30A is involved in uptake of the
CC synthetic drug alkylphospholipid perifosine (By similarity). Required
CC for the preservation of cochlear hair cells in the inner ear. May act
CC as cardiolipin transporter during inflammatory injury (By similarity).
CC {ECO:0000250|UniProtKB:O43520, ECO:0000250|UniProtKB:Q148W0,
CC ECO:0000269|PubMed:19027009}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000269|PubMed:19027009};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a
CC 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:38583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57643,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O43520};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38584;
CC Evidence={ECO:0000250|UniProtKB:O43520};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O =
CC a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:38567, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57262, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:19027009};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568;
CC Evidence={ECO:0000269|PubMed:19027009};
CC -!- SUBUNIT: Component of a P4-ATPase flippase complex which consists of a
CC catalytic alpha subunit ATP8B1 and an accessory beta subunit TMEM30A.
CC The flippase ATP8B1:TMEM30A complex can form an intermediate
CC phosphoenzyme in vitro. Also interacts with beta subunit TMEM30B.
CC {ECO:0000250|UniProtKB:O43520}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O43520};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:O43520}. Apical cell
CC membrane {ECO:0000250|UniProtKB:O43520}. Cell projection, stereocilium
CC {ECO:0000250|UniProtKB:Q148W0}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:O43520}. Golgi apparatus
CC {ECO:0000250|UniProtKB:O43520}. Note=Exit from the endoplasmic
CC reticulum requires the presence of TMEM30A or TMEM30B. Localizes to
CC apical membranes in epithelial cells. {ECO:0000250|UniProtKB:O43520}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IV subfamily. {ECO:0000305}.
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DR EMBL; AABR07032293; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07032294; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_006254904.1; XM_006254842.3.
DR AlphaFoldDB; D4AA47; -.
DR SMR; D4AA47; -.
DR STRING; 10116.ENSRNOP00000038207; -.
DR GlyGen; D4AA47; 2 sites.
DR PaxDb; D4AA47; -.
DR PRIDE; D4AA47; -.
DR GeneID; 291555; -.
DR UCSC; RGD:1308488; rat.
DR CTD; 5205; -.
DR RGD; 1308488; Atp8b1.
DR eggNOG; KOG0206; Eukaryota.
DR HOGENOM; CLU_000846_5_2_1; -.
DR InParanoid; D4AA47; -.
DR OMA; VQEPFFP; -.
DR OrthoDB; 587717at2759; -.
DR TreeFam; TF300654; -.
DR BRENDA; 7.6.2.1; 5301.
DR Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000024952; Expressed in jejunum and 16 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032420; C:stereocilium; ISO:RGD.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0015247; F:aminophospholipid flippase activity; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0140326; F:ATPase-coupled intramembrane lipid transporter activity; IBA:GO_Central.
DR GO; GO:1901612; F:cardiolipin binding; ISO:RGD.
DR GO; GO:0005319; F:lipid transporter activity; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0140345; F:phosphatidylcholine flippase activity; ISO:RGD.
DR GO; GO:0090554; F:phosphatidylcholine floppase activity; IEA:RHEA.
DR GO; GO:0140346; F:phosphatidylserine flippase activity; IMP:UniProtKB.
DR GO; GO:0090556; F:phosphatidylserine floppase activity; IEA:RHEA.
DR GO; GO:0015917; P:aminophospholipid transport; ISO:RGD.
DR GO; GO:0045176; P:apical protein localization; ISO:RGD.
DR GO; GO:0015721; P:bile acid and bile salt transport; ISO:RGD.
DR GO; GO:0008206; P:bile acid metabolic process; ISO:RGD.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0060119; P:inner ear receptor cell development; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0015711; P:organic anion transport; ISO:RGD.
DR GO; GO:0045332; P:phospholipid translocation; ISO:RGD.
DR GO; GO:2001225; P:regulation of chloride transport; ISO:RGD.
DR GO; GO:0032534; P:regulation of microvillus assembly; ISO:RGD.
DR GO; GO:1903729; P:regulation of plasma membrane organization; ISO:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR GO; GO:0021650; P:vestibulocochlear nerve formation; ISO:RGD.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; ISO:RGD.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030346; ATP8B1.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006539; P-type_ATPase_IV.
DR InterPro; IPR032631; P-type_ATPase_N.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR032630; P_typ_ATPase_c.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR PANTHER; PTHR24092:SF48; PTHR24092:SF48; 1.
DR Pfam; PF16212; PhoLip_ATPase_C; 1.
DR Pfam; PF16209; PhoLip_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01652; ATPase-Plipid; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 1.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cell projection; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1251
FT /note="Phospholipid-transporting ATPase IC"
FT /id="PRO_0000451615"
FT TOPO_DOM 1..121
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..144
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..339
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 361..385
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 386..406
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 407..952
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 953..973
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 974..982
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 983..1003
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1004..1032
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1033..1053
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1054..1071
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1072..1092
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1093..1094
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1095..1115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1116..1142
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1143..1163
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1164..1251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..38
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 454
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9HD20"
FT BINDING 893
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT BINDING 897
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8NB49"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1251 AA; 143834 MW; 3198280A109CB204 CRC64;
MNTERDSETT FDEDSQPNDE VVPYSDDETE DELEDQGPAV EPEQNRVNRE VEKKKETFRK
DCTWQVKAND RKFHEQPHFM NTKFFCIKES KYASNAIKTY KYNALTFLPM NLFEQFKRAA
NFYFLILLIL QAIPQISTLA WYTTLVPLLL VLGITAIKDL VDDVARHKMD KEINNRTCEV
IKDGRFKIIK WKDIQVGDVI RLKKNDFIPA DILLLSSSEP NSLCYVETAE LDGETNLKFK
MALEITDQYL QIEDNLATFD GFIECEEPNN RLDKFTGTLF WRNQSFPLDA DKILLRGCVI
RNTDVCHGLV IFAGADTKIM KNSGKTRFKR TKIDYLMNYM VYTIIIVLIL VSAGLAIGHA
YWEAQIGNYS WYLYDGENAT PSYRGFLNFW GYIIVLNTMV PISLYVSVEV IRLGQSHFIN
WDLQMYYAEK DTPAKSRTTT LNEQLGQIHY IFSDKTGTLT QNIMTFKKCC INGTIYGDHR
DASQHSHSKI ELVDFSWNEF ADGKLAFYDH YLIEQIQSGK EPEVRQFFFL LSICHTVMVD
RIDGQINYQA ASPDEGALVN AARNFGFAFL ARTQNTITVS ELGTERTYSV LAILDFNSDR
KRMSIIVRTP EGSIRLYCKG ADTVIYERLH RMNPMKQETQ DALDIFASET LRTLCLCYKE
IEEKEFAEWN KKFMAASVAS SNRDEALDKV YEEIERDLIL LGATAIEDKL QDGVPETISK
LAKADIKIWV LTGDKKETAE NIGFACELLT EDTTICYGED INSLLHTRME NQRNRGGVSA
KFAPPAYEPF FPPGENRALI ITGSWLNEIL LEKKTKRSKI LKLKFPRTEE ERRMRSQSRR
RLEEKKEQRQ KNFVDLACEC SAVICCRVTP KQKAMVVDLV KRYKKAITLA IGDGANDVNM
IKTAHIGVGI SGQEGMQAVM SSDYSFAQFR YLQRLLLVHG RWSYIRMCKF LRYFFYKNFA
FTLVHFWYSF FNGYSAQTAY EDWFITLYNV LYSSLPVLLM GLLDQDVSDK LSLRFPGLYV
VGQRDLLFNY KKFFVSLLHG VLTSMVLFFI PFGAYLQTVG QDGEAPSDYQ SFAVTMASAL
VITVNFQIGL DTSYWTFVNA FSIFGSIALY FGIMFDFHSA GIHVLFPSAF QFTGTASNAL
RQPYIWLTII LTVAVCLLPV VAIRFLSMTI WPSESDKIQK HRKRLKAEEQ WKRRQSVFRR
GASSRRSAYA FSHQRGYADL ISSGRSIRKK RSPLDAIIAD GTAEYRRTVE S
