AT8B4_HUMAN
ID AT8B4_HUMAN Reviewed; 1192 AA.
AC Q8TF62; Q9H727;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Probable phospholipid-transporting ATPase IM;
DE EC=7.6.2.1;
DE AltName: Full=ATPase class I type 8B member 4;
DE AltName: Full=P4-ATPase flippase complex alpha subunit ATP8B4;
GN Name=ATP8B4; Synonyms=KIAA1939;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11853319; DOI=10.1093/dnares/8.6.319;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXII. The
RT complete sequences of 50 new cDNA clones which code for large proteins.";
RL DNA Res. 8:319-327(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 907-1192.
RC TISSUE=Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP INTERACTION WITH TMEM30A, AND SUBCELLULAR LOCATION.
RX PubMed=20947505; DOI=10.1074/jbc.m110.139006;
RA van der Velden L.M., Wichers C.G., van Breevoort A.E., Coleman J.A.,
RA Molday R.S., Berger R., Klomp L.W., van de Graaf S.F.;
RT "Heteromeric interactions required for abundance and subcellular
RT localization of human CDC50 proteins and class 1 P4-ATPases.";
RL J. Biol. Chem. 285:40088-40096(2010).
RN [5]
RP INTERACTION WITH TMEM30A AND TMEM30B.
RX PubMed=20961850; DOI=10.1074/jbc.m110.139543;
RA Bryde S., Hennrich H., Verhulst P.M., Devaux P.F., Lenoir G.,
RA Holthuis J.C.;
RT "CDC50 proteins are critical components of the human class-1 P4-ATPase
RT transport machinery.";
RL J. Biol. Chem. 285:40562-40572(2010).
CC -!- FUNCTION: Component of a P4-ATPase flippase complex which catalyzes the
CC hydrolysis of ATP coupled to the transport of aminophospholipids from
CC the outer to the inner leaflet of various membranes and ensures the
CC maintenance of asymmetric distribution of phospholipids. Phospholipid
CC translocation seems also to be implicated in vesicle formation and in
CC uptake of lipid signaling molecules (Probable). {ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC -!- SUBUNIT: Component of a P4-ATPase flippase complex which consists of a
CC catalytic alpha subunit and an accessory beta subunit (Probable).
CC Interacts with beta subunits TMEM30A and TMEM30B.
CC {ECO:0000269|PubMed:20947505, ECO:0000269|PubMed:20961850,
CC ECO:0000305}.
CC -!- INTERACTION:
CC Q8TF62; Q9NV96: TMEM30A; NbExp=4; IntAct=EBI-9527207, EBI-2836942;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20947505};
CC Multi-pass membrane protein {ECO:0000269|PubMed:20947505}. Golgi
CC apparatus {ECO:0000269|PubMed:20947505}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed at moderate levels.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IV subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15072.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB85525.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin inserted in the coding sequence.; Evidence={ECO:0000305};
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DR EMBL; AB075819; BAB85525.1; ALT_SEQ; mRNA.
DR EMBL; AC009753; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC016045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025040; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK025125; BAB15072.1; ALT_FRAME; mRNA.
DR CCDS; CCDS32238.1; -.
DR RefSeq; NP_079113.2; NM_024837.3.
DR RefSeq; XP_016878081.1; XM_017022592.1.
DR AlphaFoldDB; Q8TF62; -.
DR SMR; Q8TF62; -.
DR BioGRID; 122979; 13.
DR ComplexPortal; CPX-6305; ATP8B4-CDC50A P4-ATPase complex.
DR ComplexPortal; CPX-6306; ATP8B4-CDC50B P4-ATPase complex.
DR IntAct; Q8TF62; 2.
DR STRING; 9606.ENSP00000284509; -.
DR iPTMnet; Q8TF62; -.
DR PhosphoSitePlus; Q8TF62; -.
DR BioMuta; ATP8B4; -.
DR DMDM; 209572761; -.
DR EPD; Q8TF62; -.
DR jPOST; Q8TF62; -.
DR MassIVE; Q8TF62; -.
DR PaxDb; Q8TF62; -.
DR PeptideAtlas; Q8TF62; -.
DR PRIDE; Q8TF62; -.
DR ProteomicsDB; 74562; -.
DR Antibodypedia; 24681; 25 antibodies from 8 providers.
DR DNASU; 79895; -.
DR Ensembl; ENST00000284509.11; ENSP00000284509.6; ENSG00000104043.15.
DR Ensembl; ENST00000559829.5; ENSP00000453169.1; ENSG00000104043.15.
DR GeneID; 79895; -.
DR KEGG; hsa:79895; -.
DR MANE-Select; ENST00000284509.11; ENSP00000284509.6; NM_024837.4; NP_079113.2.
DR UCSC; uc001zxu.4; human.
DR CTD; 79895; -.
DR DisGeNET; 79895; -.
DR GeneCards; ATP8B4; -.
DR HGNC; HGNC:13536; ATP8B4.
DR HPA; ENSG00000104043; Tissue enriched (bone).
DR MIM; 609123; gene.
DR neXtProt; NX_Q8TF62; -.
DR OpenTargets; ENSG00000104043; -.
DR PharmGKB; PA25169; -.
DR VEuPathDB; HostDB:ENSG00000104043; -.
DR eggNOG; KOG0206; Eukaryota.
DR GeneTree; ENSGT00940000160101; -.
DR HOGENOM; CLU_000846_3_2_1; -.
DR InParanoid; Q8TF62; -.
DR OMA; NKHKFFI; -.
DR OrthoDB; 587717at2759; -.
DR PhylomeDB; Q8TF62; -.
DR TreeFam; TF300654; -.
DR PathwayCommons; Q8TF62; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; Q8TF62; -.
DR BioGRID-ORCS; 79895; 11 hits in 1067 CRISPR screens.
DR ChiTaRS; ATP8B4; human.
DR GenomeRNAi; 79895; -.
DR Pharos; Q8TF62; Tbio.
DR PRO; PR:Q8TF62; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8TF62; protein.
DR Bgee; ENSG00000104043; Expressed in bone marrow cell and 125 other tissues.
DR ExpressionAtlas; Q8TF62; baseline and differential.
DR Genevisible; Q8TF62; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; IPI:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
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:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030348; ATP8B4.
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:SF80; PTHR24092:SF80; 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; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Golgi apparatus; Lipid transport; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Reference proteome;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1192
FT /note="Probable phospholipid-transporting ATPase IM"
FT /id="PRO_0000046368"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..66
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 67..72
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..327
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 328..349
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 350..871
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 872..892
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 893..904
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 905..924
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 925..954
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 955..976
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 977..990
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 991..1013
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1014..1019
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1020..1040
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1041..1060
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 1061..1085
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1086..1192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1104..1130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1143..1163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1106..1124
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 392
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 815
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 819
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT VARIANT 225
FT /note="N -> S (in dbSNP:rs16963151)"
FT /id="VAR_046962"
FT VARIANT 452
FT /note="H -> N (in dbSNP:rs2452524)"
FT /id="VAR_046963"
FT VARIANT 1165
FT /note="N -> K (in dbSNP:rs16962989)"
FT /id="VAR_046964"
FT VARIANT 1190
FT /note="V -> G (in dbSNP:rs16962987)"
FT /id="VAR_046965"
FT CONFLICT 631
FT /note="G -> E (in Ref. 1; BAB85525)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1192 AA; 135868 MW; FFE8D935B7544D73 CRC64;
MFCSEKKLRE VERIVKANDR EYNEKFQYAD NRIHTSKYNI LTFLPINLFE QFQRVANAYF
LCLLILQLIP EISSLTWFTT IVPLVLVITM TAVKDATDDY FRHKSDNQVN NRQSEVLINS
KLQNEKWMNV KVGDIIKLEN NQFVAADLLL LSSSEPHGLC YVETAELDGE TNLKVRHALS
VTSELGADIS RLAGFDGIVV CEVPNNKLDK FMGILSWKDS KHSLNNEKII LRGCILRNTS
WCFGMVIFAG PDTKLMQNSG KTKFKRTSID RLMNTLVLWI FGFLICLGII LAIGNSIWES
QTGDQFRTFL FWNEGEKSSV FSGFLTFWSY IIILNTVVPI SLYVSVEVIR LGHSYFINWD
RKMYYSRKAI PAVARTTTLN EELGQIEYIF SDKTGTLTQN IMTFKRCSIN GRIYGEVHDD
LDQKTEITQE KEPVDFSVKS QADREFQFFD HHLMESIKMG DPKVHEFLRL LALCHTVMSE
ENSAGELIYQ VQSPDEGALV TAARNFGFIF KSRTPETITI EELGTLVTYQ LLAFLDFNNT
RKRMSVIVRN PEGQIKLYSK GADTILFEKL HPSNEVLLSL TSDHLSEFAG EGLRTLAIAY
RDLDDKYFKE WHKMLEDANA ATEERDERIA GLYEEIERDL MLLGATAVED KLQEGVIETV
TSLSLANIKI WVLTGDKQET AINIGYACNM LTDDMNDVFV IAGNNAVEVR EELRKAKQNL
FGQNRNFSNG HVVCEKKQQL ELDSIVEETI TGDYALIING HSLAHALESD VKNDLLELAC
MCKTVICCRV TPLQKAQVVE LVKKYRNAVT LAIGDGANDV SMIKSAHIGV GISGQEGLQA
VLASDYSFAQ FRYLQRLLLV HGRWSYFRMC KFLCYFFYKN FAFTLVHFWF GFFCGFSAQT
VYDQWFITLF NIVYTSLPVL AMGIFDQDVS DQNSVDCPQL YKPGQLNLLF NKRKFFICVL
HGIYTSLVLF FIPYGAFYNV AGEDGQHIAD YQSFAVTMAT SLVIVVSVQI ALDTSYWTFI
NHVFIWGSIA IYFSILFTMH SNGIFGIFPN QFPFVGNARH SLTQKCIWLV ILLTTVASVM
PVVAFRFLKV DLYPTLSDQI RRWQKAQKKA RPPSSRRPRT RRSSSRRSGY AFAHQEGYGE
LITSGKNMRA KNPPPTSGLE KTHYNSTSWI ENLCKKTTDT VSSFSQDKTV KL
