Full text data of ATP2B4
ATP2B4
(ATP2B2, MXRA1)
[Confidence: high (present in two of the MS resources)]
Plasma membrane calcium-transporting ATPase 4; PMCA4; 3.6.3.8 (Matrix-remodeling-associated protein 1; Plasma membrane calcium ATPase isoform 4; Plasma membrane calcium pump isoform 4)
Plasma membrane calcium-transporting ATPase 4; PMCA4; 3.6.3.8 (Matrix-remodeling-associated protein 1; Plasma membrane calcium ATPase isoform 4; Plasma membrane calcium pump isoform 4)
hRBCD
IPI00012490
IPI00012490 Splice isoform XD of P23634 Plasma membrane calcium-transporting ATPase 4 Splice isoform XD of P23634 Plasma membrane calcium-transporting ATPase 4 membrane 1 3 4 2 1 n/a 1 5 11 n/a 14 1 6 13 6 1 11 8 2 4 integral membrane protein n/a expected molecular weight found in band ~ 38 kDa
IPI00012490 Splice isoform XD of P23634 Plasma membrane calcium-transporting ATPase 4 Splice isoform XD of P23634 Plasma membrane calcium-transporting ATPase 4 membrane 1 3 4 2 1 n/a 1 5 11 n/a 14 1 6 13 6 1 11 8 2 4 integral membrane protein n/a expected molecular weight found in band ~ 38 kDa
Comments
Isoform P23634-6 was detected.
Isoform P23634-6 was detected.
UniProt
P23634
ID AT2B4_HUMAN Reviewed; 1241 AA.
AC P23634; B1APW5; B1APW6; Q13450; Q13452; Q13455; Q16817; Q7Z3S1;
read moreDT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 22-JAN-2014, entry version 150.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 4;
DE Short=PMCA4;
DE EC=3.6.3.8;
DE AltName: Full=Matrix-remodeling-associated protein 1;
DE AltName: Full=Plasma membrane calcium ATPase isoform 4;
DE AltName: Full=Plasma membrane calcium pump isoform 4;
GN Name=ATP2B4; Synonyms=ATP2B2, MXRA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM XB), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Erythrocyte;
RX PubMed=2137451;
RA Strehler E.E., James P., Fischer R., Heim R., Vorherr T.E.,
RA Filoteo A.G., Penniston J.T., Carafoli E.;
RT "Peptide sequence analysis and molecular cloning reveal two calcium
RT pump isoforms in the human erythrocyte membrane.";
RL J. Biol. Chem. 265:2835-2842(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM XA).
RC TISSUE=Fetal brain;
RX PubMed=1531651;
RA Brandt P., Neve R.L., Kammesheidt A., Rhoads R.E., Vanaman T.C.;
RT "Analysis of the tissue-specific distribution of mRNAs encoding the
RT plasma membrane calcium-pumping ATPases and characterization of an
RT alternately spliced form of PMCA4 at the cDNA and genomic levels.";
RL J. Biol. Chem. 267:4376-4385(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM XB).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM XA).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS XA; XB; XK; ZA; ZB AND
RP ZK).
RC TISSUE=Heart muscle;
RX PubMed=8700162; DOI=10.1007/BF00229314;
RA Santiago-Garcia J., Mas-Oliva J., Saavedra D., Zarain-Herzberg A.;
RT "Analysis of mRNA expression and cloning of a novel plasma membrane
RT Ca(2+)-ATPase splice variant in human heart.";
RL Mol. Cell. Biochem. 155:173-182(1996).
RN [8]
RP PROTEIN SEQUENCE OF 1085-1153 (ISOFORMS XB/ZB), AND CALMODULIN-BINDING
RP SUBDOMAIN A.
RX PubMed=2963820;
RA James P., Maeda M., Fischer R., Verma A.K., Krebs J., Penniston J.T.,
RA Carafoli E.;
RT "Identification and primary structure of a calmodulin binding domain
RT of the Ca2+ pump of human erythrocytes.";
RL J. Biol. Chem. 263:2905-2910(1988).
RN [9]
RP PROTEIN SEQUENCE OF 1177-1190.
RX PubMed=2966397; DOI=10.1073/pnas.85.9.2914;
RA Brandt P., Zurini M., Neve R.L., Rhoads R.E., Vanaman T.C.;
RT "A C-terminal, calmodulin-like regulatory domain from the plasma
RT membrane Ca2+-pumping ATPase.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2914-2918(1988).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORMS X AND Z).
RC TISSUE=Heart;
RX PubMed=8245032;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RT "Quantitative analysis of alternative splicing options of human plasma
RT membrane calcium pump genes.";
RL J. Biol. Chem. 268:25993-26003(1993).
RN [11]
RP ERRATUM.
RX PubMed=7989379;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RL J. Biol. Chem. 269:32022-32022(1994).
RN [12]
RP INTERACTION WITH PDZD11.
RX PubMed=12763866;
RA Goellner G.M., DeMarco S.J., Strehler E.E.;
RT "Characterization of PISP, a novel single-PDZ protein that binds to
RT all plasma membrane Ca2+-ATPase b-splice variants.";
RL Ann. N. Y. Acad. Sci. 986:461-471(2003).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP STRUCTURE BY NMR OF 1086-1104 IN COMPLEX WITH CALMODULIN.
RX PubMed=10493800; DOI=10.1021/bi9908235;
RA Elshorst B., Hennig M., Foersterling H., Diener A., Maurer M.,
RA Schulte P., Schwalbe H., Griesinger C., Krebs J., Schmid H.,
RA Vorherr T.E., Carafoli E.;
RT "NMR solution structure of a complex of calmodulin with a binding
RT peptide of the Ca(2+) pump.";
RL Biochemistry 38:12320-12332(1999).
CC -!- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis
CC of ATP coupled with the transport of calcium out of the cell.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + Ca(2+)(Side 1) = ADP + phosphate
CC + Ca(2+)(Side 2).
CC -!- SUBUNIT: Interacts with PDZD11.
CC -!- INTERACTION:
CC P01258:CALCA; NbExp=2; IntAct=EBI-1174388, EBI-1018474;
CC Q63622:Dlg2 (xeno); NbExp=2; IntAct=EBI-1174437, EBI-396947;
CC Q62936:Dlg3 (xeno); NbExp=2; IntAct=EBI-1174437, EBI-349596;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=There is a combination of two alternatively spliced
CC domains at N-terminal site A (X and Z) and at C-terminal site
CC B/C (A, B, D and K). The splice sites have mostly been studied
CC independently. Full isoforms so far detected are isoform XA and
CC isoform XB. Experimental confirmation may be lacking for some
CC isoforms;
CC Name=XD; Synonyms=AIICIV;
CC IsoId=P23634-1; Sequence=Displayed;
CC Name=XA; Synonyms=AIICII;
CC IsoId=P23634-2; Sequence=VSP_000405;
CC Name=ZA; Synonyms=AICII;
CC IsoId=P23634-3; Sequence=VSP_000402, VSP_000405;
CC Name=XK; Synonyms=XG;
CC IsoId=P23634-4; Sequence=VSP_000403, VSP_000405;
CC Name=ZK; Synonyms=ZG;
CC IsoId=P23634-5; Sequence=VSP_000402, VSP_000403, VSP_000405;
CC Name=XB; Synonyms=AIICI;
CC IsoId=P23634-6; Sequence=VSP_000404;
CC Name=ZB; Synonyms=AICI;
CC IsoId=P23634-7; Sequence=VSP_000402, VSP_000404;
CC Name=ZD; Synonyms=AICIV;
CC IsoId=P23634-8; Sequence=VSP_000402;
CC -!- TISSUE SPECIFICITY: Isoform XB is the most abundant isoform and is
CC expressed ubiquitously. Isoforms containing segment Z have only
CC been detected in heart, while isoforms containing segment a have
CC been found in heart, stomach and brain cortex.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type)
CC (TC 3.A.3) family. Type IIB subfamily.
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DR EMBL; M25874; AAA50819.1; -; mRNA.
DR EMBL; M83363; AAA36455.1; -; mRNA.
DR EMBL; BX537444; CAD97686.1; -; mRNA.
DR EMBL; U42026; AAB17577.1; -; mRNA.
DR EMBL; U42061; AAB17578.1; -; mRNA.
DR EMBL; U42062; AAB17579.1; -; mRNA.
DR EMBL; U42378; AAB17580.1; -; mRNA.
DR EMBL; AL513343; CAI17025.1; -; Genomic_DNA.
DR EMBL; AC114402; CAI17025.1; JOINED; Genomic_DNA.
DR EMBL; AL513343; CAI17026.1; -; Genomic_DNA.
DR EMBL; AC114402; CAI17026.1; JOINED; Genomic_DNA.
DR EMBL; CH471067; EAW91483.1; -; Genomic_DNA.
DR EMBL; CH471067; EAW91486.1; -; Genomic_DNA.
DR EMBL; BC140774; AAI40775.1; -; mRNA.
DR PIR; A35547; A35547.
DR RefSeq; NP_001001396.1; NM_001001396.2.
DR RefSeq; NP_001675.3; NM_001684.4.
DR RefSeq; XP_005245281.1; XM_005245224.1.
DR RefSeq; XP_005245283.1; XM_005245226.1.
DR UniGene; Hs.343522; -.
DR UniGene; Hs.733333; -.
DR PDB; 1CFF; NMR; -; B=1086-1104.
DR PDB; 2KNE; NMR; -; B=1086-1104.
DR PDBsum; 1CFF; -.
DR PDBsum; 2KNE; -.
DR ProteinModelPortal; P23634; -.
DR SMR; P23634; 47-945.
DR DIP; DIP-6128N; -.
DR IntAct; P23634; 10.
DR MINT; MINT-219327; -.
DR STRING; 9606.ENSP00000350310; -.
DR TCDB; 3.A.3.2.1; the p-type atpase (p-atpase) superfamily.
DR PhosphoSite; P23634; -.
DR DMDM; 14286105; -.
DR PaxDb; P23634; -.
DR PRIDE; P23634; -.
DR DNASU; 493; -.
DR Ensembl; ENST00000341360; ENSP00000340930; ENSG00000058668.
DR Ensembl; ENST00000357681; ENSP00000350310; ENSG00000058668.
DR Ensembl; ENST00000367218; ENSP00000356187; ENSG00000058668.
DR Ensembl; ENST00000367219; ENSP00000356188; ENSG00000058668.
DR Ensembl; ENST00000391954; ENSP00000375816; ENSG00000058668.
DR GeneID; 493; -.
DR KEGG; hsa:493; -.
DR CTD; 493; -.
DR GeneCards; GC01P203595; -.
DR HGNC; HGNC:817; ATP2B4.
DR HPA; CAB016118; -.
DR MIM; 108732; gene.
DR neXtProt; NX_P23634; -.
DR PharmGKB; PA25110; -.
DR eggNOG; COG0474; -.
DR HOVERGEN; HBG061286; -.
DR InParanoid; P23634; -.
DR KO; K05850; -.
DR OMA; RDDMVRT; -.
DR OrthoDB; EOG7SN8BN; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; ATP2B4; human.
DR EvolutionaryTrace; P23634; -.
DR GeneWiki; ATP2B4; -.
DR GenomeRNAi; 493; -.
DR NextBio; 2071; -.
DR PRO; PR:P23634; -.
DR ArrayExpress; P23634; -.
DR Bgee; P23634; -.
DR CleanEx; HS_ATP2B2; -.
DR CleanEx; HS_ATP2B4; -.
DR Genevestigator; P23634; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0043234; C:protein complex; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:calcium-transporting ATPase activity; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097110; F:scaffold protein binding; ISS:BHF-UCL.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:1902083; P:negative regulation of peptidyl-cysteine S-nitrosylation; NAS:BHF-UCL.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; IC:BHF-UCL.
DR Gene3D; 1.20.1110.10; -; 3.
DR InterPro; IPR022141; ATP_Ca_trans_C.
DR InterPro; IPR006408; ATPase_P-typ_Ca-transp_plasma.
DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR InterPro; IPR023299; ATPase_P-typ_cyto_domN.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A.
DR InterPro; IPR001757; Cation_transp_P_typ_ATPase.
DR InterPro; IPR023214; HAD-like_dom.
DR Pfam; PF12424; ATP_Ca_trans_C; 2.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR Pfam; PF00122; E1-E2_ATPase; 1.
DR Pfam; PF00702; Hydrolase; 1.
DR PRINTS; PR00119; CATATPASE.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 2.
DR SUPFAM; SSF81660; SSF81660; 1.
DR TIGRFAMs; TIGR01517; ATPase-IIB_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 3.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Calcium;
KW Calcium transport; Calmodulin-binding; Cell membrane;
KW Complete proteome; Direct protein sequencing; Hydrolase;
KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 1241 Plasma membrane calcium-transporting
FT ATPase 4.
FT /FTId=PRO_0000046220.
FT TOPO_DOM 1 92 Cytoplasmic (Potential).
FT TRANSMEM 93 113 Helical; (Potential).
FT TOPO_DOM 114 150 Extracellular (Potential).
FT TRANSMEM 151 171 Helical; (Potential).
FT TOPO_DOM 172 356 Cytoplasmic (Potential).
FT TRANSMEM 357 376 Helical; (Potential).
FT TOPO_DOM 377 409 Extracellular (Potential).
FT TRANSMEM 410 427 Helical; (Potential).
FT TOPO_DOM 428 840 Cytoplasmic (Potential).
FT TRANSMEM 841 860 Helical; (Potential).
FT TOPO_DOM 861 870 Extracellular (Potential).
FT TRANSMEM 871 891 Helical; (Potential).
FT TOPO_DOM 892 911 Cytoplasmic (Potential).
FT TRANSMEM 912 934 Helical; (Potential).
FT TOPO_DOM 935 952 Extracellular (Potential).
FT TRANSMEM 953 974 Helical; (Potential).
FT TOPO_DOM 975 993 Cytoplasmic (Potential).
FT TRANSMEM 994 1015 Helical; (Potential).
FT TOPO_DOM 1016 1025 Extracellular (Potential).
FT TRANSMEM 1026 1047 Helical; (Potential).
FT TOPO_DOM 1048 1241 Cytoplasmic (Potential).
FT REGION 1086 1103 Calmodulin-binding subdomain A.
FT REGION 1104 1113 Calmodulin-binding subdomain B (By
FT similarity).
FT COMPBIAS 297 303 Poly-Lys.
FT COMPBIAS 1186 1190 Poly-Glu.
FT ACT_SITE 465 465 4-aspartylphosphate intermediate (By
FT similarity).
FT METAL 785 785 Magnesium (By similarity).
FT METAL 789 789 Magnesium (By similarity).
FT MOD_RES 1102 1102 Phosphothreonine; by PKC (By similarity).
FT VAR_SEQ 301 312 Missing (in isoform ZA, isoform ZK,
FT isoform ZB and isoform ZD).
FT /FTId=VSP_000402.
FT VAR_SEQ 1009 1044 Missing (in isoform XK and isoform ZK).
FT /FTId=VSP_000403.
FT VAR_SEQ 1104 1139 Missing (in isoform XB and isoform ZB).
FT /FTId=VSP_000404.
FT VAR_SEQ 1140 1241 IKVVKAFHSSLHESIQKPYNQKSIHSFMTHPEFAIEEELPR
FT TPLLDEEEEENPDKASKFGTRVLLLDGEVTPYANTNNNAVD
FT CNQVQLPQSDSSLQSLETSV -> VAVAPVKSSPTTSVPAV
FT SSPPMGNQSGQSVP (in isoform XA, isoform
FT XK, isoform ZA and isoform ZK).
FT /FTId=VSP_000405.
FT CONFLICT 492 492 S -> C (in Ref. 3; CAD97686).
FT CONFLICT 1144 1144 K -> N (in Ref. 8; AA sequence).
FT CONFLICT 1147 1147 H -> S (in Ref. 8; AA sequence).
FT CONFLICT 1153 1153 S -> F (in Ref. 8; AA sequence).
FT CONFLICT 1178 1178 L -> Q (in Ref. 9; AA sequence).
FT CONFLICT 1187 1187 E -> Q (in Ref. 9; AA sequence).
FT CONFLICT 1190 1190 E -> G (in Ref. 3; CAD97686).
FT TURN 1087 1089
FT TURN 1090 1092
FT HELIX 1093 1102
FT HELIX 1141 1147
SQ SEQUENCE 1241 AA; 137920 MW; 568544103CD5F494 CRC64;
MTNPSDRVLP ANSMAESREG DFGCTVMELR KLMELRSRDA LTQINVHYGG VQNLCSRLKT
SPVEGLSGNP ADLEKRRQVF GHNVIPPKKP KTFLELVWEA LQDVTLIILE IAAIISLVLS
FYRPAGEENE LCGQVATTPE DENEAQAGWI EGAAILFSVI IVVLVTAFND WSKEKQFRGL
QCRIEQEQKF SIIRNGQLIQ LPVAEIVVGD IAQVKYGDLL PADGILIQGN DLKIDESSLT
GESDHVKKSL DKDPMLLSGT HVMEGSGRMV VTAVGVNSQT GIILTLLGVN EDDEGEKKKK
GKKQGVPENR NKAKTQDGVA LEIQPLNSQE GIDNEEKDKK AVKVPKKEKS VLQGKLTRLA
VQIGKAGLLM SALTVFILIL YFVIDNFVIN RRPWLPECTP IYIQYFVKFF IIGITVLVVA
VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL TMNRMTVVQA
YIGGIHYRQI PSPDVFLPKV LDLIVNGISI NSAYTSKILP PEKEGGLPRQ VGNKTECALL
GFVTDLKQDY QAVRNEVPEE KLYKVYTFNS VRKSMSTVIR NPNGGFRMYS KGASEIILRK
CNRILDRKGE AVPFKNKDRD DMVRTVIEPM ACDGLRTICI AYRDFDDTEP SWDNENEILT
ELTCIAVVGI EDPVRPEVPD AIAKCKQAGI TVRMVTGDNI NTARAIATKC GILTPGDDFL
CLEGKEFNRL IRNEKGEVEQ EKLDKIWPKL RVLARSSPTD KHTLVKGIID STVGEHRQVV
AVTGDGTNDG PALKKADVGF AMGIAGTDVA KEASDIILTD DNFTSIVKAV MWGRNVYDSI
SKFLQFQLTV NVVAVIVAFT GACITQDSPL KAVQMLWVNL IMDTFASLAL ATEPPTESLL
KRRPYGRNKP LISRTMMKNI LGHAFYQLIV IFILVFAGEK FFDIDSGRKA PLHSPPSQHY
TIVFNTFVLM QLFNEINSRK IHGEKNVFSG IYRNIIFCSV VLGTFICQIF IVEFGGKPFS
CTSLSLSQWL WCLFIGIGEL LWGQFISAIP TRSLKFLKEA GHGTTKEEIT KDAEGLDEID
HAEMELRRGQ ILWFRGLNRI QTQIDVINTF QTGASFKGVL RRQNMGQHLD VKLVPSSSYI
KVVKAFHSSL HESIQKPYNQ KSIHSFMTHP EFAIEEELPR TPLLDEEEEE NPDKASKFGT
RVLLLDGEVT PYANTNNNAV DCNQVQLPQS DSSLQSLETS V
//
ID AT2B4_HUMAN Reviewed; 1241 AA.
AC P23634; B1APW5; B1APW6; Q13450; Q13452; Q13455; Q16817; Q7Z3S1;
read moreDT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 22-JAN-2014, entry version 150.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 4;
DE Short=PMCA4;
DE EC=3.6.3.8;
DE AltName: Full=Matrix-remodeling-associated protein 1;
DE AltName: Full=Plasma membrane calcium ATPase isoform 4;
DE AltName: Full=Plasma membrane calcium pump isoform 4;
GN Name=ATP2B4; Synonyms=ATP2B2, MXRA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM XB), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Erythrocyte;
RX PubMed=2137451;
RA Strehler E.E., James P., Fischer R., Heim R., Vorherr T.E.,
RA Filoteo A.G., Penniston J.T., Carafoli E.;
RT "Peptide sequence analysis and molecular cloning reveal two calcium
RT pump isoforms in the human erythrocyte membrane.";
RL J. Biol. Chem. 265:2835-2842(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM XA).
RC TISSUE=Fetal brain;
RX PubMed=1531651;
RA Brandt P., Neve R.L., Kammesheidt A., Rhoads R.E., Vanaman T.C.;
RT "Analysis of the tissue-specific distribution of mRNAs encoding the
RT plasma membrane calcium-pumping ATPases and characterization of an
RT alternately spliced form of PMCA4 at the cDNA and genomic levels.";
RL J. Biol. Chem. 267:4376-4385(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM XB).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM XA).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS XA; XB; XK; ZA; ZB AND
RP ZK).
RC TISSUE=Heart muscle;
RX PubMed=8700162; DOI=10.1007/BF00229314;
RA Santiago-Garcia J., Mas-Oliva J., Saavedra D., Zarain-Herzberg A.;
RT "Analysis of mRNA expression and cloning of a novel plasma membrane
RT Ca(2+)-ATPase splice variant in human heart.";
RL Mol. Cell. Biochem. 155:173-182(1996).
RN [8]
RP PROTEIN SEQUENCE OF 1085-1153 (ISOFORMS XB/ZB), AND CALMODULIN-BINDING
RP SUBDOMAIN A.
RX PubMed=2963820;
RA James P., Maeda M., Fischer R., Verma A.K., Krebs J., Penniston J.T.,
RA Carafoli E.;
RT "Identification and primary structure of a calmodulin binding domain
RT of the Ca2+ pump of human erythrocytes.";
RL J. Biol. Chem. 263:2905-2910(1988).
RN [9]
RP PROTEIN SEQUENCE OF 1177-1190.
RX PubMed=2966397; DOI=10.1073/pnas.85.9.2914;
RA Brandt P., Zurini M., Neve R.L., Rhoads R.E., Vanaman T.C.;
RT "A C-terminal, calmodulin-like regulatory domain from the plasma
RT membrane Ca2+-pumping ATPase.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2914-2918(1988).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORMS X AND Z).
RC TISSUE=Heart;
RX PubMed=8245032;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RT "Quantitative analysis of alternative splicing options of human plasma
RT membrane calcium pump genes.";
RL J. Biol. Chem. 268:25993-26003(1993).
RN [11]
RP ERRATUM.
RX PubMed=7989379;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RL J. Biol. Chem. 269:32022-32022(1994).
RN [12]
RP INTERACTION WITH PDZD11.
RX PubMed=12763866;
RA Goellner G.M., DeMarco S.J., Strehler E.E.;
RT "Characterization of PISP, a novel single-PDZ protein that binds to
RT all plasma membrane Ca2+-ATPase b-splice variants.";
RL Ann. N. Y. Acad. Sci. 986:461-471(2003).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP STRUCTURE BY NMR OF 1086-1104 IN COMPLEX WITH CALMODULIN.
RX PubMed=10493800; DOI=10.1021/bi9908235;
RA Elshorst B., Hennig M., Foersterling H., Diener A., Maurer M.,
RA Schulte P., Schwalbe H., Griesinger C., Krebs J., Schmid H.,
RA Vorherr T.E., Carafoli E.;
RT "NMR solution structure of a complex of calmodulin with a binding
RT peptide of the Ca(2+) pump.";
RL Biochemistry 38:12320-12332(1999).
CC -!- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis
CC of ATP coupled with the transport of calcium out of the cell.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O + Ca(2+)(Side 1) = ADP + phosphate
CC + Ca(2+)(Side 2).
CC -!- SUBUNIT: Interacts with PDZD11.
CC -!- INTERACTION:
CC P01258:CALCA; NbExp=2; IntAct=EBI-1174388, EBI-1018474;
CC Q63622:Dlg2 (xeno); NbExp=2; IntAct=EBI-1174437, EBI-396947;
CC Q62936:Dlg3 (xeno); NbExp=2; IntAct=EBI-1174437, EBI-349596;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=There is a combination of two alternatively spliced
CC domains at N-terminal site A (X and Z) and at C-terminal site
CC B/C (A, B, D and K). The splice sites have mostly been studied
CC independently. Full isoforms so far detected are isoform XA and
CC isoform XB. Experimental confirmation may be lacking for some
CC isoforms;
CC Name=XD; Synonyms=AIICIV;
CC IsoId=P23634-1; Sequence=Displayed;
CC Name=XA; Synonyms=AIICII;
CC IsoId=P23634-2; Sequence=VSP_000405;
CC Name=ZA; Synonyms=AICII;
CC IsoId=P23634-3; Sequence=VSP_000402, VSP_000405;
CC Name=XK; Synonyms=XG;
CC IsoId=P23634-4; Sequence=VSP_000403, VSP_000405;
CC Name=ZK; Synonyms=ZG;
CC IsoId=P23634-5; Sequence=VSP_000402, VSP_000403, VSP_000405;
CC Name=XB; Synonyms=AIICI;
CC IsoId=P23634-6; Sequence=VSP_000404;
CC Name=ZB; Synonyms=AICI;
CC IsoId=P23634-7; Sequence=VSP_000402, VSP_000404;
CC Name=ZD; Synonyms=AICIV;
CC IsoId=P23634-8; Sequence=VSP_000402;
CC -!- TISSUE SPECIFICITY: Isoform XB is the most abundant isoform and is
CC expressed ubiquitously. Isoforms containing segment Z have only
CC been detected in heart, while isoforms containing segment a have
CC been found in heart, stomach and brain cortex.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type)
CC (TC 3.A.3) family. Type IIB subfamily.
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DR EMBL; M25874; AAA50819.1; -; mRNA.
DR EMBL; M83363; AAA36455.1; -; mRNA.
DR EMBL; BX537444; CAD97686.1; -; mRNA.
DR EMBL; U42026; AAB17577.1; -; mRNA.
DR EMBL; U42061; AAB17578.1; -; mRNA.
DR EMBL; U42062; AAB17579.1; -; mRNA.
DR EMBL; U42378; AAB17580.1; -; mRNA.
DR EMBL; AL513343; CAI17025.1; -; Genomic_DNA.
DR EMBL; AC114402; CAI17025.1; JOINED; Genomic_DNA.
DR EMBL; AL513343; CAI17026.1; -; Genomic_DNA.
DR EMBL; AC114402; CAI17026.1; JOINED; Genomic_DNA.
DR EMBL; CH471067; EAW91483.1; -; Genomic_DNA.
DR EMBL; CH471067; EAW91486.1; -; Genomic_DNA.
DR EMBL; BC140774; AAI40775.1; -; mRNA.
DR PIR; A35547; A35547.
DR RefSeq; NP_001001396.1; NM_001001396.2.
DR RefSeq; NP_001675.3; NM_001684.4.
DR RefSeq; XP_005245281.1; XM_005245224.1.
DR RefSeq; XP_005245283.1; XM_005245226.1.
DR UniGene; Hs.343522; -.
DR UniGene; Hs.733333; -.
DR PDB; 1CFF; NMR; -; B=1086-1104.
DR PDB; 2KNE; NMR; -; B=1086-1104.
DR PDBsum; 1CFF; -.
DR PDBsum; 2KNE; -.
DR ProteinModelPortal; P23634; -.
DR SMR; P23634; 47-945.
DR DIP; DIP-6128N; -.
DR IntAct; P23634; 10.
DR MINT; MINT-219327; -.
DR STRING; 9606.ENSP00000350310; -.
DR TCDB; 3.A.3.2.1; the p-type atpase (p-atpase) superfamily.
DR PhosphoSite; P23634; -.
DR DMDM; 14286105; -.
DR PaxDb; P23634; -.
DR PRIDE; P23634; -.
DR DNASU; 493; -.
DR Ensembl; ENST00000341360; ENSP00000340930; ENSG00000058668.
DR Ensembl; ENST00000357681; ENSP00000350310; ENSG00000058668.
DR Ensembl; ENST00000367218; ENSP00000356187; ENSG00000058668.
DR Ensembl; ENST00000367219; ENSP00000356188; ENSG00000058668.
DR Ensembl; ENST00000391954; ENSP00000375816; ENSG00000058668.
DR GeneID; 493; -.
DR KEGG; hsa:493; -.
DR CTD; 493; -.
DR GeneCards; GC01P203595; -.
DR HGNC; HGNC:817; ATP2B4.
DR HPA; CAB016118; -.
DR MIM; 108732; gene.
DR neXtProt; NX_P23634; -.
DR PharmGKB; PA25110; -.
DR eggNOG; COG0474; -.
DR HOVERGEN; HBG061286; -.
DR InParanoid; P23634; -.
DR KO; K05850; -.
DR OMA; RDDMVRT; -.
DR OrthoDB; EOG7SN8BN; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; ATP2B4; human.
DR EvolutionaryTrace; P23634; -.
DR GeneWiki; ATP2B4; -.
DR GenomeRNAi; 493; -.
DR NextBio; 2071; -.
DR PRO; PR:P23634; -.
DR ArrayExpress; P23634; -.
DR Bgee; P23634; -.
DR CleanEx; HS_ATP2B2; -.
DR CleanEx; HS_ATP2B4; -.
DR Genevestigator; P23634; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0043234; C:protein complex; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:calcium-transporting ATPase activity; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097110; F:scaffold protein binding; ISS:BHF-UCL.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:1902083; P:negative regulation of peptidyl-cysteine S-nitrosylation; NAS:BHF-UCL.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; IC:BHF-UCL.
DR Gene3D; 1.20.1110.10; -; 3.
DR InterPro; IPR022141; ATP_Ca_trans_C.
DR InterPro; IPR006408; ATPase_P-typ_Ca-transp_plasma.
DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR InterPro; IPR023299; ATPase_P-typ_cyto_domN.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A.
DR InterPro; IPR001757; Cation_transp_P_typ_ATPase.
DR InterPro; IPR023214; HAD-like_dom.
DR Pfam; PF12424; ATP_Ca_trans_C; 2.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR Pfam; PF00122; E1-E2_ATPase; 1.
DR Pfam; PF00702; Hydrolase; 1.
DR PRINTS; PR00119; CATATPASE.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 2.
DR SUPFAM; SSF81660; SSF81660; 1.
DR TIGRFAMs; TIGR01517; ATPase-IIB_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 3.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Calcium;
KW Calcium transport; Calmodulin-binding; Cell membrane;
KW Complete proteome; Direct protein sequencing; Hydrolase;
KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 1241 Plasma membrane calcium-transporting
FT ATPase 4.
FT /FTId=PRO_0000046220.
FT TOPO_DOM 1 92 Cytoplasmic (Potential).
FT TRANSMEM 93 113 Helical; (Potential).
FT TOPO_DOM 114 150 Extracellular (Potential).
FT TRANSMEM 151 171 Helical; (Potential).
FT TOPO_DOM 172 356 Cytoplasmic (Potential).
FT TRANSMEM 357 376 Helical; (Potential).
FT TOPO_DOM 377 409 Extracellular (Potential).
FT TRANSMEM 410 427 Helical; (Potential).
FT TOPO_DOM 428 840 Cytoplasmic (Potential).
FT TRANSMEM 841 860 Helical; (Potential).
FT TOPO_DOM 861 870 Extracellular (Potential).
FT TRANSMEM 871 891 Helical; (Potential).
FT TOPO_DOM 892 911 Cytoplasmic (Potential).
FT TRANSMEM 912 934 Helical; (Potential).
FT TOPO_DOM 935 952 Extracellular (Potential).
FT TRANSMEM 953 974 Helical; (Potential).
FT TOPO_DOM 975 993 Cytoplasmic (Potential).
FT TRANSMEM 994 1015 Helical; (Potential).
FT TOPO_DOM 1016 1025 Extracellular (Potential).
FT TRANSMEM 1026 1047 Helical; (Potential).
FT TOPO_DOM 1048 1241 Cytoplasmic (Potential).
FT REGION 1086 1103 Calmodulin-binding subdomain A.
FT REGION 1104 1113 Calmodulin-binding subdomain B (By
FT similarity).
FT COMPBIAS 297 303 Poly-Lys.
FT COMPBIAS 1186 1190 Poly-Glu.
FT ACT_SITE 465 465 4-aspartylphosphate intermediate (By
FT similarity).
FT METAL 785 785 Magnesium (By similarity).
FT METAL 789 789 Magnesium (By similarity).
FT MOD_RES 1102 1102 Phosphothreonine; by PKC (By similarity).
FT VAR_SEQ 301 312 Missing (in isoform ZA, isoform ZK,
FT isoform ZB and isoform ZD).
FT /FTId=VSP_000402.
FT VAR_SEQ 1009 1044 Missing (in isoform XK and isoform ZK).
FT /FTId=VSP_000403.
FT VAR_SEQ 1104 1139 Missing (in isoform XB and isoform ZB).
FT /FTId=VSP_000404.
FT VAR_SEQ 1140 1241 IKVVKAFHSSLHESIQKPYNQKSIHSFMTHPEFAIEEELPR
FT TPLLDEEEEENPDKASKFGTRVLLLDGEVTPYANTNNNAVD
FT CNQVQLPQSDSSLQSLETSV -> VAVAPVKSSPTTSVPAV
FT SSPPMGNQSGQSVP (in isoform XA, isoform
FT XK, isoform ZA and isoform ZK).
FT /FTId=VSP_000405.
FT CONFLICT 492 492 S -> C (in Ref. 3; CAD97686).
FT CONFLICT 1144 1144 K -> N (in Ref. 8; AA sequence).
FT CONFLICT 1147 1147 H -> S (in Ref. 8; AA sequence).
FT CONFLICT 1153 1153 S -> F (in Ref. 8; AA sequence).
FT CONFLICT 1178 1178 L -> Q (in Ref. 9; AA sequence).
FT CONFLICT 1187 1187 E -> Q (in Ref. 9; AA sequence).
FT CONFLICT 1190 1190 E -> G (in Ref. 3; CAD97686).
FT TURN 1087 1089
FT TURN 1090 1092
FT HELIX 1093 1102
FT HELIX 1141 1147
SQ SEQUENCE 1241 AA; 137920 MW; 568544103CD5F494 CRC64;
MTNPSDRVLP ANSMAESREG DFGCTVMELR KLMELRSRDA LTQINVHYGG VQNLCSRLKT
SPVEGLSGNP ADLEKRRQVF GHNVIPPKKP KTFLELVWEA LQDVTLIILE IAAIISLVLS
FYRPAGEENE LCGQVATTPE DENEAQAGWI EGAAILFSVI IVVLVTAFND WSKEKQFRGL
QCRIEQEQKF SIIRNGQLIQ LPVAEIVVGD IAQVKYGDLL PADGILIQGN DLKIDESSLT
GESDHVKKSL DKDPMLLSGT HVMEGSGRMV VTAVGVNSQT GIILTLLGVN EDDEGEKKKK
GKKQGVPENR NKAKTQDGVA LEIQPLNSQE GIDNEEKDKK AVKVPKKEKS VLQGKLTRLA
VQIGKAGLLM SALTVFILIL YFVIDNFVIN RRPWLPECTP IYIQYFVKFF IIGITVLVVA
VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL TMNRMTVVQA
YIGGIHYRQI PSPDVFLPKV LDLIVNGISI NSAYTSKILP PEKEGGLPRQ VGNKTECALL
GFVTDLKQDY QAVRNEVPEE KLYKVYTFNS VRKSMSTVIR NPNGGFRMYS KGASEIILRK
CNRILDRKGE AVPFKNKDRD DMVRTVIEPM ACDGLRTICI AYRDFDDTEP SWDNENEILT
ELTCIAVVGI EDPVRPEVPD AIAKCKQAGI TVRMVTGDNI NTARAIATKC GILTPGDDFL
CLEGKEFNRL IRNEKGEVEQ EKLDKIWPKL RVLARSSPTD KHTLVKGIID STVGEHRQVV
AVTGDGTNDG PALKKADVGF AMGIAGTDVA KEASDIILTD DNFTSIVKAV MWGRNVYDSI
SKFLQFQLTV NVVAVIVAFT GACITQDSPL KAVQMLWVNL IMDTFASLAL ATEPPTESLL
KRRPYGRNKP LISRTMMKNI LGHAFYQLIV IFILVFAGEK FFDIDSGRKA PLHSPPSQHY
TIVFNTFVLM QLFNEINSRK IHGEKNVFSG IYRNIIFCSV VLGTFICQIF IVEFGGKPFS
CTSLSLSQWL WCLFIGIGEL LWGQFISAIP TRSLKFLKEA GHGTTKEEIT KDAEGLDEID
HAEMELRRGQ ILWFRGLNRI QTQIDVINTF QTGASFKGVL RRQNMGQHLD VKLVPSSSYI
KVVKAFHSSL HESIQKPYNQ KSIHSFMTHP EFAIEEELPR TPLLDEEEEE NPDKASKFGT
RVLLLDGEVT PYANTNNNAV DCNQVQLPQS DSSLQSLETS V
//
MIM
108732
*RECORD*
*FIELD* NO
108732
*FIELD* TI
*108732 ATPase, Ca(2+)-TRANSPORTING, PLASMA MEMBRANE, 4; ATP2B4
;;PLASMA MEMBRANE Ca(2+)-ATPase, TYPE 4; PMCA4;;
read moreATP2B2, FORMERLY
*FIELD* TX
DESCRIPTION
The Ca(2+)-ATPases are a family of plasma membrane pumps encoded by at
least 4 genes: ATP2B1 (108731) on chromosome 12q21; ATP2B2 (108733) on
3q26; ATP2B3 (300014) on Xq28; and ATP2B4.
CLONING
By PCR, Brandt et al. (1992) detected expression of the PMCA4a variant
in all tissues examined. They identified a second variant, PMCA4b, that
was primarily expressed in skeletal muscle, small intestine, heart,
spinal cord, and brain. Brandt et al. (1992) isolated the full-length
PMCA4b cDNA from a fetal brain cDNA library. The deduced 473-amino acid
protein lacks a large portion of the C terminus found in PMCA4a.
By RT-PCR, Santiago-Garcia et al. (1996) found variable expression of
the PMCA and SERCA (see 108730) genes during human fetal heart
development. PMCA4 and PMCA1 were expressed in 8-, 12-, and 20-week
fetal heart and in adult heart. Two PMCA4 splice variants were detected
in heart tissue, whereas only 1 was detected in placenta.
Okunade et al. (2004) examined Pmca1 and Pmca4 expression in mouse
tissues. Pmca1 was expressed in all tissues examined, and Pmca4 was
expressed in all tissues examined except liver. Pmca1 predominated in
brain, intestine, kidney, lung, and stomach, whereas Pmca4 predominated
in aorta, portal vein, bladder, diaphragm, seminal vesicles, and testis.
Immunostaining localized Pmca4 to the principal piece of the sperm tail,
the location of Catsper (606389), the major Ca(2+) channel required for
sperm motility.
MAPPING
Olson et al. (1991) mapped the PMCA4 gene to chromosome 1q25-q32 by
Southern analysis of human-rodent somatic cell hybrids, in situ
hybridization of human metaphase spreads, and genetic linkage analysis
in the CEPH pedigrees. No evidence was obtained for multiple copies of
the gene at this locus; however, a cross-hybridizing sequence was
detected on Xq13-qter at low stringency.
MOLECULAR GENETICS
- Associations Pending Confirmation
For discussion of a possible association between variation in the ATP2B4
gene and resistance to severe malaria, see 611162.
ANIMAL MODEL
Chen et al. (2004) expressed mouse Cd22 (107266) in mouse and chicken
B-cell lines devoid of Cd22 and examined B cells from mice deficient in
Cd22 or Pmca4. They identified an activation-dependent interaction
between phosphorylated Cd22 and Pmca4 and found that Cd22 together with
Shp1 (PTPN6; 176883) provided negative control of B-cell activation by
enhancing Pmca4-mediated calcium efflux after B-cell receptor
stimulation.
Okunade et al. (2004) found that loss of both copies of the mouse Pmca4
gene resulted in no overt phenotype. Loss of Pmca4 impaired phasic
contractions and caused apoptosis in portal vein smooth muscle in vitro,
but this phenotype was dependent on the mouse strain employed. On a
Black Swiss background, the phenotype was not expressed unless the mice
also carried a null mutation in 1 copy of the Pmca1 gene. Pmca4 -/- male
mice were infertile but had normal spermatogenesis and mating behavior.
Pmca4 -/- sperm that had not undergone capacitation exhibited normal
motility but did not achieve hyperactivated motility needed to traverse
the female genital tract. Ultrastructure of the motility apparatus of
mutant sperm tails showed mitochondrial condensation, indicating Ca(2+)
overload. Okunade et al. (2004) concluded that PMCA4 expression in the
principal piece of sperm tail is essential for hyperactivated motility
and male fertility.
*FIELD* RF
1. Brandt, P.; Neve, R. L.; Kammesheidt, A.; Rhoads, R. E.; Vanaman,
T. C.: Analysis of the tissue-specific distribution of mRNAs encoding
the plasma membrane calcium-pumping ATPases and characterization of
an alternately spliced form of PMCA4 at the cDNA and genomic levels. J.
Biol. Chem. 267: 4376-4385, 1992.
2. Chen, J.; McLean, P. A.; Neel, B. G.; Okunade, G.; Shull, G. E.;
Wortis, H. H.: CD22 attenuates calcium signaling by potentiating
plasma membrane calcium-ATPase activity. Nature Immun. 9May, 2004.
3. Okunade, G. W.; Miller, M. L.; Pyne, G. J.; Sutliff, R. L.; O'Connor,
K. T.; Neumann, J. C.; Andringa, A.; Miller, D. A.; Prasad, V.; Doetschman,
T.; Paul, R. J.; Shull, G. E.: Targeted ablation of plasma membrane
Ca(2+)-ATPase (PMCA) 1 and 4 indicates a major housekeeping function
for PMCA1 and a critical role in hyperactivated sperm motility and
male fertility for PMCA4. J. Biol. Chem. 279: 33742-33750, 2004.
4. Olson, S.; Wang, M. G.; Carafoli, E.; Strehler, E. E.; McBride,
O. W.: Localization of two genes encoding plasma membrane Ca(2+)-transporting
ATPases to human chromosomes 1q25-32 and 12q21-23. Genomics 9: 629-641,
1991.
5. Santiago-Garcia, J.; Mas-Oliva, J.; Saavedra, D.; Zarain-Herzberg,
A.: Analysis of mRNA expression and cloning of a novel plasma membrane
Ca(2+)-ATPase splice variant in human heart. Molec. Cell. Biol. 155:
173-182, 1996.
*FIELD* CN
Paul J. Converse - updated: 9/26/2012
Patricia A. Hartz - updated: 2/8/2005
Paul J. Converse - updated: 5/13/2004
*FIELD* CD
Victor A. McKusick: 2/1/1991
*FIELD* ED
mgross: 09/27/2012
terry: 9/26/2012
mgross: 2/9/2005
mgross: 2/8/2005
ckniffin: 11/22/2004
mgross: 5/13/2004
carol: 10/15/1992
carol: 8/28/1992
supermim: 3/16/1992
carol: 2/27/1992
carol: 7/2/1991
carol: 3/22/1991
*RECORD*
*FIELD* NO
108732
*FIELD* TI
*108732 ATPase, Ca(2+)-TRANSPORTING, PLASMA MEMBRANE, 4; ATP2B4
;;PLASMA MEMBRANE Ca(2+)-ATPase, TYPE 4; PMCA4;;
read moreATP2B2, FORMERLY
*FIELD* TX
DESCRIPTION
The Ca(2+)-ATPases are a family of plasma membrane pumps encoded by at
least 4 genes: ATP2B1 (108731) on chromosome 12q21; ATP2B2 (108733) on
3q26; ATP2B3 (300014) on Xq28; and ATP2B4.
CLONING
By PCR, Brandt et al. (1992) detected expression of the PMCA4a variant
in all tissues examined. They identified a second variant, PMCA4b, that
was primarily expressed in skeletal muscle, small intestine, heart,
spinal cord, and brain. Brandt et al. (1992) isolated the full-length
PMCA4b cDNA from a fetal brain cDNA library. The deduced 473-amino acid
protein lacks a large portion of the C terminus found in PMCA4a.
By RT-PCR, Santiago-Garcia et al. (1996) found variable expression of
the PMCA and SERCA (see 108730) genes during human fetal heart
development. PMCA4 and PMCA1 were expressed in 8-, 12-, and 20-week
fetal heart and in adult heart. Two PMCA4 splice variants were detected
in heart tissue, whereas only 1 was detected in placenta.
Okunade et al. (2004) examined Pmca1 and Pmca4 expression in mouse
tissues. Pmca1 was expressed in all tissues examined, and Pmca4 was
expressed in all tissues examined except liver. Pmca1 predominated in
brain, intestine, kidney, lung, and stomach, whereas Pmca4 predominated
in aorta, portal vein, bladder, diaphragm, seminal vesicles, and testis.
Immunostaining localized Pmca4 to the principal piece of the sperm tail,
the location of Catsper (606389), the major Ca(2+) channel required for
sperm motility.
MAPPING
Olson et al. (1991) mapped the PMCA4 gene to chromosome 1q25-q32 by
Southern analysis of human-rodent somatic cell hybrids, in situ
hybridization of human metaphase spreads, and genetic linkage analysis
in the CEPH pedigrees. No evidence was obtained for multiple copies of
the gene at this locus; however, a cross-hybridizing sequence was
detected on Xq13-qter at low stringency.
MOLECULAR GENETICS
- Associations Pending Confirmation
For discussion of a possible association between variation in the ATP2B4
gene and resistance to severe malaria, see 611162.
ANIMAL MODEL
Chen et al. (2004) expressed mouse Cd22 (107266) in mouse and chicken
B-cell lines devoid of Cd22 and examined B cells from mice deficient in
Cd22 or Pmca4. They identified an activation-dependent interaction
between phosphorylated Cd22 and Pmca4 and found that Cd22 together with
Shp1 (PTPN6; 176883) provided negative control of B-cell activation by
enhancing Pmca4-mediated calcium efflux after B-cell receptor
stimulation.
Okunade et al. (2004) found that loss of both copies of the mouse Pmca4
gene resulted in no overt phenotype. Loss of Pmca4 impaired phasic
contractions and caused apoptosis in portal vein smooth muscle in vitro,
but this phenotype was dependent on the mouse strain employed. On a
Black Swiss background, the phenotype was not expressed unless the mice
also carried a null mutation in 1 copy of the Pmca1 gene. Pmca4 -/- male
mice were infertile but had normal spermatogenesis and mating behavior.
Pmca4 -/- sperm that had not undergone capacitation exhibited normal
motility but did not achieve hyperactivated motility needed to traverse
the female genital tract. Ultrastructure of the motility apparatus of
mutant sperm tails showed mitochondrial condensation, indicating Ca(2+)
overload. Okunade et al. (2004) concluded that PMCA4 expression in the
principal piece of sperm tail is essential for hyperactivated motility
and male fertility.
*FIELD* RF
1. Brandt, P.; Neve, R. L.; Kammesheidt, A.; Rhoads, R. E.; Vanaman,
T. C.: Analysis of the tissue-specific distribution of mRNAs encoding
the plasma membrane calcium-pumping ATPases and characterization of
an alternately spliced form of PMCA4 at the cDNA and genomic levels. J.
Biol. Chem. 267: 4376-4385, 1992.
2. Chen, J.; McLean, P. A.; Neel, B. G.; Okunade, G.; Shull, G. E.;
Wortis, H. H.: CD22 attenuates calcium signaling by potentiating
plasma membrane calcium-ATPase activity. Nature Immun. 9May, 2004.
3. Okunade, G. W.; Miller, M. L.; Pyne, G. J.; Sutliff, R. L.; O'Connor,
K. T.; Neumann, J. C.; Andringa, A.; Miller, D. A.; Prasad, V.; Doetschman,
T.; Paul, R. J.; Shull, G. E.: Targeted ablation of plasma membrane
Ca(2+)-ATPase (PMCA) 1 and 4 indicates a major housekeeping function
for PMCA1 and a critical role in hyperactivated sperm motility and
male fertility for PMCA4. J. Biol. Chem. 279: 33742-33750, 2004.
4. Olson, S.; Wang, M. G.; Carafoli, E.; Strehler, E. E.; McBride,
O. W.: Localization of two genes encoding plasma membrane Ca(2+)-transporting
ATPases to human chromosomes 1q25-32 and 12q21-23. Genomics 9: 629-641,
1991.
5. Santiago-Garcia, J.; Mas-Oliva, J.; Saavedra, D.; Zarain-Herzberg,
A.: Analysis of mRNA expression and cloning of a novel plasma membrane
Ca(2+)-ATPase splice variant in human heart. Molec. Cell. Biol. 155:
173-182, 1996.
*FIELD* CN
Paul J. Converse - updated: 9/26/2012
Patricia A. Hartz - updated: 2/8/2005
Paul J. Converse - updated: 5/13/2004
*FIELD* CD
Victor A. McKusick: 2/1/1991
*FIELD* ED
mgross: 09/27/2012
terry: 9/26/2012
mgross: 2/9/2005
mgross: 2/8/2005
ckniffin: 11/22/2004
mgross: 5/13/2004
carol: 10/15/1992
carol: 8/28/1992
supermim: 3/16/1992
carol: 2/27/1992
carol: 7/2/1991
carol: 3/22/1991