AT2C1_HUMAN
ID AT2C1_HUMAN Reviewed; 919 AA.
AC P98194; B2RAT7; B4DSW3; B7Z3X9; G3XAH8; G8JLN9; O76005; Q86V72; Q86V73;
AC Q8N6V1; Q8NCJ7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Calcium-transporting ATPase type 2C member 1;
DE Short=ATPase 2C1 {ECO:0000303|PubMed:12707275};
DE EC=7.2.2.10 {ECO:0000269|PubMed:16192278, ECO:0000269|PubMed:30923126};
DE AltName: Full=ATP-dependent Ca(2+) pump PMR1;
DE AltName: Full=Ca(2+)/Mn(2+)-ATPase 2C1 {ECO:0000303|PubMed:12707275};
DE AltName: Full=Secretory pathway Ca(2+)-transporting ATPase type 1;
DE Short=SPCA1 {ECO:0000303|PubMed:12707275};
GN Name=ATP2C1 {ECO:0000303|PubMed:10615129, ECO:0000312|HGNC:HGNC:13211};
GN Synonyms=KIAA1347, PMR1L; ORFNames=HUSSY-28;
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 [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND VARIANTS HHD
RP THR-304; PRO-318; ARG-641; ARG-645; MET-709 AND ARG-744.
RX PubMed=10615129; DOI=10.1038/71701;
RA Hu Z., Bonifas J.M., Beech J., Bench G., Shigihara T., Ogawa H., Ikeda S.,
RA Mauro T., Epstein E.H. Jr.;
RT "Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey
RT disease.";
RL Nat. Genet. 24:61-65(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), AND VARIANTS HHD LEU-201;
RP TYR-344 AND ILE-570.
RC TISSUE=Keratinocyte;
RX PubMed=10767338; DOI=10.1093/hmg/9.7.1131;
RA Sudbrak R., Brown J., Dobson-Stone C., Carter S., Ramser J., White J.,
RA Healy E., Dissanayake M., Larregue M., Perrussel M., Lehrach H.,
RA Munro C.S., Strachan T., Burge S., Hovnanian A., Monaco A.P.;
RT "Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel
RT Ca(2+) pump.";
RL Hum. Mol. Genet. 9:1131-1140(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 9), FUNCTION, SUBCELLULAR
RP LOCATION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS HHD LEU-201;
RP CYS-309; PRO-341; TYR-344; ARG-411; ILE-570; VAL-580; TYR-742 AND ARG-789.
RC TISSUE=Keratinocyte;
RX PubMed=12707275; DOI=10.1074/jbc.m300509200;
RA Fairclough R.J., Dode L., Vanoevelen J., Andersen J.P., Missiaen L.,
RA Raeymaekers L., Wuytack F., Hovnanian A.;
RT "Effect of Hailey-Hailey Disease mutations on the function of a new variant
RT of human secretory pathway Ca2+/Mn2+-ATPase (hSPCA1).";
RL J. Biol. Chem. 278:24721-24730(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 6; 7 AND 8), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 360-919 (ISOFORM 1).
RC TISSUE=Mammary gland, Neuron, and Thalamus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Blood;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 424-919.
RX PubMed=11124703;
RX DOI=10.1002/1097-0061(200101)18:1<69::aid-yea647>3.0.co;2-h;
RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N.,
RA Zimbello R., Lanfranchi G., Valle G.;
RT "Characterization of 16 novel human genes showing high similarity to yeast
RT sequences.";
RL Yeast 18:69-80(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14632183; DOI=10.1046/j.1523-1747.2003.12528.x;
RA Behne M.J., Tu C.L., Aronchik I., Epstein E., Bench G., Bikle D.D.,
RA Pozzan T., Mauro T.M.;
RT "Human keratinocyte ATP2C1 localizes to the Golgi and controls Golgi Ca2+
RT stores.";
RL J. Invest. Dermatol. 121:688-694(2003).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=15831496; DOI=10.1074/jbc.m501026200;
RA Vanoevelen J., Dode L., Van Baelen K., Fairclough R.J., Missiaen L.,
RA Raeymaekers L., Wuytack F.;
RT "The secretory pathway Ca2+/Mn2+-ATPase 2 is a Golgi-localized pump with
RT high affinity for Ca2+ ions.";
RL J. Biol. Chem. 280:22800-22808(2005).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16192278; DOI=10.1074/jbc.m506181200;
RA Dode L., Andersen J.P., Raeymaekers L., Missiaen L., Vilsen B., Wuytack F.;
RT "Functional comparison between secretory pathway Ca2+/Mn2+-ATPase (SPCA) 1
RT and sarcoplasmic reticulum Ca2+-ATPase (SERCA) 1 isoforms by steady-state
RT and transient kinetic analyses.";
RL J. Biol. Chem. 280:39124-39134(2005).
RN [13]
RP FUNCTION.
RX PubMed=16332677; DOI=10.1074/jbc.m511547200;
RA Dode L., Andersen J.P., Vanoevelen J., Raeymaekers L., Missiaen L.,
RA Vilsen B., Wuytack F.;
RT "Dissection of the functional differences between human secretory pathway
RT Ca2+/Mn2+-ATPase (SPCA) 1 and 2 isoenzymes by steady-state and transient
RT kinetic analyses.";
RL J. Biol. Chem. 281:3182-3189(2006).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP FUNCTION.
RX PubMed=20439740; DOI=10.1073/pnas.1004702107;
RA Lissandron V., Podini P., Pizzo P., Pozzan T.;
RT "Unique characteristics of Ca2+ homeostasis of the trans-Golgi
RT compartment.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9198-9203(2010).
RN [16]
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., Buerckstuemmer T.,
RA 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 [17]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-350
RP AND GLN-747, AND CHARACTERIZATION OF VARIANT HHD CYS-309.
RX PubMed=21187401; DOI=10.1073/pnas.1013642108;
RA Mukhopadhyay S., Linstedt A.D.;
RT "Identification of a gain-of-function mutation in a Golgi P-type ATPase
RT that enhances Mn2+ efflux and protects against toxicity.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:858-863(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP MUTAGENESIS OF GLN-39; ASP-41 AND GLU-50.
RX PubMed=30923126; DOI=10.1074/jbc.ra118.006250;
RA Chen J., Smaardijk S., Mattelaer C.A., Pamula F., Vandecaetsbeek I.,
RA Vanoevelen J., Wuytack F., Lescrinier E., Eggermont J., Vangheluwe P.;
RT "An N-terminal Ca2+-binding motif regulates the secretory pathway
RT Ca2+/Mn2+-transport ATPase SPCA1.";
RL J. Biol. Chem. 294:7878-7891(2019).
RN [20]
RP VARIANTS HHD CYS-309; PRO-341; ARG-411; VAL-580; TYR-742 AND ARG-789.
RX PubMed=11841554; DOI=10.1046/j.0022-202x.2001.01675.x;
RA Dobson-Stone C., Fairclough R., Dunne E., Brown J., Dissanayake M.,
RA Munro C.S., Strachan T., Burge S., Sudbrak R., Monaco A.P., Hovnanian A.;
RT "Hailey-Hailey disease: molecular and clinical characterization of novel
RT mutations in the ATP2C1 gene.";
RL J. Invest. Dermatol. 118:338-343(2002).
RN [21]
RP VARIANTS HHD PHE-490 AND PRO-584.
RX PubMed=11874499; DOI=10.1046/j.0022-202x.2001.01686.x;
RA Yokota K., Yasukawa K., Shimizu H.;
RT "Analysis of ATP2C1 gene mutation in 10 unrelated Japanese families with
RT Hailey-Hailey disease.";
RL J. Invest. Dermatol. 118:550-551(2002).
RN [22]
RP VARIANTS HHD GLU-220; VAL-309; 609-GLN--VAL-919 DEL; 730-ASN-ALA-731 DEL
RP AND ASP-731.
RX PubMed=28035777; DOI=10.1002/humu.23164;
RG European Professional Contributors;
RA Nellen R.G., Steijlen P.M., van Steensel M.A., Vreeburg M., Frank J.,
RA van Geel M.;
RT "Mendelian Disorders of Cornification Caused by Defects in Intracellular
RT Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and
RT ATP2C1 associated with Darier disease and Hailey-Hailey disease.";
RL Hum. Mutat. 38:343-356(2017).
CC -!- FUNCTION: ATP-driven pump that supplies the Golgi apparatus with Ca(2+)
CC and Mn(2+) ions, both essential cofactors for processing and
CC trafficking of newly synthesized proteins in the secretory pathway
CC (PubMed:16192278, PubMed:30923126, PubMed:21187401, PubMed:12707275,
CC PubMed:20439740). Within a catalytic cycle, acquires Ca(2+) or Mn(2+)
CC ions on the cytoplasmic side of the membrane and delivers them to the
CC lumenal side. The transfer of ions across the membrane is coupled to
CC ATP hydrolysis and is associated with a transient phosphorylation that
CC shifts the pump conformation from inward-facing to outward-facing state
CC (PubMed:16192278, PubMed:16332677, PubMed:30923126). Plays a primary
CC role in the maintenance of Ca(2+) homeostasis in the trans-Golgi
CC compartment with a functional impact on Golgi and post-Golgi protein
CC sorting as well as a structural impact on cisternae morphology
CC (PubMed:20439740, PubMed:14632183). Responsible for loading the Golgi
CC stores with Ca(2+) ions in keratinocytes, contributing to keratinocyte
CC differentiation and epidermis integrity (PubMed:14632183,
CC PubMed:10615129, PubMed:20439740). Participates in Ca(2+) and Mn(2+)
CC ions uptake into the Golgi store of hippocampal neurons and regulates
CC protein trafficking required for neural polarity (By similarity). May
CC also play a role in the maintenance of Ca(2+) and Mn(2+) homeostasis
CC and signaling in the cytosol while preventing cytotoxicity
CC (PubMed:21187401). {ECO:0000250|UniProtKB:Q80XR2,
CC ECO:0000269|PubMed:10615129, ECO:0000269|PubMed:12707275,
CC ECO:0000269|PubMed:14632183, ECO:0000269|PubMed:16192278,
CC ECO:0000269|PubMed:16332677, ECO:0000269|PubMed:20439740,
CC ECO:0000269|PubMed:21187401, ECO:0000269|PubMed:30923126}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:18105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29108, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; EC=7.2.2.10;
CC Evidence={ECO:0000269|PubMed:16192278, ECO:0000269|PubMed:30923126};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
CC Evidence={ECO:0000305|PubMed:16192278, ECO:0000305|PubMed:30923126};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + Mn(2+)(in) = ADP + H(+) + Mn(2+)(out) + phosphate;
CC Xref=Rhea:RHEA:66820, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29035, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:21187401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66821;
CC Evidence={ECO:0000305|PubMed:21187401};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.13 uM for Ca(2+) (Ca(2+)-dependent ATP hydrolysis)
CC {ECO:0000269|PubMed:30923126};
CC KM=0.07 uM for Mn(2+) (Mn(2+)-dependent ATP hydrolysis)
CC {ECO:0000269|PubMed:30923126};
CC -!- SUBUNIT: Monomer. Homodimer. {ECO:0000269|PubMed:30923126}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:12707275, ECO:0000269|PubMed:14632183,
CC ECO:0000269|PubMed:21187401}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000269|PubMed:21187401}; Multi-pass membrane protein
CC {ECO:0000255}. Note=During neuron differentiation, shifts from
CC juxtanuclear Golgi position to multiple Golgi structures distributed
CC over the neural soma with a predominance in the apical dendritic trunk.
CC {ECO:0000250|UniProtKB:Q80XR2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Comment=Isoform 1 and isoform 2 are expressed in the same tissues.;
CC Name=1; Synonyms=ATP2C1A {ECO:0000303|PubMed:10615129};
CC IsoId=P98194-1; Sequence=Displayed;
CC Name=2; Synonyms=ATP2C1B, ATP2C1C {ECO:0000303|PubMed:10615129};
CC IsoId=P98194-2; Sequence=VSP_000409;
CC Name=3; Synonyms=ATP2C1B {ECO:0000303|PubMed:10767338};
CC IsoId=P98194-3; Sequence=VSP_000408, VSP_000410;
CC Name=4; Synonyms=ATP2C1A {ECO:0000303|PubMed:10767338};
CC IsoId=P98194-4; Sequence=VSP_000408;
CC Name=5; Synonyms=ATP2C1B {ECO:0000303|PubMed:12707275};
CC IsoId=P98194-5; Sequence=VSP_000410;
CC Name=6;
CC IsoId=P98194-6; Sequence=VSP_014102;
CC Name=7;
CC IsoId=P98194-7; Sequence=VSP_045892, VSP_000410;
CC Name=8;
CC IsoId=P98194-8; Sequence=VSP_045892, VSP_055036, VSP_055037;
CC Name=9; Synonyms=ATP2C1D {ECO:0000303|PubMed:12707275};
CC IsoId=P98194-9; Sequence=VSP_055037;
CC -!- TISSUE SPECIFICITY: Found in most tissues except colon, thymus, spleen
CC and leukocytes (PubMed:15831496). Expressed in keratinocytes (at
CC protein level) (PubMed:15831496, PubMed:14632183).
CC {ECO:0000269|PubMed:14632183, ECO:0000269|PubMed:15831496}.
CC -!- DISEASE: Hailey-Hailey disease (HHD) [MIM:169600]: Autosomal dominant
CC disorder characterized by persistent blisters and suprabasal cell
CC separation (acantholysis) of the epidermis, due to impaired
CC keratinocyte adhesion. Patients lacking all isoforms except isoform 2
CC have HHD. {ECO:0000269|PubMed:10615129, ECO:0000269|PubMed:10767338,
CC ECO:0000269|PubMed:11841554, ECO:0000269|PubMed:11874499,
CC ECO:0000269|PubMed:12707275, ECO:0000269|PubMed:21187401,
CC ECO:0000269|PubMed:28035777}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IIA subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92585.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC11142.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF181120; AAF26295.1; -; mRNA.
DR EMBL; AF181121; AAF26296.1; -; mRNA.
DR EMBL; AF189723; AAF27813.2; -; mRNA.
DR EMBL; AF225981; AAF35375.1; -; mRNA.
DR EMBL; AY268374; AAP30008.1; -; mRNA.
DR EMBL; AY268375; AAP30009.1; -; mRNA.
DR EMBL; AB037768; BAA92585.1; ALT_FRAME; mRNA.
DR EMBL; AK001684; BAA91835.1; -; mRNA.
DR EMBL; AK074692; BAC11142.1; ALT_INIT; mRNA.
DR EMBL; AK296470; BAH12365.1; -; mRNA.
DR EMBL; AK299945; BAG61775.1; -; mRNA.
DR EMBL; AK314342; BAG36984.1; -; mRNA.
DR EMBL; AC055733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097105; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79218.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79219.1; -; Genomic_DNA.
DR EMBL; BC028139; AAH28139.1; -; mRNA.
DR EMBL; AJ010953; CAA09425.1; -; mRNA.
DR CCDS; CCDS33856.1; -. [P98194-9]
DR CCDS; CCDS46912.1; -. [P98194-5]
DR CCDS; CCDS46913.1; -. [P98194-2]
DR CCDS; CCDS46914.1; -. [P98194-1]
DR CCDS; CCDS56278.1; -. [P98194-7]
DR CCDS; CCDS56279.1; -. [P98194-8]
DR CCDS; CCDS56280.1; -. [P98194-3]
DR CCDS; CCDS56281.1; -. [P98194-4]
DR RefSeq; NP_001001485.1; NM_001001485.2. [P98194-2]
DR RefSeq; NP_001001486.1; NM_001001486.1. [P98194-9]
DR RefSeq; NP_001001487.1; NM_001001487.1. [P98194-5]
DR RefSeq; NP_001186108.1; NM_001199179.1. [P98194-1]
DR RefSeq; NP_001186109.1; NM_001199180.1. [P98194-7]
DR RefSeq; NP_001186110.1; NM_001199181.1.
DR RefSeq; NP_001186111.1; NM_001199182.1. [P98194-8]
DR RefSeq; NP_001186112.1; NM_001199183.1. [P98194-3]
DR RefSeq; NP_001186113.1; NM_001199184.1. [P98194-4]
DR RefSeq; NP_001186114.1; NM_001199185.1. [P98194-2]
DR RefSeq; NP_055197.2; NM_014382.3. [P98194-1]
DR RefSeq; XP_005247412.1; XM_005247355.2.
DR RefSeq; XP_005247413.1; XM_005247356.2.
DR RefSeq; XP_016861653.1; XM_017006164.1.
DR AlphaFoldDB; P98194; -.
DR SMR; P98194; -.
DR BioGRID; 117963; 121.
DR IntAct; P98194; 28.
DR MINT; P98194; -.
DR STRING; 9606.ENSP00000421326; -.
DR DrugBank; DB01373; Calcium.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00753; Isoflurane.
DR DrugBank; DB01028; Methoxyflurane.
DR DrugBank; DB01236; Sevoflurane.
DR TCDB; 3.A.3.2.5; the p-type atpase (p-atpase) superfamily.
DR iPTMnet; P98194; -.
DR MetOSite; P98194; -.
DR PhosphoSitePlus; P98194; -.
DR SwissPalm; P98194; -.
DR BioMuta; ATP2C1; -.
DR DMDM; 68068024; -.
DR EPD; P98194; -.
DR jPOST; P98194; -.
DR MassIVE; P98194; -.
DR MaxQB; P98194; -.
DR PaxDb; P98194; -.
DR PeptideAtlas; P98194; -.
DR PRIDE; P98194; -.
DR ProteomicsDB; 33752; -.
DR ProteomicsDB; 34290; -.
DR ProteomicsDB; 57820; -. [P98194-1]
DR ProteomicsDB; 57821; -. [P98194-2]
DR ProteomicsDB; 57822; -. [P98194-3]
DR ProteomicsDB; 57823; -. [P98194-4]
DR ProteomicsDB; 57824; -. [P98194-5]
DR ProteomicsDB; 57825; -. [P98194-6]
DR Antibodypedia; 4128; 347 antibodies from 33 providers.
DR DNASU; 27032; -.
DR Ensembl; ENST00000328560.12; ENSP00000329664.8; ENSG00000017260.20. [P98194-2]
DR Ensembl; ENST00000359644.7; ENSP00000352665.3; ENSG00000017260.20. [P98194-9]
DR Ensembl; ENST00000422190.6; ENSP00000402677.2; ENSG00000017260.20. [P98194-5]
DR Ensembl; ENST00000428331.6; ENSP00000395809.2; ENSG00000017260.20. [P98194-1]
DR Ensembl; ENST00000504381.5; ENSP00000425320.2; ENSG00000017260.20. [P98194-8]
DR Ensembl; ENST00000504948.5; ENSP00000423330.1; ENSG00000017260.20. [P98194-4]
DR Ensembl; ENST00000507488.6; ENSP00000421326.3; ENSG00000017260.20. [P98194-7]
DR Ensembl; ENST00000508532.5; ENSP00000424783.1; ENSG00000017260.20. [P98194-1]
DR Ensembl; ENST00000510168.6; ENSP00000427461.1; ENSG00000017260.20. [P98194-1]
DR Ensembl; ENST00000513801.5; ENSP00000422872.1; ENSG00000017260.20. [P98194-3]
DR Ensembl; ENST00000533801.6; ENSP00000432956.3; ENSG00000017260.20. [P98194-2]
DR GeneID; 27032; -.
DR KEGG; hsa:27032; -.
DR MANE-Select; ENST00000510168.6; ENSP00000427461.1; NM_001378687.1; NP_001365616.1.
DR UCSC; uc003enk.4; human. [P98194-1]
DR CTD; 27032; -.
DR DisGeNET; 27032; -.
DR GeneCards; ATP2C1; -.
DR HGNC; HGNC:13211; ATP2C1.
DR HPA; ENSG00000017260; Low tissue specificity.
DR MalaCards; ATP2C1; -.
DR MIM; 169600; phenotype.
DR MIM; 604384; gene.
DR neXtProt; NX_P98194; -.
DR OpenTargets; ENSG00000017260; -.
DR Orphanet; 2841; Familial benign chronic pemphigus.
DR PharmGKB; PA25111; -.
DR VEuPathDB; HostDB:ENSG00000017260; -.
DR eggNOG; KOG0202; Eukaryota.
DR GeneTree; ENSGT00940000156421; -.
DR HOGENOM; CLU_002360_3_3_1; -.
DR InParanoid; P98194; -.
DR OMA; GVHRMAK; -.
DR OrthoDB; 100699at2759; -.
DR PhylomeDB; P98194; -.
DR TreeFam; TF354251; -.
DR BRENDA; 7.2.2.10; 2681.
DR PathwayCommons; P98194; -.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; P98194; -.
DR SIGNOR; P98194; -.
DR BioGRID-ORCS; 27032; 53 hits in 1082 CRISPR screens.
DR ChiTaRS; ATP2C1; human.
DR GeneWiki; ATP2C1; -.
DR GenomeRNAi; 27032; -.
DR Pharos; P98194; Tbio.
DR PRO; PR:P98194; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P98194; protein.
DR Bgee; ENSG00000017260; Expressed in cortical plate and 201 other tissues.
DR ExpressionAtlas; P98194; baseline and differential.
DR Genevisible; P98194; HS.
DR GO; GO:0033106; C:cis-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0032580; C:Golgi cisterna membrane; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:UniProtKB.
DR GO; GO:0015662; F:P-type ion transporter activity; IBA:GO_Central.
DR GO; GO:0140613; F:P-type manganese transporter activity; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; IMP:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0030026; P:cellular manganese ion homeostasis; IDA:UniProtKB.
DR GO; GO:0008544; P:epidermis development; IMP:UniProtKB.
DR GO; GO:0032468; P:Golgi calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0032472; P:Golgi calcium ion transport; IMP:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006828; P:manganese ion transport; IDA:UniProtKB.
DR GO; GO:0042998; P:positive regulation of Golgi to plasma membrane protein transport; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0098629; P:trans-Golgi network membrane organization; IMP:UniProtKB.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030336; ATP2C1.
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_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; IPR006413; P-type_ATPase_IIA_PMR1.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR PANTHER; PTHR42861:SF2; PTHR42861:SF2; 1.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR PRINTS; PR00120; HATPASE.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01522; ATPase-IIA2_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 3.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Calcium; Calcium transport;
KW Disease variant; Golgi apparatus; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..919
FT /note="Calcium-transporting ATPase type 2C member 1"
FT /id="PRO_0000046223"
FT TOPO_DOM 1..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 71..91
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 92..104
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 105..123
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 124..262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 263..282
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 283..294
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 295..312
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 313..699
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 700..719
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 720..729
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 730..750
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 751..770
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 771..793
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 794..808
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 809..828
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250"
FT TOPO_DOM 829..841
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 842..860
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250"
FT TOPO_DOM 861..875
FT /note="Lumenal"
FT /evidence="ECO:0000250"
FT TRANSMEM 876..896
FT /note="Helical; Name=10"
FT /evidence="ECO:0000250"
FT TOPO_DOM 897..919
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT ACT_SITE 350
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 303
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 304
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 306
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 308
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 644
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 648
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 738
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 742
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..16
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10767338"
FT /id="VSP_000408"
FT VAR_SEQ 1..2
FT /note="MK -> MDSLLPPSRFSYFKKYPLHAIRRYLSTLRNQRAEEQ (in
FT isoform 7 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045892"
FT VAR_SEQ 39..77
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055036"
FT VAR_SEQ 877..919
FT /note="DLLFLLGLTSSVCIVAEIIKKVERSREKIQKHVSSTSSSFLEV -> GLALG
FT EEWTAAG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10615129,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_000409"
FT VAR_SEQ 910..919
FT /note="SSTSSSFLEV -> WLWERSGQQLVEIHPHLETGLPLTEDVSCV (in
FT isoform 3, isoform 5 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:10767338,
FT ECO:0000303|PubMed:12707275, ECO:0000303|PubMed:14702039"
FT /id="VSP_000410"
FT VAR_SEQ 919
FT /note="V -> VSSTSSSFLEVWLWERSGQQLVEIHPHLETGLPLTEDVSCV (in
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:12707275,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_014102"
FT VAR_SEQ 919
FT /note="V -> VWLWERSGQQLVEIHPHLETGLPLTEDVSCV (in isoform 9
FT and isoform 8)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055037"
FT VARIANT 201
FT /note="P -> L (in HHD; has normal catalytic cycle)"
FT /evidence="ECO:0000269|PubMed:10767338,
FT ECO:0000269|PubMed:12707275"
FT /id="VAR_010130"
FT VARIANT 220
FT /note="G -> E (in HHD)"
FT /evidence="ECO:0000269|PubMed:28035777"
FT /id="VAR_079698"
FT VARIANT 304
FT /note="A -> T (in HHD; dbSNP:rs137853012)"
FT /evidence="ECO:0000269|PubMed:10615129"
FT /id="VAR_008803"
FT VARIANT 309
FT /note="G -> C (in HHD; impairs manganese-dependent
FT autophosphorylation in the presence of ATP; impairs
FT manganese transporter activity)"
FT /evidence="ECO:0000269|PubMed:11841554,
FT ECO:0000269|PubMed:12707275, ECO:0000269|PubMed:21187401"
FT /id="VAR_022672"
FT VARIANT 309
FT /note="G -> V (in HHD; dbSNP:rs1393570830)"
FT /evidence="ECO:0000269|PubMed:28035777"
FT /id="VAR_079699"
FT VARIANT 318
FT /note="L -> P (in HHD)"
FT /evidence="ECO:0000269|PubMed:10615129"
FT /id="VAR_008804"
FT VARIANT 341
FT /note="L -> P (in HHD; decreases protein expression)"
FT /evidence="ECO:0000269|PubMed:11841554,
FT ECO:0000269|PubMed:12707275"
FT /id="VAR_022673"
FT VARIANT 344
FT /note="C -> Y (in HHD; decreases protein expression)"
FT /evidence="ECO:0000269|PubMed:10767338,
FT ECO:0000269|PubMed:12707275"
FT /id="VAR_010131"
FT VARIANT 411
FT /note="C -> R (in HHD; decreases protein expression)"
FT /evidence="ECO:0000269|PubMed:11841554,
FT ECO:0000269|PubMed:12707275"
FT /id="VAR_022674"
FT VARIANT 450
FT /note="A -> T (in dbSNP:rs41434650)"
FT /id="VAR_048373"
FT VARIANT 490
FT /note="C -> F (in HHD; dbSNP:rs137853014)"
FT /evidence="ECO:0000269|PubMed:11874499"
FT /id="VAR_019523"
FT VARIANT 570
FT /note="T -> I (in HHD; decreases protein expression)"
FT /evidence="ECO:0000269|PubMed:10767338,
FT ECO:0000269|PubMed:12707275"
FT /id="VAR_010132"
FT VARIANT 580
FT /note="I -> V (in HHD; impairs phosphoenzyme
FT dephosphorylation; dbSNP:rs1282232888)"
FT /evidence="ECO:0000269|PubMed:11841554,
FT ECO:0000269|PubMed:12707275"
FT /id="VAR_022675"
FT VARIANT 584
FT /note="L -> P (in HHD; dbSNP:rs137853015)"
FT /evidence="ECO:0000269|PubMed:11874499"
FT /id="VAR_019524"
FT VARIANT 609..919
FT /note="Missing (in HHD)"
FT /evidence="ECO:0000269|PubMed:28035777"
FT /id="VAR_079700"
FT VARIANT 641
FT /note="M -> R (in HHD)"
FT /evidence="ECO:0000269|PubMed:10615129"
FT /id="VAR_008805"
FT VARIANT 645
FT /note="G -> R (in HHD)"
FT /evidence="ECO:0000269|PubMed:10615129"
FT /id="VAR_008806"
FT VARIANT 709
FT /note="T -> M (in HHD; dbSNP:rs778865612)"
FT /evidence="ECO:0000269|PubMed:10615129"
FT /id="VAR_008807"
FT VARIANT 730..731
FT /note="Missing (in HHD)"
FT /evidence="ECO:0000269|PubMed:28035777"
FT /id="VAR_079701"
FT VARIANT 731
FT /note="A -> D (in HHD)"
FT /evidence="ECO:0000269|PubMed:28035777"
FT /id="VAR_079702"
FT VARIANT 742
FT /note="D -> Y (in HHD; impairs calcium- and manganese-
FT dependent autophosphorylation)"
FT /evidence="ECO:0000269|PubMed:11841554,
FT ECO:0000269|PubMed:12707275"
FT /id="VAR_022676"
FT VARIANT 744
FT /note="P -> R (in HHD)"
FT /evidence="ECO:0000269|PubMed:10615129"
FT /id="VAR_008808"
FT VARIANT 789
FT /note="G -> R (in HHD; decreases protein expression)"
FT /evidence="ECO:0000269|PubMed:11841554,
FT ECO:0000269|PubMed:12707275"
FT /id="VAR_022677"
FT MUTAGEN 39
FT /note="Q->C: Decreases calcium-dependent
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:30923126"
FT MUTAGEN 41
FT /note="D->A: Decreases calcium-dependent
FT autophosphorylation and the ATPase activity; when
FT associated with A-50."
FT /evidence="ECO:0000269|PubMed:30923126"
FT MUTAGEN 50
FT /note="E->A: Decreases calcium-dependent
FT autophosphorylation and the ATPase activity; when
FT associated with A-41."
FT /evidence="ECO:0000269|PubMed:30923126"
FT MUTAGEN 50
FT /note="E->S: Decreases calcium-dependent
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:30923126"
FT MUTAGEN 350
FT /note="D->A: Impairs pump activity."
FT /evidence="ECO:0000269|PubMed:21187401"
FT MUTAGEN 747
FT /note="Q->A: Increases manganese transporter activity."
FT /evidence="ECO:0000269|PubMed:21187401"
FT CONFLICT 62
FT /note="E -> K (in Ref. 1; AAF26295/AAF26296)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="I -> F (in Ref. 2; AAF35375)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="T -> I (in Ref. 5; BAC11142)"
FT /evidence="ECO:0000305"
FT CONFLICT 346
FT /note="V -> A (in Ref. 5; BAH12365)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="A -> T (in Ref. 1; AAF26295/AAF26296)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="R -> H (in Ref. 9; CAA09425)"
FT /evidence="ECO:0000305"
FT CONFLICT 713
FT /note="A -> T (in Ref. 5; BAC11142)"
FT /evidence="ECO:0000305"
FT CONFLICT 868
FT /note="F -> L (in Ref. 5; BAG61775)"
FT /evidence="ECO:0000305"
FT CONFLICT 901
FT /note="S -> G (in Ref. 5; BAC11142)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 919 AA; 100577 MW; 4C1495D58FDA7EA1 CRC64;
MKVARFQKIP NGENETMIPV LTSKKASELP VSEVASILQA DLQNGLNKCE VSHRRAFHGW
NEFDISEDEP LWKKYISQFK NPLIMLLLAS AVISVLMHQF DDAVSITVAI LIVVTVAFVQ
EYRSEKSLEE LSKLVPPECH CVREGKLEHT LARDLVPGDT VCLSVGDRVP ADLRLFEAVD
LSIDESSLTG ETTPCSKVTA PQPAATNGDL ASRSNIAFMG TLVRCGKAKG VVIGTGENSE
FGEVFKMMQA EEAPKTPLQK SMDLLGKQLS FYSFGIIGII MLVGWLLGKD ILEMFTISVS
LAVAAIPEGL PIVVTVTLAL GVMRMVKKRA IVKKLPIVET LGCCNVICSD KTGTLTKNEM
TVTHIFTSDG LHAEVTGVGY NQFGEVIVDG DVVHGFYNPA VSRIVEAGCV CNDAVIRNNT
LMGKPTEGAL IALAMKMGLD GLQQDYIRKA EYPFSSEQKW MAVKCVHRTQ QDRPEICFMK
GAYEQVIKYC TTYQSKGQTL TLTQQQRDVY QQEKARMGSA GLRVLALASG PELGQLTFLG
LVGIIDPPRT GVKEAVTTLI ASGVSIKMIT GDSQETAVAI ASRLGLYSKT SQSVSGEEID
AMDVQQLSQI VPKVAVFYRA SPRHKMKIIK SLQKNGSVVA MTGDGVNDAV ALKAADIGVA
MGQTGTDVCK EAADMILVDD DFQTIMSAIE EGKGIYNNIK NFVRFQLSTS IAALTLISLA
TLMNFPNPLN AMQILWINII MDGPPAQSLG VEPVDKDVIR KPPRNWKDSI LTKNLILKIL
VSSIIIVCGT LFVFWRELRD NVITPRDTTM TFTCFVFFDM FNALSSRSQT KSVFEIGLCS
NRMFCYAVLG SIMGQLLVIY FPPLQKVFQT ESLSILDLLF LLGLTSSVCI VAEIIKKVER
SREKIQKHVS STSSSFLEV
