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ATP2B4 (ATPase, Ca++ transporting, plasma membrane 4)

Written2014-11Esra Bozgeyik, Kaifee Arman, Yusuf Ziya Igci
University of Gaziantep, Faculty of Medicine, Department of Medical Biology, Gaziantep, Turkey

Abstract Review on ATP2B4, with data on DNA/RNA, on the protein encoded and where the gene is implicated.

(Note : for Links provided by Atlas : click)

Identity

Alias_namesATP2B2
MXRA1
matrix-remodelling associated 1
ATPase, Ca? transporting, plasma membrane 4
Alias_symbol (synonym)PMCA4
Other aliasPMCA4b
PMCA4x
HGNC (Hugo) ATP2B4
LocusID (NCBI) 493
Atlas_Id 51257
Location 1q32.1  [Link to chromosome band 1q32]
Location_base_pair Starts at 203626787 and ends at 203744081 bp from pter ( according to hg19-Feb_2009)  [Mapping ATP2B4.png]
Fusion genes
(updated 2016)
ADD1 (4p16.3) / ATP2B4 (1q32.1)ATP2B4 (1q32.1) / ASRGL1 (11q12.3)ATP2B4 (1q32.1) / ATP2B4 (1q32.1)
ATP2B4 (1q32.1) / ERBB4 (2q34)ATP2B4 (1q32.1) / H2AFY (5q31.1)ATP2B4 (1q32.1) / NFASC (1q32.1)
ATP2B4 (1q32.1) / SIRT3 (11p15.5)FAM136A (2p13.3) / ATP2B4 (1q32.1)ING4 (12p13.31) / ATP2B4 (1q32.1)
LOC389831 () / ATP2B4 (1q32.1)NEK7 (1q31.3) / ATP2B4 (1q32.1)POR (7q11.23) / ATP2B4 (1q32.1)

DNA/RNA

 
  Figure 1. Location of ATP2B4 gene and representation of its transcripts. ATP2B4 is localized on chromosome 1q32.1 and consists of 2 transcript variant. Small RNA gene SNORA77, non-coding RNA LINC00260 and pseudogene LOC100421749 are encoded in this region.
Description The human ATP2B4 gene (ATPase, Ca++ transporting, plasma membrane 4) is coding subunit of plasma membrane Ca2+ ATPase (PMCA). The ATP2B4 gene is located on the plus strand and spans 117295 bps of genomic region (203626787 - 203744081). There are 22 exons and 2 transcript variants for ATP2B4 gene (figure 1). The size of transcript variant 1 and transcript variant 2 is 8920 nt and 8742 nt, respectively. Transcript variant 1 represents the longer transcript and encodes the shorter isoform (4a). Plasma membrane calcium-transporting ATPase 4 isoform 4a (accession number NP_001001396.1) protein product comprise of 1170 amino acids (aa). Plasma membrane calcium-transporting ATPase 4 isoform 4b (accession number NP_001675.3) products of transcript variant 2 comprise of 1205 aa.
Transcription ATP2B4 gene has 2 transcript variants. But Ensembl database shows 7 transcripts (splice variants). ATP2B4 mRNA transcript variant 1 (accession number NM_001001396.2) includes 22 exons and total annotated spliced exon length is 8920. It has 21 coding exons. Transcript variant 2 (accession number NM_001684.4) has 21 exons and 20 coding exons. It has total annotated spliced exon length 8742 (figure 1). ATP2B4 gene has an important role in maintaining intracellular calcium balance as it is involved in taking the calcium ions out of the cells. The extreme elevation of ATP2B4 gene expression during the differentiation of cells in colon cancer is thought to be associated with the calcium stream. Though not very clear with evidences, changes in expression levels of PMCA gene is shown as a distinctive feature of some colon cancer (Aung et al., 2007). An increase the expression of the ATP2B4 gene has been found in colorectal tumor patients (Geyik et al., 2014).
A pseudogene LOC100421749 is encoded in the intronic region of the ATP2B4 gene. At the same time, long intergenic non-protein coding RNA 260 (LINC00260), LOC102723543 and small nucleolar RNA, H/ACA box 77 (SNORA77) are also encoded by this gene. LINC00260 and SNORA77 are encoded in the same strand while LOC100421749 and LOC102723543 are encoded in the opposite strands (figure 1).
Pseudogene There is no known pseudogene for ATP2B4.

Protein

 
  Figure 2. Figure showing different domains of ATP2B4 protein. Plasma-membrane calcium-translocating P-type ATPase (orange colored), E1-E2 ATPase (green colored), HAD_like (red coloures), cation transporting ATPase, C-terminus (purple coloured).
Description ATP2B4 protein is among one of the isoform of plasma membrane Ca2 + ATPase (PMCA). 4a and 4b are the two isoforms of this protein. Plasma membrane calcium-transporting ATPase 4 isoform 4a is encoded by transcript variant 1 and comprise of 1170 aa. Its molecular weight is 129.4 kDa with an isoelectric point of 7.4995. Plasma membrane calcium-transporting ATPase 4 isoform 4b comprising of 1205 aa is encoded by transcript variant 2. The molecular weight of this isoform is about 134 kDa and its isoelectric point is 6.3516.
Different regions like ATP2B4 protein, cation transporter/ATPase, N-terminus, plasma-membrane calcium-translocating P-type ATPase, E1-E2 ATPase, haloacid dehalogenase-like hydrolases; HAD_like domain, Putative hydrolase of sodium-potassium ATPase alpha subunit; HAD_like II domain and cation transporting ATPase, C-terminus are formed from plasma membrane calcium transporter ATPase C terminal domain (figure 2). Isoform 4a includes both calmodulin binding subdomain A and calmodulin binding subdomain B. But isoform 4b does not include these domains (figure 2).
Calcium ions are involved in the regulation of several cellular processes, including activation or inactivation of the cellular signaling pathways like calcium regulatory proteins (Berridge et al., 2003). Active transport of calcium ions in the plasma membrane which requires ATP hydrolysis is achieved through calcium pump (Monteith et al., 2007). P-type ATPase is responsible for translocating the extracellular calcium ions in eukaryotes. There are several isoforms of PMCA in human and mouse but without any additional functions. There are many diseases in humans which are supposed to be caused by errors in PMCA. P-type ATPase in the plasma membrane calcium ATPase (PMCA) plays an important role in determining the amount of intracellular calcium (Jensen et al., 2004). Both N and C terminal of the calcium pump are located inside cells and contain 10 transmembrane regions. The C terminal is typically 70-200 aa in length and is considered to take part in the regulation of the calcium pump. Furthermore calcium ions are also responsible for stimulating tasks inside cells and this stimulus is generally provided by the calmodulin residing in the C terminal. Calmodulin is a calcium binding protein and is activated by its binding to calcium. Moreover, there are 4 isoforms and more than 30 alternative variants known for PMCA (Strehler and Zacharias, 2001). PMCA1 (ATP2B1) and PMCA4 (ATP2B4) were found in many cell types while PMCA2 (ATP2B2) and PMCA3 (ATP2B3) is reported to exist in different tissues (Carafoli, 1991; Strehler and Zacharias, 2001).
Expression The expression of ATP2B4 protein varies according to the type of cancer. For example; ATP2B4 was found to be upregulated in the breast cancer cell lines (Varga et al., 2014). An increase the protein levels of ATP2B4 have been reported in the gastric cancer cell line (KATO-III) (Ribiczey et al., 2007). In another study with colon cancer, ATP2B4 protein expression from PMCA was found to be upregulated (Aung et al., 2007).
Localisation ATP2B4 protein is localized in the plasma membrane. There are 10 transmembrane domains of this protein (figure 3). Cytoplasmic region, transmembrane region and extracellular regions of ATP2B4 are shown in figure 3.
 
  Figure3. Figure showing cytoplasmic region of plasma membrane of ATP2B4 protein. Localization of transmembranes and extracellular regions are shown. Ten transmembrane domains are also cited.
Function As shown in the structural form as well, ATP2B4 protein has role in the ATP binding as well as calmodulin binding activities. Calmodulin gets activated after binding to calcium ions and eventually activates the stimulating tasks of these ions. ATP2B4 is located in the tail of the C-terminal end (Brini et al., 2013).
Plasma membrane Ca2 + ATPases are dependent on ATP and are involved in the removal of calcium from the cell and thus are classified as transporter proteins in plasma membrane. These proteins have an important role in determining the amount of intracellular calcium (Jensen et al., 2004). The short term increase of intracellular Ca2+ in specific locations play a major role in muscle contraction and stimulus transduction pathways (Monteith et al., 2007; Roberts-Thomson et al., 2010).
Acidic phospholipids particularly polyphosphoinositides are strong stimulants of PMCA. As PMCA isoforms increase the access of phospholipids to acidic phospholipid binding sites, it effects the regulation of phospholipids (Strehler and Zacharias, 2001).
In a study related to ATP2B4 protein, it has been found that several members of MAGUK (membrane-associated guanylate kinase) protein show high interaction with PZD domains. This interaction was shown to take place due to the C terminal sequence (Kim et al., 1998). In another study, interaction of ATP2B4 with NOS-II has been shown in HEK293 cells. The interaction of NOS-I with PZD domain has also been shown (Schuh et al., 2001). The dose dependent inactivation of NOS-I has been shown to be mediated by ATP2B4 (Schuh et al., 2001).
ATP2B4 protein was found to be expressed in heart (Strehler and Zacharias, 2001). An interaction of nNOS with ATP2B4 proteins have been shown in cardiomyocytes. It also has been found to be overexpressed in cardiomyocytes (Williams et al., 2006).
ATP2B4 protein has two isoforms i.e 4a and 4b. 4b isoform showed low basal activity in the absence of calmodulin. This isoform is also slowly activated by Ca2+-calmodulin complex. The calmodulin-activated pump is slowly inactivated in 4b isoform (Caride et al., 2001a; Caride et al., 2001b; Penheiter et al., 2002).
The full PMCA4b isoform as well as the C-terminally truncated PMCA4a splice variant is coded by PMCA4. Biochemically, PMCA4b has several distinguishing features: first, it shows low basal activity when there is no calmodulin; second, it gets slowly activated by the Ca2+-calmodulin complex; and third it slowly inactivates the calmodulin-activated pump (Caride et al., 2001a; Caride et al., 2001b; Penheiter et al., 2002).
Homology ATP2B4 gene and domains of its protein have been found to be partially conserved in some animals. For example, the DNA sequence in P. troglodytes shows 99.6% similarity to humans and protein shows 99.9% similarity, the DNA sequence in M.musculus shows 84.1% similarity and protein shows 84.1% similarity. In S. pombe (ATP2B4 gene name; SPAPB2B4.04c), there is 50% DNA similarity and 44.8% protein similarity (data from NCBI BLAST).

Mutations

Somatic 6 somatic mutations have been identified in ATP2B4 gene.
1- NM_001001396.2(ATP2B4):c.-464-21082A>G: there is conversion of A>G at the region located 203661660 (GRCh38) of ATP2B4 gene. This mutation has been associated with lung cancer.
2- NM_001001396.2(ATP2B4):c.2027C>T (p.Pro676Leu): a missense mutation has been identified at the region located 203711104 of this gene. There is transformation of proline to leucine with conversion of C>T at 676 position. It is associated with malignant melanoma.
3- NM_001001396.2(ATP2B4):c.466C>T (p.Leu156Phe): a missense mutation has been identified at the region located 203699534 of this gene. There is transformation of leucine to phenylalanine at position 156 with conversion of C>T at 466 position. It is also associated with malignant melanoma.
4- NM_001001396.2(ATP2B4):c.760C>T (p.Pro254Ser): a missense mutation has been identified at the region located 203700316 of this gene. It is associated with malignant melanoma. There is transformation of proline to serine with conversion of C>T at 760 position.
5- NM_001001396.2(ATP2B4):c.2799C>T (p.Ile933=): there is no change in the amino acid sequence with C>T transformation at region located at 203721397. Isoleucine remains isoleucine even after C>T transformation at 933 position. This type of mutation is termed as synonymous or silent mutations.
6- GRCh38/hg38 1q31.1-42.11(chr1:187143981-224299417)x3: this mutation location is Chr1:187143981 - 224299417 (on Assembly GRCh38). Copy number gain variant has been found at a cytogenetic location 1q31-42.1 (Kaminsky et al., 2011). ATP2B4 gene is also localized at this region. It belongs to pathogenic allele class.

Implicated in

Note
  
Entity Colorectal cancer
Prognosis ATP2B4 mRNA levels have been shown to reduce in a significant way in adenocarcinoma and benign colon tumors as compared to normal colon tissue. In spite of increased ATP2B4 expression levels in differentiated colon cancer cells, decreased expression of levels of ATP2B4 in some colon cancers supports it to be their characteristic feature (Roberts-Thomson et al., 2010). In our previous study involving normal and tumor tissues of colorectal cancer patients, increased expression of ATP2B4 has been shown. Furthermore, ATP2B4 mRNA level in rectal cancer patients was found to be significantly increased when they were separately studied (Geyik et al., 2014). It is believed that ATP2B4 plays an important and specific role tumorigenesis of colon cells and colon cancer (Aung et al., 2007; Aung et al., 2009).
  
  
Entity Gastric cancer
Prognosis KATO-III, a gastric cancer cell line was treated with short chain fatty acids (SCFAs), Na+-valerate or Na+-butyrate. Na+-valerate and Na+-butyrate are well known differentiating agents and butyrate are physiologically located in the intestinal lumen (Ribiczey et al., 2007). ATP2B4 was found to be upregulated in KATO III cancer cell line after treatment with SCFAs. Both mRNA and protein level of ATP2B4 was to be significantly increased in gastric cancer cell line (Ribiczey et al., 2007).
  
  
Entity Breast cancer
Prognosis ATP2B4 was found to be overexpressed in breast cancer. The expression level of ATP2B4 was studied in some breast cancer cell lines like MCF-7, MDA-MB-231, and MCF-10A according to their confluence and subconfluence states. However, a significant difference was not found (Lee et al., 2005). However, ATP2B4 mRNA level was found to be significantly lower in tumorigenic cell lines (ZR-75-1, T-47D, BT-483, and SK-BR-3) as compared to non-tumorigenic breast epithelial cell lines (184A1 and 184B5) (Lee et al., 2005). The breast cancer cell MCF-7 cells were treated with SCFAs like butyrate, phenylbutyrate, and valerate. ATP2B4 protein level was found to increase after this treatment. The remodeling of Ca2 + homeostasis in cancer cells is a distinguishing feature of tumor progression and the role of ATP2B4 during this process has been supported by many studies (Varga et al., 2014).
  

Bibliography

Plasma membrane Ca2+-ATPase expression during colon cancer cell line differentiation.
Aung CS, Kruger WA, Poronnik P, Roberts-Thomson SJ, Monteith GR.
Biochem Biophys Res Commun. 2007 Apr 20;355(4):932-6. Epub 2007 Feb 20.
PMID 17321497
 
Plasma membrane calcium ATPase 4 and the remodeling of calcium homeostasis in human colon cancer cells.
Aung CS, Ye W, Plowman G, Peters AA, Monteith GR, Roberts-Thomson SJ.
Carcinogenesis. 2009 Nov;30(11):1962-9. doi: 10.1093/carcin/bgp223. Epub 2009 Sep 15.
PMID 19755660
 
Calcium signalling: dynamics, homeostasis and remodelling.
Berridge MJ, Bootman MD, Roderick HL.
Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29. (REVIEW)
PMID 12838335
 
The plasma membrane calcium pump in health and disease.
Brini M, Cali T, Ottolini D, Carafoli E.
FEBS J. 2013 Nov;280(21):5385-97. doi: 10.1111/febs.12193. Epub 2013 Mar 11. (REVIEW)
PMID 23413890
 
Calcium pump of the plasma membrane.
Carafoli E.
Physiol Rev. 1991 Jan;71(1):129-53. (REVIEW)
PMID 1986387
 
Delayed activation of the plasma membrane calcium pump by a sudden increase in Ca2+: fast pumps reside in fast cells.
Caride AJ, Filoteo AG, Penheiter AR, Paszty K, Enyedi A, Penniston JT.
Cell Calcium. 2001a Jul;30(1):49-57.
PMID 11396987
 
The plasma membrane calcium pump displays memory of past calcium spikes. Differences between isoforms 2b and 4b.
Caride AJ, Penheiter AR, Filoteo AG, Bajzer Z, Enyedi A, Penniston JT.
J Biol Chem. 2001b Oct 26;276(43):39797-804. Epub 2001 Aug 20.
PMID 11514555
 
Investigation of the association between ATP2B4 and ATP5B genes with colorectal cancer.
Geyik E, Igci YZ, Pala E, Suner A, Borazan E, Bozgeyik I, Bayraktar E, Bayraktar R, Ergun S, Cakmak EA, Gokalp A, Arslan A.
Gene. 2014 May 1;540(2):178-82. doi: 10.1016/j.gene.2014.02.050. Epub 2014 Feb 26.
PMID 24583174
 
Expression of plasma membrane Ca2+ ATPase family members and associated synaptic proteins in acute and cultured organotypic hippocampal slices from rat.
Jensen TP, Buckby LE, Empson RM.
Brain Res Dev Brain Res. 2004 Sep 17;152(2):129-36.
PMID 15351500
 
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities.
Kaminsky EB, Kaul V, Paschall J, Church DM, Bunke B, Kunig D, Moreno-De-Luca D, Moreno-De-Luca A, Mulle JG, Warren ST, Richard G, Compton JG, Fuller AE, Gliem TJ, Huang S, Collinson MN, Beal SJ, Ackley T, Pickering DL, Golden DM, Aston E, Whitby H, Shetty S, Rossi MR, Rudd MK, South ST, Brothman AR, Sanger WG, Iyer RK, Crolla JA, Thorland EC, Aradhya S, Ledbetter DH, Martin CL.
Genet Med. 2011 Sep;13(9):777-84. doi: 10.1097/GIM.0b013e31822c79f9.
PMID 21844811
 
Plasma membrane Ca2+ ATPase isoform 4b binds to membrane-associated guanylate kinase (MAGUK) proteins via their PDZ (PSD-95/Dlg/ZO-1) domains.
Kim E, DeMarco SJ, Marfatia SM, Chishti AH, Sheng M, Strehler EE.
J Biol Chem. 1998 Jan 16;273(3):1591-5.
PMID 9430700
 
Plasma membrane calcium-ATPase 2 and 4 in human breast cancer cell lines.
Lee WJ, Roberts-Thomson SJ, Monteith GR.
Biochem Biophys Res Commun. 2005 Nov 25;337(3):779-83. Epub 2005 Sep 28.
PMID 16216224
 
Calcium and cancer: targeting Ca2+ transport.
Monteith GR, McAndrew D, Faddy HM, Roberts-Thomson SJ.
Nat Rev Cancer. 2007 Jul;7(7):519-30. (REVIEW)
PMID 17585332
 
Tryptophan 1093 is largely responsible for the slow off rate of calmodulin from plasma membrane Ca2+ pump 4b.
Penheiter AR, Caride AJ, Enyedi A, Penniston JT.
J Biol Chem. 2002 May 17;277(20):17728-32. Epub 2002 Mar 8.
PMID 11886854
 
Isoform-specific up-regulation of plasma membrane Ca2+ATPase expression during colon and gastric cancer cell differentiation.
Ribiczey P, Tordai A, Andrikovics H, Filoteo AG, Penniston JT, Enouf J, Enyedi A, Papp B, Kovacs T.
Cell Calcium. 2007 Dec;42(6):590-605. Epub 2007 Apr 11.
PMID 17433436
 
Plasma membrane calcium pumps and their emerging roles in cancer.
Roberts-Thomson SJ, Curry MC, Monteith GR.
World J Biol Chem. 2010 Aug 26;1(8):248-53. doi: 10.4331/wjbc.v1.i8.248.
PMID 21537481
 
The plasmamembrane calmodulin-dependent calcium pump: a major regulator of nitric oxide synthase I.
Schuh K, Uldrijan S, Telkamp M, Rothlein N, Neyses L.
J Cell Biol. 2001 Oct 15;155(2):201-5. Epub 2001 Oct 8.
PMID 11591728
 
Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps.
Strehler EE, Zacharias DA.
Physiol Rev. 2001 Jan;81(1):21-50. (REVIEW)
PMID 11152753
 
Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells.
Varga K, Paszty K, Padanyi R, Hegedus L, Brouland JP, Papp B, Enyedi A.
Cell Calcium. 2014 Feb;55(2):78-92. doi: 10.1016/j.ceca.2013.12.003. Epub 2013 Dec 28.
PMID 24439526
 
The sarcolemmal calcium pump, alpha-1 syntrophin, and neuronal nitric-oxide synthase are parts of a macromolecular protein complex.
Williams JC, Armesilla AL, Mohamed TM, Hagarty CL, McIntyre FH, Schomburg S, Zaki AO, Oceandy D, Cartwright EJ, Buch MH, Emerson M, Neyses L.
J Biol Chem. 2006 Aug 18;281(33):23341-8. Epub 2006 May 30.
PMID 16735509
 

Citation

This paper should be referenced as such :
Bozgeyik E, Arman K, Igci YZ
ATP2B4 (ATPase, Ca++ transporting, plasma membrane 4);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/ATP2B4ID51257ch1q32.html


External links

Nomenclature
HGNC (Hugo)ATP2B4   817
Cards
AtlasATP2B4ID51257ch1q32
Entrez_Gene (NCBI)ATP2B4  493  ATPase plasma membrane Ca2+ transporting 4
AliasesATP2B2; MXRA1; PMCA4; PMCA4b; 
PMCA4x
GeneCards (Weizmann)ATP2B4
Ensembl hg19 (Hinxton)ENSG00000058668 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000058668 [Gene_View]  chr1:203626787-203744081 [Contig_View]  ATP2B4 [Vega]
ICGC DataPortalENSG00000058668
TCGA cBioPortalATP2B4
AceView (NCBI)ATP2B4
Genatlas (Paris)ATP2B4
WikiGenes493
SOURCE (Princeton)ATP2B4
Genetics Home Reference (NIH)ATP2B4
Genomic and cartography
GoldenPath hg38 (UCSC)ATP2B4  -     chr1:203626787-203744081 +  1q32.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ATP2B4  -     1q32.1   [Description]    (hg19-Feb_2009)
EnsemblATP2B4 - 1q32.1 [CytoView hg19]  ATP2B4 - 1q32.1 [CytoView hg38]
Mapping of homologs : NCBIATP2B4 [Mapview hg19]  ATP2B4 [Mapview hg38]
OMIM108732   
Gene and transcription
Genbank (Entrez)AK026443 AK292458 AK307104 AL601702 AL706212
RefSeq transcript (Entrez)NM_001001396 NM_001684
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ATP2B4
Cluster EST : UnigeneHs.733333 [ NCBI ]
CGAP (NCI)Hs.733333
Alternative Splicing GalleryENSG00000058668
Gene ExpressionATP2B4 [ NCBI-GEO ]   ATP2B4 [ EBI - ARRAY_EXPRESS ]   ATP2B4 [ SEEK ]   ATP2B4 [ MEM ]
Gene Expression Viewer (FireBrowse)ATP2B4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)493
GTEX Portal (Tissue expression)ATP2B4
Protein : pattern, domain, 3D structure
UniProt/SwissProtP23634   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP23634  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP23634
Splice isoforms : SwissVarP23634
PhosPhoSitePlusP23634
Domaine pattern : Prosite (Expaxy)ATPASE_E1_E2 (PS00154)   
Domains : Interpro (EBI)ATP2B4    ATP_Ca_trans_C    ATPase_P-typ_cation-transptr_C    ATPase_P-typ_cation-transptr_N    ATPase_P-typ_cyto_domN    ATPase_P-typ_P_site    ATPase_P-typ_TM_dom    ATPase_P-typ_transduc_dom_A    HAD-like_dom    P-type_ATPase_IIB    P_typ_ATPase   
Domain families : Pfam (Sanger)ATP_Ca_trans_C (PF12424)    Cation_ATPase_C (PF00689)    Cation_ATPase_N (PF00690)    E1-E2_ATPase (PF00122)   
Domain families : Pfam (NCBI)pfam12424    pfam00689    pfam00690    pfam00122   
Domain families : Smart (EMBL)Cation_ATPase_N (SM00831)  
Conserved Domain (NCBI)ATP2B4
DMDM Disease mutations493
Blocks (Seattle)ATP2B4
PDB (SRS)1CFF    2KNE   
PDB (PDBSum)1CFF    2KNE   
PDB (IMB)1CFF    2KNE   
PDB (RSDB)1CFF    2KNE   
Structural Biology KnowledgeBase1CFF    2KNE   
SCOP (Structural Classification of Proteins)1CFF    2KNE   
CATH (Classification of proteins structures)1CFF    2KNE   
SuperfamilyP23634
Human Protein AtlasENSG00000058668
Peptide AtlasP23634
HPRD00159
IPIIPI00012490   IPI00217164   IPI00217165   IPI00217166   IPI00217168   IPI00217169   IPI00217170   IPI00217171   IPI00642992   
Protein Interaction databases
DIP (DOE-UCLA)P23634
IntAct (EBI)P23634
FunCoupENSG00000058668
BioGRIDATP2B4
STRING (EMBL)ATP2B4
ZODIACATP2B4
Ontologies - Pathways
QuickGOP23634
Ontology : AmiGOneural retina development  calcium-transporting ATPase activity  calcium-transporting ATPase activity  protein binding  calmodulin binding  ATP binding  plasma membrane  plasma membrane  integral component of plasma membrane  caveola  regulation of transcription from RNA polymerase II promoter  cellular calcium ion homeostasis  cellular calcium ion homeostasis  cellular calcium ion homeostasis  spermatogenesis  negative regulation of nitric oxide mediated signal transduction  membrane  basolateral plasma membrane  sodium channel regulator activity  protein kinase binding  hippocampus development  Z disc  PDZ domain binding  T-tubule  flagellated sperm motility  protein phosphatase 2B binding  positive regulation of peptidyl-serine phosphorylation  ion transmembrane transport  sperm flagellum  nitric-oxide synthase inhibitor activity  nitric-oxide synthase inhibitor activity  neuron projection  intracellular membrane-bounded organelle  protein complex  negative regulation of nitric oxide biosynthetic process  metal ion binding  nitric-oxide synthase binding  negative regulation of nitric-oxide synthase activity  response to hydrostatic pressure  calcium ion transmembrane transport  negative regulation of calcineurin-NFAT signaling cascade  cellular response to epinephrine stimulus  scaffold protein binding  sperm principal piece  calcium ion transmembrane import into cytosol  calcium ion import across plasma membrane  negative regulation of the force of heart contraction  ATP hydrolysis coupled cation transmembrane transport  negative regulation of arginine catabolic process  negative regulation of adrenergic receptor signaling pathway involved in heart process  calcium ion export  negative regulation of peptidyl-cysteine S-nitrosylation  regulation of sodium ion transmembrane transport  regulation of cell cycle G1/S phase transition  negative regulation of cardiac muscle hypertrophy in response to stress  negative regulation of citrulline biosynthetic process  regulation of cardiac conduction  positive regulation of cAMP-dependent protein kinase activity  
Ontology : EGO-EBIneural retina development  calcium-transporting ATPase activity  calcium-transporting ATPase activity  protein binding  calmodulin binding  ATP binding  plasma membrane  plasma membrane  integral component of plasma membrane  caveola  regulation of transcription from RNA polymerase II promoter  cellular calcium ion homeostasis  cellular calcium ion homeostasis  cellular calcium ion homeostasis  spermatogenesis  negative regulation of nitric oxide mediated signal transduction  membrane  basolateral plasma membrane  sodium channel regulator activity  protein kinase binding  hippocampus development  Z disc  PDZ domain binding  T-tubule  flagellated sperm motility  protein phosphatase 2B binding  positive regulation of peptidyl-serine phosphorylation  ion transmembrane transport  sperm flagellum  nitric-oxide synthase inhibitor activity  nitric-oxide synthase inhibitor activity  neuron projection  intracellular membrane-bounded organelle  protein complex  negative regulation of nitric oxide biosynthetic process  metal ion binding  nitric-oxide synthase binding  negative regulation of nitric-oxide synthase activity  response to hydrostatic pressure  calcium ion transmembrane transport  negative regulation of calcineurin-NFAT signaling cascade  cellular response to epinephrine stimulus  scaffold protein binding  sperm principal piece  calcium ion transmembrane import into cytosol  calcium ion import across plasma membrane  negative regulation of the force of heart contraction  ATP hydrolysis coupled cation transmembrane transport  negative regulation of arginine catabolic process  negative regulation of adrenergic receptor signaling pathway involved in heart process  calcium ion export  negative regulation of peptidyl-cysteine S-nitrosylation  regulation of sodium ion transmembrane transport  regulation of cell cycle G1/S phase transition  negative regulation of cardiac muscle hypertrophy in response to stress  negative regulation of citrulline biosynthetic process  regulation of cardiac conduction  positive regulation of cAMP-dependent protein kinase activity  
Pathways : KEGGCalcium signaling pathway    Adrenergic signaling in cardiomyocytes    Salivary secretion    Pancreatic secretion   
REACTOMEP23634 [protein]
REACTOME PathwaysR-HSA-936837 [pathway]   
NDEx NetworkATP2B4
Atlas of Cancer Signalling NetworkATP2B4
Wikipedia pathwaysATP2B4
Orthology - Evolution
OrthoDB493
GeneTree (enSembl)ENSG00000058668
Phylogenetic Trees/Animal Genes : TreeFamATP2B4
HOVERGENP23634
HOGENOMP23634
Homologs : HomoloGeneATP2B4
Homology/Alignments : Family Browser (UCSC)ATP2B4
Gene fusions - Rearrangements
Fusion : MitelmanADD1/ATP2B4 [4p16.3/1q32.1]  [t(1;4)(q32;p16)]  
Fusion : MitelmanATP2B4/ERBB4 [1q32.1/2q34]  [t(1;2)(q32;q34)]  
Fusion : MitelmanATP2B4/H2AFY [1q32.1/5q31.1]  [t(1;5)(q32;q31)]  
Fusion : MitelmanATP2B4/NFASC [1q32.1/1q32.1]  [t(1;1)(q32;q32)]  
Fusion : MitelmanNEK7/ATP2B4 [1q31.3/1q32.1]  [t(1;1)(q31;q32)]  
Fusion: TCGAADD1 4p16.3 ATP2B4 1q32.1 LGG
Fusion: TCGAATP2B4 1q32.1 ERBB4 2q34 LUAD
Fusion: TCGAATP2B4 1q32.1 NFASC 1q32.1 GBM
Fusion: TCGANEK7 1q31.3 ATP2B4 1q32.1 LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerATP2B4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ATP2B4
dbVarATP2B4
ClinVarATP2B4
1000_GenomesATP2B4 
Exome Variant ServerATP2B4
ExAC (Exome Aggregation Consortium)ATP2B4 (select the gene name)
Genetic variants : HAPMAP493
Genomic Variants (DGV)ATP2B4 [DGVbeta]
DECIPHERATP2B4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisATP2B4 
Mutations
ICGC Data PortalATP2B4 
TCGA Data PortalATP2B4 
Broad Tumor PortalATP2B4
OASIS PortalATP2B4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICATP2B4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDATP2B4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ATP2B4
DgiDB (Drug Gene Interaction Database)ATP2B4
DoCM (Curated mutations)ATP2B4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ATP2B4 (select a term)
intoGenATP2B4
NCG5 (London)ATP2B4
Cancer3DATP2B4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM108732   
Orphanet
MedgenATP2B4
Genetic Testing Registry ATP2B4
NextProtP23634 [Medical]
TSGene493
GENETestsATP2B4
Target ValidationATP2B4
Huge Navigator ATP2B4 [HugePedia]
snp3D : Map Gene to Disease493
BioCentury BCIQATP2B4
ClinGenATP2B4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD493
Chemical/Pharm GKB GenePA25110
Clinical trialATP2B4
Miscellaneous
canSAR (ICR)ATP2B4 (select the gene name)
Probes
Litterature
PubMed93 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineATP2B4
EVEXATP2B4
GoPubMedATP2B4
iHOPATP2B4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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