ID FXYD5_HUMAN Reviewed; 178 AA. AC Q96DB9; B7WNZ8; Q6UW44; Q9HC34; Q9P039; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 2. DT 02-SEP-2026, entry version 184. DE RecName: Full=FXYD domain-containing ion transport regulator 5; DE AltName: Full=Dysadherin {ECO:0000303|PubMed:11756660}; DE Flags: Precursor; GN Name=FXYD5; Synonyms=DYSAD, IWU1; ORFNames=HSPC113, UNQ2561/PRO6241; 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] (ISOFORM 2), AND VARIANT HIS-176. RC TISSUE=Bone marrow; RX PubMed=11342114; DOI=10.1016/s0167-4781(00)00251-7; RA Omasa T., Chen Y.G., Mantalaris A., Wu J.H.D.; RT "A cDNA from human bone marrow encoding a protein exhibiting homology to RT the ATP11/PLM/MAT8 family of transmembrane proteins."; RL Biochim. Biophys. Acta 1517:307-310(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP GLYCOSYLATION, AND VARIANT HIS-176. RC TISSUE=Leukocyte; RX PubMed=11756660; DOI=10.1073/pnas.012425299; RA Ino Y., Gotoh M., Sakamoto M., Tsukagoshi K., Hirohashi S.; RT "Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates RT E-cadherin and promotes metastasis."; RL Proc. Natl. Acad. Sci. U.S.A. 99:365-370(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-176. RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-176. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-176. RC TISSUE=Pancreas; 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 [8] RP FUNCTION. RX PubMed=18263667; DOI=10.1152/ajplung.00430.2007; RA Miller T.J., Davis P.B.; RT "FXYD5 modulates Na+ absorption and is increased in cystic fibrosis airway RT epithelia."; RL Am. J. Physiol. 294:L654-L664(2008). CC -!- FUNCTION: Associates with and regulates the activity of the CC sodium/potassium-transporting ATPase (NKA) which catalyzes the CC hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions CC across the plasma membrane (By similarity). May increase NKA activity CC by increasing the apparent affinity for Na(+) (PubMed:18263667). CC Involved in down-regulation of E-cadherin which results in reduced cell CC adhesion. Promotes metastasis (PubMed:11756660). CC {ECO:0000250|UniProtKB:P97808, ECO:0000269|PubMed:11756660, CC ECO:0000269|PubMed:18263667}. CC -!- SUBUNIT: Regulatory subunit of the sodium/potassium-transporting ATPase CC which is composed of a catalytic alpha subunit, a non-catalytic beta CC subunit and an additional regulatory subunit. The regulatory subunit, a CC member of the FXYD protein family, modulates the enzymatic activity in CC a tissue- and isoform-specific way by changing affinities of the CC Na+/K+-ATPase toward Na(+), K(+) or ATP. CC {ECO:0000250|UniProtKB:P97808}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11756660}; CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P97808}. CC Basolateral cell membrane {ECO:0000250|UniProtKB:P97808}; Single-pass CC type I membrane protein {ECO:0000250|UniProtKB:P97808}. Note=In kidneys CC localizes to the basolateral membrane of the connecting tubule. CC {ECO:0000250|UniProtKB:P97808}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96DB9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96DB9-2; Sequence=VSP_001584; CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:11756660}. CC -!- SIMILARITY: Belongs to the FXYD family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40652/FXYD5"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF177940; AAG09301.1; -; mRNA. DR EMBL; AB072911; BAB83766.1; -; mRNA. DR EMBL; AF161462; AAF29077.1; -; mRNA. DR EMBL; AY358991; AAQ89350.1; -; mRNA. DR EMBL; BT007343; AAP36007.1; -; mRNA. DR EMBL; AC002390; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC020907; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009642; AAH09642.1; -; mRNA. DR CCDS; CCDS12447.1; -. [Q96DB9-1] DR RefSeq; NP_001158077.1; NM_001164605.2. [Q96DB9-1] DR RefSeq; NP_001307842.1; NM_001320913.2. DR RefSeq; NP_054883.3; NM_014164.6. [Q96DB9-1] DR RefSeq; NP_659003.1; NM_144779.3. [Q96DB9-1] DR PDB; 9KCG; EM; 3.10 A; C=1-178. DR PDB; 9KCI; EM; 2.90 A; C=1-178. DR PDB; 9KCJ; EM; 3.10 A; C=1-178. DR AlphaFoldDB; Q96DB9; -. DR EMDB; EMD-62250; -. DR EMDB; EMD-62252; -. DR EMDB; EMD-62253; -. DR SMR; Q96DB9; -. DR BioGRID; 119800; 3. DR ComplexPortal; CPX-8143; Sodium:potassium-exchanging ATPase complex, FXYD5 variant. DR FunCoup; Q96DB9; 85. DR IntAct; Q96DB9; 2. DR STRING; 9606.ENSP00000444839; -. DR TCDB; 1.A.27.3.1; the phospholemman (plm) family. DR GlyCosmos; Q96DB9; 2 sites, 2 glycans. DR GlyGen; Q96DB9; 15 sites, 4 O-linked glycans (14 sites). DR iPTMnet; Q96DB9; -. DR PhosphoSitePlus; Q96DB9; -. DR SwissPalm; Q96DB9; -. DR BioMuta; FXYD5; -. DR DMDM; 311033386; -. DR jPOST; Q96DB9; -. DR MassIVE; Q96DB9; -. DR PaxDb; 9606-ENSP00000444839; -. DR PeptideAtlas; Q96DB9; -. DR ProteomicsDB; 76270; -. [Q96DB9-1] DR Pumba; Q96DB9; -. DR Antibodypedia; 2277; 204 antibodies from 32 providers. DR DNASU; 53827; -. DR Ensembl; ENST00000342879.7; ENSP00000344254.3; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000392217.3; ENSP00000376051.3; ENSG00000089327.17. [Q96DB9-2] DR Ensembl; ENST00000392219.7; ENSP00000376053.2; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000423817.7; ENSP00000393848.2; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000541435.6; ENSP00000443390.1; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000590686.5; ENSP00000465667.1; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000876483.1; ENSP00000546542.1; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000876484.1; ENSP00000546543.1; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000922561.1; ENSP00000592620.1; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000922572.1; ENSP00000592631.1; ENSG00000089327.17. [Q96DB9-1] DR Ensembl; ENST00000922576.1; ENSP00000592635.1; ENSG00000089327.17. [Q96DB9-1] DR GeneID; 53827; -. DR KEGG; hsa:53827; -. DR MANE-Select; ENST00000392219.7; ENSP00000376053.2; NM_014164.6; NP_054883.3. DR UCSC; uc002nyg.3; human. [Q96DB9-1] DR AGR; HGNC:4029; -. DR ClinPGx; PA28445; -. DR CTD; 53827; -. DR DisGeNET; 53827; -. DR GeneCards; FXYD5; -. DR HGNC; HGNC:4029; FXYD5. DR HPA; ENSG00000089327; Low tissue specificity. DR MIM; 606669; gene. DR OpenTargets; ENSG00000089327; -. DR VEuPathDB; HostDB:ENSG00000089327; -. DR eggNOG; ENOG502SA05; Eukaryota. DR GeneTree; ENSGT00940000153062; -. DR HOGENOM; CLU_109413_0_0_1; -. DR InParanoid; Q96DB9; -. DR OMA; PRLCRNY; -. DR OrthoDB; 9451811at2759; -. DR PAN-GO; Q96DB9; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q96DB9; -. DR PathwayCommons; Q96DB9; -. DR SignaLink; Q96DB9; -. DR Agora; ENSG00000089327; -. DR BioGRID-ORCS; 53827; 12 hits in 1159 CRISPR screens. DR ChiTaRS; FXYD5; human. DR GeneWiki; FXYD5; -. DR GenomeRNAi; 53827; -. DR Pharos; Q96DB9; Tbio. DR PRO; PR:Q96DB9; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q96DB9; protein. DR Bgee; ENSG00000089327; Expressed in granulocyte and 169 other cell types or tissues. DR ExpressionAtlas; Q96DB9; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0003779; F:actin binding; IDA:UniProtKB. DR GO; GO:0045296; F:cadherin binding; IDA:UniProtKB. DR GO; GO:0017080; F:sodium channel regulator activity; IDA:UniProtKB. DR GO; GO:0010248; P:establishment or maintenance of transmembrane electrochemical gradient; NAS:ComplexPortal. DR GO; GO:0030007; P:intracellular potassium ion homeostasis; ISS:ComplexPortal. DR GO; GO:0006883; P:intracellular sodium ion homeostasis; ISS:ComplexPortal. DR GO; GO:0030033; P:microvillus assembly; NAS:UniProtKB. DR GO; GO:0046588; P:negative regulation of calcium-dependent cell-cell adhesion; NAS:UniProtKB. DR GO; GO:1903278; P:positive regulation of sodium ion export across plasma membrane; IBA:GO_Central. DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISS:ComplexPortal. DR GO; GO:1902600; P:proton transmembrane transport; NAS:ComplexPortal. DR GO; GO:0036376; P:sodium ion export across plasma membrane; ISS:ComplexPortal. DR CDD; cd20323; FXYD_FXYD5; 1. DR FunFam; 1.20.5.780:FF:000005; FXYD domain-containing ion transport regulator; 1. DR Gene3D; 1.20.5.780; Single helix bin; 1. DR InterPro; IPR047297; FXYD_motif. DR InterPro; IPR000272; Ion-transport_regulator_FXYD. DR PANTHER; PTHR14132:SF14; FXYD DOMAIN-CONTAINING ION TRANSPORT REGULATOR 5; 1. DR PANTHER; PTHR14132; SODIUM/POTASSIUM-TRANSPORTING ATPASE SUBUNIT GAMMA; 1. DR Pfam; PF02038; ATP1G1_PLM_MAT8; 1. DR PROSITE; PS01310; FXYD; 1. DR PDBsum; 9KCG; -. DR PDBsum; 9KCI; -. DR PDBsum; 9KCJ; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Glycoprotein; KW Ion transport; Membrane; Potassium; Potassium transport; KW Proteomics identification; Reference proteome; Signal; Sodium; KW Sodium transport; Sodium/potassium transport; Transmembrane; KW Transmembrane helix; Transport. FT SIGNAL 1..21 FT /evidence="ECO:0000250|UniProtKB:P97808" FT CHAIN 22..178 FT /note="FXYD domain-containing ion transport regulator 5" FT /id="PRO_0000010369" FT TOPO_DOM 22..145 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 146..164 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 165..178 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 23..131 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 26..36 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 68..77 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 103..125 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..97 FT /note="MSPSGRLCLLTIVGLILPTRGQTLKDTTSSSSADSTIMDIQVPTRAPDAVYT FT ELQPTSPTPTWPADETPQPQTQTQQLEGTDGPLVTDPETHKSTKA -> MQTLSNIPCF FT CLHGSLLPSTDLATLS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11342114" FT /id="VSP_001584" FT VARIANT 35 FT /note="S -> A (in dbSNP:rs1688005)" FT /id="VAR_012349" FT VARIANT 176 FT /note="R -> H (in dbSNP:rs12110)" FT /evidence="ECO:0000269|PubMed:11042152, FT ECO:0000269|PubMed:11342114, ECO:0000269|PubMed:11756660, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5" FT /id="VAR_027959" FT CONFLICT 140..141 FT /note="HT -> SH (in Ref. 3; AAF29077)" FT /evidence="ECO:0000305" SQ SEQUENCE 178 AA; 19472 MW; 7429C04838B75AA1 CRC64; MSPSGRLCLL TIVGLILPTR GQTLKDTTSS SSADSTIMDI QVPTRAPDAV YTELQPTSPT PTWPADETPQ PQTQTQQLEG TDGPLVTDPE THKSTKAAHP TDDTTTLSER PSPSTDVQTD PQTLKPSGFH EDDPFFYDEH TLRKRGLLVA AVLFITGIII LTSGKCRQLS RLCRNRCR //