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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

FXYD5 Gene

protein-coding GIFtS: 54
GCID: GC19P035645

FXYD domain containing ion transport regulator 5

(Previous name: FXYD domain-containing ion transport regulator 5 )

Explore 31 diseases affiliated with
FXYD5 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 3

Aliases
FXYD Domain Containing Ion Transport Regulator 5¹ ²		PRO6241²
OIT2¹ ²		RIC²
FXYD Domain-Containing Ion Transport Regulator 5¹ ²		Dysadherin³
DYSAD² ³		Keratinocytes Associated Transmembrane Protein 1²
IWU1² ³		Dysadherin³
KCT1²

External Ids:	HGNC: 4029¹	Entrez Gene: 53827²	Ensembl: ENSG00000089327⁷	OMIM: 606669⁵	UniProtKB: Q96DB9³

ORGUL members:
	NONCODE:n408239

Export aliases for FXYD5 gene to outside databases

Previous GC identifers: GC19P036263 GC19P036094 GC19P040321 GC19P040337 GC19P032154

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for FXYD5:

This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain,

beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human

gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC

(Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that

enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce

channel activity in experimental expression systems. Transmembrane topology has been established for two family

members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the

membrane. This gene product, FXYD5, is a glycoprotein that functions in the up-regulation of chemokine production, and

it is involved in the reduction of cell adhesion via its ability to down-regulate E-cadherin. It also promotes

metastasis, and has been linked to a variety of cancers. Alternative splicing results in multiple transcript variants.

(RefSeq curation by Kathleen J. Sweadner, Ph.D., sweadner@helix.mgh.harvard.edu., Sep 2009)

UniProtKB/Swiss-Prot: FXYD5_HUMAN, Q96DB9

Function: Involved in down-regulation of E-cadherin which results in reduced cell adhesion. Promotes metastasis

Gene Wiki entry for FXYD5

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000019.9 NC_018930.1 NT_011109.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the FXYD5 gene promoter:
AML1a
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: FXYD5 promoter sequence

Search SABiosciences Chromatin IP Primers for FXYD5

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat FXYD5

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19q13.12 Ensembl cytogenetic band: 19q13.12 HGNC cytogenetic band: 19q13.12

FXYD5 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FXYD5 gene location

GeneLoc information about chromosome 19 GeneLoc Exon Structure

GeneLoc location for GC19P035645: view genomic region (about GC identifiers)

Start:	35,645,625 bp from pter	End:	35,660,788 bp from pter
Size:	15,164 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: FXYD5_HUMAN, Q96DB9 (See protein sequence)

Recommended Name: FXYD domain-containing ion transport regulator 5 precursor

Size: 178 amino acids; 19472 Da

Subcellular location: Membrane; Single-pass type I membrane protein (Potential)

Secondary accessions: B7WNZ8 Q6UW44 Q9HC34 Q9P039

Alternative splicing: 2 isoforms: Q96DB9-1 Q96DB9-2

Explore the universe of human proteins at neXtProt for FXYD5: NX_Q96DB9

Post-translational modifications:

Glycosylated¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q96DB9

FXYD5 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_001158077.1 NP_054883.3 NP_659003.1

ENSEMBL proteins:

ENSP00000376052 ENSP00000444839 ENSP00000376053 ENSP00000465174 ENSP00000443390

ENSP00000465667 ENSP00000468168 ENSP00000344254 ENSP00000467053 ENSP00000393848

ENSP00000376051

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	Uscn Proteins for FXYD5

Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0016020	membrane	--	--
GO:0016021	integral to membrane	IDA	11756660

FXYD5 for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for FXYD5

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

FXYD5 for domains About GeneDecksing

1 InterPro domain/family:

IPR000272 Ion-transport_regulator_FXYD

Graphical View of Domain Structure for InterPro Entry Q96DB9

ProtoNet protein and cluster: Q96DB9

1 Blocks protein family: IPB000272 FXYD protein

UniProtKB/Swiss-Prot: FXYD5_HUMAN, Q96DB9

Similarity: Belongs to the FXYD family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: FXYD5_HUMAN, Q96DB9

Function: Involved in down-regulation of E-cadherin which results in reduced cell adhesion. Promotes metastasis

miRNA Products:		OriGene 3'-UTR Clone (see all 3): FXYD5 Browse MicroRNA Expression Plasmids
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In Situ Assay
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Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003779	actin binding	IDA	11756660
GO:0005216	ion channel activity	IEA	--
GO:0045296	cadherin binding	IDA	11756660

FXYD5 for ontologies About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for FXYD5

STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

1 Interacting protein for FXYD5 (ENSP00000344254⁴) via UniProtKB, MINT, STRING, and/or I2D

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
UBC	ENSP00000344818⁴	STRING: ENSP00000344818

About this table

Gene Ontology (GO): 2 biological process terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0030033	microvillus assembly	NAS	11756660
GO:0046588	negative regulation of calcium-dependent cell-cell adhesion	NAS	11756660

FXYD5 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for FXYD5
Search CenterWatch for drugs/clinical trials and news about FXYD5

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for FXYD5 gene (3 alternative transcripts):

NM_001164605.1 NM_014164.5 NM_144779.2

Unigene Cluster for FXYD5:

FXYD domain containing ion transport regulator 5

Hs.333418 [show with all ESTs]

Unigene Representative Sequence: BX648809

13 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000392218 ENST00000543307(uc010xsq.2) ENST00000392219(uc002nyg.2)

ENST00000592290 ENST00000541435(uc021usk.1) ENST00000590686 ENST00000496493

ENST00000342879(uc002nyh.2) ENST00000588699 ENST00000423817(uc021usl.1)

ENST00000591716 ENST00000586925 ENST00000392217(uc002nyi.2)

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Additional cDNA sequence:

AB072911.1 AF161462.1 AK304012.1 AY157582.1 AY358991.1 BC009642.2 BC013834.1 BC018798.1

BT007343.1 BX648809.1 NR_028406.1

13 DOTS entries:

DT.447051 DT.95226378 DT.95378318 DT.91903060 DT.100794284 DT.95378213 DT.97860203 DT.121497607

DT.121497616 DT.95333277 DT.100794285 DT.91725463 DT.92438425

24/310 AceView cDNA sequences (see all 310):

BI908365 BG574566 AW954217 BE552409 BE253565 BU178888 AJ713839 BQ183683

AA643965 BM914725 BM550889 BM915371 BQ420778 BM703034 AI651952 AA297863

BI792844 BM831389 CB124603 W95348 NM_144779 BU164524 AA485829 BQ181537

GeneLoc Exon Structure

5/12 Alternative Splicing Database (ASD) splice patterns (SP) for FXYD5 (see all 12) About this scheme

ExUns:	1a	·	1b	·	1c	·	1d	^	2	^	3a	·	3b	·	3c	·	3d	^	4	^	5a	·	5b	^	6	^	7	^	8	^	9	^	10	^	11	^	12	^	13a	·	13b
SP1:							-		-		-		-		-				-				-		-				-
SP2:							-		-		-		-		-								-		-				-
SP3:																			-				-		-				-
SP4:							-		-		-		-		-				-						-				-
SP5:							-		-		-		-						-				-		-				-

ECgene alternative splicing isoforms for FXYD5

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

FXYD5 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AGGATGACCC

About this image
See FXYD5 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for FXYD5

SOURCE GeneReport for Unigene cluster: Hs.333418

SABiosciences Expression via Pathway-Focused PCR Array including FXYD5:

Tumor Metastasis in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of human and mouse.

Orthologs for FXYD5 gene from 1/5 species (see all 5) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Fxyd5^{1 , 5}	FXYD domain-containing ion transport regulator 5^{1, 5}	64.34(n)¹ 52.91(a)¹		7 (19.29 cM)⁵ 18301¹ NM_001111073.1¹ NP_001104543.1¹ 31032722⁵

ENSEMBL Gene Tree for FXYD5 (if available)
TreeFam Gene Tree for FXYD5 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 19 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs2451992^1,2	C,H,	--	35645727(+)	`TCTCGC/TGCGCC`	4	--	ut5¹ int¹ us2k¹ nc-transcript-variantese³		14		NS EA NA CSA WA	789
rs73041999^1,2		--	35645813(+)	`CCCCCC/TATCCA`	4	--	int¹ us2k¹ nc-transcript-variant		0	--	--	--	--
rs62111371^1,2	C,F,	--	35645877(+)	`CTCCCG/TCCCGC`	4	--	int¹ ut5¹ nc-transcript-variant		4		NA EA	244
rs1633925^1,2	C,	--	35645915(+)	`ACCCCC/TCTCGG`	4	--	nc-transcript-variantint¹ ut5¹ ese³		6		MN NA CSA WA EA	545
rs184750314^1,2		--	35645998(+)	`CTGAGC/TGCGGG`	4	--	int¹ nc-transcript-variant		0	--	--	--	--
rs147943342^1,2		--	35646262(+)	`GAAGCA/TGGGTG`	4	--	int¹ nc-transcript-variant		0	--	--	--	--
rs138009017^1,2	C,	--	35646311(+)	`TGAGG-/CCCAGC`	4	--	int¹ nc-transcript-variant		0	--	--	--	--
rs112124104^1,2	F	--	35646317(+)	`CCAGCC/AGTCAG`	4	--	int¹ nc-transcript-variant		2		CSA	4
rs149005229^1,2		--	35646399(+)	`GCTGCC/TGGAGG`	4	--	int¹ nc-transcript-variant		0	--	--	--	--
rs112880548^1,2	C	--	35646453(+)	`CCACAC/GATGTC`	4	--	spa¹ nc-transcript-variant		1		CSA	1

HapMap Linkage Disequilibrium report for FXYD5 (35645625 - 35660788 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 4 variations for FXYD5
4 CNVs: 50133 35635 3189 35636

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing FXYD5

DNA2.0 Custom Variant and Variant Library Synthesis for FXYD5

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

FXYD5 for disorders           About GeneDecksing

OMIM gene information: 606669    OMIM disorders: --

20/31 diseases for FXYD5 (see all 31):    About MalaCards

invasive aspergillosis intracranial hypotension squamous cell carcinoma cutaneous malignant melanoma

epithelioid sarcoma esophageal squamous cell carcinoma cervical squamous cell carcinoma aspergillosis

pancreatic ductal adenocarcinoma synovial sarcoma papillary thyroid carcinoma rhabdoid tumors

tongue cancer cystic fibrosis thyroid carcinoma carcinoma

gastric cancer sarcoma breast cancer thyroiditis

1 disease from the University of Copenhagen DISEASES database for FXYD5:

Intracranial hypotension

10 Novoseek disease relationships for FXYD5 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
metastasis	57	34	15102690 (4), 16570180 (4), 12970317 (2), 15459499 (2) (see all 20)
primary tumor	33.3	4	16570180 (3), 12970317 (1)
tumors	33	35	15751018 (3), 12586803 (3), 15536331 (2), 18677652 (2) (see all 15)
cancer	32.4	17	17442482 (4), 15536331 (2), 15459499 (2), 12618882 (1) (see all 10)
colorectal carcinoma	25.7	4	12618882 (3), 16570180 (1)
carcinoma squamous cell	14.6	7	16434892 (2), 15536331 (2), 15459499 (2)
gastric cancer	11.2	8	15102690 (5)
carcinoma	0.853	6	12970317 (3), 12672699 (1), 15102690 (1)
melanoma	0.597	4	15751018 (4)
breast cancer	0	8	16849564 (5), 17437014 (2)

Human Genome Epidemiology (HuGE) Navigator: FXYD5 (3 documents)

Export disorders for FXYD5 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for FXYD5 gene, integrated from 9 sources (see all 55):
(articles sorted by number of sources associating them with FXYD5)

Utopia: connect your pdf to the dynamic
world of online information

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. (PubMed id 12975309)^{1, 2} Clark H.F.... Gray A.M. (2003)
Dysadherin, a cancer-associated cell membrane glycoprotein, down- regulates E-cadherin and promotes metastasis. (PubMed id 11756660)^{1, 2} Ino Y.... Hirohashi S. (2002)
A cDNA from human bone marrow encoding a protein exhibiting homology to the ATP11/PLM/MAT8 family of transmembrane proteins. (PubMed id 11342114)^{1, 2} Omasa T.... Wu J.H.D. (2001)
Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. (PubMed id 11042152)^{1, 2} Zhang Q.-H.... Chen Z. (2000)
Clinical significance of dysadherin expression in gastric cancer patients. (PubMed id 15102690)^{1, 9} Shimada Y....Imamura M. (2004)
FXYD5 modulates Na+ absorption and is increased in cystic fibrosis airway epithelia. (PubMed id 18263667)^{1, 9} Miller T.J. and Davis P.B. (2008)
Prognostic significance of dysadherin expression in esophageal squamous cell carcinoma. (PubMed id 15459499)^{1, 9} Shimada Y....Imamura M. (2004)
Involvement of dysadherin and E-cadherin in the development of testicular tumours. (PubMed id 16333245)^{1, 9} Batistatou A....Charalabopoulos K.A. (2005)
Dysadherin expression facilitates cell motility and metastatic potential of human pancreatic cancer cells. (PubMed id 15466191)^{1, 9} Shimamura T....Hirohashi S. (2004)

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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 53827	HGNC: 4029	AceView: FXYD5	Ensembl:ENSG00000089327	euGenes: HUgn53827
ECgene: FXYD5	H-InvDB: FXYD5

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
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Name	Description
PharmGKB entry for FXYD5	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for FXYD5	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for FXYD5 gene
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Patent Information for FXYD5 gene:
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Weizmann Institute:

FXYD5 TARGET TO ANTI CANCER AND ANTI-INFLAMMATORY DRUGS

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FXYD domain containing ion transport regulator 5

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FXYD domain containing ion transport regulator 5

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