FXYD1

Functionⁱ

Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na⁺ out of the cell and K⁺ into the cell. Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated. Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1. Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone.By similarity

GO - Molecular functionⁱ

chloride channel activity
Source: ProtInc
Traceable author statementⁱ
- 9169143
ion channel binding Source: BHF-UCL
sodium channel regulator activity Source: BHF-UCL

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

chloride transport
Source: ProtInc
Traceable author statementⁱ
- 9169143
muscle contraction
Source: ProtInc
Traceable author statementⁱ
- 9169143
negative regulation of protein glutathionylation Source: UniProtKB
positive regulation of sodium ion export across plasma membrane Source: UniProtKB
potassium ion transport Source: UniProtKB-KW
regulation of cardiac muscle cell membrane potential Source: BHF-UCL
regulation of heart contraction
Source: BHF-UCL
Traceable author statementⁱ
- 19683723
regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
sodium ion transport Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Ion transport, Potassium transport, Sodium transport, Sodium/potassium transport, Transport
Ligand	Potassium, Sodium

Enzyme and pathway databases

Reactomeⁱ	R-HSA-5578775 Ion homeostasis R-HSA-936837 Ion transport by P-type ATPases
SIGNORⁱ	O00168

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: PhospholemmanBy similarity Alternative name(s): FXYD domain-containing ion transport regulator 1Imported Sodium/potassium-transporting ATPase subunit FXYD1Curated
Gene namesⁱ	Name:FXYD1Imported Synonyms:PLM1 Publication
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 19

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000266964.5
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:4025 FXYD1
MIMⁱ	602359 gene
neXtProtⁱ	NX_O00168

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	21 – 35	ExtracellularSequence analysisAdd BLAST	15
Transmembraneⁱ	36 – 56	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	57 – 92	CytoplasmicSequence analysisAdd BLAST	36

Keywords - Cellular componentⁱ

Cell membrane, Membrane

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	60	C → S: Significantly reduced half-life; when associated with S-62. 1 Publication		1
Mutagenesisⁱ	62	C → S: Significantly reduced half-life; when associated with S-60. 1 Publication		1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	5348
Open Targets More...OpenTargetsⁱ	ENSG00000266964
PharmGKBⁱ	PA28441

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 20	By similarityAdd BLAST		20
ChainⁱPRO_0000010359	21 – 92	PhospholemmanAdd BLAST		72

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Lipidationⁱ	60	S-palmitoyl cysteine1 Publication	1
Modified residueⁱ	62	S-glutathionyl cysteine; alternateBy similarity	1
Lipidationⁱ	62	S-palmitoyl cysteine; alternate1 Publication	1
Modified residueⁱ	79	PhosphothreonineBy similarity	1
Modified residueⁱ	82	PhosphoserineBy similarity	1
Modified residueⁱ	83	Phosphoserine; by PKA and PKCBy similarity	1
Modified residueⁱ	88	Phosphoserine; by PKA1 Publication	1
Modified residueⁱ	89	Phosphothreonine; by PKCBy similarity	1

Post-translational modificationⁱ

Major plasma membrane substrate for cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in several different tissues (By similarity). Phosphorylated in response to insulin and adrenergic stimulation (By similarity). Phosphorylation at Ser-88 stimulates sodium/potassium-transporting ATPase activity while the unphosphorylated form inhibits sodium/potassium-transporting ATPase activity (By similarity). Phosphorylation increases tetramerization, decreases binding to ATP1A1 and reduces inhibition of ATP1A1 activity (By similarity). Phosphorylation at Ser-83 leads to greatly reduced interaction with ATP1A1, ATP1A2 and ATP1A3 (By similarity). May be phosphorylated by DMPK (PubMed:10811636).By similarity1 Publication

Palmitoylation increases half-life and stability and is enhanced upon phosphorylation at Ser-88 by PKA.1 Publication

Keywords - PTMⁱ

Glutathionylation, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQB - The MaxQuant DataBase More...MaxQBⁱ	O00168
PaxDbⁱ	O00168
PeptideAtlas More...PeptideAtlasⁱ	O00168
PRIDEⁱ	O00168
ProteomicsDBⁱ	47759

PTM databases

iPTMnetⁱ	O00168
PhosphoSitePlusⁱ	O00168
SwissPalmⁱ	O00168

Expressionⁱ

Tissue specificityⁱ

Highest expression in skeletal muscle and heart. Moderate levels in brain, placenta, lung, liver, pancreas, uterus, bladder, prostate, small intestine and colon with mucosal lining. Very low levels in kidney, colon and small intestine without mucosa, prostate without endothelial lining, spleen, and testis.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000266964 Expressed in 90 organ(s), highest expression level in tibial nerve
CleanExⁱ	HS_FXYD1
ExpressionAtlasⁱ	O00168 baseline and differential
Genevisibleⁱ	O00168 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA026873

HPAⁱ

HPA026873

Interactionⁱ

Subunit structureⁱ

Homotetramer (PubMed:16597826). Monomer (PubMed:17511473). Regulatory subunit of the sodium/potassium-transporting ATPase (NKA) which is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit (By similarity). The monomeric form associates with NKA while the oligomeric form does not (By similarity). Interacts with the catalytic alpha-1 subunit ATP1A1 (By similarity). Also interacts with the catalytic alpha-2 and alpha-3 subunits ATP1A2 and ATP1A3 (By similarity). Very little interaction with ATP1A1, ATP1A2 or ATP1A3 when phosphorylated at Ser-83 (By similarity). Interacts with the non-catalytic beta-1 subunit ATP1B1 (By similarity). Oxidative stress decreases interaction with ATP1A1 but increases interaction with ATP1B1 (By similarity).By similarity2 Publications

GO - Molecular functionⁱ

ion channel binding Source: BHF-UCL

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	111363, 16 interactors
STRINGⁱ	9606.ENSP00000343314

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	23 – 26	Combined sources	4
Helixⁱ	28 – 30	Combined sources	3
Helixⁱ	34 – 64	Combined sources	31
Turnⁱ	66 – 68	Combined sources	3
Beta strandⁱ	69 – 71	Combined sources	3
Turnⁱ	75 – 77	Combined sources	3
Helixⁱ	80 – 89	Combined sources	10

Show more details

3D structure databases

ProteinModelPortalⁱ	O00168
SMRⁱ	O00168
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ

O00168

Family & Domainsⁱ

Domainⁱ

The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity.By similarity

Sequence similaritiesⁱ

Belongs to the FXYD family.Curated

Keywords - Domainⁱ

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	ENOG410J08K Eukaryota ENOG410YYN6 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00530000063932
HOGENOMⁱ	HOG000234467
HOVERGENⁱ	HBG008212
InParanoidⁱ	O00168
KEGG Orthology (KO) More...KOⁱ	K13360
PhylomeDBⁱ	O00168
TreeFamⁱ	TF333443

Family and domain databases

InterProⁱ	View protein in InterPro IPR000272 Ion-transport_regulator_FXYD
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF02038 ATP1G1_PLM_MAT8, 1 hit
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD005989 PD005989, 1 hit
PROSITEⁱ	View protein in PROSITE PS01310 FXYD, 1 hit

Sequence (1+)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show all Align All

O00168-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MASLGHILVF CVGLLTMAKA ESPKEHDPFT YDYQSLQIGG LVIAGILFIL 
        60         70         80         90 
GILIVLSRRC RCKFNQQQRT GEPDEEEGTF RSSIRRLSTR RR

Length:92

Mass (Da):10,441

Last modified:August 30, 2002 - v2

Checksum:ⁱ11602EFEAFFD8BD8

GO

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	K7EQG4	K7EQG4_HUMAN		FXYD domain-containing ion transpor... FXYD domain-containing ion transport regulator	FXYD1	115	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	3	S → P in AAC51286 (PubMed:9169143).Curated		1
Sequence conflictⁱ	5	G → H in AAC51286 (PubMed:9169143).Curated		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U72245 mRNA Translation: AAC51286.1 AK289811 mRNA Translation: BAF82500.1 BC032800 mRNA Translation: AAH32800.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS12445.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001265646.1, NM_001278717.1 NP_001265647.1, NM_001278718.1 NP_005022.2, NM_005031.4 NP_068702.1, NM_021902.3 XP_016882363.1, XM_017026874.1
UniGeneⁱ	Hs.442498

Genome annotation databases

Ensemblⁱ	ENST00000351325; ENSP00000343314; ENSG00000266964 ENST00000455515; ENSP00000393611; ENSG00000266964 ENST00000588081; ENSP00000467727; ENSG00000266964 ENST00000588607; ENSP00000468535; ENSG00000266964 ENST00000588715; ENSP00000465289; ENSG00000266964 ENST00000589209; ENSP00000466398; ENSG00000266964 ENST00000612146; ENSP00000481244; ENSG00000266964
GeneIDⁱ	5348
KEGGⁱ	hsa:5348
UCSC genome browser More...UCSCⁱ	uc002nyc.5 human

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
O00168	FXYD domain-containing ion transport regulator		PANTR		92	UniRef100_O00168
FXYD domain-containing ion transport regulator		PONAB		92
FXYD domain-containing ion transport regulator		NOMLE		70
UPI0002744B2B		HUMAN		110
UPI00017539A2		HUMAN		72

Protein	Similar proteins		Species	Score	Length	Source
O00168	FXYD domain-containing ion transport regulator		PANTR		92	UniRef90_O00168
FXYD domain-containing ion transport regulator		PONAB		92
FXYD domain-containing ion transport regulator		NOMLE		70
FXYD domain-containing ion transport regulator		MACMU		92
FXYD domain-containing ion transport regulator		CERAT		92
+18

Protein	Similar proteins		Species	Score	Length	Source
O00168	FXYD domain-containing ion transport regulator		PANTR		92	UniRef50_O00168
FXYD domain-containing ion transport regulator		PONAB		92
FXYD domain-containing ion transport regulator		NOMLE		70
FXYD domain-containing ion transport regulator		TUPCH		92
FXYD domain-containing ion transport regulator		COLAP		92
+46

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U72245 mRNA Translation: AAC51286.1 AK289811 mRNA Translation: BAF82500.1 BC032800 mRNA Translation: AAH32800.1
CCDSⁱ	CCDS12445.1
RefSeqⁱ	NP_001265646.1, NM_001278717.1 NP_001265647.1, NM_001278718.1 NP_005022.2, NM_005031.4 NP_068702.1, NM_021902.3 XP_016882363.1, XM_017026874.1
UniGeneⁱ	Hs.442498

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2J1I	model	-	A/B/C/D	32-59	[»]
	2JO1	NMR	-	A	21-92	[»]
ProteinModelPortalⁱ	O00168
SMRⁱ	O00168
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	111363, 16 interactors
STRINGⁱ	9606.ENSP00000343314

PTM databases

iPTMnetⁱ	O00168
PhosphoSitePlusⁱ	O00168
SwissPalmⁱ	O00168

Proteomic databases

MaxQBⁱ	O00168
PaxDbⁱ	O00168
PeptideAtlasⁱ	O00168
PRIDEⁱ	O00168
ProteomicsDBⁱ	47759

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	5348
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000351325; ENSP00000343314; ENSG00000266964 ENST00000455515; ENSP00000393611; ENSG00000266964 ENST00000588081; ENSP00000467727; ENSG00000266964 ENST00000588607; ENSP00000468535; ENSG00000266964 ENST00000588715; ENSP00000465289; ENSG00000266964 ENST00000589209; ENSP00000466398; ENSG00000266964 ENST00000612146; ENSP00000481244; ENSG00000266964
GeneIDⁱ	5348
KEGGⁱ	hsa:5348
UCSCⁱ	uc002nyc.5 human

Organism-specific databases

CTDⁱ	5348
DisGeNETⁱ	5348
EuPathDBⁱ	HostDB:ENSG00000266964.5
GeneCardsⁱ	FXYD1
HGNCⁱ	HGNC:4025 FXYD1
HPAⁱ	HPA026873
MIMⁱ	602359 gene
neXtProtⁱ	NX_O00168
OpenTargetsⁱ	ENSG00000266964
PharmGKBⁱ	PA28441
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410J08K Eukaryota ENOG410YYN6 LUCA
GeneTreeⁱ	ENSGT00530000063932
HOGENOMⁱ	HOG000234467
HOVERGENⁱ	HBG008212
InParanoidⁱ	O00168
KOⁱ	K13360
PhylomeDBⁱ	O00168
TreeFamⁱ	TF333443

Enzyme and pathway databases

Reactomeⁱ	R-HSA-5578775 Ion homeostasis R-HSA-936837 Ion transport by P-type ATPases
SIGNORⁱ	O00168

Miscellaneous databases

EvolutionaryTraceⁱ	O00168
GeneWikiⁱ	FXYD1
GenomeRNAiⁱ	5348
Protein Ontology More...PROⁱ	PR:O00168
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000266964 Expressed in 90 organ(s), highest expression level in tibial nerve
CleanExⁱ	HS_FXYD1
ExpressionAtlasⁱ	O00168 baseline and differential
Genevisibleⁱ	O00168 HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR000272 Ion-transport_regulator_FXYD
Pfamⁱ	View protein in Pfam PF02038 ATP1G1_PLM_MAT8, 1 hit
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD005989 PD005989, 1 hit
PROSITEⁱ	View protein in PROSITE PS01310 FXYD, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	PLM_HUMAN
Accessionⁱ	O00168Primary (citable) accession number: O00168 Secondary accession number(s): A8K196
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
	Last sequence update:	August 30, 2002
	Last modified:	September 12, 2018
	This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM
PDB cross-references
Index of Protein Data Bank (PDB) cross-references

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Supporting data

UniProtKB - O00168 (PLM_HUMAN)

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Phospholemman

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Other locations

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ