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Protein

Phospholemman

Gene

FXYD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May have a functional role in muscle contraction. Induces a hyperpolarization-activated chloride current when exogenously expressed.

GO - Molecular functioni

  • chloride channel activity Source: ProtInc
  • ion channel binding Source: BHF-UCL
  • sodium channel regulator activity Source: BHF-UCL

GO - Biological processi

  • cellular calcium ion homeostasis Source: Ensembl
  • chloride transmembrane transport Source: GOC
  • chloride transport Source: ProtInc
  • ion transmembrane transport Source: Reactome
  • muscle contraction Source: ProtInc
  • positive regulation of sodium ion export from cell Source: BHF-UCL
  • regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  • regulation of heart contraction Source: BHF-UCL
  • regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
  • transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Chloride

Enzyme and pathway databases

ReactomeiREACT_25149. Ion transport by P-type ATPases.

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholemman
Alternative name(s):
FXYD domain-containing ion transport regulator 1
Gene namesi
Name:FXYD1
Synonyms:PLM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:4025. FXYD1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 3515ExtracellularSequence AnalysisAdd
BLAST
Transmembranei36 – 5621HelicalSequence AnalysisAdd
BLAST
Topological domaini57 – 9236CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi60 – 601C → S: Significantly reduced half-life; when associated with S-62. 1 Publication
Mutagenesisi62 – 621C → S: Significantly reduced half-life; when associated with S-60. 1 Publication

Organism-specific databases

PharmGKBiPA28441.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020By similarityAdd
BLAST
Chaini21 – 9272PhospholemmanPRO_0000010359Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi60 – 601S-palmitoyl cysteine1 Publication
Lipidationi62 – 621S-palmitoyl cysteine1 Publication
Modified residuei79 – 791PhosphothreonineBy similarity
Modified residuei83 – 831Phosphoserine; by PKA and PKCBy similarity
Modified residuei88 – 881Phosphoserine; by PKA1 Publication

Post-translational modificationi

Major plasma membrane substrate for cAMP-dependent protein kinase (PK-A) and protein kinase C (PK-C) in several different tissues (By similarity). Phosphorylated in response to insulin and adrenergic stimulation. May be phosphorylated by DMPK.By similarity
Palmitoylation increases half-life and stability, it is enhanced upon phosphorylation at Ser-88 by PKA.2 Publications

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiO00168.
PaxDbiO00168.
PeptideAtlasiO00168.
PRIDEiO00168.

PTM databases

PhosphoSiteiO00168.

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.

Gene expression databases

BgeeiO00168.
CleanExiHS_FXYD1.
ExpressionAtlasiO00168. baseline.
GenevisibleiO00168. HS.

Organism-specific databases

HPAiHPA026873.

Interactioni

Protein-protein interaction databases

BioGridi111363. 3 interactions.
STRINGi9606.ENSP00000343314.

Structurei

Secondary structure

1
92
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi23 – 264Combined sources
Helixi28 – 303Combined sources
Helixi34 – 6431Combined sources
Turni66 – 683Combined sources
Beta strandi69 – 713Combined sources
Turni75 – 773Combined sources
Helixi80 – 8910Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2J1Imodel-A/B/C/D32-59[»]
2JO1NMR-A21-92[»]
ProteinModelPortaliO00168.
SMRiO00168. Positions 21-92.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00168.

Family & Domainsi

Sequence similaritiesi

Belongs to the FXYD family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42110.
GeneTreeiENSGT00530000063932.
HOGENOMiHOG000234467.
HOVERGENiHBG008212.
InParanoidiO00168.
KOiK13360.
OrthoDBiEOG7WHHDM.
PhylomeDBiO00168.
TreeFamiTF333443.

Family and domain databases

InterProiIPR000272. Ion-transport_regulator_FXYD.
[Graphical view]
PfamiPF02038. ATP1G1_PLM_MAT8. 1 hit.
[Graphical view]
ProDomiPD005989. PD005989. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEiPS01310. FXYD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O00168-1 [UniParc]FASTAAdd 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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 31S → P in AAC51286 (PubMed:9169143).Curated
Sequence conflicti5 – 51G → H in AAC51286 (PubMed:9169143).Curated

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.
CCDSiCCDS12445.1.
RefSeqiNP_001265646.1. NM_001278717.1.
NP_001265647.1. NM_001278718.1.
NP_005022.2. NM_005031.4.
NP_068702.1. NM_021902.3.
UniGeneiHs.442498.

Genome annotation databases

EnsembliENST00000351325; ENSP00000343314; ENSG00000266964.
ENST00000455515; ENSP00000393611; ENSG00000266964.
ENST00000588081; ENSP00000467727; ENSG00000266964.
ENST00000588607; ENSP00000468535; ENSG00000266964.
ENST00000588715; ENSP00000465289; ENSG00000266964.
ENST00000589209; ENSP00000466398; ENSG00000266964.
ENST00000612146; ENSP00000481244; ENSG00000266964.
GeneIDi5348.
KEGGihsa:5348.
UCSCiuc002nyc.3. human.

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.
CCDSiCCDS12445.1.
RefSeqiNP_001265646.1. NM_001278717.1.
NP_001265647.1. NM_001278718.1.
NP_005022.2. NM_005031.4.
NP_068702.1. NM_021902.3.
UniGeneiHs.442498.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2J1Imodel-A/B/C/D32-59[»]
2JO1NMR-A21-92[»]
ProteinModelPortaliO00168.
SMRiO00168. Positions 21-92.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111363. 3 interactions.
STRINGi9606.ENSP00000343314.

PTM databases

PhosphoSiteiO00168.

Proteomic databases

MaxQBiO00168.
PaxDbiO00168.
PeptideAtlasiO00168.
PRIDEiO00168.

Protocols and materials databases

DNASUi5348.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000351325; ENSP00000343314; ENSG00000266964.
ENST00000455515; ENSP00000393611; ENSG00000266964.
ENST00000588081; ENSP00000467727; ENSG00000266964.
ENST00000588607; ENSP00000468535; ENSG00000266964.
ENST00000588715; ENSP00000465289; ENSG00000266964.
ENST00000589209; ENSP00000466398; ENSG00000266964.
ENST00000612146; ENSP00000481244; ENSG00000266964.
GeneIDi5348.
KEGGihsa:5348.
UCSCiuc002nyc.3. human.

Organism-specific databases

CTDi5348.
GeneCardsiGC19P035629.
HGNCiHGNC:4025. FXYD1.
HPAiHPA026873.
MIMi602359. gene.
neXtProtiNX_O00168.
PharmGKBiPA28441.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG42110.
GeneTreeiENSGT00530000063932.
HOGENOMiHOG000234467.
HOVERGENiHBG008212.
InParanoidiO00168.
KOiK13360.
OrthoDBiEOG7WHHDM.
PhylomeDBiO00168.
TreeFamiTF333443.

Enzyme and pathway databases

ReactomeiREACT_25149. Ion transport by P-type ATPases.

Miscellaneous databases

EvolutionaryTraceiO00168.
GeneWikiiFXYD1.
GenomeRNAii5348.
NextBioi20726.
PROiO00168.
SOURCEiSearch...

Gene expression databases

BgeeiO00168.
CleanExiHS_FXYD1.
ExpressionAtlasiO00168. baseline.
GenevisibleiO00168. HS.

Family and domain databases

InterProiIPR000272. Ion-transport_regulator_FXYD.
[Graphical view]
PfamiPF02038. ATP1G1_PLM_MAT8. 1 hit.
[Graphical view]
ProDomiPD005989. PD005989. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEiPS01310. FXYD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of the human and rat phospholemman (PLM) cDNAs and localization of the human PLM gene to chromosome 19q13.1."
    Chen L.-S.K., Lo C.F., Numann R., Cuddy M.
    Genomics 41:435-443(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Heart.
  2. "The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression."
    Sweadner K.J., Rael E.
    Genomics 68:41-56(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain, Lung and Testis.
  5. Cited for: PHOSPHORYLATION BY DMPK.
  6. "The inhibitory effect of phospholemman on the sodium pump requires its palmitoylation."
    Tulloch L.B., Howie J., Wypijewski K.J., Wilson C.R., Bernard W.G., Shattock M.J., Fuller W.
    J. Biol. Chem. 286:36020-36031(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT CYS-60 AND CYS-62, PHOSPHORYLATION AT SER-88, MUTAGENESIS OF CYS-60 AND CYS-62.

Entry informationi

Entry nameiPLM_HUMAN
AccessioniPrimary (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: June 24, 2015
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.