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Protein

Junctophilin-2

Gene

JPH2

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

Functioni

Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH2 is necessary for proper intracellular Ca2+ signaling in cardiac myocytes via its involvement in ryanodine receptor-mediated calcium ion release. Contributes to the construction of skeletal muscle triad junctions.1 Publication

GO - Molecular functioni

  • calcium-release channel activity Source: UniProtKB
  • phosphatidic acid binding Source: UniProtKB
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
  • phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol-3-phosphate binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol-4-phosphate binding Source: UniProtKB
  • phosphatidylinositol-5-phosphate binding Source: UniProtKB
  • phosphatidylserine binding Source: UniProtKB

GO - Biological processi

  • calcium ion homeostasis Source: UniProtKB
  • calcium ion transport into cytosol Source: BHF-UCL
  • positive regulation of ryanodine-sensitive calcium-release channel activity Source: UniProtKB
  • regulation of cardiac muscle tissue development Source: Ensembl
  • regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149596-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Junctophilin-2
Short name:
JP-2
Alternative name(s):
Junctophilin type 2
Gene namesi
Name:JPH2
Synonyms:JP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:14202. JPH2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 674CytoplasmicSequence analysisAdd BLAST674
Transmembranei675 – 695Helical; Anchor for type IV membrane proteinSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane, Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, familial hypertrophic 17 (CMH17)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
See also OMIM:613873
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065471101S → R in CMH17; modifies the secondary structure of the protein which is more flexible but does not undergo structural transition upon binding to membrane lipids; increases the affinity for phosphatidylserine; affects intracellular calcium handling and homeostasis. 2 Publications1
Natural variantiVAR_065472141Y → H in CMH17; results in vacuolization of intracellular structures and cardiomyocyte hypertrophy; affects intracellular calcium handling and homeostasis. 1 PublicationCorresponds to variant rs387906897dbSNPEnsembl.1
Natural variantiVAR_065473165S → F in CMH17; results in vacuolization of intracellular structures and cardiomyocyte hypertrophy; affects intracellular calcium handling and homeostasis. Greatly reduced phosphorylation. Increased myotube diameter. Reduced RYR1 activity and EC gain. Disruption of interaction with TRPC3. 2 PublicationsCorresponds to variant rs387906898dbSNPEnsembl.1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi57158.
MalaCardsiJPH2.
MIMi613873. phenotype.
OpenTargetsiENSG00000149596.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA29999.

Polymorphism and mutation databases

BioMutaiJPH2.
DMDMi27805486.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001598471 – 696Junctophilin-2Add BLAST696

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei162PhosphoserineBy similarity1
Modified residuei165Phosphoserine1 Publication1
Modified residuei446PhosphoserineBy similarity1
Modified residuei448PhosphoserineBy similarity1
Modified residuei469PhosphoserineCombined sources1
Modified residuei477PhosphothreonineBy similarity1
Modified residuei484PhosphoserineCombined sources1
Modified residuei486PhosphoserineCombined sources1
Modified residuei490PhosphothreonineCombined sources1
Modified residuei534PhosphoserineBy similarity1
Modified residuei594PhosphoserineBy similarity1
Modified residuei598PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation on Ser-165, probably by PKC, affects RYR1-mediated calcium ion release, interaction with TRPC3, and skeletal muscle myotubule development.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9BR39.
MaxQBiQ9BR39.
PaxDbiQ9BR39.
PeptideAtlasiQ9BR39.
PRIDEiQ9BR39.

PTM databases

iPTMnetiQ9BR39.
PhosphoSitePlusiQ9BR39.

Expressioni

Tissue specificityi

Specifically expressed in skeletal muscle and heart.1 Publication

Gene expression databases

BgeeiENSG00000149596.
CleanExiHS_JPH2.
GenevisibleiQ9BR39. HS.

Organism-specific databases

HPAiHPA052646.

Interactioni

Protein-protein interaction databases

BioGridi121414. 1 interactor.
STRINGi9606.ENSP00000362071.

Structurei

3D structure databases

ProteinModelPortaliQ9BR39.
SMRiQ9BR39.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati14 – 36MORN 1Add BLAST23
Repeati38 – 59MORN 2Add BLAST22
Repeati60 – 79MORN 3Add BLAST20
Repeati82 – 104MORN 4Add BLAST23
Repeati106 – 128MORN 5Add BLAST23
Repeati129 – 151MORN 6Add BLAST23
Repeati291 – 313MORN 7Add BLAST23
Repeati314 – 336MORN 8Add BLAST23

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 142Gly-richAdd BLAST140
Compositional biasi373 – 408Ala-richAdd BLAST36
Compositional biasi452 – 633Pro-richAdd BLAST182

Domaini

The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, by interacting with phospholipids. Has affinity for phosphatidylserine, and phosphorylated phosphatidylinositols including PtdIns3P, PtdIns4P, PtdIns5P, PtdIns(3,5)P2 and PtdIns(3,4,5)P3.1 Publication

Sequence similaritiesi

Belongs to the junctophilin family.Curated
Contains 8 MORN repeats.Curated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0231. Eukaryota.
COG4642. LUCA.
GeneTreeiENSGT00730000110639.
HOGENOMiHOG000264244.
HOVERGENiHBG031648.
InParanoidiQ9BR39.
KOiK19530.
OMAiHERETPR.
OrthoDBiEOG091G03WX.
PhylomeDBiQ9BR39.
TreeFamiTF317210.

Family and domain databases

InterProiIPR017191. Junctophilin.
IPR003409. MORN.
[Graphical view]
PfamiPF02493. MORN. 8 hits.
[Graphical view]
PIRSFiPIRSF037387. Junctophilin. 1 hit.
SMARTiSM00698. MORN. 6 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BR39-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGGRFDFDD GGAYCGGWEG GKAHGHGLCT GPKGQGEYSG SWNFGFEVAG
60 70 80 90 100
VYTWPSGNTF EGYWSQGKRH GLGIETKGRW LYKGEWTHGF KGRYGIRQSS
110 120 130 140 150
SSGAKYEGTW NNGLQDGYGT ETYADGGTYQ GQFTNGMRHG YGVRQSVPYG
160 170 180 190 200
MAVVVRSPLR TSLSSLRSEH SNGTVAPDSP ASPASDGPAL PSPAIPRGGF
210 220 230 240 250
ALSLLANAEA AARAPKGGGL FQRGALLGKL RRAESRTSVG SQRSRVSFLK
260 270 280 290 300
SDLSSGASDA ASTASLGEAA EGADEAAPFE ADIDATTTET YMGEWKNDKR
310 320 330 340 350
SGFGVSERSS GLRYEGEWLD NLRHGYGCTT LPDGHREEGK YRHNVLVKDT
360 370 380 390 400
KRRMLQLKSN KVRQKVEHSV EGAQRAAAIA RQKAEIAASR TSHAKAKAEA
410 420 430 440 450
AEQAALAANQ ESNIARTLAR ELAPDFYQPG PEYQKRRLLQ EILENSESLL
460 470 480 490 500
EPPDRGAGAA GLPQPPRESP QLHERETPRP EGGSPSPAGT PPQPKRPRPG
510 520 530 540 550
VSKDGLLSPG AWNGEPSGEG SRSVTPSEGA GRRSPARPAT ERMAIEALQA
560 570 580 590 600
PPAPSREPEV ALYQGYHSYA VRTTPPEPPP FEDQPEPEVS GSESAPSSPA
610 620 630 640 650
TAPLQAPTLR GPEPARETPA KLEPKPIIPK AEPRAKARKT EARGLTKAGA
660 670 680 690
KKKARKEAAL AAEAEVEVEE VPNTILICMV ILLNIGLAIL FVHLLT
Length:696
Mass (Da):74,222
Last modified:January 17, 2003 - v2
Checksum:i80D62652CE48548B
GO
Isoform 2 (identifier: Q9BR39-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     128-129: TY → MC
     130-696: Missing.

Note: No experimental confirmation available.
Show »
Length:129
Mass (Da):13,951
Checksum:iF2008165B64B104B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065471101S → R in CMH17; modifies the secondary structure of the protein which is more flexible but does not undergo structural transition upon binding to membrane lipids; increases the affinity for phosphatidylserine; affects intracellular calcium handling and homeostasis. 2 Publications1
Natural variantiVAR_065472141Y → H in CMH17; results in vacuolization of intracellular structures and cardiomyocyte hypertrophy; affects intracellular calcium handling and homeostasis. 1 PublicationCorresponds to variant rs387906897dbSNPEnsembl.1
Natural variantiVAR_065473165S → F in CMH17; results in vacuolization of intracellular structures and cardiomyocyte hypertrophy; affects intracellular calcium handling and homeostasis. Greatly reduced phosphorylation. Increased myotube diameter. Reduced RYR1 activity and EC gain. Disruption of interaction with TRPC3. 2 PublicationsCorresponds to variant rs387906898dbSNPEnsembl.1
Natural variantiVAR_053447396A → T.Corresponds to variant rs3810510dbSNPEnsembl.1
Natural variantiVAR_065474436R → C.1 Publication1
Natural variantiVAR_065475505G → S in patients with cardiomyopathy; does not affect protein conformation as shown by circular dichroism; a patient with cardiomyopathy also carries V-26 and C-513 in MYH7. 1 PublicationCorresponds to variant rs140740776dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002785128 – 129TY → MC in isoform 2. 1 Publication2
Alternative sequenceiVSP_002786130 – 696Missing in isoform 2. 1 PublicationAdd BLAST567

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL132999 mRNA. Translation: CAB61347.1.
AL035447, AL034419 Genomic DNA. Translation: CAI19380.1.
AL034419, AL035447 Genomic DNA. Translation: CAI42199.1.
AL035447 Genomic DNA. Translation: CAC18785.1.
CH471077 Genomic DNA. Translation: EAW75940.1.
CH471077 Genomic DNA. Translation: EAW75943.1.
CCDSiCCDS13325.1. [Q9BR39-1]
CCDS13326.1. [Q9BR39-2]
RefSeqiNP_065166.2. NM_020433.4. [Q9BR39-1]
NP_787109.2. NM_175913.3. [Q9BR39-2]
UniGeneiHs.441737.

Genome annotation databases

EnsembliENST00000342272; ENSP00000344590; ENSG00000149596. [Q9BR39-2]
ENST00000372980; ENSP00000362071; ENSG00000149596. [Q9BR39-1]
GeneIDi57158.
KEGGihsa:57158.
UCSCiuc002xli.2. human. [Q9BR39-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL132999 mRNA. Translation: CAB61347.1.
AL035447, AL034419 Genomic DNA. Translation: CAI19380.1.
AL034419, AL035447 Genomic DNA. Translation: CAI42199.1.
AL035447 Genomic DNA. Translation: CAC18785.1.
CH471077 Genomic DNA. Translation: EAW75940.1.
CH471077 Genomic DNA. Translation: EAW75943.1.
CCDSiCCDS13325.1. [Q9BR39-1]
CCDS13326.1. [Q9BR39-2]
RefSeqiNP_065166.2. NM_020433.4. [Q9BR39-1]
NP_787109.2. NM_175913.3. [Q9BR39-2]
UniGeneiHs.441737.

3D structure databases

ProteinModelPortaliQ9BR39.
SMRiQ9BR39.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121414. 1 interactor.
STRINGi9606.ENSP00000362071.

PTM databases

iPTMnetiQ9BR39.
PhosphoSitePlusiQ9BR39.

Polymorphism and mutation databases

BioMutaiJPH2.
DMDMi27805486.

Proteomic databases

EPDiQ9BR39.
MaxQBiQ9BR39.
PaxDbiQ9BR39.
PeptideAtlasiQ9BR39.
PRIDEiQ9BR39.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342272; ENSP00000344590; ENSG00000149596. [Q9BR39-2]
ENST00000372980; ENSP00000362071; ENSG00000149596. [Q9BR39-1]
GeneIDi57158.
KEGGihsa:57158.
UCSCiuc002xli.2. human. [Q9BR39-1]

Organism-specific databases

CTDi57158.
DisGeNETi57158.
GeneCardsiJPH2.
H-InvDBHIX0015833.
HGNCiHGNC:14202. JPH2.
HPAiHPA052646.
MalaCardsiJPH2.
MIMi605267. gene.
613873. phenotype.
neXtProtiNX_Q9BR39.
OpenTargetsiENSG00000149596.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA29999.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0231. Eukaryota.
COG4642. LUCA.
GeneTreeiENSGT00730000110639.
HOGENOMiHOG000264244.
HOVERGENiHBG031648.
InParanoidiQ9BR39.
KOiK19530.
OMAiHERETPR.
OrthoDBiEOG091G03WX.
PhylomeDBiQ9BR39.
TreeFamiTF317210.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149596-MONOMER.

Miscellaneous databases

ChiTaRSiJPH2. human.
GeneWikiiJPH2.
GenomeRNAii57158.
PROiQ9BR39.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149596.
CleanExiHS_JPH2.
GenevisibleiQ9BR39. HS.

Family and domain databases

InterProiIPR017191. Junctophilin.
IPR003409. MORN.
[Graphical view]
PfamiPF02493. MORN. 8 hits.
[Graphical view]
PIRSFiPIRSF037387. Junctophilin. 1 hit.
SMARTiSM00698. MORN. 6 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiJPH2_HUMAN
AccessioniPrimary (citable) accession number: Q9BR39
Secondary accession number(s): E1P5X1
, O95913, Q5JY74, Q9UJN4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 17, 2003
Last sequence update: January 17, 2003
Last modified: November 2, 2016
This is version 140 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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 one 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.