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Q9BR39 (JPH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Junctophilin-2

Short name=JP-2
Alternative name(s):
Junctophilin type 2
Gene names
Name:JPH2
Synonyms:JP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length696 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7

Subcellular location

Cell membrane; Peripheral membrane protein By similarity. Endoplasmic reticulum membrane; Single-pass type IV membrane protein By similarity. Sarcoplasmic reticulum membrane; Single-pass type IV membrane protein By similarity. Note: Localized predominantly on the plasma membrane. The transmembrane domain is anchored in endoplasmic/sarcoplasmic reticulum membrane, while the N-terminal part associates with the plasma membrane. In heart cells, it predominantly associates along Z lines within myocytes. In skeletal muscle, it is specifically localized at the junction of A and I bands By similarity.

Tissue specificity

Specifically expressed in skeletal muscle and heart. Ref.4

Domain

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.

Post-translational modification

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

Involvement in disease

Cardiomyopathy, familial hypertrophic 17 (CMH17) [MIM:613873]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10

Sequence similarities

Belongs to the junctophilin family.

Contains 8 MORN repeats.

Ontologies

Keywords
   Cellular componentCell membrane
Endoplasmic reticulum
Membrane
Sarcoplasmic reticulum
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCardiomyopathy
Disease mutation
   DomainRepeat
Transmembrane
Transmembrane helix
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion homeostasis

Inferred from direct assay Ref.7. Source: UniProtKB

calcium ion transmembrane transport

Inferred from direct assay Ref.7. Source: GOC

calcium ion transport into cytosol

Traceable author statement PubMed 19095005. Source: BHF-UCL

positive regulation of ryanodine-sensitive calcium-release channel activity

Inferred from direct assay Ref.7. Source: UniProtKB

regulation of cardiac muscle tissue development

Inferred from electronic annotation. Source: Ensembl

regulation of ryanodine-sensitive calcium-release channel activity

Traceable author statement PubMed 19095005. Source: BHF-UCL

   Cellular_componentZ disc

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

junctional membrane complex

Inferred from electronic annotation. Source: Ensembl

junctional sarcoplasmic reticulum membrane

Traceable author statement PubMed 19095005. Source: BHF-UCL

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium-release channel activity

Inferred from direct assay Ref.7. Source: UniProtKB

phosphatidic acid binding

Inferred from direct assay Ref.10. Source: UniProtKB

phosphatidylinositol-3,4,5-trisphosphate binding

Inferred from direct assay Ref.10. Source: UniProtKB

phosphatidylinositol-3,5-bisphosphate binding

Inferred from direct assay Ref.10. Source: UniProtKB

phosphatidylinositol-3-phosphate binding

Inferred from direct assay Ref.10. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from direct assay Ref.10. Source: UniProtKB

phosphatidylinositol-4-phosphate binding

Inferred from direct assay Ref.10. Source: UniProtKB

phosphatidylinositol-5-phosphate binding

Inferred from direct assay Ref.10. Source: UniProtKB

phosphatidylserine binding

Inferred from direct assay Ref.10. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BR39-1)

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.
Isoform 2 (identifier: Q9BR39-2)

The sequence of this isoform differs from the canonical sequence as follows:
     128-129: TY → MC
     130-696: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 696696Junctophilin-2
PRO_0000159847

Regions

Topological domain1 – 674674Cytoplasmic Potential
Transmembrane675 – 69521Helical; Anchor for type IV membrane protein; Potential
Repeat14 – 3623MORN 1
Repeat38 – 5922MORN 2
Repeat60 – 7920MORN 3
Repeat82 – 10423MORN 4
Repeat106 – 12823MORN 5
Repeat129 – 15123MORN 6
Repeat291 – 31323MORN 7
Repeat314 – 33623MORN 8
Compositional bias3 – 142140Gly-rich
Compositional bias373 – 40836Ala-rich
Compositional bias452 – 633182Pro-rich

Amino acid modifications

Modified residue1651Phosphoserine Ref.7
Modified residue4691Phosphoserine Ref.5
Modified residue4841Phosphoserine Ref.6
Modified residue4861Phosphoserine Ref.6
Modified residue4901Phosphothreonine Ref.6

Natural variations

Alternative sequence128 – 1292TY → MC in isoform 2.
VSP_002785
Alternative sequence130 – 696567Missing in isoform 2.
VSP_002786
Natural variant1011S → 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. Ref.9 Ref.10
VAR_065471
Natural variant1411Y → H in CMH17; results in vacuolization of intracellular structures and cardiomyocyte hypertrophy; affects intracellular calcium handling and homeostasis. Ref.9
VAR_065472
Natural variant1651S → 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. Ref.7 Ref.9
VAR_065473
Natural variant3961A → T.
Corresponds to variant rs3810510 [ dbSNP | Ensembl ].
VAR_053447
Natural variant4361R → C. Ref.8
VAR_065474
Natural variant5051G → 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. Ref.8
Corresponds to variant rs140740776 [ dbSNP | Ensembl ].
VAR_065475

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 17, 2003. Version 2.
Checksum: 80D62652CE48548B

FASTA69674,222
        10         20         30         40         50         60 
MSGGRFDFDD GGAYCGGWEG GKAHGHGLCT GPKGQGEYSG SWNFGFEVAG VYTWPSGNTF 

        70         80         90        100        110        120 
EGYWSQGKRH GLGIETKGRW LYKGEWTHGF KGRYGIRQSS SSGAKYEGTW NNGLQDGYGT 

       130        140        150        160        170        180 
ETYADGGTYQ GQFTNGMRHG YGVRQSVPYG MAVVVRSPLR TSLSSLRSEH SNGTVAPDSP 

       190        200        210        220        230        240 
ASPASDGPAL PSPAIPRGGF ALSLLANAEA AARAPKGGGL FQRGALLGKL RRAESRTSVG 

       250        260        270        280        290        300 
SQRSRVSFLK SDLSSGASDA ASTASLGEAA EGADEAAPFE ADIDATTTET YMGEWKNDKR 

       310        320        330        340        350        360 
SGFGVSERSS GLRYEGEWLD NLRHGYGCTT LPDGHREEGK YRHNVLVKDT KRRMLQLKSN 

       370        380        390        400        410        420 
KVRQKVEHSV EGAQRAAAIA RQKAEIAASR TSHAKAKAEA AEQAALAANQ ESNIARTLAR 

       430        440        450        460        470        480 
ELAPDFYQPG PEYQKRRLLQ EILENSESLL EPPDRGAGAA GLPQPPRESP QLHERETPRP 

       490        500        510        520        530        540 
EGGSPSPAGT PPQPKRPRPG VSKDGLLSPG AWNGEPSGEG SRSVTPSEGA GRRSPARPAT 

       550        560        570        580        590        600 
ERMAIEALQA PPAPSREPEV ALYQGYHSYA VRTTPPEPPP FEDQPEPEVS GSESAPSSPA 

       610        620        630        640        650        660 
TAPLQAPTLR GPEPARETPA KLEPKPIIPK AEPRAKARKT EARGLTKAGA KKKARKEAAL 

       670        680        690 
AAEAEVEVEE VPNTILICMV ILLNIGLAIL FVHLLT 

« Hide

Isoform 2 [UniParc].

Checksum: F2008165B64B104B
Show »

FASTA12913,951

References

« Hide 'large scale' references
[1]Stavrides G.S., Huckle E.J., Deloukas P.
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Characterization of human junctophilin subtype genes."
Nishi M., Mizushima A., Nakagawara K., Takeshima H.
Biochem. Biophys. Res. Commun. 273:920-927(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 1), TISSUE SPECIFICITY.
[5]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484; SER-486 AND THR-490, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"S165F mutation of junctophilin 2 affects Ca2+ signalling in skeletal muscle."
Woo J.S., Hwang J.H., Ko J.K., Weisleder N., Kim do H., Ma J., Lee E.H.
Biochem. J. 427:125-134(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-165, INTERACTION WITH TRPC3, FUNCTION, CHARACTERIZATION OF VARIANT PHE-165.
[8]"Mutation of junctophilin type 2 associated with hypertrophic cardiomyopathy."
Matsushita Y., Furukawa T., Kasanuki H., Nishibatake M., Kurihara Y., Ikeda A., Kamatani N., Takeshima H., Matsuoka R.
J. Hum. Genet. 52:543-548(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYS-436 AND SER-505, CHARACTERIZATION OF VARIANT SER-505.
[9]"Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans."
Landstrom A.P., Weisleder N., Batalden K.B., Bos J.M., Tester D.J., Ommen S.R., Wehrens X.H., Claycomb W.C., Ko J.K., Hwang M., Pan Z., Ma J., Ackerman M.J.
J. Mol. Cell. Cardiol. 42:1026-1035(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH17 ARG-101; HIS-141 AND PHE-165, CHARACTERIZATION OF VARIANTS CMH17 ARG-101; HIS-141 AND PHE-165.
[10]"Human junctophilin-2 undergoes a structural rearrangement upon binding PtdIns(3,4,5)P3 and the S101R mutation identified in hypertrophic cardiomyopathy obviates this response."
Bennett H.J., Davenport J.B., Collins R.F., Trafford A.W., Pinali C., Kitmitto A.
Biochem. J. 456:205-217(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: MEMBRANE LIPID-BINDING, CHARACTERIZATION OF VARIANT CMH17 ARG-101.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_065166.2. NM_020433.4.
NP_787109.2. NM_175913.3.
UniGeneHs.441737.

3D structure databases

ProteinModelPortalQ9BR39.
SMRQ9BR39. Positions 8-45, 53-144, 318-346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121414. 2 interactions.
STRING9606.ENSP00000362071.

PTM databases

PhosphoSiteQ9BR39.

Polymorphism databases

DMDM27805486.

Proteomic databases

PaxDbQ9BR39.
PRIDEQ9BR39.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000342272; ENSP00000344590; ENSG00000149596. [Q9BR39-2]
ENST00000372980; ENSP00000362071; ENSG00000149596. [Q9BR39-1]
GeneID57158.
KEGGhsa:57158.
UCSCuc002xli.1. human. [Q9BR39-1]
uc002xlj.3. human. [Q9BR39-2]

Organism-specific databases

CTD57158.
GeneCardsGC20M042740.
H-InvDBHIX0015833.
HGNCHGNC:14202. JPH2.
HPAHPA052646.
MIM605267. gene.
613873. phenotype.
neXtProtNX_Q9BR39.
Orphanet155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBPA29999.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG324165.
HOGENOMHOG000264244.
HOVERGENHBG031648.
InParanoidQ9BR39.
OMAHERETPR.
OrthoDBEOG7J4463.
PhylomeDBQ9BR39.
TreeFamTF317210.

Gene expression databases

ArrayExpressQ9BR39.
BgeeQ9BR39.
CleanExHS_JPH2.
GenevestigatorQ9BR39.

Family and domain databases

InterProIPR017191. Junctophilin.
IPR003409. MORN.
[Graphical view]
PfamPF02493. MORN. 8 hits.
[Graphical view]
PIRSFPIRSF037387. Junctophilin. 1 hit.
SMARTSM00698. MORN. 6 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiJPH2.
GenomeRNAi57158.
NextBio63151.
PROQ9BR39.
SOURCESearch...

Entry information

Entry nameJPH2_HUMAN
AccessionPrimary (citable) accession number: Q9BR39
Secondary accession number(s): E1P5X1 expand/collapse secondary AC list , O95913, Q5JY74, Q9UJN4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 17, 2003
Last sequence update: January 17, 2003
Last modified: April 16, 2014
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM