JPH2_HUMAN
ID JPH2_HUMAN Reviewed; 696 AA.
AC Q9BR39; E1P5X1; O95913; Q5JY74; Q9UJN4;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-JAN-2003, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Junctophilin-2 {ECO:0000303|PubMed:10891348};
DE Short=JP-2 {ECO:0000303|PubMed:10891348};
DE AltName: Full=Junctophilin type 2 {ECO:0000303|PubMed:10891348};
DE Contains:
DE RecName: Full=Junctophilin-2 N-terminal fragment {ECO:0000250|UniProtKB:Q9ET78};
DE Short=JP2NT {ECO:0000250|UniProtKB:Q9ET78};
GN Name=JPH2 {ECO:0000312|HGNC:HGNC:14202};
GN Synonyms=JP2 {ECO:0000303|PubMed:10891348};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Stavrides G.S., Huckle E.J., Deloukas P.;
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=10891348; DOI=10.1006/bbrc.2000.3011;
RA Nishi M., Mizushima A., Nakagawara K., Takeshima H.;
RT "Characterization of human junctophilin subtype genes.";
RL Biochem. Biophys. Res. Commun. 273:920-927(2000).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484; SER-486 AND THR-490, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION AT SER-165, INTERACTION WITH TRPC3, FUNCTION, AND
RP CHARACTERIZATION OF VARIANT PHE-165.
RX PubMed=20095964; DOI=10.1042/bj20091225;
RA Woo J.S., Hwang J.H., Ko J.K., Weisleder N., Kim do H., Ma J., Lee E.H.;
RT "S165F mutation of junctophilin 2 affects Ca2+ signalling in skeletal
RT muscle.";
RL Biochem. J. 427:125-134(2010).
RN [8]
RP MEMBRANE LIPID-BINDING, CHARACTERIZATION OF VARIANT CMH17 ARG-101, AND
RP DOMAIN.
RX PubMed=24001019; DOI=10.1042/bj20130591;
RA Bennett H.J., Davenport J.B., Collins R.F., Trafford A.W., Pinali C.,
RA Kitmitto A.;
RT "Human junctophilin-2 undergoes a structural rearrangement upon binding
RT PtdIns(3,4,5)P3 and the S101R mutation identified in hypertrophic
RT cardiomyopathy obviates this response.";
RL Biochem. J. 456:205-217(2013).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-490, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP SUBCELLULAR LOCATION (JUNCTOPHILIN-2 N-TERMINAL FRAGMENT).
RX PubMed=30409805; DOI=10.1126/science.aan3303;
RA Guo A., Wang Y., Chen B., Wang Y., Yuan J., Zhang L., Hall D., Wu J.,
RA Shi Y., Zhu Q., Chen C., Thiel W.H., Zhan X., Weiss R.M., Zhan F.,
RA Musselman C.A., Pufall M., Zhu W., Au K.F., Hong J., Anderson M.E.,
RA Grueter C.E., Song L.S.;
RT "E-C coupling structural protein junctophilin-2 encodes a stress-adaptive
RT transcription regulator.";
RL Science 0:0-0(2018).
RN [11]
RP VARIANTS CYS-436 AND SER-505, AND CHARACTERIZATION OF VARIANT SER-505.
RX PubMed=17476457; DOI=10.1007/s10038-007-0149-y;
RA Matsushita Y., Furukawa T., Kasanuki H., Nishibatake M., Kurihara Y.,
RA Ikeda A., Kamatani N., Takeshima H., Matsuoka R.;
RT "Mutation of junctophilin type 2 associated with hypertrophic
RT cardiomyopathy.";
RL J. Hum. Genet. 52:543-548(2007).
RN [12]
RP VARIANTS CMH17 ARG-101; HIS-141 AND PHE-165, AND CHARACTERIZATION OF
RP VARIANTS CMH17 ARG-101; HIS-141 AND PHE-165.
RX PubMed=17509612; DOI=10.1016/j.yjmcc.2007.04.006;
RA Landstrom A.P., Weisleder N., Batalden K.B., Bos J.M., Tester D.J.,
RA Ommen S.R., Wehrens X.H., Claycomb W.C., Ko J.K., Hwang M., Pan Z., Ma J.,
RA Ackerman M.J.;
RT "Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic
RT cardiomyopathy in humans.";
RL J. Mol. Cell. Cardiol. 42:1026-1035(2007).
RN [13]
RP VARIANT LYS-169.
RX PubMed=23973696; DOI=10.1016/j.jacc.2013.06.052;
RA Beavers D.L., Wang W., Ather S., Voigt N., Garbino A., Dixit S.S.,
RA Landstrom A.P., Li N., Wang Q., Olivotto I., Dobrev D., Ackerman M.J.,
RA Wehrens X.H.T.;
RT "Mutation E169K in junctophilin-2 causes atrial fibrillation due to
RT impaired RyR2 stabilization.";
RL J. Am. Coll. Cardiol. 62:2010-2019(2013).
RN [14]
RP VARIANT LYS-85.
RX PubMed=27471098; DOI=10.1111/cge.12825;
RA Sabater-Molina M., Navarro M., Garcia-Molina Saez E., Garrido I.,
RA Pascual-Figal D., Gonzalez Carrillo J., Gimeno Blanes J.R.;
RT "Mutation in JPH2 cause dilated cardiomyopathy.";
RL Clin. Genet. 90:468-469(2016).
RN [15]
RP CLASSIFICATION OF VARIANT SER-505 AS BENIGN IN CARDIOMYOPATHY.
RX PubMed=27532831; DOI=10.1056/nejmsa1507092;
RA Manrai A.K., Funke B.H., Rehm H.L., Olesen M.S., Maron B.A., Szolovits P.,
RA Margulies D.M., Loscalzo J., Kohane I.S.;
RT "Genetic misdiagnoses and the motential for mealth misparities.";
RL N. Engl. J. Med. 375:655-665(2016).
RN [16]
RP VARIANT CMH17 SER-405.
RX PubMed=28393127; DOI=10.1016/j.jacbts.2016.11.004;
RA Quick A.P., Landstrom A.P., Wang Q., Beavers D.L., Reynolds J.O.,
RA Barreto-Torres G., Tran V., Showell J., Philippen L.E., Morris S.A.,
RA Skapura D., Bos J.M., Pedersen S.E., Pautler R.G., Ackerman M.J.,
RA Wehrens X.H.;
RT "Novel junctophilin-2 mutation A405S is associated with basal septal
RT hypertrophy and diastolic dysfunction.";
RL JACC Basic Transl. Sci. 2:56-67(2017).
RN [17]
RP VARIANT CMH17 LYS-161.
RX PubMed=30235249; DOI=10.1371/journal.pone.0203422;
RA Vanninen S.U.M., Leivo K., Seppaelae E.H., Aalto-Setaelae K., Pitkaenen O.,
RA Suursalmi P., Annala A.P., Anttila I., Alastalo T.P., Myllykangas S.,
RA Helioe T.M., Koskenvuo J.W.;
RT "Heterozygous junctophilin-2 (JPH2) p.(Thr161Lys) is a monogenic cause for
RT HCM with heart failure.";
RL PLoS ONE 13:E0203422-E0203422(2018).
RN [18]
RP INVOLVEMENT IN CMD2E, AND VARIANT CMD2E 428-GLN--THR-696 DEL.
RX PubMed=30384889; DOI=10.1016/j.jacc.2018.08.2171;
RA Vasilescu C., Ojala T.H., Brilhante V., Ojanen S., Hinterding H.M.,
RA Palin E., Alastalo T.P., Koskenvuo J., Hiippala A., Jokinen E.,
RA Jahnukainen T., Lohi J., Pihkala J., Tyni T.A., Carroll C.J.,
RA Suomalainen A.;
RT "Genetic basis of severe childhood-onset cardiomyopathies.";
RL J. Am. Coll. Cardiol. 72:2324-2338(2018).
RN [19]
RP INVOLVEMENT IN CMD2E.
RX PubMed=31227780; DOI=10.1038/s41598-019-44987-6;
RA Jones E.G., Mazaheri N., Maroofian R., Zamani M., Seifi T., Sedaghat A.,
RA Shariati G., Jamshidi Y., Allen H.D., Wehrens X.H.T., Galehdari H.,
RA Landstrom A.P.;
RT "Analysis of enriched rare variants in JPH2-encoded junctophilin-2 among
RT Greater Middle Eastern individuals reveals a novel homozygous variant
RT associated with neonatal dilated cardiomyopathy.";
RL Sci. Rep. 9:9038-9038(2019).
CC -!- FUNCTION: [Junctophilin-2]: Membrane-binding protein that provides a
CC structural bridge between the plasma membrane and the sarcoplasmic
CC reticulum and is required for normal excitation-contraction coupling in
CC cardiomyocytes (PubMed:20095964). Provides a structural foundation for
CC functional cross-talk between the cell surface and intracellular Ca(2+)
CC release channels by maintaining the 12-15 nm gap between the sarcolemma
CC and the sarcoplasmic reticulum membranes in the cardiac dyads (By
CC similarity). Necessary for proper intracellular Ca(2+) signaling in
CC cardiac myocytes via its involvement in ryanodine receptor-mediated
CC calcium ion release (By similarity). Contributes to the construction of
CC skeletal muscle triad junctions (By similarity).
CC {ECO:0000250|UniProtKB:Q9ET78, ECO:0000269|PubMed:20095964}.
CC -!- FUNCTION: [Junctophilin-2 N-terminal fragment]: Transcription repressor
CC required to safeguard against the deleterious effects of cardiac
CC stress. Generated following cleavage of the Junctophilin-2 chain by
CC calpain in response to cardiac stress in cardiomyocytes. Following
CC cleavage and release from the membrane, translocates to the nucleus,
CC binds DNA and represses expression of genes implicated in cell growth
CC and differentiation, hypertrophy, inflammation and fibrosis. Modifies
CC the transcription profile and thereby attenuates pathological
CC remodeling in response to cardiac stress. Probably acts by competing
CC with MEF2 transcription factors and TATA-binding proteins.
CC {ECO:0000250|UniProtKB:Q9ET78}.
CC -!- SUBUNIT: Interacts with TRPC3 (PubMed:20095964).
CC {ECO:0000269|PubMed:20095964}.
CC -!- SUBUNIT: [Junctophilin-2 N-terminal fragment]: Interacts with MEF2C (By
CC similarity). {ECO:0000250|UniProtKB:Q9ET78}.
CC -!- SUBCELLULAR LOCATION: [Junctophilin-2]: Cell membrane
CC {ECO:0000250|UniProtKB:Q9ET78}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9ET78}. Sarcoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9ET78}; Single-pass type IV membrane protein
CC {ECO:0000250|UniProtKB:Q9ET78}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9ET78}; Single-pass type IV membrane protein
CC {ECO:0000250|UniProtKB:Q9ET78}. Note=The transmembrane domain is
CC anchored in sarcoplasmic reticulum membrane, while the N-terminal part
CC associates with the plasma membrane. In heart cells, it predominantly
CC associates along Z lines within myocytes. In skeletal muscle, it is
CC specifically localized at the junction of A and I bands.
CC {ECO:0000250|UniProtKB:Q9ET78}.
CC -!- SUBCELLULAR LOCATION: [Junctophilin-2 N-terminal fragment]: Nucleus
CC {ECO:0000269|PubMed:30409805}. Note=Accumulates in the nucleus of
CC stressed hearts. {ECO:0000250|UniProtKB:Q9ET78}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BR39-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BR39-2; Sequence=VSP_002785, VSP_002786;
CC -!- TISSUE SPECIFICITY: Specifically expressed in skeletal muscle and
CC heart. {ECO:0000269|PubMed:10891348}.
CC -!- DOMAIN: The MORN (membrane occupation and recognition nexus) repeats
CC contribute to the plasma membrane binding, by interacting with
CC phospholipids (PubMed:24001019). Has affinity for phosphatidylserine,
CC and phosphorylated phosphatidylinositols including PtdIns3P, PtdIns4P,
CC PtdIns5P, PtdIns(3,5)P2 and PtdIns(3,4,5)P3 (PubMed:24001019).
CC {ECO:0000269|PubMed:24001019}.
CC -!- DOMAIN: [Junctophilin-2 N-terminal fragment]: The bipartite nuclear
CC localization signal (bNLS) and Ala-rich (alanine-rich; ARR) regions are
CC involved in DNA-binding. {ECO:0000250|UniProtKB:Q9ET78}.
CC -!- PTM: Phosphorylation on Ser-165, probably by PKC, affects RYR1-mediated
CC calcium ion release, interaction with TRPC3, and skeletal muscle
CC myotubule development. {ECO:0000269|PubMed:20095964}.
CC -!- PTM: Proteolytically cleaved by calpain in response to cardiac stress.
CC The major cleavage site takes place at the C-terminus and leads to the
CC release of the Junctophilin-2 N-terminal fragment chain (JP2NT).
CC {ECO:0000250|UniProtKB:Q9ET78}.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 17 (CMH17) [MIM:613873]:
CC A hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. {ECO:0000269|PubMed:17509612, ECO:0000269|PubMed:24001019,
CC ECO:0000269|PubMed:28393127, ECO:0000269|PubMed:30235249}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cardiomyopathy, dilated 2E (CMD2E) [MIM:619492]: A form of
CC dilated cardiomyopathy, a disorder characterized by ventricular
CC dilation and impaired systolic function, resulting in congestive heart
CC failure and arrhythmia. Patients are at risk of premature death. CMD2E
CC is an autosomal recessive form with neonatal or early childhood onset
CC and rapid progression to cardiac failure. {ECO:0000269|PubMed:30384889,
CC ECO:0000269|PubMed:31227780}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the junctophilin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL132999; CAB61347.1; -; mRNA.
DR EMBL; AL035447; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL034419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75940.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75943.1; -; Genomic_DNA.
DR CCDS; CCDS13325.1; -. [Q9BR39-1]
DR CCDS; CCDS13326.1; -. [Q9BR39-2]
DR RefSeq; NP_065166.2; NM_020433.4. [Q9BR39-1]
DR RefSeq; NP_787109.2; NM_175913.3. [Q9BR39-2]
DR PDB; 7RXE; X-ray; 2.35 A; A=1-437.
DR PDB; 7RXQ; X-ray; 2.03 A; A=1-437.
DR PDBsum; 7RXE; -.
DR PDBsum; 7RXQ; -.
DR AlphaFoldDB; Q9BR39; -.
DR SMR; Q9BR39; -.
DR BioGRID; 121414; 19.
DR IntAct; Q9BR39; 15.
DR STRING; 9606.ENSP00000362071; -.
DR TCDB; 8.A.110.1.4; the junctophilin (jp) family.
DR iPTMnet; Q9BR39; -.
DR PhosphoSitePlus; Q9BR39; -.
DR SwissPalm; Q9BR39; -.
DR BioMuta; JPH2; -.
DR DMDM; 27805486; -.
DR EPD; Q9BR39; -.
DR jPOST; Q9BR39; -.
DR MassIVE; Q9BR39; -.
DR MaxQB; Q9BR39; -.
DR PaxDb; Q9BR39; -.
DR PeptideAtlas; Q9BR39; -.
DR PRIDE; Q9BR39; -.
DR ProteomicsDB; 78740; -. [Q9BR39-1]
DR ProteomicsDB; 78741; -. [Q9BR39-2]
DR Antibodypedia; 27340; 339 antibodies from 32 providers.
DR DNASU; 57158; -.
DR Ensembl; ENST00000342272.3; ENSP00000344590.3; ENSG00000149596.7. [Q9BR39-2]
DR Ensembl; ENST00000372980.4; ENSP00000362071.3; ENSG00000149596.7. [Q9BR39-1]
DR GeneID; 57158; -.
DR KEGG; hsa:57158; -.
DR MANE-Select; ENST00000372980.4; ENSP00000362071.3; NM_020433.5; NP_065166.2.
DR UCSC; uc002xli.2; human. [Q9BR39-1]
DR CTD; 57158; -.
DR DisGeNET; 57158; -.
DR GeneCards; JPH2; -.
DR HGNC; HGNC:14202; JPH2.
DR HPA; ENSG00000149596; Tissue enhanced (heart muscle, skeletal muscle).
DR MalaCards; JPH2; -.
DR MIM; 605267; gene.
DR MIM; 613873; phenotype.
DR MIM; 619492; phenotype.
DR neXtProt; NX_Q9BR39; -.
DR OpenTargets; ENSG00000149596; -.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA29999; -.
DR VEuPathDB; HostDB:ENSG00000149596; -.
DR eggNOG; KOG0231; Eukaryota.
DR GeneTree; ENSGT00940000159411; -.
DR HOGENOM; CLU_008078_1_0_1; -.
DR InParanoid; Q9BR39; -.
DR OMA; AWNGEPS; -.
DR PhylomeDB; Q9BR39; -.
DR TreeFam; TF317210; -.
DR PathwayCommons; Q9BR39; -.
DR SignaLink; Q9BR39; -.
DR BioGRID-ORCS; 57158; 8 hits in 1070 CRISPR screens.
DR ChiTaRS; JPH2; human.
DR GeneWiki; JPH2; -.
DR GenomeRNAi; 57158; -.
DR Pharos; Q9BR39; Tbio.
DR PRO; PR:Q9BR39; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9BR39; protein.
DR Bgee; ENSG00000149596; Expressed in left ventricle myocardium and 117 other tissues.
DR Genevisible; Q9BR39; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030314; C:junctional membrane complex; IBA:GO_Central.
DR GO; GO:0014701; C:junctional sarcoplasmic reticulum membrane; TAS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0055074; P:calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0060402; P:calcium ion transport into cytosol; TAS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0060316; P:positive regulation of ryanodine-sensitive calcium-release channel activity; IDA:UniProtKB.
DR GO; GO:0055024; P:regulation of cardiac muscle tissue development; IEA:Ensembl.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; TAS:BHF-UCL.
DR InterPro; IPR017191; Junctophilin.
DR InterPro; IPR003409; MORN.
DR PANTHER; PTHR23085; PTHR23085; 1.
DR Pfam; PF02493; MORN; 8.
DR PIRSF; PIRSF037387; Junctophilin; 1.
DR SMART; SM00698; MORN; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cardiomyopathy; Cell membrane;
KW Developmental protein; Disease variant; DNA-binding; Endoplasmic reticulum;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Sarcoplasmic reticulum; Transcription; Transcription regulation;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..696
FT /note="Junctophilin-2"
FT /id="PRO_0000159847"
FT CHAIN 1..572
FT /note="Junctophilin-2 N-terminal fragment"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT /id="PRO_0000446375"
FT TOPO_DOM 1..674
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 675..695
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT REPEAT 14..36
FT /note="MORN 1"
FT /evidence="ECO:0000255"
FT REPEAT 38..59
FT /note="MORN 2"
FT /evidence="ECO:0000255"
FT REPEAT 60..79
FT /note="MORN 3"
FT /evidence="ECO:0000255"
FT REPEAT 82..104
FT /note="MORN 4"
FT /evidence="ECO:0000255"
FT REPEAT 106..128
FT /note="MORN 5"
FT /evidence="ECO:0000255"
FT REPEAT 129..151
FT /note="MORN 6"
FT /evidence="ECO:0000255"
FT REPEAT 291..313
FT /note="MORN 7"
FT /evidence="ECO:0000255"
FT REPEAT 314..336
FT /note="MORN 8"
FT /evidence="ECO:0000255"
FT REGION 164..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 250..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 448..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 351..365
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOTIF 495..499
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT COMPBIAS 164..179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..498
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..604
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 627..652
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 155..156
FT /note="Cleavage; by calpain"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT SITE 204..205
FT /note="Cleavage; by calpain"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT SITE 572..573
FT /note="Cleavage; by calpain"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2PS20"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20095964"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2PS20"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2PS20"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 477
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 490
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 534
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2PS20"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOD_RES 598
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT VAR_SEQ 128..129
FT /note="TY -> MC (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_002785"
FT VAR_SEQ 130..696
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_002786"
FT VARIANT 85
FT /note="E -> K (probable disease-associated variant found in
FT a patient with dilated cardiomyopathy)"
FT /evidence="ECO:0000269|PubMed:27471098"
FT /id="VAR_081287"
FT VARIANT 101
FT /note="S -> R (in CMH17; modifies the secondary structure
FT of the protein which is more flexible but does not undergo
FT structural transition upon binding to membrane lipids;
FT increases the affinity for phosphatidylserine; affects
FT intracellular calcium handling and homeostasis;
FT dbSNP:rs1600482909)"
FT /evidence="ECO:0000269|PubMed:17509612,
FT ECO:0000269|PubMed:24001019"
FT /id="VAR_065471"
FT VARIANT 141
FT /note="Y -> H (in CMH17; results in vacuolization of
FT intracellular structures and cardiomyocyte hypertrophy;
FT affects intracellular calcium handling and homeostasis;
FT dbSNP:rs387906897)"
FT /evidence="ECO:0000269|PubMed:17509612"
FT /id="VAR_065472"
FT VARIANT 161
FT /note="T -> K (in CMH17; dbSNP:rs587782951)"
FT /evidence="ECO:0000269|PubMed:30235249"
FT /id="VAR_081288"
FT VARIANT 165
FT /note="S -> F (in CMH17; results in vacuolization of
FT intracellular structures and cardiomyocyte hypertrophy;
FT affects intracellular calcium handling and homeostasis.
FT Greatly reduced phosphorylation. Increased myotube
FT diameter. Reduced RYR1 activity and EC gain. Disruption of
FT interaction with TRPC3; dbSNP:rs387906898)"
FT /evidence="ECO:0000269|PubMed:17509612,
FT ECO:0000269|PubMed:20095964"
FT /id="VAR_065473"
FT VARIANT 169
FT /note="E -> K (probable disease-associated variant found in
FT a patient with atrial fibrillation)"
FT /evidence="ECO:0000269|PubMed:23973696"
FT /id="VAR_081289"
FT VARIANT 396
FT /note="A -> T (in dbSNP:rs3810510)"
FT /id="VAR_053447"
FT VARIANT 405
FT /note="A -> S (in CMH17; unknown pathological significance;
FT dbSNP:rs557878787)"
FT /evidence="ECO:0000269|PubMed:28393127"
FT /id="VAR_081290"
FT VARIANT 428..696
FT /note="Missing (in CMD2E; unknown pathological
FT significance; dbSNP:rs199896820)"
FT /evidence="ECO:0000269|PubMed:30384889"
FT /id="VAR_086117"
FT VARIANT 436
FT /note="R -> C (in dbSNP:rs1326977511)"
FT /evidence="ECO:0000269|PubMed:17476457"
FT /id="VAR_065474"
FT VARIANT 505
FT /note="G -> S (does not affect protein conformation as
FT shown by circular dichroism; dbSNP:rs140740776)"
FT /evidence="ECO:0000269|PubMed:17476457,
FT ECO:0000303|PubMed:27532831"
FT /id="VAR_065475"
SQ SEQUENCE 696 AA; 74222 MW; 80D62652CE48548B CRC64;
MSGGRFDFDD GGAYCGGWEG GKAHGHGLCT GPKGQGEYSG SWNFGFEVAG VYTWPSGNTF
EGYWSQGKRH GLGIETKGRW LYKGEWTHGF KGRYGIRQSS SSGAKYEGTW NNGLQDGYGT
ETYADGGTYQ GQFTNGMRHG YGVRQSVPYG MAVVVRSPLR TSLSSLRSEH SNGTVAPDSP
ASPASDGPAL PSPAIPRGGF ALSLLANAEA AARAPKGGGL FQRGALLGKL RRAESRTSVG
SQRSRVSFLK SDLSSGASDA ASTASLGEAA EGADEAAPFE ADIDATTTET YMGEWKNDKR
SGFGVSERSS GLRYEGEWLD NLRHGYGCTT LPDGHREEGK YRHNVLVKDT KRRMLQLKSN
KVRQKVEHSV EGAQRAAAIA RQKAEIAASR TSHAKAKAEA AEQAALAANQ ESNIARTLAR
ELAPDFYQPG PEYQKRRLLQ EILENSESLL EPPDRGAGAA GLPQPPRESP QLHERETPRP
EGGSPSPAGT PPQPKRPRPG VSKDGLLSPG AWNGEPSGEG SRSVTPSEGA GRRSPARPAT
ERMAIEALQA PPAPSREPEV ALYQGYHSYA VRTTPPEPPP FEDQPEPEVS GSESAPSSPA
TAPLQAPTLR GPEPARETPA KLEPKPIIPK AEPRAKARKT EARGLTKAGA KKKARKEAAL
AAEAEVEVEE VPNTILICMV ILLNIGLAIL FVHLLT
