JPH2_RABIT
ID JPH2_RABIT Reviewed; 694 AA.
AC Q9GKY7;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 25-MAY-2022, entry version 94.
DE RecName: Full=Junctophilin-2;
DE Short=JP-2;
DE AltName: Full=Junctophilin type 2;
DE Contains:
DE RecName: Full=Junctophilin-2 N-terminal fragment {ECO:0000250|UniProtKB:Q9ET78};
DE Short=JP2NT {ECO:0000250|UniProtKB:Q9ET78};
GN Name=JPH2; Synonyms=JP2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RA Takeshima H.;
RT "Structure, distribution and gene mapping of junctophilin/mitsugumin72
RT subtypes.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
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. Provides a structural foundation for functional cross-
CC talk between the cell surface and intracellular Ca(2+) release channels
CC by maintaining the 12-15 nm gap between the sarcolemma and the
CC sarcoplasmic reticulum membranes in the cardiac dyads. Necessary for
CC proper intracellular Ca(2+) signaling in cardiac myocytes via its
CC involvement in ryanodine receptor-mediated calcium ion release.
CC Contributes to the construction of skeletal muscle triad junctions.
CC {ECO:0000250|UniProtKB:Q9ET78}.
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 (By similarity). Junctophilin-2 N-
CC terminal fragment: Interacts with MEF2C (By similarity).
CC {ECO:0000250|UniProtKB:Q9BR39, 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:0000250|UniProtKB:Q9ET78}. Note=Accumulates in the nucleus of
CC stressed hearts. {ECO:0000250|UniProtKB:Q9ET78}.
CC -!- DOMAIN: [Junctophilin-2]: The MORN (membrane occupation and recognition
CC nexus) repeats contribute to the plasma membrane binding, by
CC interacting with phospholipids. Has affinity for phosphatidylserine,
CC and phosphorylated phosphatidylinositols including PtdIns3P, PtdIns4P,
CC PtdIns5P, PtdIns(3,5)P2 and PtdIns(3,4,5)P3.
CC {ECO:0000250|UniProtKB:Q9BR39}.
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: 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 -!- 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:0000250|UniProtKB:Q9BR39}.
CC -!- SIMILARITY: Belongs to the junctophilin family. {ECO:0000305}.
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DR EMBL; AB024444; BAB20318.1; -; mRNA.
DR RefSeq; NP_001075467.1; NM_001081998.1.
DR AlphaFoldDB; Q9GKY7; -.
DR SMR; Q9GKY7; -.
DR GeneID; 100008613; -.
DR KEGG; ocu:100008613; -.
DR CTD; 57158; -.
DR eggNOG; KOG0231; Eukaryota.
DR InParanoid; Q9GKY7; -.
DR OrthoDB; 904294at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030314; C:junctional membrane complex; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISS:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISS:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:UniProtKB.
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 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 2: Evidence at transcript level;
KW Cell membrane; Developmental protein; 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..694
FT /note="Junctophilin-2"
FT /id="PRO_0000159849"
FT CHAIN 1..574
FT /note="Junctophilin-2 N-terminal fragment"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT /id="PRO_0000446377"
FT TOPO_DOM 1..672
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 673..693
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 290..312
FT /note="MORN 7"
FT /evidence="ECO:0000255"
FT REPEAT 313..335
FT /note="MORN 8"
FT /evidence="ECO:0000255"
FT REGION 164..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..278
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 448..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 350..364
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOTIF 492..496
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT COMPBIAS 164..178
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 234..261
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 478..495
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 611..625
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 629..661
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 574..575
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:0000250|UniProtKB:Q9BR39"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2PS20"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2PS20"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BR39"
FT MOD_RES 474
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BR39"
FT MOD_RES 487
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9BR39"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2PS20"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2PS20"
FT MOD_RES 596
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOD_RES 600
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
SQ SEQUENCE 694 AA; 73343 MW; B0C3811BC2540016 CRC64;
MSGGRFDFDD GGAYCGGWEG GKAHGHGLCT GPKGQGEYSG SWNFGFEVAG VYTWPSGNTF
EGYWSQGKRH GLGIETKGRW LYKGEWTHGF KGRYGTRQST SSGAKYEGTW NNGLQDGYGT
ETYADGGTYQ GQFTNGMRHG YGVRQSVPYG MAVVVRSPLR TSLSSLRSEH SNGTVAPDSP
ASPAADGPAL PSPAIPRGGF ALSLLANAEA ARAPKGGGLF PRGALLGKLR RAESRTSVGS
QRSRVSFLKS DLSSGASDAA STASLGEGAE GADDAAPFEA DIDATTTETY MGEWKNDKRS
GFGVSERSSG LRYEGEWLDN LRHGYGCTTL PDGHREEGKY RHNVLVKGTK RRVLPLKSNK
VRQKVEHSVE GAQRAAAIAR QKAEIAVSRT SHARAKAEAA EQAALAANQE SNIARSLARE
LAPDFYQPGP EYQKRRLLQE ILEHSESLLE PPDRGAAGLP QPPRESPQLH ERETPRPEGG
PPSPAGTPPQ PKRPRPGASK DGLLGPGAWN GEPSGGSGGE GSRPATPAAA GAGRRSPARP
ASEHMAIEAL QAPPAPSREP EVALYRGYHS YAVRTAPPAP PPFEDDPQPE AADPDSAPAS
PATAPGQAPA LGNPEPAPES PAKLEPKPIV PKAKARKTEA RGLSKTGAKK KPRKEAAQAA
EAEVEVEEVP NTVLICMVIL LNIGLAILFV HLLT
