JPH2_RAT
ID JPH2_RAT Reviewed; 692 AA.
AC Q2PS20;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 101.
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 {ECO:0000312|RGD:1305196};
GN Synonyms=Jp2 {ECO:0000250|UniProtKB:Q9ET78};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:ABC02402.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:ABC02402.1};
RC TISSUE=Heart {ECO:0000312|EMBL:ABC02402.1};
RA Bai Z., Geng X., Bi Q., Wang S.;
RT "The cloning of rat junctophilin-2 coding sequence.";
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162; SER-440; SER-442;
RP SER-462; SER-479; THR-483; SER-527; SER-533; SER-593 AND SER-604, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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; DQ304564; ABC02402.1; -; mRNA.
DR RefSeq; NP_001033063.1; NM_001037974.1.
DR RefSeq; XP_006235588.1; XM_006235526.3.
DR AlphaFoldDB; Q2PS20; -.
DR SMR; Q2PS20; -.
DR BioGRID; 255327; 1.
DR IntAct; Q2PS20; 2.
DR STRING; 10116.ENSRNOP00000010938; -.
DR iPTMnet; Q2PS20; -.
DR PhosphoSitePlus; Q2PS20; -.
DR PaxDb; Q2PS20; -.
DR PRIDE; Q2PS20; -.
DR Ensembl; ENSRNOT00000010939; ENSRNOP00000010938; ENSRNOG00000008170.
DR GeneID; 296345; -.
DR KEGG; rno:296345; -.
DR UCSC; RGD:1305196; rat.
DR CTD; 57158; -.
DR RGD; 1305196; Jph2.
DR eggNOG; KOG0231; Eukaryota.
DR GeneTree; ENSGT00940000159411; -.
DR HOGENOM; CLU_008078_1_0_1; -.
DR InParanoid; Q2PS20; -.
DR OMA; AWNGEPS; -.
DR OrthoDB; 904294at2759; -.
DR PhylomeDB; Q2PS20; -.
DR TreeFam; TF317210; -.
DR PRO; PR:Q2PS20; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000008170; Expressed in quadriceps femoris and 14 other tissues.
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; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISO:RGD.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030018; C:Z disc; ISO:RGD.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISS:UniProtKB.
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:0055074; P:calcium ion homeostasis; ISO:RGD.
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:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:0060316; P:positive regulation of ryanodine-sensitive calcium-release channel activity; ISO:RGD.
DR GO; GO:0055024; P:regulation of cardiac muscle tissue development; ISO:RGD.
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 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..692
FT /note="Junctophilin-2"
FT /id="PRO_0000259403"
FT CHAIN 1..565
FT /note="Junctophilin-2 N-terminal fragment"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT /id="PRO_0000446378"
FT TOPO_DOM 1..670
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 671..691
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 285..307
FT /note="MORN 7"
FT /evidence="ECO:0000255"
FT REPEAT 308..330
FT /note="MORN 8"
FT /evidence="ECO:0000255"
FT REGION 164..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 246..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 439..661
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 345..359
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOTIF 488..492
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT COMPBIAS 439..468
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..491
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 625..658
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 201..202
FT /note="Cleavage; by calpain"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT SITE 565..566
FT /note="Cleavage; by calpain"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BR39"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 470
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOD_RES 479
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 483
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 589
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 604
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 609
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ET78"
SQ SEQUENCE 692 AA; 74259 MW; B24055782462322F CRC64;
MSGGRFDFDD GGAYCGGWEG GKAHGHGLCT GPKGQGEYSG SWNFGFEVAG VYTWPSGNTF
EGYWSQGKRH GLGIETKGRW LYKGEWTHGF KGRYGIRQST NSGAKYEGTW NNGLQDGYGT
ETYADGGTYQ GQFTNGMRHG YGVRQSVPYG MAVVVRSPLR TSLSSLRSEH SNGTVAPDSP
AADGPTLPLP PVPRGGFALS LLATAEAARP PGLFTRGALL GRLRRSESRT SLGSQRSRLS
FLKSELSSGA SDAASTGSLA EGAEGPDDAA APFDADIDAT TTETYMGEWK NDKRSGFGVS
ERSSGLRYEG EWLDNLRHGY GRTTLPDGHR EEGKYRHNVL VKGTKRRVLP LKSNKVRQKV
EHGVEGAQRA AAIARQKAEI AASRTSHAKA KAEAAEQAAL AANQESNIAR TLAKELAPDF
YQPGPEYQKR RLLQEILENS ESLLEPRERG PGTGLPERPR ESPQLHERET PQPEGGPPSP
AGTPPQPKRP RPGSSKDGLL SPGAWNGEPG GEGSRPATPS DGAGRRSPAR PASEHMAIEA
LQPPPAPSRE PEVALYRGYH SYAVRTGPPE PPPLEDEPEP EPEVPRSDSE PPSPVSATVQ
EEESPAPRSR VPAKPATLEP KPIVPKAEPK AKARKTEARG LSKAGAKKKG RKEVAQEAEA
EVEVEEVPNT VLICMVILLN IGLAILFVHL LT
