CaMPDB :: Substrate

SB0146 : Junctophilin-2

* Basic Information

Organism	Mus musculus (house mouse)
Protein Names	junctophilin-2 [Mus musculus]; junctophilin-2; junctophilin type 2
Gene Names	Jph2; junctophilin 2
Gene Locus	2; chromosome 2
GO Function	Not available

Entrez Protein	Entrez Nucleotide	Entrez Gene	UniProt	OMIM	HGNC	HPRD	KEGG
NP_067541	NM_021566	59091	N/A	N/A	N/A	N/A	N/A

* Information From OMIM

Not Available.

* Structure Information

1. Primary Information

Length: 696 aa

Average Mass: 74.691 kDa

Monoisotopic Mass: 74.647 kDa

2. Domain Information

Annotated Domains: Not Available.

Computationally Assigned Domains (Pfam+HMMER):

domain name	begin	end	score	e-value
MORN repeat 1.	14	34	1.0	6.2
MORN repeat 2.	38	59	1.0	0.8
MORN repeat 3.	60	76	1.0	1.7
MORN repeat 4.	82	101	1.0	2.1
MORN repeat 5.	106	128	1.0	3.2
MORN repeat 6.	129	146	1.0	1.5
--- cleavage 201 ---
MORN repeat 7.	285	306	1.0	0.2
MORN repeat 8.	308	330	1.0	0.2
Protein of unknown function (DUF3359) 1.	366	414	39.0	10.1

3. Sequence Information

Fasta Sequence: SB0146.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Not Available.

* Cleavage Information

1 [sites] cleaved by Calpain in vivo

Source Reference: [PubMed ID: 24958777] Wu CY, Chen B, Jiang YP, Jia Z, Martin DW, Liu S, Entcheva E, Song LS, Lin RZ, Calpain-dependent cleavage of junctophilin-2 and T-tubule remodeling in a mouse model of reversible heart failure. J Am Heart Assoc. 2014 Jun 23;3(3):e000527. doi: 10.1161/JAHA.113.000527.

Cleavage sites (±10aa)

[Site 1] VPRGGFALTL²⁰¹-LATAEAARPQ

Leu²⁰¹ Leu

P10	P9	P8	P7	P6	P5	P4	P3	P2	P1

Val¹⁹²	Pro¹⁹³	Arg¹⁹⁴	Gly¹⁹⁵	Gly¹⁹⁶	Phe¹⁹⁷	Ala¹⁹⁸	Leu¹⁹⁹	Thr²⁰⁰	Leu²⁰¹

P1'	P2'	P3'	P4'	P5'	P6'	P7'	P8'	P9'	P10'
Leu²⁰²	Ala²⁰³	Thr²⁰⁴	Ala²⁰⁵	Glu²⁰⁶	Ala²⁰⁷	Ala²⁰⁸	Arg²⁰⁹	Pro²¹⁰	Gln²¹¹

Sequence conservation (by blast) Sequence conservation (by blast)

Reference peptide (cleaved bond±30 residues)
NGTVAPDSPAADGPMLPSPPVPRGGFALTLLATAEAARPQGLFTRGTLLGRLRRSESRTS

Summary

#	organism	max score	hits	top seq
1	Mus musculus	118.00	1	junctophilin 2
2	Rattus norvegicus	106.00	1	junctophilin 2
3	Oryctolagus cuniculus	85.90	1	junctophilin type 2
4	Homo sapiens	65.50	4	junctophilin 2 isoform 1
5	Tetraodon nigroviridis	37.40	4	unnamed protein product
6	Danio rerio	37.00	2	hypothetical protein LOC556485

Top-ranked sequences

organism	matching
Mus musculus	Query 172 NGTVAPDSPAADGPMLPSPPVPRGGFALTL#LATAEAARPQGLFTRGTLLGRLRRSESRTS 231 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 172 NGTVAPDSPAADGPMLPSPPVPRGGFALTL#LATAEAARPQGLFTRGTLLGRLRRSESRTS 231
Rattus norvegicus	Query 172 NGTVAPDSPAADGPMLPSPPVPRGGFALTL#LATAEAARPQGLFTRGTLLGRLRRSESRTS 231 \|\|\|\|\|\|\|\|\|\|\|\|\|\| \|\| \|\|\|\|\|\|\|\|\|\|+\|#\|\|\|\|\|\|\|\|\| \|\|\|\|\|\| \|\|\|\|\|\|\|\|\|\|\|\|\| Sbjct 172 NGTVAPDSPAADGPTLPLPPVPRGGFALSL#LATAEAARPPGLFTRGALLGRLRRSESRTS 231
Oryctolagus cuniculus	Query 172 NGTVAPDSPA---ADGPMLPSPPVPRGGFALTL#LATAEAAR-PQ--GLFTRGTLLGRLRR 225 \|\|\|\|\|\|\|\|\|\| \|\|\|\| \|\|\|\| +\|\|\|\|\|\|\|+\|#\|\| \|\|\|\|\| \|+ \|\|\| \|\| \|\|\|+\|\|\| Sbjct 172 NGTVAPDSPASPAADGPALPSPAIPRGGFALSL#LANAEAARAPKGGGLFPRGALLGKLRR 231 Query 226 SESRTS 231 +\|\|\|\|\| Sbjct 232 AESRTS 237
Homo sapiens	Query 172 NGTVAPDSPAA---DGPMLPSPPVPRGGFALTL#LATAEAA----RPQGLFTRGTLLGRLR 224 \|\|\|\|\|\|\|\|\|\|+ \|\|\| \|\|\|\| +\|\|\|\|\|\|\|+\|#\|\| \|\|\|\| + \|\|\| \|\| \|\|\|+\|\| Sbjct 172 NGTVAPDSPASPASDGPALPSPAIPRGGFALSL#LANAEAAARAPKGGGLFQRGALLGKLR 231 Query 225 RSESRTS 231 \|+\|\|\|\|\| Sbjct 232 RAESRTS 238
Tetraodon nigroviridis	Query 189 SPPVPRGGFALTL#LATAEAA--RPQGLFTRGTLLG---RLRRSESRTS 231 +\| \|\|\|\| \| # + \| + +\|\|\| \|\|+\| \| +\|\|+\|+\|\|\|\| Sbjct 185 TPTGSRGGFVLNF#HSDTEVVTGKKKGLFRRGSLFGSLRQLRKSDSRTS 232
Danio rerio	Query 172 NGTVAPDSPAADGPMLPSPPVPRGGFALTL#LATAE--AARPQGLFTRGTLLGRLRR 225 \|\|+\| \| \| \|\| \|\|\|\| \| # + +\| + + +\|\|\| \|\|+\| \| \|++ Sbjct 172 NGSVLHDH------MSDSPAGTRGGFVLNF#HSDSEVVSGKKKGLFRRGSLFGSLKQ 221

* References

[PubMed ID: 23973696] Beavers DL, Wang W, Ather S, Voigt N, Garbino A, Dixit SS, Landstrom AP, Li N, Wang Q, Olivotto I, Dobrev D, Ackerman MJ, Wehrens XH, Mutation E169K in junctophilin-2 causes atrial fibrillation due to impaired RyR2 stabilization. J Am Coll Cardiol. 2013 Nov 19;62(21):2010-9. doi: 10.1016/j.jacc.2013.06.052.

» More (9) « Hide Below

[PubMed ID: 23148318] ... Murphy RM, Dutka TL, Horvath D, Bell JR, Delbridge LM, Lamb GD, Ca2+-dependent proteolysis of junctophilin-1 and junctophilin-2 in skeletal and cardiac muscle. J Physiol. 2013 Feb 1;591(Pt 3):719-29. doi: 10.1113/jphysiol.2012.243279. Epub

[PubMed ID: 22511307] ... Liang X, Mei Y, Huang X, Shen G, Zhu D, Yu Y, Wang J, Lou Y, Junctophilin 2 knockdown interfere with mitochondrium status in ESC-CMs and cardiogenesis of ES cells. J Cell Biochem. 2012 Sep;113(9):2884-94. doi: 10.1002/jcb.24164.

[PubMed ID: 22389502] ... Woo JS, Cho CH, Lee KJ, Kim do H, Ma J, Lee EH, Hypertrophy in skeletal myotubes induced by junctophilin-2 mutant, Y141H, involves an increase in store-operated Ca2+ entry via Orai1. J Biol Chem. 2012 Apr 27;287(18):14336-48. doi: 10.1074/jbc.M111.304808. Epub

[PubMed ID: 22020936] ... Golini L, Chouabe C, Berthier C, Cusimano V, Fornaro M, Bonvallet R, Formoso L, Giacomello E, Jacquemond V, Sorrentino V, Junctophilin 1 and 2 proteins interact with the L-type Ca2+ channel dihydropyridine receptors (DHPRs) in skeletal muscle. J Biol Chem. 2011 Dec 23;286(51):43717-25. doi: 10.1074/jbc.M111.292755. Epub

[PubMed ID: 17509612] ... Landstrom AP, Weisleder N, Batalden KB, Bos JM, Tester DJ, Ommen SR, Wehrens XH, Claycomb WC, Ko JK, Hwang M, Pan Z, Ma J, Ackerman MJ, Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans. J Mol Cell Cardiol. 2007 Jun;42(6):1026-35. Epub 2007 Apr 18.

[PubMed ID: 15541368] ... Minamisawa S, Oshikawa J, Takeshima H, Hoshijima M, Wang Y, Chien KR, Ishikawa Y, Matsuoka R, Junctophilin type 2 is associated with caveolin-3 and is down-regulated in the hypertrophic and dilated cardiomyopathies. Biochem Biophys Res Commun. 2004 Dec 17;325(3):852-6.

[PubMed ID: 12135771] ... Komazaki S, Ito K, Takeshima H, Nakamura H, Deficiency of triad formation in developing skeletal muscle cells lacking junctophilin type 1. FEBS Lett. 2002 Jul 31;524(1-3):225-9.

[PubMed ID: 11535622] ... Ito K, Komazaki S, Sasamoto K, Yoshida M, Nishi M, Kitamura K, Takeshima H, Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1. J Cell Biol. 2001 Sep 3;154(5):1059-67.

[PubMed ID: 10949023] ... Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K, Junctophilins: a novel family of junctional membrane complex proteins. Mol Cell. 2000 Jul;6(1):11-22.