Q9BR39 (JPH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Junctophilin-2
Short name=JP-2

Alternative name(s):
Junctophilin type 2

Gene names

Name:	JPH2
Synonyms:	JP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	696 AA.
Sequence status	Complete.
Protein existence	Evidence 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, possibly by interacting with phospholipids By similarity.
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	Defects in JPH2 are the cause of familial hypertrophic cardiomyopathy type 17 (CMH17) [MIM:613873]. CMH17 is 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. Ref.9
Sequence similarities	Belongs to the junctophilin family. Contains 8 MORN repeats.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Membrane Sarcoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cardiomyopathy Disease mutation
Domain	Repeat Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	calcium ion transport into cytosol Traceable author statement. Source: BHF-UCL positive regulation of ryanodine-sensitive calcium-release channel activity Inferred from direct assay Ref.7. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW junctional sarcoplasmic reticulum membrane Traceable author statement. Source: BHF-UCL plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium-release channel activity Inferred from direct assay Ref.7. Source: UniProtKB protein binding Inferred from physical interaction Ref.7. 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 696	696	Junctophilin-2		PRO_0000159847
Regions
	Topological domain	1 – 674	674	Cytoplasmic Potential
	Transmembrane	675 – 695	21	Helical; Anchor for type IV membrane protein; Potential
	Repeat	14 – 36	23	MORN 1
	Repeat	38 – 59	22	MORN 2
	Repeat	60 – 79	20	MORN 3
	Repeat	82 – 104	23	MORN 4
	Repeat	106 – 128	23	MORN 5
	Repeat	129 – 151	23	MORN 6
	Repeat	291 – 313	23	MORN 7
	Repeat	314 – 336	23	MORN 8
	Compositional bias	3 – 142	140	Gly-rich
	Compositional bias	373 – 408	36	Ala-rich
	Compositional bias	452 – 633	182	Pro-rich
Amino acid modifications
	Modified residue	165	1	Phosphoserine Ref.7
	Modified residue	469	1	Phosphoserine Ref.5
	Modified residue	484	1	Phosphoserine Ref.6
	Modified residue	486	1	Phosphoserine Ref.5 Ref.6
	Modified residue	490	1	Phosphothreonine Ref.5 Ref.6
Natural variations
	Alternative sequence	128 – 129	2	TY → MC in isoform 2.		VSP_002785
	Alternative sequence	130 – 696	567	Missing in isoform 2.		VSP_002786
	Natural variant	101	1	S → R in CMH17; affects intracellular calcium handling and homeostasis. Ref.9		VAR_065471
	Natural variant	141	1	Y → H in CMH17; results in vacuolization of intracellular structures and cardiomyocyte hypertrophy; affects intracellular calcium handling and homeostasis. Ref.9		VAR_065472
	Natural variant	165	1	S → 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 variant	396	1	A → T. Corresponds to variant rs3810510 [ dbSNP | Ensembl ].		VAR_053447
	Natural variant	436	1	R → C. Ref.8		VAR_065474
	Natural variant	505	1	G → 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		VAR_065475

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 17, 2003. Version 2. Checksum: 80D62652CE48548B	FASTA	696	74,222
	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
	Isoform 2 [UniParc]. Checksum: F2008165B64B104B	FASTA	129	13,951
	10 20 30 40 50 60 MSGGRFDFDD GGAYCGGWEG GKAHGHGLCT GPKGQGEYSG SWNFGFEVAG VYTWPSGNTF 70 80 90 100 110 120 EGYWSQGKRH GLGIETKGRW LYKGEWTHGF KGRYGIRQSS SSGAKYEGTW NNGLQDGYGT ETYADGGMC

References

	« Hide 'large scale' referencesShow '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. , 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: 11780052] [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. , 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: 10891348] [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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469; SER-486 AND THR-490, MASS SPECTROMETRY. 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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484; SER-486 AND THR-490, MASS SPECTROMETRY. 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: 20095964] [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: 17476457] [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: 17509612] [Abstract] Cited for: VARIANTS CMH17 ARG-101; HIS-141 AND PHE-165, CHARACTERIZATION OF VARIANTS CMH17 ARG-101; HIS-141 AND PHE-165.
+	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.
IPI	IPI00176532. IPI00218603.
RefSeq	NP_065166.2. NM_020433.4. NP_787109.2. NM_175913.3.
UniGene	Hs.441737.
3D structure databases
ProteinModelPortal	Q9BR39.
SMR	Q9BR39. Positions 30-138, 287-356.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9BR39.
PTM databases
PhosphoSite	Q9BR39.
Polymorphism databases
DMDM	27805486.
Proteomic databases
PRIDE	Q9BR39.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000372980; ENSP00000362071; ENSG00000149596.
GeneID	57158.
KEGG	hsa:57158.
UCSC	uc002xli.1. human. uc002xlj.1. human.
Organism-specific databases
CTD	57158.
GeneCards	GC20M042740.
HGNC	HGNC:14202. JPH2.
MIM	605267. gene. 613873. phenotype.
neXtProt	NX_Q9BR39.
Orphanet	155. Familial isolated hypertrophic cardiomyopathy.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07066.
GeneTree	ENSGT00600000084242.
HOGENOM	HBG715737.
HOVERGEN	HBG031648.
InParanoid	Q9BR39.
OMA	NTILICM.
OrthoDB	EOG4B8JDX.
PhylomeDB	Q9BR39.
Gene expression databases
ArrayExpress	Q9BR39.
Bgee	Q9BR39.
CleanEx	HS_JPH2.
Genevestigator	Q9BR39.
GermOnline	ENSG00000149596. Homo sapiens.
Family and domain databases
InterPro	IPR017191. Junctophilin. IPR003409. MORN. [Graphical view]
Pfam	PF02493. MORN. 8 hits. [Graphical view]
PIRSF	PIRSF037387. Junctophilin. 1 hit.
SMART	SM00698. MORN. 6 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	63151.
SOURCE	Search...

Entry information

Entry name

JPH2_HUMAN

Accession

Primary (citable) accession number: Q9BR39
Secondary accession number(s): E1P5X1 , O95913, Q5JY74, Q9UJN4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 17, 2003
Last sequence update:	January 17, 2003
Last modified:	January 25, 2012
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.