Q8WXH2 (JPH3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Junctophilin-3
Short name=JP-3

Alternative name(s):
Junctophilin type 3
Trinucleotide repeat-containing gene 22 protein

Gene names

Name:	JPH3
Synonyms:	JP3, TNRC22

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	748 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. JPH3 is brain-specific and appears to have an active role in certain neurons involved in motor coordination and memory.
Subcellular location	Cell membrane; Peripheral membrane protein By similarity. Endoplasmic reticulum membrane; Single-pass type IV membrane protein By similarity. Note: Localized predominantly on the plasma membrane. The transmembrane domain is anchored in endoplasmic reticulum membrane, while the N-terminal part associates with the plasma membrane By similarity.
Tissue specificity	Specifically expressed in brain. Ref.1
Domain	The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, possibly by interacting with phospholipids By similarity.
Polymorphism	Isoform 2 length of the poly-Ala region is variable (6 to 27 CTG/CAG triplets) in the normal population and may be expanded (41 to 58 CTG/CAG triplets) in patients suffering from Huntington disease-like type 2.
Involvement in disease	Huntington disease-like 2 (HDL2) [MIM:606438]: Huntington disease (HD) is a neurodegenerative disorder resulting primarily from the loss of medium spiny projection neurons in the striatum, especially in the caudate nucleus, and, to a lesser extent, atrophy of mesencephalic and cortical structures. The typical clinical picture of HD combines familial adult onset chorea and subcortical dementia that usually begin during the fourth decade of life. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6
Sequence similarities	Belongs to the junctophilin family. Contains 8 MORN repeats.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism Triplet repeat expansion
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 PubMed 19095005. Source: BHF-UCL exploration behavior Inferred from electronic annotation. Source: Compara locomotion Inferred from electronic annotation. Source: Compara memory Inferred from electronic annotation. Source: Compara regulation of neuronal synaptic plasticity Inferred from electronic annotation. Source: Compara regulation of ryanodine-sensitive calcium-release channel activity Traceable author statement PubMed 19095005. Source: BHF-UCL
Cellular_component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB junctional membrane complex Inferred from electronic annotation. Source: Compara junctional sarcoplasmic reticulum membrane Traceable author statement PubMed 19095005. Source: BHF-UCL plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium-release channel activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
STK24	Q9Y6E0	1	EBI-1055254,EBI-740175

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q8WXH2-1)

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: Q8WXH2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     128-188: GTYQGQWVGG...PDASPAVAGS → DATAFGAEPG...DSPISTPQCT
     189-748: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 748	748	Junctophilin-3		PRO_0000159850
Regions
	Topological domain	1 – 727	727	Cytoplasmic Potential
	Transmembrane	728 – 748	21	Helical; Anchor for type IV membrane protein; Potential
	Repeat	15 – 37	23	MORN 1
	Repeat	39 – 60	22	MORN 2
	Repeat	61 – 82	22	MORN 3
	Repeat	83 – 105	23	MORN 4
	Repeat	107 – 129	23	MORN 5
	Repeat	130 – 152	23	MORN 6
	Repeat	288 – 310	23	MORN 7
	Repeat	311 – 333	23	MORN 8
	Compositional bias	4 – 143	140	Gly-rich
	Compositional bias	366 – 416	51	Ala-rich
Amino acid modifications
	Modified residue	420	1	Phosphoserine By similarity
	Modified residue	506	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	128 – 188	61	GTYQG…AVAGS → DATAFGAEPGPEARELPAAA AAAAAAAAAAAAVRWFLCRE PWPALQLPACLDSPISTPQC T in isoform 2.		VSP_002787
	Alternative sequence	189 – 748	560	Missing in isoform 2.		VSP_002788
	Natural variant	376	1	I → T. Ref.3 Corresponds to variant rs17857118 [ dbSNP | Ensembl ].		VAR_032494
	Natural variant	472	1	P → T. Ref.3 Corresponds to variant rs17853660 [ dbSNP | Ensembl ].		VAR_032495
	Natural variant	645	1	P → L. Ref.3 Corresponds to variant rs17853661 [ dbSNP | Ensembl ].		VAR_032496
Experimental info
	Sequence conflict	176	1	A → P in BAB11983. Ref.1
	Sequence conflict	186	1	A → D in BAB11983. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 17, 2003. Version 2. Checksum: B88E5065FD7BCD02	FASTA	748	81,469
	10 20 30 40 50 60 MSSGGRFNFD DGGSYCGGWE DGKAHGHGVC TGPKGQGEYT GSWSHGFEVL GVYTWPSGNT 70 80 90 100 110 120 YQGTWAQGKR HGIGLESKGK WVYKGEWTHG FKGRYGVREC AGNGAKYEGT WSNGLQDGYG 130 140 150 160 170 180 TETYSDGGTY QGQWVGGMRQ GYGVRQSVPY GMAAVIRSPL RTSINSLRSE HTNGTALHPD 190 200 210 220 230 240 ASPAVAGSPA VSRGGFVLVA HSDSEILKSK KKGLFRRSLL SGLKLRKSES KSSLASQRSK 250 260 270 280 290 300 QSSFRSEAGM STVSSTASDI HSTISLGEAE AELAVIEDDI DATTTETYVG EWKNDKRSGF 310 320 330 340 350 360 GVSQRSDGLK YEGEWASNRR HGYGCMTFPD GTKEEGKYKQ NILVGGKRKN LIPLRASKIR 370 380 390 400 410 420 EKVDRAVEAA ERAATIAKQK AEIAASRTSH SRAKAEAALT AAQKAQEEAR IARITAKEFS 430 440 450 460 470 480 PSFQHRENGL EYQRPKRQTS CDDIEVLSTG TPLQQESPEL YRKGTTPSDL TPDDSPLQSF 490 500 510 520 530 540 PTSPAATPPP APAARNKVAH FSRQVSVDEE RGGDIQMLLE GRAGDCARSS WGEEQAGGSR 550 560 570 580 590 600 GVRSGALRGG LLVDDFRTRG SGRKQPGNPK PRERRTESPP VFTWTSHHRA SNHSPGGSRL 610 620 630 640 650 660 LELQEEKLSN YRMEMKPLLR METHPQKRRY SKGGACRGLG DDHRPEDRGF GVQRLRSKAQ 670 680 690 700 710 720 NKENFRPASS AEPAVQKLAS LRLGGAEPRL LRWDLTFSPP QKSLPVALES DEENGDELKS 730 740 STGSAPILVV MVILLNIGVA ILFINFFI
	Isoform 2 [UniParc]. Checksum: 1B7895E8FDFB4310	FASTA	188	19,766
	10 20 30 40 50 60 MSSGGRFNFD DGGSYCGGWE DGKAHGHGVC TGPKGQGEYT GSWSHGFEVL GVYTWPSGNT 70 80 90 100 110 120 YQGTWAQGKR HGIGLESKGK WVYKGEWTHG FKGRYGVREC AGNGAKYEGT WSNGLQDGYG 130 140 150 160 170 180 TETYSDGDAT AFGAEPGPEA RELPAAAAAA AAAAAAAAAV RWFLCREPWP ALQLPACLDS PISTPQCT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of human junctophilin subtype genes." Nishi M., Mizushima A., Nakagawara K., Takeshima H. Biochem. Biophys. Res. Commun. 273:920-927(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[2]	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].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS THR-376; THR-472 AND LEU-645. Tissue: Brain.
[4]	"A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2." Holmes S.E., O'Hearn E., Rosenblatt A., Callahan C., Hwang H.S., Ingersoll-Ashworth R.G., Fleisher A., Stevanin G., Brice A., Potter N.T., Ross C.A., Margolis R.L. Nat. Genet. 29:377-378(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-127, IDENTIFICATION (ISOFORM 2), POLYMORPHISM OF POLY-ALA REGION (ISOFORM 2).
[5]	"CAG/CTG repeat expansions at the Huntington's disease-like 2 locus are rare in Huntington's disease patients." Stevanin G., Camuzat A., Holmes S.E., Julien C., Sahloul R., Dode C., Hahn-Barma V., Ross C.A., Margolis R.L., Durr A., Brice A. Neurology 58:965-967(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN HDL2.
[6]	"Huntington's disease-like 2 can present as chorea-acanthocytosis." Walker R.H., Rasmussen A., Rudnicki D., Holmes S.E., Alonso E., Matsuura T., Ashizawa T., Davidoff-Feldman B., Margolis R.L. Neurology 61:1002-1004(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN HDL2.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB042636 mRNA. Translation: BAB11983.1. AB042640 Genomic DNA. Translation: BAB11987.1. CH471114 Genomic DNA. Translation: EAW95386.1. CH471114 Genomic DNA. Translation: EAW95387.1. BC036533 mRNA. Translation: AAH36533.1. AF429315 Genomic DNA. Translation: AAL40941.1. BE042890 mRNA. No translation available.
IPI	IPI00166646. IPI00218117.
RefSeq	NP_065706.2. NM_020655.3.
UniGene	Hs.592068.
3D structure databases
ProteinModelPortal	Q8WXH2.
SMR	Q8WXH2. Positions 7-145, 287-344.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WXH2. 1 interaction.
MINT	MINT-1208946.
STRING	9606.ENSP00000284262.
PTM databases
PhosphoSite	Q8WXH2.
Polymorphism databases
DMDM	27805485.
Proteomic databases
PaxDb	Q8WXH2.
PRIDE	Q8WXH2.
Protocols and materials databases
DNASU	57338.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000284262; ENSP00000284262; ENSG00000154118.
GeneID	57338.
KEGG	hsa:57338.
UCSC	uc002fkd.3. human.
Organism-specific databases
CTD	57338.
GeneCards	GC16P087636.
H-InvDB	HIX0013325.
HGNC	HGNC:14203. JPH3.
HPA	HPA026958.
MIM	605268. gene. 606438. phenotype.
neXtProt	NX_Q8WXH2.
Orphanet	98934. Huntington disease-like 2.
PharmGKB	PA30000.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG324165.
HOGENOM	HOG000264244.
HOVERGEN	HBG031648.
InParanoid	Q8WXH2.
OMA	HPQKRRY.
OrthoDB	EOG4F7NJZ.
PhylomeDB	Q8WXH2.
Gene expression databases
ArrayExpress	Q8WXH2.
Bgee	Q8WXH2.
CleanEx	HS_JPH3.
Genevestigator	Q8WXH2.
GermOnline	ENSG00000154118. 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. 7 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	JPH3. human.
GenomeRNAi	57338.
NextBio	63460.
SOURCE	Search...

Entry information

Entry name

JPH3_HUMAN

Accession

Primary (citable) accession number: Q8WXH2
Secondary accession number(s): D3DUN2 , Q8N471, Q9HDC3, Q9HDC4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 17, 2003
Last sequence update:	January 17, 2003
Last modified:	May 1, 2013
This is version 109 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.