TRDN_HUMAN
ID TRDN_HUMAN Reviewed; 729 AA.
AC Q13061; A5D6W5; F5H2W7; Q6NSB8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 4.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Triadin;
GN Name=TRDN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-201 AND SER-438.
RC TISSUE=Skeletal muscle;
RX PubMed=7588753; DOI=10.1111/j.1432-1033.1995.258_1.x;
RA Taske N.L., Eyre H.J., O'Brien R.O., Sutherland G.R., Denborough M.A.,
RA Foster P.S.;
RT "Molecular cloning of the cDNA encoding human skeletal muscle triadin and
RT its localisation to chromosome 6q22-6q23.";
RL Eur. J. Biochem. 233:258-265(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANTS
RP SER-128 AND VAL-201.
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH CASQ2.
RX PubMed=15485681; DOI=10.1016/j.cardiores.2004.09.009;
RA Houle T.D., Ram M.L., Cala S.E.;
RT "Calsequestrin mutant D307H exhibits depressed binding to its protein
RT targets and a depressed response to calcium.";
RL Cardiovasc. Res. 64:227-233(2004).
RN [5]
RP SUBCELLULAR LOCATION, VARIANT CPVT5 ARG-59, CHARACTERIZATION OF VARIANT
RP CPVT5 ARG-59, AND FUNCTION.
RX PubMed=22422768; DOI=10.1093/hmg/dds104;
RA Roux-Buisson N., Cacheux M., Fourest-Lieuvin A., Fauconnier J., Brocard J.,
RA Denjoy I., Durand P., Guicheney P., Kyndt F., Leenhardt A., Le Marec H.,
RA Lucet V., Mabo P., Probst V., Monnier N., Ray P.F., Santoni E.,
RA Tremeaux P., Lacampagne A., Faure J., Lunardi J., Marty I.;
RT "Absence of triadin, a protein of the calcium release complex, is
RT responsible for cardiac arrhythmia with sudden death in human.";
RL Hum. Mol. Genet. 21:2759-2767(2012).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH RYR1 AND CASQ1.
RX PubMed=24325401; DOI=10.1042/bj20130719;
RA Rossi D., Bencini C., Maritati M., Benini F., Lorenzini S., Pierantozzi E.,
RA Scarcella A.M., Paolini C., Protasi F., Sorrentino V.;
RT "Distinct regions of triadin are required for targeting and retention at
RT the junctional domain of the sarcoplasmic reticulum.";
RL Biochem. J. 458:407-417(2014).
CC -!- FUNCTION: Contributes to the regulation of lumenal Ca2+ release via the
CC sarcoplasmic reticulum calcium release channels RYR1 and RYR2, a key
CC step in triggering skeletal and heart muscle contraction. Required for
CC normal organization of the triad junction, where T-tubules and the
CC sarcoplasmic reticulum terminal cisternae are in close contact (By
CC similarity). Required for normal skeletal muscle strength. Plays a role
CC in excitation-contraction coupling in the heart and in regulating the
CC rate of heart beats. {ECO:0000250|UniProtKB:E9Q9K5,
CC ECO:0000269|PubMed:22422768}.
CC -!- SUBUNIT: Homooligomer of variable subunit number; disulfide-linked (By
CC similarity). Interacts with CASQ1 and RYR1 in skeletal muscle.
CC Interacts with CASQ2. {ECO:0000250|UniProtKB:Q28820,
CC ECO:0000269|PubMed:15485681, ECO:0000269|PubMed:24325401}.
CC -!- INTERACTION:
CC Q13061-2; Q8WWG9: KCNE4; NbExp=3; IntAct=EBI-17257686, EBI-11750916;
CC Q13061-2; P23284: PPIB; NbExp=3; IntAct=EBI-17257686, EBI-359252;
CC Q13061-2; Q16849-3: PTPRN; NbExp=3; IntAct=EBI-17257686, EBI-10200782;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22422768}.
CC Sarcoplasmic reticulum membrane {ECO:0000269|PubMed:22422768,
CC ECO:0000269|PubMed:24325401}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:22422768, ECO:0000269|PubMed:24325401}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q13061-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13061-2; Sequence=VSP_045563, VSP_045564, VSP_045565;
CC Name=3;
CC IsoId=Q13061-3; Sequence=VSP_045561, VSP_045562;
CC -!- PTM: Phosphorylated by CaMK2. {ECO:0000250|UniProtKB:Q28820}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:E9Q9K5}.
CC -!- DISEASE: Ventricular tachycardia, catecholaminergic polymorphic, 5,
CC with or without muscle weakness (CPVT5) [MIM:615441]: An arrhythmogenic
CC disorder characterized by stress-induced, bidirectional ventricular
CC tachycardia that may degenerate into cardiac arrest and cause sudden
CC death. Patients present with recurrent syncope, or sudden death after
CC physical activity or emotional stress. Some patients have muscle
CC weakness. CPVT5 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:22422768}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; U18985; AAA75315.1; -; mRNA.
DR EMBL; AL133257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357352; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445259; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL603902; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL603911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC070290; AAH70290.1; -; mRNA.
DR EMBL; BC139910; AAI39911.1; -; mRNA.
DR CCDS; CCDS55053.1; -. [Q13061-1]
DR CCDS; CCDS59034.1; -. [Q13061-2]
DR CCDS; CCDS59035.1; -. [Q13061-3]
DR PIR; S68191; S68191.
DR RefSeq; NP_001242949.1; NM_001256020.1. [Q13061-2]
DR RefSeq; NP_001242951.1; NM_001256022.1. [Q13061-3]
DR RefSeq; NP_006064.2; NM_006073.3. [Q13061-1]
DR AlphaFoldDB; Q13061; -.
DR BioGRID; 115627; 59.
DR IntAct; Q13061; 38.
DR STRING; 9606.ENSP00000439281; -.
DR TCDB; 8.A.28.1.3; the ankyrin (ankyrin) family.
DR GlyGen; Q13061; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q13061; -.
DR PhosphoSitePlus; Q13061; -.
DR BioMuta; TRDN; -.
DR EPD; Q13061; -.
DR MassIVE; Q13061; -.
DR PaxDb; Q13061; -.
DR PeptideAtlas; Q13061; -.
DR PRIDE; Q13061; -.
DR ProteomicsDB; 26096; -.
DR ProteomicsDB; 59126; -. [Q13061-1]
DR Antibodypedia; 51878; 47 antibodies from 12 providers.
DR DNASU; 10345; -.
DR Ensembl; ENST00000334268.9; ENSP00000333984.5; ENSG00000186439.14. [Q13061-1]
DR Ensembl; ENST00000542443.5; ENSP00000437684.1; ENSG00000186439.14. [Q13061-3]
DR Ensembl; ENST00000628709.2; ENSP00000486095.1; ENSG00000186439.14. [Q13061-2]
DR GeneID; 10345; -.
DR KEGG; hsa:10345; -.
DR MANE-Select; ENST00000334268.9; ENSP00000333984.5; NM_006073.4; NP_006064.2.
DR UCSC; uc010keo.3; human. [Q13061-1]
DR CTD; 10345; -.
DR DisGeNET; 10345; -.
DR GeneCards; TRDN; -.
DR GeneReviews; TRDN; -.
DR HGNC; HGNC:12261; TRDN.
DR HPA; ENSG00000186439; Tissue enhanced (heart muscle, skeletal muscle, tongue).
DR MalaCards; TRDN; -.
DR MIM; 603283; gene.
DR MIM; 615441; phenotype.
DR neXtProt; NX_Q13061; -.
DR OpenTargets; ENSG00000186439; -.
DR Orphanet; 3286; Catecholaminergic polymorphic ventricular tachycardia.
DR Orphanet; 101016; Romano-Ward syndrome.
DR PharmGKB; PA36941; -.
DR VEuPathDB; HostDB:ENSG00000186439; -.
DR eggNOG; ENOG502S0X4; Eukaryota.
DR GeneTree; ENSGT00510000049207; -.
DR HOGENOM; CLU_104022_2_0_1; -.
DR InParanoid; Q13061; -.
DR OMA; EKADMKH; -.
DR OrthoDB; 1200049at2759; -.
DR TreeFam; TF350396; -.
DR PathwayCommons; Q13061; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR SignaLink; Q13061; -.
DR BioGRID-ORCS; 10345; 11 hits in 1039 CRISPR screens.
DR ChiTaRS; TRDN; human.
DR GeneWiki; Triadin; -.
DR GenomeRNAi; 10345; -.
DR Pharos; Q13061; Tbio.
DR PRO; PR:Q13061; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q13061; protein.
DR Bgee; ENSG00000186439; Expressed in skeletal muscle tissue of rectus abdominis and 121 other tissues.
DR ExpressionAtlas; Q13061; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0030314; C:junctional membrane complex; ISS:BHF-UCL.
DR GO; GO:0014701; C:junctional sarcoplasmic reticulum membrane; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; TAS:BHF-UCL.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; TAS:BHF-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IEA:InterPro.
DR GO; GO:0044325; F:transmembrane transporter binding; ISS:BHF-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:BHF-UCL.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; ISS:BHF-UCL.
DR GO; GO:0090158; P:endoplasmic reticulum membrane organization; ISS:BHF-UCL.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0060047; P:heart contraction; IMP:BHF-UCL.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; TAS:BHF-UCL.
DR GO; GO:1901846; P:positive regulation of cell communication by electrical coupling involved in cardiac conduction; ISS:BHF-UCL.
DR GO; GO:0060316; P:positive regulation of ryanodine-sensitive calcium-release channel activity; ISS:BHF-UCL.
DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; ISS:BHF-UCL.
DR GO; GO:0010649; P:regulation of cell communication by electrical coupling; TAS:BHF-UCL.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; TAS:BHF-UCL.
DR GO; GO:0010880; P:regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR InterPro; IPR007943; Asp-B-hydro/Triadin_dom.
DR InterPro; IPR010798; Triadin.
DR PANTHER; PTHR14106; PTHR14106; 3.
DR Pfam; PF05279; Asp-B-Hydro_N; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Membrane; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Transmembrane; Transmembrane helix.
FT CHAIN 1..729
FT /note="Triadin"
FT /id="PRO_0000065626"
FT TOPO_DOM 1..47
FT /note="Cytoplasmic"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 69..729
FT /note="Lumenal"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 117..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..682
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 705..729
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 117..131
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 132..265
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..300
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..357
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..566
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 573..678
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 713..729
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 647
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 270
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q28820"
FT DISULFID 691
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q28820"
FT VAR_SEQ 162..167
FT /note="VTHKEK -> EVGHSS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045561"
FT VAR_SEQ 168..729
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045562"
FT VAR_SEQ 265..284
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045563"
FT VAR_SEQ 311..317
FT /note="EKEGEKK -> GKYFFFS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045564"
FT VAR_SEQ 318..729
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045565"
FT VARIANT 59
FT /note="T -> R (in CPVT5; results in intracellular retention
FT and degradation of the mutant protein; dbSNP:rs397515459)"
FT /evidence="ECO:0000269|PubMed:22422768"
FT /id="VAR_067350"
FT VARIANT 128
FT /note="T -> S (in dbSNP:rs9490809)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_057008"
FT VARIANT 201
FT /note="L -> V (in dbSNP:rs6902416)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7588753"
FT /id="VAR_065263"
FT VARIANT 339
FT /note="S -> N (in dbSNP:rs35766971)"
FT /id="VAR_057009"
FT VARIANT 396
FT /note="K -> N (in dbSNP:rs6901953)"
FT /id="VAR_065264"
FT VARIANT 404
FT /note="V -> G (in dbSNP:rs28494009)"
FT /id="VAR_057010"
FT VARIANT 419
FT /note="D -> E (in dbSNP:rs17737379)"
FT /id="VAR_057011"
FT VARIANT 438
FT /note="I -> S (in dbSNP:rs2873479)"
FT /evidence="ECO:0000269|PubMed:7588753"
FT /id="VAR_065265"
FT VARIANT 470
FT /note="L -> M (in dbSNP:rs6569336)"
FT /id="VAR_057012"
FT VARIANT 540
FT /note="I -> M (in dbSNP:rs7771303)"
FT /id="VAR_057013"
SQ SEQUENCE 729 AA; 81595 MW; 0D9653203D52FA05 CRC64;
MTEITAEGNA STTTTVIDSK NGSVPKSPGK VLKRTVTEDI VTTFSSPAAW LLVIALIITW
SAVAIVMFDL VDYKNFSASS IAKIGSDPLK LVRDAMEETT DWIYGFFSLL SDIISSEDEE
DDDGDEDTDK GEIDEPPLRK KEIHKDKTEK QEKPERKIQT KVTHKEKEKG KEKVREKEKP
EKKATHKEKI EKKEKPETKT LAKEQKKAKT AEKSEEKTKK EVKGGKQEKV KQTAAKVKEV
QKTPSKPKEK EDKEKAAVSK HEQKDQYAFC RYMIDIFVHG DLKPGQSPAI PPPLPTEQAS
RPTPASPALE EKEGEKKKAE KKVTSETKKK EKEDIKKKSE KETAIDVEKK EPGKASETKQ
GTVKIAAQAA AKKDEKKEDS KKTKKPAEVE QPKGKKQEKK EKHVEPAKSP KKEHSVPSDK
QVKAKTERAK EEIGAVSIKK AVPGKKEEKT TKTVEQEIRK EKSGKTSSIL KDKEPIKGKE
EKVPASLKEK EPETKKDEKM SKAGKEVKPK PPQLQGKKEE KPEPQIKKEA KPAISEKVQI
HKQDIVKPEK TVSHGKPEEK VLKQVKAVTI EKTAKPKPTK KAEHREREPP SIKTDKPKPT
PKGTSEVTES GKKKTEISEK ESKEKADMKH LREEKVSTRK ESLQLHNVTK AEKPARVSKD
VEDVPASKKA KEGTEDVSPT KQKSPISFFQ CVYLDGYNGY GFQFPFTPAD RPGESSGQAN
SPGQKQQGQ
