TTN titin [Homo sapiens (human)] - Gene

Summary

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Official Symbol: TTNprovided by HGNC
Official Full Name: titinprovided by HGNC
Primary source: HGNC:12403
See related: Ensembl:ENSG00000155657; HPRD:01787; MIM:188840; Vega:OTTHUMG00000154448
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TMD; CMH9; CMD1G; CMPD4; EOMFC; HMERF; MYLK5; LGMD2J
Summary: This gene encodes a large abundant protein of striated muscle. The product of this gene is divided into two regions, a N-terminal I-band and a C-terminal A-band. The I-band, which is the elastic part of the molecule, contains two regions of tandem immunoglobulin domains on either side of a PEVK region that is rich in proline, glutamate, valine and lysine. The A-band, which is thought to act as a protein-ruler, contains a mixture of immunoglobulin and fibronectin repeats, and possesses kinase activity. An N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the sarcomere, respectively, so that a single titin molecule spans half the length of a sarcomere. Titin also contains binding sites for muscle associated proteins so it serves as an adhesion template for the assembly of contractile machinery in muscle cells. It has also been identified as a structural protein for chromosomes. Alternative splicing of this gene results in multiple transcript variants. Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Mutations in this gene are associated with familial hypertrophic cardiomyopathy 9, and autoantibodies to titin are produced in patients with the autoimmune disease scleroderma. [provided by RefSeq, Feb 2012]

Genomic context

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Location :: 2q31

Sequence :: Chromosome: 2; NC_000002.11 (179390716..179672150, complement)

See TTN in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

[review] Signal pathways of titin isoforms are described in a major human cardiovascular disease.
Title: Titin is a major human disease gene.
Human end-stage failing hearts revealed higher CaMKII expression/activity & phosphorylation at PEVK/titin N2B-unique sequence sites than donor hearts. Deranged CaMKII-dependent titin phosphorylation contributes to altered diastolic stress.
Title: Crucial role for Ca2(+)/calmodulin-dependent protein kinase-II in regulating diastolic stress of normal and failing hearts via titin phosphorylation.
titin-12670 fragment is present in both individuals with undiagnosed and diagnosed CVD. The statistically significant increase in level of the marker in the AMI group is indicative that this neoepitope biomarker may be a useful serological marker in AMI
Title: Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker.
Different pressure-temperature behavior of the structured and unstructured regions of titin.
Title: Different pressure-temperature behavior of the structured and unstructured regions of titin.
A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics.
Title: A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics.
Spontaneous dimerization of titin protein Z1Z2 domains induces strong nanomechanical anchoring.
Title: Spontaneous dimerization of titin protein Z1Z2 domains induces strong nanomechanical anchoring.
This study identified three different Swedish Hereditary myopathy with early respiratory failure families with a new mutation in the A-band titin.
Title: Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin.
This study presented that patients with hereditary myopathy with early respiratory failure linke with Titin mutation.
Title: Titin mutation segregates with hereditary myopathy with early respiratory failure.
In addition to titin (TTN), we identified a set of 30 genes with conserved splicing regulation between humans and rats
Title: RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing.
in response to the increased compliance of the extracellular matrix in muscle of tenascin-X deficient Ehlers-Danlos Syndrome patients, a marked intracellular stiffening occurs of the giant protein titin
Title: Titin-based stiffening of muscle fibers in Ehlers-Danlos Syndrome.

Submit: New GeneRIF Correction See all (89)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion). Arrhythmias and/or conduction system disease. Thromboembolic disease (from left ventricular mural thrombus) including stroke .

Diagnosis Testing

Genetic forms of DCM must be distinguished from other identifiable causes. After exclusion of all identifiable non-genetic causes, DCM is traditionally referred to as idiopathic dilated cardiomyopathy. When two or more closely related family members meet a formal diagnostic standard for idiopathic dilated cardiomyopathy, the diagnosis of familial dilated cardiomyopathy (FDC) is made. The genetic forms of DCM are diagnosed by family history and molecular genetic testing.

Genetic Counseling

Genetic DCM can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Maternal mitochondrial inheritance has also been reported; however, mitochondrial forms of DCM, although highly variable in presentation (including mild adult-onset forms), are usually syndromic and thus outside the scope of this review. Genetic counseling and risk assessment depend on determination of the specific DCM subtype in an individual.

References

PMID: 20301486

Distal myopathy Markesbery-Griggs type

MIM: 600334

Genetic Testing Registry

Summary from GeneReviews: Udd Distal Myopathy

Disease Characteristics

Udd distal myopathy is characterized by weakness of ankle dorsiflexion and inability to walk on the heels after age 35 years. Disease progression is slow and muscle weakness remains confined to the anterior tibial muscles. The long toe extensors become clinically involved after ten to 20 years, leading to foot drop and clumsiness when walking. In the mildest form, Udd distal myopathy can remain unnoticed even in the elderly.

Diagnosis Testing

EMG shows profound myopathic changes in the anterior tibial muscle. CT or MRI confirm fatty degeneration of the anterior tibial muscles and also show large patchy lesions in other clinically unaffected muscles. TTN, encoding the protein titin (TTN), is the only gene in which mutations are known to cause Udd distal myopathy. All affected Finnish families have a founder mutation termed FINmaj, a unique 11-bp deletion/insertion mutation that changes four amino-acid residues in exon Mex6. Seven other mutations have been identified in exons Mex5 and Mex6 in families from different European populations.

Genetic Counseling

Udd distal myopathy is inherited in an autosomal dominant manner. Most individuals diagnosed with Udd distal myopathy have an affected parent. Each child of an individual with Udd distal myopathy has a 50% chance of inheriting the mutation. Prenatal testing for pregnancies at increased risk is possible if the disease-causing mutation has been identified in the family.

Summary from GeneReviews: Salih Myopathy

Disease Characteristics

Salih myopathy is characterized by muscle weakness (manifest during the neonatal period or in early infancy) and delayed motor development; children acquire independent walking between age 20 months and four years. In the first decade of life, global motor performances are stable or tend to improve. Moderate joint and neck contractures and spinal rigidity may start in the first decade but become more obvious in the second decade. Scoliosis develops after age 11 years. Cardiac dysfunction starts between ages five and 16 years, progresses rapidly, and leads to death between ages eight and 20 years, usually from heart rhythm disturbances.

Diagnosis Testing

Diagnosis is based on clinical findings, marginally to moderately increased serum creatine kinase levels, characteristic skeletal muscle histology, and biallelic small frameshift deletions in the exons Mex1 and Mex3 of TTN, the only gene in which mutations are known to cause Salih myopathy.

Genetic Counseling

Salih myopathy is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes (i.e., carriers of one mutant allele) and are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations in the family have been identified.

References

PMID: 22238790

Primary dilated cardiomyopathy

Genetic Testing Registry

Summary from GeneReviews: Dilated Cardiomyopathy Overview

Disease Characteristics

Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion). Arrhythmias and/or conduction system disease. Thromboembolic disease (from left ventricular mural thrombus) including stroke .

Diagnosis Testing

Genetic forms of DCM must be distinguished from other identifiable causes. After exclusion of all identifiable non-genetic causes, DCM is traditionally referred to as idiopathic dilated cardiomyopathy. When two or more closely related family members meet a formal diagnostic standard for idiopathic dilated cardiomyopathy, the diagnosis of familial dilated cardiomyopathy (FDC) is made. The genetic forms of DCM are diagnosed by family history and molecular genetic testing.

Genetic Counseling

Genetic DCM can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Maternal mitochondrial inheritance has also been reported; however, mitochondrial forms of DCM, although highly variable in presentation (including mild adult-onset forms), are usually syndromic and thus outside the scope of this review. Genetic counseling and risk assessment depend on determination of the specific DCM subtype in an individual.

References

PMID: 20301486

NHGRI GWAS Catalog

A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project.

Genetic variants associated with breast size also influence breast cancer risk.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_003310.2		FHL2	BIND	PubMed	An unspecified isoform of FHL2 (DRAL) interacts with TTN (titin).
Q8WZ42	P68133	ACTA1	HPRD	PubMed
Q8WZ42	P12814	ACTN1	HPRD	PubMed
Q8WZ42	P35609	ACTN2	HPRD	PubMed
Q8WZ42	P16157	ANK1	HPRD	PubMed
Q8WZ42	Q15327	ANKRD1	HPRD	PubMed
Q8WZ42	Q9GZV1	ANKRD2	HPRD	PubMed
Q8WZ42	Q86SG2	ANKRD23	HPRD	PubMed
Q8WZ42	Calmodulin 1	CALM1	HPRD	PubMed
Q8WZ42	P20807	CAPN3	HPRD	PubMed
Q8WZ42	P02511	CRYAB	HPRD	PubMed
Q8WZ42	Q14192	FHL2	HPRD	PubMed
Q8WZ42	P21333	FLNA	HPRD	PubMed
Q8WZ42	Q00872	MYBPC1	HPRD	PubMed
Q8WZ42	Q14896	MYBPC3	HPRD	PubMed
Q8WZ42	P35579	MYH9	HPRD	PubMed
Q8WZ42	P52179	MYOM1	HPRD	PubMed
Q8WZ42	P54296	MYOM2	HPRD	PubMed
Q8WZ42	Q14596	NBR1	HPRD	PubMed
Q8WZ42	P20929	NEB	HPRD	PubMed
Q8WZ42	Q5VST9	OBSCN	HPRD	PubMed
Q8WZ42	O15273	TCAP	HPRD	PubMed
Q8WZ42	Q969Q1	TRIM63	HPRD	PubMed
BioGRID:113124	BioGRID:106602	ACTN1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:113124	BioGRID:106715	ALB	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:106783	ANK1	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:113124	BioGRID:117975	ANKRD1	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:113124	BioGRID:117669	ANKRD2	BioGRID	PubMed	Reconstituted Complex
BioGRID:113124	BioGRID:128333	ANKRD23	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:113124	BioGRID:106901	ARRB1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:120845	ASF1B	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:107275	CAPN3	BioGRID	PubMed	Two-hybrid
BioGRID:113124	BioGRID:107452	CDK2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:116183	COPS5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:116238	CPSF6	BioGRID	PubMed	Co-fractionation
BioGRID:113124	BioGRID:107800	CRYAB	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113124	BioGRID:114031	CUL2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:114030	CUL3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:114028	CUL4B	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:238025	Cep135	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:199230	Dlg4	BioGRID	PubMed	Protein-peptide
BioGRID:113124	BioGRID:108565	FHL2	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
	NP_848649.2	KY	BIND	PubMed	KY interacts with an unspecified isoform of TTN. This interaction was modeled on a demonstrated interaction between mouse KY and human TTN.
BioGRID:113124	BioGRID:110692	MYBPC3	BioGRID	PubMed	Far Western
BioGRID:113124	BioGRID:124185	MYPN	BioGRID	PubMed	Two-hybrid
BioGRID:113124	BioGRID:110253	NBR1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Two-hybrid
BioGRID:113124	BioGRID:110815	NEDD8	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:123847	OBSCN	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:113124	BioGRID:116502	PUF60	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:112550	SP1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:116655	SPEN	BioGRID	PubMed	Co-fractionation
	NP_003891.1	SQSTM1	BIND	PubMed	Titin interacts with p62. This interaction was modelled on a demonstrated interaction between human Titin and rat p62.
BioGRID:113124	BioGRID:114397	SQSTM1	BioGRID	PubMed	Biochemical Activity
BioGRID:113124	BioGRID:112325	SRSF2	BioGRID	PubMed	Co-fractionation
	NP_003664.1	TCAP	BIND	PubMed	Titin interacts with telethonin. This interaction was modelled on a demonstrated interaction between human Titin and telethonin from unspecified species.
BioGRID:113124	BioGRID:114127	TCAP	BioGRID	PubMed	Biochemical Activity; Co-purification; Reconstituted Complex; Two-hybrid
BioGRID:113124	BioGRID:124195	TRIM63	BioGRID	PubMed	Co-crystal Structure; Reconstituted Complex; Two-hybrid
BioGRID:113124	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:113124	BioGRID:113253	VAV2	BioGRID	PubMed	Two-hybrid
BioGRID:113124	BioGRID:116168	YWHAQ	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Dilated cardiomyopathy, organism-specific biosystem (from KEGG)
Dilated cardiomyopathy, organism-specific biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
Dilated cardiomyopathy, conserved biosystem (from KEGG)
Dilated cardiomyopathy, conserved biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Hypertrophic cardiomyopathy (HCM), organism-specific biosystem (from KEGG)
Hypertrophic cardiomyopathy (HCM), organism-specific biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
Hypertrophic cardiomyopathy (HCM), conserved biosystem (from KEGG)
Hypertrophic cardiomyopathy (HCM), conserved biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
Muscle contraction, organism-specific biosystem (from REACTOME)
Muscle contraction, organism-specific biosystemIn this module, the processes by which calcium binding triggers actin - myosin interactions and force generation in smooth and striated muscle tissues are annotated.
Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
Platelet degranulation, organism-specific biosystem (from REACTOME)
Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
Striated Muscle Contraction, organism-specific biosystem (from WikiPathways)
Striated Muscle Contraction, organism-specific biosystemMuscle contraction is the process where muscle tissue is activated by a signal from the nervous system. In case of voluntary action the nervous signals are initiated from the brain by so called actio...
Striated Muscle Contraction, organism-specific biosystem (from REACTOME)
Striated Muscle Contraction, organism-specific biosystemStriated muscle contraction is a process whereby force is generated within striated muscle tissue, resulting in a change in muscle geometry, or in short, increased force being exerted on the tendons....

General gene information

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Markers

TTN_3879 (e-PCR)
- UniSTS:462604

D2S385 (e-PCR), detects polymorphism
- UniSTS:14095

D2S324 (e-PCR), detects polymorphism
- UniSTS:16911

SHGC-62013 (e-PCR)
- UniSTS:27408

D2S2648 (e-PCR)
- UniSTS:75793

RH48674 (e-PCR)
- UniSTS:32026

MARC_21540-21541:1033053987:1 (e-PCR)
- UniSTS:268573

RH65366 (e-PCR)
- UniSTS:73247

D2S385 (e-PCR), detects polymorphism
- UniSTS:50480

RH44253 (e-PCR)
- UniSTS:31799

D2S1524E (e-PCR)
- UniSTS:45880

TTN-1 (e-PCR)
- UniSTS:254009

A004O05 (e-PCR)
- UniSTS:81724

RH65766 (e-PCR)
- UniSTS:17479

SHGC-150597 (e-PCR)
- UniSTS:173393

D2S1518E (e-PCR)
- UniSTS:150612

D2S1532E (e-PCR)
- UniSTS:150620

D2S1540E (e-PCR)
- UniSTS:150626

D2S1546E (e-PCR)
- UniSTS:150631

D2S1550E (e-PCR)
- UniSTS:150635

RH98821 (e-PCR)
- UniSTS:85869

D2S1553E (e-PCR)
- UniSTS:150638

D2S1555E (e-PCR)
- UniSTS:150640

D2S1560E (e-PCR)
- UniSTS:150645

D2S1564E (e-PCR)
- UniSTS:150649

D2S1568E (e-PCR)
- UniSTS:150652

D2S1570E (e-PCR)
- UniSTS:150654

D2S1571E (e-PCR)
- UniSTS:150655

D2S1572E (e-PCR)
- UniSTS:150656

D2S1574E (e-PCR)
- UniSTS:150658

D2S1580E (e-PCR)
- UniSTS:150664

RH78892 (e-PCR)
- UniSTS:398

A008T22 (e-PCR)
- UniSTS:24210

D2S1591E (e-PCR)
- UniSTS:150675

D2S1593E (e-PCR)
- UniSTS:150677

RH65621 (e-PCR)
- UniSTS:70042

D2S324 (e-PCR), detects polymorphism
- UniSTS:76702

RH65575 (e-PCR)
- UniSTS:58532

MARC_23497-23498:1027358865:1 (e-PCR)
- UniSTS:268713

D2S1519E (e-PCR)
- UniSTS:22697

G59490 (e-PCR)
- UniSTS:136654

D2S2384 (e-PCR)
- UniSTS:9422

D2S1881 (e-PCR)
- UniSTS:153573

RH91877 (e-PCR)
- UniSTS:89075

D2S364 (e-PCR), detects polymorphism
- UniSTS:5883

Genotypes

See TTN SNP Geneview Report
See TTN SNP Genotype Report
See TTN SNP Variation Viewer Report

Homology

Homologs of the TTN gene: The TTN gene is conserved in Rhesus monkey, dog, cow, mouse, chicken, and zebrafish.
Map Viewer (Mouse)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

FLJ26020, FLJ26409, FLJ32040, FLJ34413, FLJ39564, FLJ43066, DKFZp451N061

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
actin filament binding	IDA Inferred from Direct Assay more info	PubMed
actinin binding	IDA Inferred from Direct Assay more info	PubMed
actinin binding	IPI Inferred from Physical Interaction more info	PubMed
calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
calmodulin binding	IPI Inferred from Physical Interaction more info	PubMed
calmodulin binding	TAS Traceable Author Statement more info	PubMed
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
muscle alpha-actinin binding	IPI Inferred from Physical Interaction more info	PubMed
nucleic acid binding	IEA Inferred from Electronic Annotation more info
protease binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein self-association	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
structural constituent of muscle	IMP Inferred from Mutant Phenotype more info	PubMed
structural constituent of muscle	TAS Traceable Author Statement more info	PubMed
telethonin binding	IPI Inferred from Physical Interaction more info	PubMed
telethonin binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
adult heart development	IEA Inferred from Electronic Annotation more info
blood coagulation	TAS Traceable Author Statement more info
cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
cardiac muscle fiber development	IMP Inferred from Mutant Phenotype more info	PubMed
cardiac muscle hypertrophy	IMP Inferred from Mutant Phenotype more info	PubMed
cardiac muscle tissue morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
cardiac myofibril assembly	IMP Inferred from Mutant Phenotype more info	PubMed
detection of muscle stretch	TAS Traceable Author Statement more info	PubMed
forward locomotion	IEA Inferred from Electronic Annotation more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
mitotic chromosome condensation	IEP Inferred from Expression Pattern more info	PubMed
muscle contraction	NAS Non-traceable Author Statement more info	PubMed
muscle contraction	TAS Traceable Author Statement more info	PubMed
muscle filament sliding	TAS Traceable Author Statement more info
platelet activation	TAS Traceable Author Statement more info
platelet degranulation	TAS Traceable Author Statement more info
regulation of catalytic activity	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
response to calcium ion	IDA Inferred from Direct Assay more info	PubMed
sarcomere organization	IMP Inferred from Mutant Phenotype more info	PubMed
sarcomerogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
skeletal muscle myosin thick filament assembly	IMP Inferred from Mutant Phenotype more info	PubMed
skeletal muscle thin filament assembly	IMP Inferred from Mutant Phenotype more info	PubMed
striated muscle contraction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info
I band	IDA Inferred from Direct Assay more info	PubMed
M band	IDA Inferred from Direct Assay more info	PubMed
M band	IEA Inferred from Electronic Annotation more info
Z disc	IDA Inferred from Direct Assay more info	PubMed
condensed nuclear chromosome	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
extracellular region	TAS Traceable Author Statement more info
NOT nucleolus	IDA Inferred from Direct Assay more info
nucleus	IDA Inferred from Direct Assay more info
striated muscle thin filament	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: titin

Names: titin; connectin; rhabdomyosarcoma antigen MU-RMS-40.14

NP_001243779.1

EC 2.7.11.1

NP_001254479.1

EC 2.7.11.1

NP_003310.4

EC 2.7.11.1

NP_596869.4

EC 2.7.11.1

NP_596870.2

EC 2.7.11.1

NP_597676.3

EC 2.7.11.1

NP_597681.3

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011618.3 RefSeqGene

Range

28380..309814

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_391

mRNA and Protein(s)

NM_001256850.1 → NP_001243779.1 titin isoform N2BA

Status: REVIEWED

Description

Transcript Variant: This variant (N2BA) encodes another major cardiac isoform (N2BA). It includes the N2A and N2B exons, and also the PEVK region. This variant is supported by annotation on DNA accession AJ277892.2 and by accompanying data in PMIDs 10850961 and 11717165.

Source sequence(s)

AC009948, AC010680, AC023270, FJ695199

UniProtKB/Swiss-Prot

Q8WZ42

Related

ENSP00000465570, OTTHUMP00000268795, ENST00000591111, OTTHUMT00000460310

Conserved Domains (13) summary

cd00063
Location:21499 – 21589
Blast Score: 221

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00096
Location:4682 – 4751
Blast Score: 164

Ig; Immunoglobulin domain

cd04979
Location:13221 – 13299
Blast Score: 113

Ig_Semaphorin_C; Immunoglobulin (Ig)-like domain of semaphorin

cd05747
Location:33485 – 33576
Blast Score: 443

Ig5_Titin_like; M5, fifth immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins

cd05748
Location:20926 – 20999
Blast Score: 275

Ig_Titin_like; Immunoglobulin (Ig)-like domain of titin and similar proteins

pfam09042
Location:644 – 685
Blast Score: 143

Titin_Z; Titin Z

cd00180
Location:32184 – 32430
Blast Score: 420

PKc; Catalytic domain of Protein Kinases

pfam07679
Location:7385 – 7473
Blast Score: 279

I-set; Immunoglobulin I-set domain

smart00220
Location:32178 – 32432
Blast Score: 651

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00409
Location:13 – 97
Blast Score: 183

IG; Immunoglobulin

smart00410
Location:111 – 193
Blast Score: 168

IG_like; Immunoglobulin like

pfam02818
Location:10587 – 10614
Blast Score: 106

PPAK; PPAK motif

cl11960
Location:24569 – 24642
Blast Score: 198

Ig; Immunoglobulin domain
NM_001267550.1 → NP_001254479.1 titin isoform IC

Status: REVIEWED

Description

Transcript Variant: This variant (IC) represents an inferred complete model that includes all possible supported in-frame coding exons. The exons included in this inferred variant are supported by the original sequence analysis and publication (PMID:11717165), available cDNA and EST data, and additional sequence analysis of the repetitive exons. This transcript is the longest which represents a 363-exon model with a predicted protein (isoform IC) length of 35,991 amino acids.

Source sequence(s)

AC009948, AC010680, AC023270, FJ695199

Consensus CDS

CCDS59435.1

UniProtKB/Swiss-Prot

Q8WZ42

Related

ENSP00000467141, OTTHUMP00000263894, ENST00000589042, OTTHUMT00000450680

Conserved Domains (13) summary

cd00063
Location:23140 – 23230
Blast Score: 221

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00096
Location:4999 – 5068
Blast Score: 165

Ig; Immunoglobulin domain

cd04979
Location:14862 – 14940
Blast Score: 113

Ig_Semaphorin_C; Immunoglobulin (Ig)-like domain of semaphorin

cd05747
Location:35126 – 35217
Blast Score: 442

Ig5_Titin_like; M5, fifth immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins

cd05748
Location:22567 – 22640
Blast Score: 275

Ig_Titin_like; Immunoglobulin (Ig)-like domain of titin and similar proteins

pfam09042
Location:644 – 685
Blast Score: 143

Titin_Z; Titin Z

cd00180
Location:33825 – 34071
Blast Score: 420

PKc; Catalytic domain of Protein Kinases

pfam07679
Location:7702 – 7790
Blast Score: 279

I-set; Immunoglobulin I-set domain

smart00220
Location:33819 – 34073
Blast Score: 651

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00409
Location:9704 – 9788
Blast Score: 178

IG; Immunoglobulin

smart00410
Location:13 – 97
Blast Score: 183

IG_like; Immunoglobulin like

pfam02818
Location:10904 – 10931
Blast Score: 106

PPAK; PPAK motif

cl11960
Location:26210 – 26283
Blast Score: 198

Ig; Immunoglobulin domain
NM_003319.4 → NP_003310.4 titin isoform N2-B

Status: REVIEWED

Description

Transcript Variant: This variant (N2-B) encodes the major cardiac muscle isoform (N2-B). It lacks multiple exons in the region encoding PEVK repeats. This results in a shortened PEVK region in isoform N2-B compared to isoform IC. This variant is supported by data in PMIDs 10850961 and 11717165.

Source sequence(s)

AC009948, AC010680, AC023270, FJ695199

Consensus CDS

CCDS54421.1

UniProtKB/Swiss-Prot

Q8WZ42

Related

ENSP00000434586, OTTHUMP00000233810, ENST00000460472, OTTHUMT00000335575

Conserved Domains (12) summary

cd00063
Location:14075 – 14165
Blast Score: 219

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00096
Location:914 – 981
Blast Score: 158

Ig; Immunoglobulin domain

cd04979
Location:5797 – 5875
Blast Score: 113

Ig_Semaphorin_C; Immunoglobulin (Ig)-like domain of semaphorin

cd05747
Location:26061 – 26152
Blast Score: 443

Ig5_Titin_like; M5, fifth immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins

cd05748
Location:13502 – 13575
Blast Score: 274

Ig_Titin_like; Immunoglobulin (Ig)-like domain of titin and similar proteins

pfam09042
Location:598 – 639
Blast Score: 143

Titin_Z; Titin Z

cd00180
Location:24760 – 25006
Blast Score: 421

PKc; Catalytic domain of Protein Kinases

pfam07679
Location:26065 – 26153
Blast Score: 277

I-set; Immunoglobulin I-set domain

smart00220
Location:24754 – 25008
Blast Score: 651

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00409
Location:26643 – 26726
Blast Score: 171

IG; Immunoglobulin

smart00410
Location:13 – 97
Blast Score: 184

IG_like; Immunoglobulin like

cl11960
Location:17145 – 17218
Blast Score: 198

Ig; Immunoglobulin domain
NM_133378.4 → NP_596869.4 titin isoform N2-A

Status: REVIEWED

Description

Transcript Variant: This variant (N2-A) encodes isoform N2-A, which is the predominant titin isoform in skeletal muscle. This variant lacks the N2B region but includes the PEVK region. This variant is supported by data in PMIDs 7569978, 10850961 and 11717165.

Source sequence(s)

AC009948, AC010680, AC023270, FJ695199

Consensus CDS

CCDS54424.1

UniProtKB/Swiss-Prot

Q8WZ42

Related

ENSP00000343764, OTTHUMP00000233809, ENST00000342992, OTTHUMT00000335574

Conserved Domains (14) summary

cd00063
Location:20572 – 20662
Blast Score: 221

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00096
Location:3755 – 3824
Blast Score: 164

Ig; Immunoglobulin domain

cd04979
Location:12294 – 12372
Blast Score: 113

Ig_Semaphorin_C; Immunoglobulin (Ig)-like domain of semaphorin

cd05747
Location:32558 – 32649
Blast Score: 443

Ig5_Titin_like; M5, fifth immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins

cd05748
Location:19999 – 20072
Blast Score: 274

Ig_Titin_like; Immunoglobulin (Ig)-like domain of titin and similar proteins

pfam09042
Location:644 – 685
Blast Score: 143

Titin_Z; Titin Z

cd00180
Location:31257 – 31503
Blast Score: 421

PKc; Catalytic domain of Protein Kinases

pfam07679
Location:6458 – 6546
Blast Score: 279

I-set; Immunoglobulin I-set domain

smart00220
Location:31251 – 31505
Blast Score: 651

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00408
Location:3845 – 3910
Blast Score: 126

IGc2; Immunoglobulin C-2 Type

smart00409
Location:13 – 97
Blast Score: 183

IG; Immunoglobulin

smart00410
Location:8460 – 8544
Blast Score: 178

IG_like; Immunoglobulin like

pfam02818
Location:9660 – 9687
Blast Score: 106

PPAK; PPAK motif

cl11960
Location:23642 – 23715
Blast Score: 198

Ig; Immunoglobulin domain
NM_133379.4 → NP_596870.2 titin isoform novex-3

Status: REVIEWED

Description

Transcript Variant: This variant (novex-3) is the shortest transcript and encodes the shortest isoform (novex-3). Its last exon is nearly 8 kb and is not found in the other variants. The novex-3 isoform, which is found in all striated muscle, lacks the PEVK region and has a C-terminal truncation compared to longer isoforms. This variant is supported by data in PMID:11717165.

Source sequence(s)

AC023270, BX537998

Consensus CDS

CCDS33337.1

UniProtKB/TrEMBL

Q7Z3B7

UniProtKB/Swiss-Prot

Q8WZ42

Related

ENSP00000354117, OTTHUMP00000205904, ENST00000360870, OTTHUMT00000335713

Conserved Domains (7) summary

cd00096
Location:960 – 1027
Blast Score: 161

Ig; Immunoglobulin domain

pfam09042
Location:644 – 685
Blast Score: 135

Titin_Z; Titin Z

pfam07679
Location:6 – 97
Blast Score: 274

I-set; Immunoglobulin I-set domain

smart00408
Location:2369 – 2426
Blast Score: 98

IGc2; Immunoglobulin C-2 Type

smart00409
Location:3352 – 3432
Blast Score: 161

IG; Immunoglobulin

smart00410
Location:13 – 97
Blast Score: 186

IG_like; Immunoglobulin like

cl11960
Location:1722 – 1794
Blast Score: 102

Ig; Immunoglobulin domain
NM_133432.3 → NP_597676.3 titin isoform novex-1

Status: REVIEWED

Description

Transcript Variant: This variant (novex-1) encodes the minor cardiac muscle isoform (novex-1 or novex-1/N2B), which is nearly identical to the major cardiac isoform N2-B but contains a unique stretch of 125 aa in the I-band region. This variant is supported by data in PMID:11717165.

Source sequence(s)

AC009948, AC010680, AC023270, FJ695199

Consensus CDS

CCDS54423.1

UniProtKB/Swiss-Prot

Q8WZ42

Related

ENSP00000352154, ENST00000359218

Conserved Domains (12) summary

cd00063
Location:14200 – 14290
Blast Score: 219

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00096
Location:914 – 981
Blast Score: 158

Ig; Immunoglobulin domain

cd04979
Location:5922 – 6000
Blast Score: 113

Ig_Semaphorin_C; Immunoglobulin (Ig)-like domain of semaphorin

cd05747
Location:26186 – 26277
Blast Score: 443

Ig5_Titin_like; M5, fifth immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins

cd05748
Location:13627 – 13700
Blast Score: 274

Ig_Titin_like; Immunoglobulin (Ig)-like domain of titin and similar proteins

pfam09042
Location:598 – 639
Blast Score: 143

Titin_Z; Titin Z

cd00180
Location:24885 – 25131
Blast Score: 421

PKc; Catalytic domain of Protein Kinases

pfam07679
Location:26190 – 26278
Blast Score: 278

I-set; Immunoglobulin I-set domain

smart00220
Location:24879 – 25133
Blast Score: 651

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00409
Location:13 – 97
Blast Score: 184

IG; Immunoglobulin

smart00410
Location:111 – 193
Blast Score: 168

IG_like; Immunoglobulin like

cl11960
Location:17270 – 17343
Blast Score: 198

Ig; Immunoglobulin domain
NM_133437.3 → NP_597681.3 titin isoform novex-2

Status: REVIEWED

Description

Transcript Variant: This variant (novex-2) encodes the minor cardiac and skeletal muscle isoform (novex-2 or novex-2/N2B), which is nearly identical to the major cardiac isoform N2-B but contains a unique stretch of 192 aa in the I-band region. This variant is supported by data in PMID:11717165.

Source sequence(s)

AC009948, AC010680, AC023270, FJ695199

Consensus CDS

CCDS54422.1

UniProtKB/Swiss-Prot

Q8WZ42

Related

ENSP00000340554, ENST00000342175

Conserved Domains (12) summary

cd00063
Location:14267 – 14357
Blast Score: 220

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00096
Location:914 – 981
Blast Score: 158

Ig; Immunoglobulin domain

cd04979
Location:5989 – 6067
Blast Score: 113

Ig_Semaphorin_C; Immunoglobulin (Ig)-like domain of semaphorin

cd05747
Location:26253 – 26344
Blast Score: 443

Ig5_Titin_like; M5, fifth immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins

cd05748
Location:13694 – 13767
Blast Score: 274

Ig_Titin_like; Immunoglobulin (Ig)-like domain of titin and similar proteins

pfam09042
Location:598 – 639
Blast Score: 143

Titin_Z; Titin Z

cd00180
Location:24952 – 25198
Blast Score: 421

PKc; Catalytic domain of Protein Kinases

pfam07679
Location:26257 – 26345
Blast Score: 277

I-set; Immunoglobulin I-set domain

smart00220
Location:24946 – 25200
Blast Score: 651

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00409
Location:13 – 97
Blast Score: 184

IG; Immunoglobulin

smart00410
Location:26835 – 26918
Blast Score: 171

IG_like; Immunoglobulin like

cl11960
Location:17337 – 17410
Blast Score: 198

Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p10 Primary Assembly

Range

179390716..179672150, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

171261156..171540118, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018913.1 Alternate CHM1_1.0

Range

178779746..179061152, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01062246.1 (47338..81894)	None
genomic	ABBA01062247.1	None
genomic	ABBA01062248.1	None
genomic	AC009948.3 (132579..172628)	None
genomic	AC010680.10	None
genomic	AC023270.7	AAX88844.1
genomic	AF058332.1	AAD22603.1
		AAD22604.1
genomic	AJ277892.2	CAD12455.1
		CAD12456.1
		CAD12457.1
		CAD12458.1
		CAD12459.1
		CAD12460.1
genomic	AMYH01011305.1 (344337..473463)	None
genomic	AMYH01011306.1	None
genomic	AMYH01011307.1	None
genomic	AMYH01011308.1	None
genomic	CH471058.2	EAX11013.1
		EAX11014.1
		EAX11015.1
		EAX11016.1
		EAX11017.1
		EAX11018.1
		EAX11019.1
genomic	FJ525883.1	ACN81321.1
genomic	FJ695199.1	None
genomic	X64699.1	CAA45940.1
genomic	X92412.1	None
mRNA	AF321609.2	AAT09768.1
mRNA	AF525413.1	AAP80791.1
mRNA	AK056602.1	None
mRNA	AK091732.1	None
mRNA	AK092284.1	BAC03850.1
mRNA	AK096883.1	None
mRNA	AK125056.1	None
mRNA	AK129531.1	None
mRNA	AK129919.1	None
mRNA	AL713647.1	CAD28458.1
mRNA	AL832094.1	None
mRNA	AL832351.1	None
mRNA	AL833110.1	None
mRNA	AL833292.1	None
mRNA	BC013396.2	AAH13396.1
mRNA	BC017983.1	None
mRNA	BC026297.1	None
mRNA	BC029400.1	None
mRNA	BC030823.1	None
mRNA	BC058824.1	AAH58824.1
mRNA	BC070170.1	AAH70170.1
mRNA	BC107797.1	AAI07798.1
mRNA	BX537998.1	CAD97954.1
mRNA	DQ248309.1	ABB55264.1
mRNA	EF212153.1	ABN05229.1
mRNA	EF212154.1	ABN05230.1
mRNA	EF212155.1	ABN05231.1
mRNA	EF212156.1	ABN05232.1
mRNA	EU428784.1	ACA00206.1
mRNA	X64697.1	CAA45938.1
mRNA	X64698.1	CAA45939.1
mRNA	X69490.1	CAA49245.1
mRNA	X83270.1	CAA58243.1
mRNA	X90568.1	CAA62188.1
mRNA	X90569.1	CAA62189.1
mRNA	X98114.1	CAA66795.1
mRNA	X98115.1	CAA66796.1