TTN Gene (Protein Coding)

Titin

GC02M178525
GIFtS:
48
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 t... See more...

Aliases for TTN Gene

Aliases for TTN Gene

  • Titin 2 3 4 5
  • Rhabdomyosarcoma Antigen MU-RMS-40.14 3 4
  • Connectin 3 4
  • Cardiomyopathy, Dilated 1G (Autosomal Dominant) 2
  • EC 2.7.11.1 4
  • LGMDR10 3
  • LGMD2J 3
  • CMPD4 3
  • EOMFC 3
  • HMERF 3
  • MYLK5 3
  • SALMY 3
  • CMD1G 3
  • CMH9 3
  • TMD 3

External Ids for TTN Gene

Previous HGNC Symbols for TTN Gene

  • CMD1G

Previous GeneCards Identifiers for TTN Gene

  • GC02M177454
  • GC02M178061
  • GC02M179355
  • GC02M179593
  • GC02M179216
  • GC02M179098
  • GC02M171261

Summaries for TTN Gene

Entrez Gene Summary for TTN Gene

  • 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]

GeneCards Summary for TTN Gene

TTN (Titin) is a Protein Coding gene. Diseases associated with TTN include Myopathy, Myofibrillar, 9, With Early Respiratory Failure and Tibial Muscular Dystrophy, Tardive. Among its related pathways are Dilated cardiomyopathy (DCM) and Cardiac conduction. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and identical protein binding.

UniProtKB/Swiss-Prot Summary for TTN Gene

  • Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation during mitosis. Might link the lamina network to chromatin or nuclear actin, or both during interphase.

Gene Wiki entry for TTN Gene

Additional gene information for TTN Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TTN Gene

Genomics for TTN Gene

GeneHancer (GH) Regulatory Elements for TTN Gene

Promoters and enhancers for TTN Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH02J178801 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE dbSUPER 750.3 +25.3 25301 5.8 CTCF PKNOX1 ZNF10 TTN RPS6P2 FKBP7 LOC105373766 LOC101927055
GH02J178828 Enhancer 1 FANTOM5 Ensembl ENCODE dbSUPER 750.6 +1.5 1501 4.2 HLF SOX13 NR2F2 KDM1A ENSG00000287149 LOC105373766 TTN RPS6P2 FKBP7 CHROMR RF00066-109 RNU7-104P lnc-TTN-1 CCDC141
GH02J178794 Promoter/Enhancer 0.6 EPDnew dbSUPER 750.3 +35.8 35815 0.1 NRF1 TTN LOC101927055 LOC105373766
GH02J178862 Enhancer 0.7 ENCODE dbSUPER 11.5 -33.7 -33749 3.4 LCORL NFIB IKZF1 IKZF2 POLR2A NFIC ZFHX2 GABPA JUND NFIA RNU7-104P TTN CCDC141 PRKRA HSALNG0020728 lnc-TTN-1 ENSG00000287149 LOC105373766
GH02J178858 Enhancer 0.7 Ensembl ENCODE dbSUPER 11.5 -29.6 -29596 3.2 RCOR1 JUND TTN RNU7-104P PRKRA CCDC141 OSBPL6 HSALNG0020728 lnc-TTN-1 LOC105373766 ENSG00000287149
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TTN on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TTN gene promoter:
  • HNF-1
  • HNF-1A
  • IRF-1
  • STAT1
  • STAT1alpha
  • STAT1beta

Genomic Locations for TTN Gene

Genomic Locations for TTN Gene
chr2:178,525,989-178,830,802
(GRCh38/hg38)
Size:
304,814 bases
Orientation:
Minus strand
chr2:179,390,716-179,695,529
(GRCh37/hg19)
Size:
304,814 bases
Orientation:
Minus strand

Genomic View for TTN Gene

Genes around TTN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TTN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TTN Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for TTN Gene

Proteins for TTN Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for TTN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WZ42-TITIN_HUMAN
    Recommended name:
    Titin
    Protein Accession:
    Q8WZ42
    Secondary Accessions:
    • A6NKB1
    • E7EQE6
    • E7ET18
    • K7ENY1
    • Q10465
    • Q10466
    • Q15598
    • Q2XUS3
    • Q32Q60
    • Q4U1Z6
    • Q4ZG20
    • Q6NSG0
    • Q6PDB1
    • Q6PJP0
    • Q7KYM2
    • Q7KYN4
    • Q7KYN5
    • Q7LDM3
    • Q7Z2X3
    • Q8TCG8
    • Q8WZ51
    • Q8WZ52
    • Q8WZ53
    • Q8WZB3
    • Q92761
    • Q92762
    • Q9UD97
    • Q9UP84
    • Q9Y6L9

    Protein attributes for TTN Gene

    Size:
    34350 amino acids
    Molecular mass:
    3816030 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with MYOM1, MYOM2, tropomyosin and myosin. Interacts with actin, primarily via the PEVK domains and with MYPN (By similarity). Interacts with FHL2, NEB, CRYAB, LMNA/lamin-A and LMNB/lamin-B. Interacts with TCAP/telethonin and/or ANK1 isoform Mu17/ank1.5, via the first two N-terminal immunoglobulin domains. Interacts with TRIM63 and TRIM55, through several domains including immunoglobulin domains 141 and 142. Interacts with ANKRD1, ANKRD2 and ANKRD23, via the region between immunoglobulin domains 77 and 78 and interacts with CAPN3, via immunoglobulin domain 79. Interacts with NBR1 through the protein kinase domain. Interacts with CALM/calmodulin. Isoform 6 interacts with OBSCN isoform 3. Interacts with CMYA5.
    Miscellaneous:
    • In some isoforms, after the PEVK repeat region there is a long PEVK duplicated region. On account of this region, it has been very difficult to sequence the whole protein. The length of this region (ranging from 183 to 2174 residues), may be a key elastic element of titin.
    SequenceCaution:
    • Sequence=AAH58824.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 553.; Evidence={ECO:0000305}; Sequence=AAH70170.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 627.; Evidence={ECO:0000305}; Sequence=CAA62188.1; Type=Frameshift; Positions=17036, 17043; Evidence={ECO:0000305}; Sequence=CAD12455.1; Type=Frameshift; Positions=17036, 17043; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TTN Gene

    Alternative splice isoforms for TTN Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TTN Gene

Protein Expression for TTN Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for TTN Gene

Other Protein References for TTN Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TTN Gene

Domains & Families for TTN Gene

Gene Families for TTN Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for TTN Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TTN Gene

GenScript: Design optimal peptide antigens:
  • Titin (B1A7R7_HUMAN)
  • Titin (C0JYZ2_HUMAN)
  • Titin, isoform CRA_b (D3DPF9_HUMAN)
  • Titin, isoform CRA_a (D3DPG0_HUMAN)
  • Titin (Q71S18_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8WZ42

UniProtKB/Swiss-Prot:

TITIN_HUMAN :
  • ZIS1 and ZIS5 regions contain multiple SPXR consensus sites for ERK- and CDK-like protein kinases as well as multiple SP motifs. ZIS1 could adopt a closed conformation which would block the TCAP-binding site.
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
Domain:
  • ZIS1 and ZIS5 regions contain multiple SPXR consensus sites for ERK- and CDK-like protein kinases as well as multiple SP motifs. ZIS1 could adopt a closed conformation which would block the TCAP-binding site.
  • The PEVK region may serve as an entropic spring of a chain of structural folds and may also be an interaction site to other myofilament proteins to form interfilament connectivity in the sarcomere.
Family:
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
genes like me logo Genes that share domains with TTN: view

Function for TTN Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for TTN Gene

UniProtKB/Swiss-Prot Function:
Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation during mitosis. Might link the lamina network to chromatin or nuclear actin, or both during interphase.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Full activation of the protein kinase domain requires both phosphorylation of Tyr-32341, preventing it from blocking the catalytic aspartate residue, and binding of Ca/CALM to the C-terminal regulatory tail of the molecule which results in ATP binding to the kinase.
GENATLAS Biochemistry:
titin,giant sarcomeric protein,extending from the M line to the Z line of striated muscle sarcomere,essential in the temporal and spatial control of the assembly of the highly ordered sarcomeres of striated muscles,responsible for the elasticity of relaxed striated muscle

Enzyme Numbers (IUBMB) for TTN Gene

Phenotypes From GWAS Catalog for TTN Gene

Gene Ontology (GO) - Molecular Function for TTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 9642272
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IEA,IDA 9804419
GO:0004713 protein tyrosine kinase activity IDA 18765796
GO:0005509 calcium ion binding IDA 7607248
genes like me logo Genes that share ontologies with TTN: view
genes like me logo Genes that share phenotypes with TTN: view

Human Phenotype Ontology for TTN Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TTN Gene

MGI Knock Outs for TTN:
  • Ttn Ttn<tm1.1Hgra>
  • Ttn Ttn<tm1Mgot>
  • Ttn Ttn<tm1.1Her>
  • Ttn Ttn<tm2.1Mgot>
  • Ttn Ttn<tm3.1Mgot>

Animal Model Products

CRISPR Products

miRNA for TTN Gene

miRTarBase miRNAs that target TTN

Clone Products

  • Addgene plasmids for TTN

No data available for Transcription Factor Targets and HOMER Transcription for TTN Gene

Localization for TTN Gene

Subcellular locations from UniProtKB/Swiss-Prot for TTN Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TTN gene
Compartment Confidence
cytoskeleton 5
extracellular 4
nucleus 4
cytosol 4
endoplasmic reticulum 2
plasma membrane 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for TTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000794 condensed nuclear chromosome IDA 9548712
GO:0005576 extracellular region TAS --
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with TTN: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TTN Gene

Pathways & Interactions for TTN Gene

genes like me logo Genes that share pathways with TTN: view

SIGNOR curated interactions for TTN Gene

Other effect:

Gene Ontology (GO) - Biological Process for TTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002576 platelet degranulation TAS --
GO:0003300 cardiac muscle hypertrophy IMP 11846417
GO:0006468 protein phosphorylation IEA --
GO:0006936 muscle contraction TAS 11911777
GO:0006941 striated muscle contraction TAS 7569978
genes like me logo Genes that share ontologies with TTN: view

Drugs & Compounds for TTN Gene

Products:

  1. Drug

(17) Drugs for TTN Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Flavin Mononucleotide Approved, Investigational Pharma Target 10
Magnesium Approved, Experimental, Investigational Pharma 0

(9) Additional Compounds for TTN Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TTN: view

Transcripts for TTN Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for TTN Gene

(7) REFSEQ mRNAs :
(38) Additional mRNA sequences :
(481) Selected AceView cDNA sequences:
(17) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for TTN

Alternative Splicing Database (ASD) splice patterns (SP) for TTN Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22a · 22b ^ 23a ·
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ExUns: 116 ^ 117 ^ 118 ^ 119 ^ 120 ^ 121 ^ 122 ^ 123 ^ 124 ^ 125 ^ 126 ^ 127 ^ 128 ^ 129 ^ 130 ^ 131a · 131b ^ 132a · 132b ^ 133 ^ 134 ^ 135 ^ 136 ^ 137 ^ 138 ^ 139 ^
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ExUns: 140 ^ 141a · 141b ^ 142 ^ 143 ^ 144 ^ 145 ^ 146 ^ 147 ^ 148 ^ 149 ^ 150a · 150b ^ 151a · 151b · 151c ^ 152a · 152b ^ 153a · 153b ^ 154 ^ 155 ^ 156 ^ 157 ^ 158 ^ 159 ^
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Relevant External Links for TTN Gene

GeneLoc Exon Structure for
TTN
ECgene alternative splicing isoforms for
TTN

Expression for TTN Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TTN Gene

mRNA expression in normal human tissues for TTN Gene
mRNA expression by BioGPS for TTN GenemRNA expression by GTEx for TTN Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TTN Gene

This gene is overexpressed in Muscle - Skeletal (x36.8), Heart - Left Ventricle (x9.5), and Heart - Atrial Appendage (x4.9).

Protein differential expression in normal tissues from HIPED for TTN Gene

This gene is overexpressed in Heart (52.8) and Fetal heart (12.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TTN Gene



NURSA nuclear receptor signaling pathways regulating expression of TTN Gene:

TTN

SOURCE GeneReport for Unigene cluster for TTN Gene:

Hs.134602

mRNA Expression by UniProt/SwissProt for TTN Gene:

Q8WZ42-TITIN_HUMAN
Tissue specificity: Isoforms 3, 7 and 8 are expressed in cardiac muscle. Isoform 4 is expressed in vertebrate skeletal muscle. Isoform 6 is expressed in skeletal muscle (at protein level).

Evidence on tissue expression from TISSUES for TTN Gene

  • Heart(5)
  • Muscle(5)
  • Liver(3.2)
  • Lung(3)
  • Nervous system(2.6)
  • Thyroid gland(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TTN Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • jaw
  • larynx
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • pharynx
  • skull
  • tongue
  • vocal cord
Thorax:
  • chest wall
  • diaphragm
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • sternum
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • finger
  • foot
  • forearm
  • hand
  • hip
  • knee
  • lower limb
  • shin
  • shoulder
  • thigh
  • toe
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with TTN: view

No data available for Protein tissue co-expression partners for TTN Gene

Orthologs for TTN Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TTN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia TTN 33
  • 100 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia TTN 33 32
  • 90.09 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia TTN 33 32
  • 88.12 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Ttn 17 33 32
  • 86.69 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia TTN 33
  • 86 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Ttn 32
  • 79.79 (n)
chicken
(Gallus gallus)
 Aves TTN 32
  • 73.65 (n)
zebrafish
(Danio rerio)
 Actinopterygii ttna 32
  • 65.76 (n)
zgc:153952 33
  • 30 (a)
 ManyToMany
-- 32
rainbow trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.8272 32