MGP Database

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MGP003216

UniProt Annotations

Entry Information
Gene Nametitin
Protein Entry
UniProt ID
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=13; Comment=A number of isoforms may be produced, ranging from 27000 to 33000 residues in different striated muscle tissues, the size of the full length protein may be up to 38138 residues.; Name=1; IsoId=Q8WZ42-1; Sequence=Displayed; Note=No experimental confirmation available.; Name=2; IsoId=Q8WZ42-2; Sequence=VSP_019138; Note=No experimental confirmation available.; Name=3; Synonyms=Small cardiac N2-B; IsoId=Q8WZ42-3; Sequence=VSP_019139, VSP_019145; Name=4; Synonyms=Soleus; IsoId=Q8WZ42-4; Sequence=VSP_019142, VSP_019151; Note=No experimental confirmation available.; Name=5; IsoId=Q8WZ42-5; Sequence=VSP_019147, VSP_019148, VSP_019149, VSP_019150, VSP_019152; Note=No experimental confirmation available.; Name=6; Synonyms=Small cardiac novex-3; IsoId=Q8WZ42-6; Sequence=VSP_019143, VSP_019146; Note=Ref.3 (CAD12457) sequence is in conflict in positions: 3732:L->F, 5139:R->M. {ECO:0000305}; Name=7; Synonyms=Cardiac novex-2; IsoId=Q8WZ42-7; Sequence=VSP_019141, VSP_019144; Name=8; Synonyms=Cardiac novex-1; IsoId=Q8WZ42-8; Sequence=VSP_019140; Name=9; IsoId=Q8WZ42-9; Sequence=VSP_019139, VSP_042903, VSP_019145; Name=10; IsoId=Q8WZ42-10; Sequence=VSP_019139, VSP_019140, VSP_019145; Name=11; IsoId=Q8WZ42-11; Sequence=VSP_019142; Name=12; IsoId=Q8WZ42-12; Sequence=VSP_045935, VSP_045929, VSP_045930, VSP_045931, VSP_045932, VSP_045933, VSP_045934; Note=No experimental confirmation available.; Name=13; IsoId=Q8WZ42-13; Sequence=VSP_047142; Note=No experimental confirmation available.;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420;
DiseaseCardiomyopathy, dilated 1G (CMD1G) [MIM:604145]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:11788824, ECO:0000269|PubMed:11846417, ECO:0000269|PubMed:16465475}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseCardiomyopathy, familial hypertrophic 9 (CMH9) [MIM:613765]: 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. {ECO:0000269|PubMed:10462489}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseEarly-onset myopathy with fatal cardiomyopathy (EOMFC) [MIM:611705]: Early-onset myopathies are inherited muscle disorders that manifest typically from birth or infancy with hypotonia, muscle weakness, and delayed motor development. EOMFC is a titinopathy that, in contrast with the previously described examples, involves both heart and skeletal muscle, has a congenital onset, and is purely recessive. This phenotype is due to homozygous out-of-frame TTN deletions, which lead to a total absence of titin's C-terminal end from striated muscles and to secondary CAPN3 depletion. {ECO:0000269|PubMed:17444505}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseHereditary myopathy with early respiratory failure (HMERF) [MIM:603689]: Autosomal dominant, adult-onset myopathy with early respiratory muscle involvement. {ECO:0000269|PubMed:15802564}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseLimb-girdle muscular dystrophy 2J (LGMD2J) [MIM:608807]: An autosomal recessive degenerative myopathy characterized by progressive weakness of the pelvic and shoulder girdle muscles. Severe disability is observed within 20 years of onset. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseTardive tibial muscular dystrophy (TMD) [MIM:600334]: Autosomal dominant, late-onset distal myopathy. Muscle weakness and atrophy are usually confined to the anterior compartment of the lower leg, in particular the tibialis anterior muscle. Clinical symptoms usually occur at age 35-45 years or much later. {ECO:0000269|PubMed:12145747, ECO:0000269|PubMed:12891679}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe 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.
DomainZIS1 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.
Enzyme RegulationFull 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. {ECO:0000269|PubMed:9804419}.
FunctionKey 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. {ECO:0000269|PubMed:9804419}.
InteractionSelf; NbExp=16; IntAct=EBI-681210, EBI-681210; P12814:ACTN1; NbExp=2; IntAct=EBI-681210, EBI-351710; P35609:ACTN2; NbExp=16; IntAct=EBI-681210, EBI-77797; P62158:CALM3; NbExp=2; IntAct=EBI-681210, EBI-397435; P20807:CAPN3; NbExp=4; IntAct=EBI-681210, EBI-5655000; O75953:DNAJB5; NbExp=4; IntAct=EBI-681210, EBI-5655937; O75923:DYSF; NbExp=17; IntAct=EBI-681210, EBI-2799016; P06733:ENO1; NbExp=3; IntAct=EBI-681210, EBI-353877; Q14324:MYBPC2; NbExp=14; IntAct=EBI-681210, EBI-5653200; Q13203:MYBPH; NbExp=3; IntAct=EBI-681210, EBI-5655165; P54296:MYOM2; NbExp=2; IntAct=EBI-681210, EBI-5357134; P20929:NEB; NbExp=6; IntAct=EBI-681210, EBI-1049657; Q5VST9:OBSCN; NbExp=11; IntAct=EBI-681210, EBI-941850; O75147:OBSL1; NbExp=8; IntAct=EBI-681210, EBI-1223896; Q96CV9:OPTN; NbExp=2; IntAct=EBI-681210, EBI-748974; O15273:TCAP; NbExp=7; IntAct=EBI-681210, EBI-954089; Q969Q1:TRIM63; NbExp=3; IntAct=EBI-681210, EBI-5661333;
MiscellaneousIn 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.
PtmAutophosphorylated. {ECO:0000250}.
Sequence CautionSequence=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};
SimilarityBelongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. {ECO:0000305}.
SimilarityContains 132 fibronectin type-III domains. {ECO:0000255|PROSITE-ProRule:PRU00316}.
SimilarityContains 14 TPR repeats. {ECO:0000305}.
SimilarityContains 152 Ig-like (immunoglobulin-like) domains. {ECO:0000305}.
SimilarityContains 15 WD repeats. {ECO:0000305}.
SimilarityContains 17 RCC1 repeats. {ECO:0000305}.
SimilarityContains 19 Kelch repeats. {ECO:0000305}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationCytoplasm {ECO:0000305|PubMed:16410549}. Nucleus {ECO:0000269|PubMed:16410549}.
SubunitInteracts 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. {ECO:0000250, ECO:0000269|PubMed:11717165, ECO:0000269|PubMed:12432079, ECO:0000269|PubMed:12444090, ECO:0000269|PubMed:12482578, ECO:0000269|PubMed:14583192, ECO:0000269|PubMed:14676215, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15967462, ECO:0000269|PubMed:16407954, ECO:0000269|PubMed:16410549, ECO:0000269|PubMed:20634290, ECO:0000269|PubMed:9645487, ECO:0000269|PubMed:9804419}.
Tissue SpecificityIsoforms 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). {ECO:0000269|PubMed:11717165, ECO:0000269|PubMed:7819249}.
Web ResourceName=Wikipedia; Note=Titin entry; URL="http://en.wikipedia.org/wiki/Titin";
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