[1]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. STRAIN=C57BL/6J; The mouse genome sequencing consortium; Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
[2]	DEVELOPMENTAL STAGE. PubMed=9440711 [NCBI, ExPASy, EBI, Israel, Japan] Gautel M., Fuerst D.O., Cocco A., Schiaffino S.; "Isoform transitions of the myosin binding protein C family in developing human and mouse muscles: lack of isoform transcomplementation in cardiac muscle."; Circ. Res. 82:124-129(1998).
[3]	FUNCTION. DOI=10.1083/jcb.200601014; PubMed=16702235 [NCBI, ExPASy, EBI, Israel, Japan] Weinert S., Bergmann N., Luo X., Erdmann B., Gotthardt M.; "M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere."; J. Cell Biol. 173:559-570(2006).
[4]	UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-10665; LYS-10679; LYS-10686; LYS-30428 AND LYS-31008, AND MASS SPECTROMETRY. TISSUE=Heart; DOI=10.1016/j.bbrc.2007.04.015; PubMed=17451654 [NCBI, ExPASy, EBI, Israel, Japan] Jeon H.B., Choi E.S., Yoon J.H., Hwang J.H., Chang J.W., Lee E.K., Choi H.W., Park Z.-Y., Yoo Y.J.; "A proteomics approach to identify the ubiquitinated proteins in mouse heart."; Biochem. Biophys. Res. Commun. 357:731-736(2007).
[5]	FUNCTION. DOI=10.1161/CIRCULATIONAHA.106.645499; PubMed=17261657 [NCBI, ExPASy, EBI, Israel, Japan] Peng J., Raddatz K., Molkentin J.D., Wu Y., Labeit S., Granzier H., Gotthardt M.; "Cardiac hypertrophy and reduced contractility in hearts deficient in the titin kinase region."; Circulation 115:743-751(2007).

Comments

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.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium (By similarity).
ENZYME REGULATION: Full activation of the protein kinase domain requires both phosphorylation of Tyr-33203, 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 (By similarity).
SUBUNIT: Interacts with MYOM1, MYOM2, tropomyosin and myosin. Interacts with actin, primarily via the PEVK domains and with MYPN. 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, TRIM55, ANKRD1, ANKRD2, ANKRD23, and CAPN3 through several Ig domains. Interacts with NBR1 through the protein kinase domain (By similarity).
SUBCELLULAR LOCATION: Cytoplasm (Probable). Nucleus (By similarity).

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.

Name	1
Isoform ID	A2ASS6-1
This is the isoform sequence displayed in this entry.

Name	2
Isoform ID	A2ASS6-2
Features which should be applied to build the isoform sequence: VSP_052606, VSP_052608.

Name	3
Isoform ID	A2ASS6-3
Note: Gene prediction based on EST data.
Features which should be applied to build the isoform sequence: VSP_052606, VSP_052607, VSP_052609.

DEVELOPMENTAL STAGE: Expressed in cardiac muscle from 8 dpc and in skeletal muscle from 9 dpc.
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 (By similarity).
DOMAIN: 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 (By similarity).
PTM: Autophosphorylated. Phosphorylated upon DNA damage, probably by ATM or ATR (By similarity).
SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
SIMILARITY: Contains 134 fibronectin type-III domains.
SIMILARITY: Contains 144 Ig-like (immunoglobulin-like) domains.
SIMILARITY: Contains 18 Kelch repeats.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 12 RCC1 repeats.
SIMILARITY: Contains 15 TPR repeats.
SIMILARITY: Contains 17 WD repeats.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AL928681; CAM27058.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928721; CAM27058.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928789; CAM27058.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928681; CAM27059.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928721; CAM27059.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928789; CAM27059.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928681; CAM27060.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928721; CAM27060.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928721; CAM23448.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928681; CAM23448.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928789; CAM23448.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928721; CAM23449.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928681; CAM23449.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928789; CAM23449.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928721; CAM23450.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928681; CAM23450.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928789; CAM24262.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928681; CAM24262.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928721; CAM24262.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928789; CAM24263.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928681; CAM24263.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL928721; CAM24263.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

UniGene

Mm.373672

3D structure databases

ModBase

A2ASS6.

Organism-specific databases

MGI

MGI:98864; Ttn.

GeneLynx

Ttn; Mus musculus.

Gene expression databases

CleanEx

MM_TTN; -.

Ontologies

GO:0031430;	Cellular component: M band (inferred from direct assay from MGI).
GO:0005859;	Cellular component: muscle myosin complex (traceable author statement from MGI).
GO:0030018;	Cellular component: Z disc (inferred from direct assay from MGI).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from MGI).
GO:0005200;	Molecular function: structural constituent of cytoskeleton (traceable author statement from MGI).
GO:0007512;	Biological process: adult heart development (inferred from mutant phenotype from MGI).
GO:0055003;	Biological process: cardiac myofibril assembly (inferred from mutant phenotype from MGI).
GO:0043056;	Biological process: forward locomotion (inferred from mutant phenotype from MGI).
GO:0003007;	Biological process: heart morphogenesis (inferred from mutant phenotype from MGI).
GO:0001701;	Biological process: in utero embryonic development (inferred from mutant phenotype from MGI).
GO:0006936;	Biological process: muscle contraction (inferred from mutant phenotype from MGI).
GO:0045214;	Biological process: sarcomere organization (inferred from mutant phenotype from MGI).
QuickGo view.

Family and domain databases

InterPro

IPR008957; Fibronectin_typ-III-like_fold.
IPR003961; FN_III.
IPR007110; Ig-like.
IPR013783; Ig-like_fold.
IPR013098; Ig_I-set.
IPR003599; Ig_sub.
IPR003598; Ig_sub2.
IPR004168; PPAK_motif.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR000408; Reg_chr_condens.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
IPR015129; Titin_Z.
IPR001680; WD40_repeat.
Graphical view of domain structure.

Gene3D

G3DSA:2.60.40.30; FN_III-like; 131.
G3DSA:2.60.40.10; Ig-like_fold; 142.

Pfam

PF00041; fn3; 132.
PF07679; I-set; 167.
PF00069; Pkinase; 1.
PF02818; PPAK; 76.
PF09042; Titin_Z; 6.
Pfam graphical view of domain structure.

ProDom

PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00060; FN3; 132.
SM00409; IG; 93.
SM00408; IGc2; 70.
SM00220; S_TKc; 1.
SMART graphical view of domain structure.

PROSITE

PS50853; FN3; 134.
PS50835; IG_LIKE; 144.
PS00107; PROTEIN_KINASE_ATP; FALSE_NEG.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; FALSE_NEG.
PS00625; RCC1_1; FALSE_NEG.
PS00626; RCC1_2; FALSE_NEG.
PS50012; RCC1_3; FALSE_NEG.
PS50005; TPR; FALSE_NEG.
PS50293; TPR_REGION; FALSE_NEG.
PS00678; WD_REPEATS_1; FALSE_NEG.
PS50082; WD_REPEATS_2; FALSE_NEG.
PS50294; WD_REPEATS_REGION; FALSE_NEG.
PROSITE graphical view of domain structure (profiles).

BLOCKS

A2ASS6.

Genome annotation databases

Ensembl

ENSMUSG00000051747; Mus musculus. [Contig view]

Phylogenomic databases

HOVERGEN

A2ASS6; -.

Other

Ttn; Mus musculus.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; ATP-binding; Calcium; Calmodulin-binding; Coiled coil; Cytoplasm; Immunoglobulin domain; Kelch repeat; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Repeat; Serine/threonine-protein kinase; TPR repeat; Transferase; Ubl conjugation; WD repeat.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 35213`	`35213`	`Titin.`	`PRO_0000311696`
`DOMAIN`	`6 98`	`93`	`Ig-like 1.`
`DOMAIN`	`104 192`	`89`	`Ig-like 2.`
`REPEAT`	`412 454`	`43`	`Z-repeat 1.`
`REPEAT`	`463 504`	`42`	`Z-repeat 2.`
`REPEAT`	`509 548`	`40`	`Z-repeat 3.`
`REPEAT`	`553 594`	`42`	`Z-repeat 4.`
`REPEAT`	`599 640`	`42`	`Z-repeat 5.`
`REPEAT`	`645 686`	`42`	`Z-repeat 6.`
`DOMAIN`	`942 1037`	`96`	`Fibronectin type-III 1.`
`DOMAIN`	`946 1034`	`89`	`Ig-like 3.`
`DOMAIN`	`1084 1174`	`91`	`Ig-like 4.`
`DOMAIN`	`1293 1384`	`92`	`Ig-like 5.`
`DOMAIN`	`1463 1552`	`90`	`Ig-like 6.`
`DOMAIN`	`1562 1652`	`91`	`Ig-like 7.`
`DOMAIN`	`1709 1799`	`91`	`Ig-like 8.`
`DOMAIN`	`1847 1934`	`88`	`Ig-like 9.`
`DOMAIN`	`2084 2173`	`90`	`Ig-like 10.`
`REPEAT`	`2095 2128`	`34`	`TPR 1.`
`DOMAIN`	`2177 2268`	`92`	`Ig-like 11.`
`DOMAIN`	`2270 2356`	`87`	`Ig-like 12.`
`DOMAIN`	`2359 2449`	`91`	`Ig-like 13.`
`DOMAIN`	`2436 2535`	`100`	`Ig-like 14.`
`DOMAIN`	`2626 2709`	`84`	`Ig-like 15.`
`REPEAT`	`2810 2844`	`35`	`TPR 2.`
`DOMAIN`	`2886 2971`	`86`	`Ig-like 16.`
`REPEAT`	`3028 3068`	`41`	`WD 1.`
`DOMAIN`	`3064 3147`	`84`	`Ig-like 17.`
`REPEAT`	`3208 3248`	`41`	`WD 2.`
`DOMAIN`	`3245 3333`	`89`	`Ig-like 18.`
`DOMAIN`	`3350 3438`	`89`	`Ig-like 19.`
`DOMAIN`	`3509 3599`	`91`	`Ig-like 20.`
`DOMAIN`	`3625 3716`	`92`	`Ig-like 21.`
`DOMAIN`	`4251 4337`	`87`	`Ig-like 22.`
`DOMAIN`	`4344 4432`	`89`	`Ig-like 23.`
`DOMAIN`	`4439 4527`	`89`	`Ig-like 24.`
`DOMAIN`	`4532 4620`	`89`	`Ig-like 25.`
`DOMAIN`	`4625 4716`	`92`	`Ig-like 26.`
`DOMAIN`	`4719 4807`	`89`	`Ig-like 27.`
`DOMAIN`	`4812 4897`	`86`	`Ig-like 28.`
`DOMAIN`	`4904 4993`	`90`	`Ig-like 29.`
`DOMAIN`	`5001 5089`	`89`	`Ig-like 30.`
`DOMAIN`	`5094 5182`	`89`	`Ig-like 31.`
`REPEAT`	`5131 5164`	`34`	`TPR 3.`
`DOMAIN`	`5186 5276`	`91`	`Ig-like 32.`
`DOMAIN`	`5281 5369`	`89`	`Ig-like 33.`
`DOMAIN`	`5374 5462`	`89`	`Ig-like 34.`
`DOMAIN`	`5466 5555`	`90`	`Ig-like 35.`
`DOMAIN`	`5563 5651`	`89`	`Ig-like 36.`
`DOMAIN`	`5656 5744`	`89`	`Ig-like 37.`
`DOMAIN`	`5749 5838`	`90`	`Ig-like 38.`
`DOMAIN`	`5842 5931`	`90`	`Ig-like 39.`
`DOMAIN`	`5936 6024`	`89`	`Ig-like 40.`
`DOMAIN`	`6028 6117`	`90`	`Ig-like 41.`
`DOMAIN`	`6125 6213`	`89`	`Ig-like 42.`
`DOMAIN`	`6218 6308`	`91`	`Ig-like 43.`
`DOMAIN`	`6311 6401`	`91`	`Ig-like 44.`
`DOMAIN`	`6405 6493`	`89`	`Ig-like 45.`
`REPEAT`	`6435 6468`	`34`	`TPR 4.`
`DOMAIN`	`6498 6587`	`90`	`Ig-like 46.`
`DOMAIN`	`6591 6682`	`92`	`Ig-like 47.`
`REPEAT`	`6615 6653`	`39`	`WD 3.`
`DOMAIN`	`6688 6776`	`89`	`Ig-like 48.`
`DOMAIN`	`6781 6869`	`89`	`Ig-like 49.`
`DOMAIN`	`6873 6962`	`90`	`Ig-like 50.`
`DOMAIN`	`6966 7054`	`89`	`Ig-like 51.`
`DOMAIN`	`7063 7151`	`89`	`Ig-like 52.`
`DOMAIN`	`7159 7247`	`89`	`Ig-like 53.`
`DOMAIN`	`7252 7343`	`92`	`Ig-like 54.`
`DOMAIN`	`7346 7434`	`89`	`Ig-like 55.`
`DOMAIN`	`7439 7528`	`90`	`Ig-like 56.`
`DOMAIN`	`7532 7623`	`92`	`Ig-like 57.`
`DOMAIN`	`7629 7717`	`89`	`Ig-like 58.`
`DOMAIN`	`7722 7810`	`89`	`Ig-like 59.`
`DOMAIN`	`7814 7903`	`90`	`Ig-like 60.`
`DOMAIN`	`7907 7996`	`90`	`Ig-like 61.`
`DOMAIN`	`8004 8094`	`91`	`Ig-like 62.`
`DOMAIN`	`8099 8190`	`92`	`Ig-like 63.`
`DOMAIN`	`8193 8282`	`90`	`Ig-like 64.`
`DOMAIN`	`8287 8375`	`89`	`Ig-like 65.`
`DOMAIN`	`8380 8469`	`90`	`Ig-like 66.`
`DOMAIN`	`8473 8564`	`92`	`Ig-like 67.`
`DOMAIN`	`8570 8658`	`89`	`Ig-like 68.`
`DOMAIN`	`8663 8751`	`89`	`Ig-like 69.`
`DOMAIN`	`8755 8844`	`90`	`Ig-like 70.`
`DOMAIN`	`8849 8937`	`89`	`Ig-like 71.`
`DOMAIN`	`8945 9035`	`91`	`Ig-like 72.`
`DOMAIN`	`9040 9129`	`90`	`Ig-like 73.`
`DOMAIN`	`9137 9226`	`90`	`Ig-like 74.`
`REPEAT`	`9145 9182`	`38`	`TPR 5.`
`DOMAIN`	`9233 9322`	`90`	`Ig-like 75.`
`DOMAIN`	`9331 9431`	`101`	`Ig-like 76.`
`DOMAIN`	`9621 9716`	`96`	`Ig-like 77.`
`REPEAT`	`9662 9695`	`34`	`TPR 6.`
`DOMAIN`	`9721 9812`	`92`	`Ig-like 78.`
`REPEAT`	`9865 9892`	`28`	`PEVK 1.`
`REPEAT`	`9940 9963`	`24`	`PEVK 2.`
`REPEAT`	`9991 10024`	`34`	`TPR 7.`
`REPEAT`	`10001 10050`	`50`	`Kelch 1.`
`REPEAT`	`10062 10085`	`24`	`PEVK 3.`
`REPEAT`	`10091 10115`	`25`	`PEVK 4.`
`REPEAT`	`10145 10169`	`25`	`PEVK 5.`
`REPEAT`	`10170 10197`	`28`	`PEVK 6.`
`REPEAT`	`10198 10225`	`28`	`PEVK 7.`
`REPEAT`	`10227 10254`	`28`	`PEVK 8.`
`REPEAT`	`10255 10281`	`27`	`PEVK 9.`