Reviewed, UniProtKB/Swiss-Prot A2ASS6 (TITIN_MOUSE)

Names and origin

Protein names

Recommended name:
    Titin
    EC=2.7.11.1
Alternative name(s):
    Connectin

Gene names

Name:

Ttn

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	35213 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (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 structure	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	CytoplasmProbable. NucleusBy similarity.
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. 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.
Post-translational modification	Autophosphorylated. Phosphorylated upon DNA damage, probably by ATM or ATR By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 134 fibronectin type-III domains. Contains 144 Ig-like (immunoglobulin-like) domains. Contains 18 Kelch repeats. Contains 1 protein kinase domain. Contains 12 RCC1 repeats. Contains 15 TPR repeats. Contains 17 WD repeats.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Immunoglobulin domain Kelch repeat Repeat TPR repeat WD repeat
Ligand	ATP-binding Calcium Calmodulin-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	adult heart development Ref.3 Inferred from mutant phenotype. Source: MGI cardiac myofibril assembly Ref.3 Inferred from mutant phenotype. Source: MGI forward locomotion Inferred from mutant phenotype. Source: MGI heart morphogenesis Ref.3 Inferred from mutant phenotype. Source: MGI in utero embryonic development Ref.3 Inferred from mutant phenotype. Source: MGI muscle contraction Inferred from mutant phenotype. Source: MGI sarcomere organization Ref.3 Inferred from mutant phenotype. Source: MGI
Cellular component	M band Ref.3 Inferred from direct assay. Source: MGI Z disc Inferred from direct assay. Source: MGI muscle myosin complex Traceable author statement. Source: MGI
Molecular function	protein binding Inferred from physical interaction. Source: MGI structural constituent of cytoskeleton Traceable author statement. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: A2ASS6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: A2ASS6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     556-601: Missing.
     4435-12715: Missing.

Isoform 3 (identifier: A2ASS6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     556-601: Missing.
     3461-5499: IASLLSAEED...FSGTKEISAK → ELFEGEADGS...ARSSAILTLS
     5500-35213: Missing.

Notes: Gene prediction based on EST data.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 35213	35213	Titin
Regions
	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