![Cardiac sarcomere structure](https://upload.wikimedia.org/wikipedia/commons/7/7f/Cardiac_sarcomere_structure.png)
Titin
(contraction for
Titan prote
in) (also called connectin) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''TTN''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Titin is a giant protein, greater than 1
µm in length, that functions as a molecular
spring
Spring(s) may refer to:
Common uses
* Spring (season)
Spring, also known as springtime, is one of the four temperate seasons, succeeding winter and preceding summer. There are various technical definitions of spring, but local usage of ...
that is responsible for the passive elasticity of
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
. It comprises 244 individually folded
protein domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
s connected by unstructured
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
sequences.
These domains
unfold when the protein is stretched and
refold when the tension is removed.
Titin is important in the contraction of
striated muscle tissues. It connects the
Z line to the
M line in the
sarcomere
A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called mus ...
. The protein contributes to force transmission at the Z line and resting tension in the
I band region.
It limits the range of motion of the sarcomere in tension, thus contributing to the passive stiffness of muscle. Variations in the sequence of titin between different types of striated muscle (
cardiac
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
or
skeletal) have been correlated with differences in the mechanical properties of these muscles.
Titin is the third most abundant protein in muscle (after
myosin and
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
), and an adult human contains approximately 0.5 kg of titin.
With its length of ~27,000 to ~35,000
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s (depending on the
splice isoform), titin is the largest known
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
.
Furthermore, the gene for titin contains the largest number of
exons (363) discovered in any single gene,
as well as the longest single exon (17,106
bp).
Discovery
Reiji Natori in 1954 was the first to propose an elastic structure in muscle fiber to account for the return to the resting state when muscles are stretched and then released.
In 1977, Koscak Maruyama and coworkers isolated an elastic protein from muscle fiber that they called connectin.
Two years later, Kuan Wang and coworkers identified a doublet band on
electrophoresis gel
Gel electrophoresis is a method for separation and analysis of biomolecule, biomacromolecules (DNA, RNA, proteins, etc.) and their fragments, based on their size and charge. It is used in clinical chemistry to separate proteins by charge or ...
corresponding to a high molecular weight, elastic protein that they named titin.
Siegfried Labeit
Siegfried is a German-language male given name, composed from the Germanic elements ''sig'' "victory" and ''frithu'' "protection, peace".
The German name has the Old Norse cognate ''Sigfriðr, Sigfrøðr'', which gives rise to Swedish ''Sigfrid' ...
in 1990 isolated a partial
cDNA clone of titin.
In 1995, Labeit and
Bernhard Kolmerer determined the cDNA sequence of human cardiac titin.
Labeit and colleagues in 2001 determined the complete sequence of the human titin gene.
Genetics
The human gene encoding for titin is located on the long arm of chromosome 2 and contains 363 exons, which together code for 38,138
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
residues (4200 kDa).
Within the gene are found a large number of PEVK (proline-glutamate-valine-lysine -abundant
structural motif
In a polymer, chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common Biomolecular structure#Tertiary structure, three-dimensional structure that appears in a variety of different, evolutionarily unrel ...
s) exons 84 to 99 nucleotides in length, which code for conserved 28- to 33-residue motifs that may represent structural units of the titin PEVK spring. The number of PEVK motifs in the titin gene appears to have increased during evolution, apparently modifying the genomic region responsible for titin's spring properties.
Isoforms
A number of titin
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...
s are produced in different striated muscle tissues as a result of
alternative splicing.
All but one of these isoforms are in the range of ~27,000 to ~36,000 amino acid residues in length. The exception is the small cardiac novex-3 isoform, which is only 5,604 amino acid residues in length. The following table lists the known titin isoforms:
Structure
Titin is the largest known protein; its human variant consists of 34,350
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s, with the
molecular weight
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
of the mature "canonical" isoform of the protein being approximately 3,816,030.05
Da.
Its mouse homologue is even larger, comprising 35,213 amino acids with a molecular weight of 3,906,487.6
Da.
It has a theoretical
isoelectric point
The isoelectric point (pI, pH(I), IEP), is the pH at which a molecule carries no net electrical charge or is electrically neutral in the statistical mean. The standard nomenclature to represent the isoelectric point is pH(I). However, pI is also u ...
of 6.02.
The protein's
empirical chemical formula
In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...
is C
169,719H
270,466N
45,688O
52,238S
911.
It has a theoretical
instability index (II) of 42.38, classifying the protein as unstable.
The protein's
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
, the time it takes for half of the amount of protein in a cell to break down after its synthesis in the cell, is predicted to be approximately 30 hours (in
mammalian
Mammals () are a group of vertebrate animals constituting the class (biology), class Mammalia (), characterized by the presence of mammary glands which in Female#Mammalian female, females produce milk for feeding (nursing) their young, a ...
reticulocyte
Reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), reticulocytes develop and mature in the bone marrow and then circulatory system, circulate for about a day in the blood stream before ...
s).
![Titin_IG_Domains](https://upload.wikimedia.org/wikipedia/commons/b/b3/Titin_IG_Domains.jpg)
The titin protein is located between the
myosin thick filament and the Z disk.
Titin consists primarily of a linear array of two types of modules, also referred to as
protein domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
s (244 copies in total): type I
fibronectin type III domain
The Fibronectin type III domain is an evolutionarily conserved protein domain that is widely found in animal proteins. The fibronectin protein in which this domain was first identified contains 16 copies of this domain. The domain is about 100 am ...
(132 copies) and type II
immunoglobulin domain
The immunoglobulin domain, also known as the immunoglobulin fold, is a type of protein domain that consists of a 2-layer sandwich of 7-9 antiparallel β-strands arranged in two β-sheets with a Greek key topology, consisting of about 125 amino a ...
(112 copies).
However, the exact number of these domains is different in different species. This linear array is further organized into two regions:
*
N-terminal I-band: acts as the elastic part of the molecule and is composed mainly of type II modules. More specifically the I-band contains two regions of tandem type II immunoglobulin domains on either side of a PEVK region that is rich in
proline (P),
glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
(E),
valine
Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotona ...
(V) and
lysine (K).
*
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
A-band: is thought to act as a protein-ruler and is composed of alternating type I (Fn3) and II (Ig) modules with super-repeat segments. These have been shown to align to the 43 nm axial repeats of myosin thick filaments with immunoglobulin domains correlating to myosin crowns.
The C-terminal region also contains a serine
kinase domain
that is primarily known for adapting the muscle to mechanical strain.
It is “stretch-sensitive” and helps repair overstretching of the sarcomere.
The N-terminal (the Z-disc end) contains a "Z repeat" that recognizes
Actinin alpha 2
Alpha-actinin-2 is a protein which in humans is encoded by the ''ACTN2'' gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to ...
.
![Titin_IG_and_FN3_Domains_as_well_as_Protein_Kinase_Domain](https://upload.wikimedia.org/wikipedia/commons/2/25/Titin_IG_and_FN3_Domains_as_well_as_Protein_Kinase_Domain.png)
The elasticity of the PEVK region has both
entropic
Entropy is a scientific concept, as well as a measurable physical property, that is most commonly associated with a state of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynam ...
and
enthalpic
Enthalpy , a property of a thermodynamic system, is the sum of the system's internal energy and the product of its pressure and volume. It is a state function used in many measurements in chemical, biological, and physical systems at a constant p ...
contributions and is characterized by a polymer
persistence length
The persistence length is a basic mechanical property quantifying the bending stiffness of a polymer.
The molecule behaves like a flexible elastic rod/beam (beam theory). Informally, for pieces of the polymer that are shorter than the persistence l ...
and a
stretch modulus. At low to moderate extensions PEVK elasticity can be modeled with a standard
worm-like chain
The worm-like chain (WLC) model in polymer physics is used to describe the behavior of polymers that are semi-flexible: fairly stiff with successive segments pointing in roughly the same direction, and with persistence length within a few orders o ...
(WLC) model of
entropic elasticity. At high extensions PEVK stretching can be modeled with a modified WLC model that incorporates enthalpic elasticity. The difference between low-and high- stretch elasticity is due to electrostatic stiffening and
hydrophobic effect
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and exclude water molecules. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpolar ...
s.
Embedded between the PEVK and Ig residues are N2A domains.
Evolution
The titin domains have evolved from a common ancestor through many gene duplication events. Domain duplication was facilitated by the fact that most domains are encoded by single exons. Other giant sarcomeric proteins made out of Fn3/Ig repeats include
obscurin
Obscurin is a protein that in humans is encoded by the ''OBSCN'' gene. Obscurin belongs to the family of giant sarcomeric signaling proteins that includes titin and nebulin. Obscurin is expressed in cardiac and skeletal muscle, and plays a role in ...
and
myomesin
Myomesin is a protein family found in the M-line of the sarcomere structure. Myomesin has various forms throughout the body in striated muscles with specialized functions. This includes both slow and fast muscle fibers. Myomesin are made of 13 dom ...
. Throughout evolution, titin mechanical strength appears to decrease through the loss of disulfide bonds as the organism becomes heavier.
Titin A-band has homologs in invertebrates, such as twitchin (unc-22) and projectin, which also contain Ig and FNIII repeats and a protein kinase domain.
The gene duplication events took place independently but were from the same ancestral Ig and FNIII domains. It is said that the protein titin was the first to diverge out of the family.
''Drosophila'' projectin, officially known as bent (''bt''), is associated with lethality by failing to escape the egg in some mutations as well as dominant changes in wing angles.
''Drosophila'' Titin, also known as Kettin or
sallimus (''sls''), is kinase-free. It has roles in the elasticity of both muscle and chromosomes. It is homologous to vertebrate titin I-band and contains Ig PEVK domains, the many repeats being a hot target for splicing. There also exists a titin homologue, ''ttn-1'', in ''
C. elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
''. It has a kinase domain, some Ig/Fn3 repeats, and PEVT repeats that are similarly elastic.
Function
![Sarcomere](https://upload.wikimedia.org/wikipedia/commons/6/6e/Sarcomere.svg)
Titin is a large abundant protein of striated muscle. Titin's primary functions are to stabilize the thick filament, center it between the thin filaments, prevent overstretching of the sarcomere, and to recoil the sarcomere like a spring after it is stretched. An N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the
sarcomere
A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called mus ...
, 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
chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
s.
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. Of the many titin variants identified, five are described with complete transcript information available.
Dominant mutation in TTN causes predisposition to
hernia
A hernia is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. Various types of hernias can occur, most commonly involving the abdomen, and specifically the groin. Groin herni ...
s.
Titin interacts with many
sarcomeric proteins including:
* Z line region:
telethonin
Telethonin, also known as Tcap, is a protein that in humans is encoded by the ''TCAP'' gene. Telethonin is expressed in cardiac and skeletal muscle at Z-discs and functions to regulate sarcomere assembly, T-tubule function and apoptosis. Teletho ...
and
alpha-actinin
* I band region:
calpain-3 and
obscurin
Obscurin is a protein that in humans is encoded by the ''OBSCN'' gene. Obscurin belongs to the family of giant sarcomeric signaling proteins that includes titin and nebulin. Obscurin is expressed in cardiac and skeletal muscle, and plays a role in ...
* M line region:
myosin-binding protein C,
calmodulin 1
Calmodulin 1 is a protein that in humans is encoded by the ''CALM1'' gene.
Function
Calmodulin 1 is the archetype of the family of calcium-modulated (calmodulin) proteins of which nearly 20 members have been found. They are identified by their ...
,
CAPN3
Calpain-3 is a protein that in humans is encoded by the ''CAPN3'' gene.
Function
Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene ...
, and
MURF1
Clinical relevance
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...
s anywhere within the unusually long sequence of this gene can cause
premature stop codon
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a ''nonsense codon'' in the transcribed mRNA, and in leading to a truncated, incomplete, and usually nonfunctional protein produc ...
s or other defects. Titin mutations are associated with hereditary
myopathy
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
with early respiratory failure, early-onset myopathy with fatal
cardiomyopathy
Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
, core myopathy with heart disease,
centronuclear myopathy
Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in the center of muscle cells instead of their normal location at the periphery.
Symptoms of CNM include severe hypotonia, hypoxia-requi ...
,
limb-girdle muscular dystrophy type 2J,
familial dilated cardiomyopathy
Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Co ...
9,
hypertrophic cardiomyopathy and
tibial muscular dystrophy.
Further research also suggests that no genetically linked form of any
dystrophy
Dystrophy is the degeneration of tissue, due to disease or malnutrition, most likely due to heredity.
Types
* Muscular dystrophy
** Duchenne muscular dystrophy
** Becker's muscular dystrophy
** Myotonic dystrophy
* Reflex neurovascular dyst ...
or myopathy can be safely excluded from being caused by a mutation on the TTN gene.
Truncating mutations in dilated cardiomyopathy patients are most commonly found in the A region; although truncations in the upstream I region might be expected to prevent translation of the A region entirely,
alternative splicing creates some transcripts that do not encounter the premature stop codon, ameliorating its effect.
mRNA splicing factors such as RBM20 and
SLM2 (
KHDRBS3
KH domain-containing, RNA-binding, signal transduction-associated protein 3 is a protein that in humans is encoded by the ''KHDRBS3'' gene.
Interactions
KHDRBS3 has been shown to interact with SIAH1.
KHDRBS3 interacts with splicing protein Sa ...
) were shown to mediated alternative mRNA splicing of titin mRNA contributing to the development of
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
due to
cardiomyopathies
Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
.
Autoantibodies to titin are produced in patients with the autoimmune disease
Myasthenia gravis.
Interactions
Titin has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
ANK1
Ankyrin 1, also known as ANK-1, and erythrocyte ankyrin, is a protein that in humans is encoded by the ''ANK1'' gene.
Tissue distribution
The protein encoded by this gene, Ankyrin 1, is the prototype of the ankyrin family, was first discovered in ...
,
*
ANKRD1
Ankyrin repeat domain-containing protein 1, or Cardiac ankyrin repeat protein is a protein that in humans is encoded by the ''ANKRD1'' gene also known as ''CARP''. CARP is highly expressed in cardiac and skeletal muscle, and is a transcription f ...
,
*
ANKRD23
Ankyrin repeat domain-containing protein 23 is a protein that in humans is encoded by the ''ANKRD23'' gene.
This gene is a member of the muscle ankyrin repeat protein (MARP) family and encodes a protein with four tandem ankyrin-like repeats. The ...
[
* ]CAPN3
Calpain-3 is a protein that in humans is encoded by the ''CAPN3'' gene.
Function
Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene ...
,
* FHL2
Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the ''FHL2'' gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain.
Function
FHL-2 is thought to have ...
,
* OBSCN
Obscurin is a protein that in humans is encoded by the ''OBSCN'' gene. Obscurin belongs to the family of giant sarcomeric signaling proteins that includes titin and nebulin. Obscurin is expressed in cardiac and skeletal muscle, and plays a role in ...
,
* TCAP, and
* TRIM63
E3 ubiquitin-protein ligase TRIM63, also known as "MuRF1" (Muscle Ring-Finger Protein-1), is an enzyme that in humans is encoded by the ''TRIM63'' gene.
This gene encodes a member of the RING zinc finger protein family found in striated muscle a ...
.
Linguistic significance
The name titin is derived from the Greek Titan (a giant deity, anything of great size).
As the largest known protein, titin also has the longest IUPAC name
In chemical nomenclature, a preferred IUPAC name (PIN) is a unique name, assigned to a chemical substance and preferred among the possible names generated by IUPAC nomenclature. The "preferred IUPAC nomenclature" provides a set of rules for choo ...
of a protein. The full chemical name of the human canonical form of titin, which starts '' methionyl...'' and ends ''... isoleucine'', contains 189,819 letters and is sometimes stated to be the longest word in the English language
The identity of the longest word in the English language depends upon the definition of what constitutes a word in the English language, as well as how length should be compared.
Words may be derived naturally from the language's roots or forme ...
, or of any language. However, lexicographers regard generic names of chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
s as ''verbal formulae
In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...
'' rather than English words.
References
Further reading
*
*
*
*
*
*
*
*
*
External links
GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview
GeneReviews/NCBI/NIH/UW entry on Udd Distal Myopathy, Tibial Muscular Dystrophy, Udd Myopathy
GeneReviews/NIH/NCBI/UW entry on Salih Myopathy or Early-Onset Myopathy with Fatal Cardiomyopathy
InterPro domain organization of titin
{{NLM content
Structural proteins
Genes on human chromosome 2
EC 2.7.11
Muscular system