TNNT3

Protein identityUniProt · HPA

UniProt accession

P45378

Gene

TNNT3

Ensembl

ENSG00000130595

Chromosome

11

Canonical length

269 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

The binding of Ca(2+) to the trimeric troponin complex initiates the process of muscle contraction. Increased Ca(2+) concentrations produce a conformational change in the troponin complex that is transmitted to tropomyosin dimers situated along actin filaments. The altered conformation permits increased interaction between a myosin head and an actin filament which, ultimately, produces a muscle contraction. The troponin complex has protein subunits C, I, and T. Subunit C binds Ca(2+) and subunit I binds to actin and inhibits actin-myosin interaction. Subunit T binds the troponin complex to the tropomyosin complex and is also required for Ca(2+)-mediated activation of actomyosin ATPase activity. There are 3 different troponin T genes that encode tissue-specific isoforms of subunit T for fast skeletal-, slow skeletal-, and cardiac-muscle. This gene encodes fast skeletal troponin T protein; also known as troponin T type 3. Alternative splicing results in multiple transcript variants encoding additional distinct troponin T type 3 isoforms. A developmentally regulated switch between fetal/neonatal and adult troponin T type 3 isoforms occurs. Additional splice variants have been described but their biological validity has not been established. Mutations in this gene may cause distal arthrogryposis multiplex congenita type 2B (DA2B). [provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

269 residues, UniProt reviewed canonical sequence.

>P45378|TNNT3
     1  MSDEEVEQVE EQYEEEEEAQ EEAAEVHEEV HEPEEVQEDT AEEDAEEEKP RPKLTAPKIP
    61  EGEKVDFDDI QKKRQNKDLM ELQALIDSHF EARKKEEEEL VALKERIEKR RAERAEQQRI
   121  RAEKERERQN RLAEEKARRE EEDAKRRAED DLKKKKALSS MGANYSSYLA KADQKRGKKQ
   181  TAREMKKKIL AERRKPLNID HLGEDKLRDK AKELWETLHQ LEIDKFEFGE KLKRQKYDIT
   241  TLRSRIDQAQ KHSKKAGTPA KGKVGGRWK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNNT3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.55

Highest tissue expression

13,033 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNNT3.

Disease | AllUniProt

Conditions TNNT3 is implicated in, by any mechanism.

• Arthrogryposis, distal, 2B2 (DA2B2) MIM:618435

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 312 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Arthrogryposis, distal, type 2B2
• Sheldon-Hall syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.98

gnomAD pLI

0

gnomAD missense Z

0.46

DepMap mean gene effect

0.16

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• regulation of ATP-dependent activity
• regulation of striated muscle contraction
• sarcomere organization
• skeletal muscle contraction
• positive regulation of calcium-dependent ATPase activity

Molecular functions

• calcium-dependent protein binding
• tropomyosin binding
• troponin C binding
• troponin I binding

Cellular components

• cytosol
• troponin complex

Protein domainsUniProt · Pfam · InterPro

• Troponin
• Troponin T
• Troponin domain superfamily
• Troponin

KeywordsUniProt

• Acetylation
• Muscle protein
• Phosphoprotein