Q8TDI7 · TMC2_HUMAN
- ProteinTransmembrane channel-like protein 2
- GeneTMC2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids906 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Pore-forming subunit of the mechanotransducer (MET) non-selective cation channel complex located at the tips of stereocilia of cochlear hair cells and that mediates sensory transduction in the auditory system (PubMed:11850618).
The MET complex is composed of two dimeric pore-forming ion-conducting transmembrane TMC (TMC1 or TMC2) subunits, and aided by several auxiliary proteins including LHFPL5, TMIE, CIB2/3 and TOMT, and the tip-link PCDH15. MET channel is activated by tension in the tip-link extending from the side wall of one stereocilium to the tip of the adjacent shorter stereocilium, where the channel is located (By similarity).
TMC2 MET channel is highly permeable to calcium and likely transports monovalent cations. Also involved in vestibular hair cell transduction current of the mammalian inner ear (By similarity).
The MET complex is composed of two dimeric pore-forming ion-conducting transmembrane TMC (TMC1 or TMC2) subunits, and aided by several auxiliary proteins including LHFPL5, TMIE, CIB2/3 and TOMT, and the tip-link PCDH15. MET channel is activated by tension in the tip-link extending from the side wall of one stereocilium to the tip of the adjacent shorter stereocilium, where the channel is located (By similarity).
TMC2 MET channel is highly permeable to calcium and likely transports monovalent cations. Also involved in vestibular hair cell transduction current of the mammalian inner ear (By similarity).
Catalytic activity
- Ca2+(in) = Ca2+(out)
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cuticular plate | |
Cellular Component | plasma membrane | |
Cellular Component | stereocilium | |
Cellular Component | stereocilium tip | |
Molecular Function | calcium channel activity | |
Molecular Function | mechanosensitive monoatomic ion channel activity | |
Molecular Function | voltage-gated calcium channel activity | |
Biological Process | detection of mechanical stimulus involved in sensory perception of sound | |
Biological Process | regulation of calcium ion transmembrane transport | |
Biological Process | vestibular reflex |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTransmembrane channel-like protein 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8TDI7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: Localized to the stereocilia tips of the cochlear hair cells and plasma membranes of cuticular plates.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-263 | Cytoplasmic | ||||
Sequence: MSHQVKGLKEEARGGVKGRVKSGSPHTGDRLGRRSSSKRALKAEGTPGRRGAQRSQKERAGGSPSPGSPRRKQTGRRRHREELGEQERGEAERTCEGRRKRDERASFQERTAAPKREKEIPRREEKSKRQKKPRSSSLASSASGGESLSEEELAQILEQVEEKKKLIATMRSKPWPMAKKLTELREAQEFVEKYEGALGKGKGKQLYAYKMLMAKKWVKFKRDFDNFKTQCIPWEMKIKDIESHFGSSVASYFIFLRWMYGVN | ||||||
Transmembrane | 264-284 | Helical | ||||
Sequence: LVLFGLIFGLVIIPEVLMGMP | ||||||
Topological domain | 285-336 | Extracellular | ||||
Sequence: YGSIPRKTVPRAEEEKAMDFSVLWDFEGYIKYSALFYGYYNNQRTIGWLRYR | ||||||
Transmembrane | 337-357 | Helical | ||||
Sequence: LPMAYFMVGVSVFGYSLIIVI | ||||||
Topological domain | 358-431 | Cytoplasmic | ||||
Sequence: RSMASNTQGSTGEGESDNFTFSFKMFTSWDYLIGNSETADNKYASITTSFKESIVDEQESNKEENIHLTRFLRV | ||||||
Transmembrane | 432-452 | Helical | ||||
Sequence: LANFLIICCLCGSGYLIYFVV | ||||||
Topological domain | 453-508 | Extracellular | ||||
Sequence: KRSQQFSKMQNVSWYERNEVEIVMSLLGMFCPPLFETIAALENYHPRTGLKWQLGR | ||||||
Transmembrane | 509-529 | Helical | ||||
Sequence: IFALFLGNLYTFLLALMDDVH | ||||||
Topological domain | 530-693 | Cytoplasmic | ||||
Sequence: LKLANEETIKNITHWTLFNYYNSSGWNESVPRPPLHPADVPRGSCWETAVGIEFMRLTVSDMLVTYITILLGDFLRACFVRFMNYCWCWDLEAGFPSYAEFDISGNVLGLIFNQGMIWMGSFYAPGLVGINVLRLLTSMYFQCWAVMSSNVPHERVFKASRSNN | ||||||
Transmembrane | 694-714 | Helical | ||||
Sequence: FYMGLLLLVLFLSLLPVAYTI | ||||||
Topological domain | 715-750 | Extracellular | ||||
Sequence: MSLPPSFDCGPFSGKNRMYDVLQETIENDFPTFLGK | ||||||
Transmembrane | 751-771 | Helical | ||||
Sequence: IFAFLANPGLIIPAILLMFLA | ||||||
Topological domain | 772-906 | Cytoplasmic | ||||
Sequence: IYYLNSVSKSLSRANAQLRKKIQVLREVEKSHKSVKGKATARDSEDTPKSSSKNATQLQLTKEETTPPSASQSQAMDKKAQGPGTSNSASRTTLPASGHLPISRPPGIGPDSGHAPSQTHPWRSASGKSAQRPPH |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_023360 | 123 | in dbSNP:rs6050063 | |||
Sequence: R → K | ||||||
Natural variant | VAR_057281 | 205 | in dbSNP:rs11908093 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_057282 | 217 | in dbSNP:rs34884202 | |||
Sequence: W → R | ||||||
Natural variant | VAR_030621 | 573 | in dbSNP:rs16987592 | |||
Sequence: S → C | ||||||
Natural variant | VAR_057283 | 589 | in dbSNP:rs16987592 | |||
Sequence: S → C | ||||||
Natural variant | VAR_030622 | 800 | in dbSNP:rs768537423 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_057284 | 816 | in dbSNP:rs6115242 | |||
Sequence: E → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,157 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000185382 | 1-906 | Transmembrane channel-like protein 2 | |||
Sequence: MSHQVKGLKEEARGGVKGRVKSGSPHTGDRLGRRSSSKRALKAEGTPGRRGAQRSQKERAGGSPSPGSPRRKQTGRRRHREELGEQERGEAERTCEGRRKRDERASFQERTAAPKREKEIPRREEKSKRQKKPRSSSLASSASGGESLSEEELAQILEQVEEKKKLIATMRSKPWPMAKKLTELREAQEFVEKYEGALGKGKGKQLYAYKMLMAKKWVKFKRDFDNFKTQCIPWEMKIKDIESHFGSSVASYFIFLRWMYGVNLVLFGLIFGLVIIPEVLMGMPYGSIPRKTVPRAEEEKAMDFSVLWDFEGYIKYSALFYGYYNNQRTIGWLRYRLPMAYFMVGVSVFGYSLIIVIRSMASNTQGSTGEGESDNFTFSFKMFTSWDYLIGNSETADNKYASITTSFKESIVDEQESNKEENIHLTRFLRVLANFLIICCLCGSGYLIYFVVKRSQQFSKMQNVSWYERNEVEIVMSLLGMFCPPLFETIAALENYHPRTGLKWQLGRIFALFLGNLYTFLLALMDDVHLKLANEETIKNITHWTLFNYYNSSGWNESVPRPPLHPADVPRGSCWETAVGIEFMRLTVSDMLVTYITILLGDFLRACFVRFMNYCWCWDLEAGFPSYAEFDISGNVLGLIFNQGMIWMGSFYAPGLVGINVLRLLTSMYFQCWAVMSSNVPHERVFKASRSNNFYMGLLLLVLFLSLLPVAYTIMSLPPSFDCGPFSGKNRMYDVLQETIENDFPTFLGKIFAFLANPGLIIPAILLMFLAIYYLNSVSKSLSRANAQLRKKIQVLREVEKSHKSVKGKATARDSEDTPKSSSKNATQLQLTKEETTPPSASQSQAMDKKAQGPGTSNSASRTTLPASGHLPISRPPGIGPDSGHAPSQTHPWRSASGKSAQRPPH |
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in fetal cochlea.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Forms the MET channel composed of TMC dimer (TMC1 or TMC2), TMIE, TOMT, CIB (CIB2 or CIB3), LHFPL5 and PDH15. The interaction of TMC1 and TMC2 with TOMT is required for the transportation of TMC1/2 into the stereocilia of hair cells. Interacts (via N-terminus) with both isoforms CD1 and CD3 of PCDH15. Can form a heterodimer with TMC1, TMC5 or TMC7.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-56 | Basic and acidic residues | ||||
Sequence: MSHQVKGLKEEARGGVKGRVKSGSPHTGDRLGRRSSSKRALKAEGTPGRRGAQRSQ | ||||||
Region | 1-150 | Disordered | ||||
Sequence: MSHQVKGLKEEARGGVKGRVKSGSPHTGDRLGRRSSSKRALKAEGTPGRRGAQRSQKERAGGSPSPGSPRRKQTGRRRHREELGEQERGEAERTCEGRRKRDERASFQERTAAPKREKEIPRREEKSKRQKKPRSSSLASSASGGESLSE | ||||||
Compositional bias | 78-132 | Basic and acidic residues | ||||
Sequence: RHREELGEQERGEAERTCEGRRKRDERASFQERTAAPKREKEIPRREEKSKRQKK | ||||||
Compositional bias | 134-148 | Polar residues | ||||
Sequence: RSSSLASSASGGESL | ||||||
Compositional bias | 800-820 | Basic and acidic residues | ||||
Sequence: EKSHKSVKGKATARDSEDTPK | ||||||
Region | 800-906 | Disordered | ||||
Sequence: EKSHKSVKGKATARDSEDTPKSSSKNATQLQLTKEETTPPSASQSQAMDKKAQGPGTSNSASRTTLPASGHLPISRPPGIGPDSGHAPSQTHPWRSASGKSAQRPPH | ||||||
Compositional bias | 821-868 | Polar residues | ||||
Sequence: SSSKNATQLQLTKEETTPPSASQSQAMDKKAQGPGTSNSASRTTLPAS |
Sequence similarities
Belongs to the TMC family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q8TDI7-1
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.
- Name1
- Length906
- Mass (Da)102,610
- Last updated2010-11-30 v3
- Checksum0EB7A3E35C870E2A
Q8TDI7-3
- Name2
Q8TDI7-4
- Name3
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8YFP4 | A0A2R8YFP4_HUMAN | TMC2 | 240 |
Sequence caution
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-56 | Basic and acidic residues | ||||
Sequence: MSHQVKGLKEEARGGVKGRVKSGSPHTGDRLGRRSSSKRALKAEGTPGRRGAQRSQ | ||||||
Alternative sequence | VSP_015279 | 1-644 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 78-132 | Basic and acidic residues | ||||
Sequence: RHREELGEQERGEAERTCEGRRKRDERASFQERTAAPKREKEIPRREEKSKRQKK | ||||||
Compositional bias | 134-148 | Polar residues | ||||
Sequence: RSSSLASSASGGESL | ||||||
Alternative sequence | VSP_015281 | 625-665 | in isoform 2 | |||
Sequence: PSYAEFDISGNVLGLIFNQGMIWMGSFYAPGLVGINVLRLL → VGHHFMDIPHKGISTIFFDTYSQMHSWAFHFFGSLMTVSAL | ||||||
Alternative sequence | VSP_015282 | 666-906 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_015283 | 727-806 | in isoform 3 | |||
Sequence: SGKNRMYDVLQETIENDFPTFLGKIFAFLANPGLIIPAILLMFLAIYYLNSVSKSLSRANAQLRKKIQVLREVEKSHKSV → RCRVSVAREHLPSRGSLLRGPRPRIPVLVSCQPVKGHGTLGESPMPFKRVFCQDGNVRSFCVCAVHFSSHQPPVAVECLK | ||||||
Compositional bias | 800-820 | Basic and acidic residues | ||||
Sequence: EKSHKSVKGKATARDSEDTPK | ||||||
Alternative sequence | VSP_015284 | 807-906 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 821-868 | Polar residues | ||||
Sequence: SSSKNATQLQLTKEETTPPSASQSQAMDKKAQGPGTSNSASRTTLPAS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF417580 EMBL· GenBank· DDBJ | AAL86401.2 EMBL· GenBank· DDBJ | mRNA | ||
AK094789 EMBL· GenBank· DDBJ | BAC04423.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK127751 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AL049712 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AY358613 EMBL· GenBank· DDBJ | AAQ88976.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |