P35523 · CLCN1_HUMAN
- ProteinChloride channel protein 1
- GeneCLCN1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids988 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Voltage-gated chloride channel involved in skeletal muscle excitability. Generates most of the plasma membrane chloride conductance in skeletal muscle fibers, stabilizes the resting membrane potential and contributes to the repolarization phase during action potential firing (PubMed:12456816, PubMed:16027167, PubMed:22521272, PubMed:22641783, PubMed:26007199, PubMed:26502825, PubMed:26510092, PubMed:7951242, PubMed:8112288, PubMed:8130334, PubMed:9122265, PubMed:9565403, PubMed:9736777).
Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Has a significant open probability at muscle resting potential and is further activated upon membrane depolarization (PubMed:10051520, PubMed:10962018, PubMed:29809153, PubMed:31022181).
Permeable to small monovalent anions with ion selectivity for chloride > thiocyanate > bromide > nitrate > iodide (PubMed:9122265, PubMed:9565403).
Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Has a significant open probability at muscle resting potential and is further activated upon membrane depolarization (PubMed:10051520, PubMed:10962018, PubMed:29809153, PubMed:31022181).
Permeable to small monovalent anions with ion selectivity for chloride > thiocyanate > bromide > nitrate > iodide (PubMed:9122265, PubMed:9565403).
Miscellaneous
Each monomer is composed of 18 alpha helices arranged in an internal pseudo-symmetry with an inverted membrane orientation. Most helices do not traverse the membrane completely.
Catalytic activity
- chloride(in) = chloride(out)
- thiocyanate(in) = thiocyanate(out)
- bromide(in) = bromide(out)
- nitrate(in) = nitrate(out)
- iodide(out) = iodide(in)
Activity regulation
Modulated by membrane voltage with depolarization favouring channel opening and hyperpolarization favouring channel closure. Inhibited by acidic pH and ATP binding due to a shift of voltage dependence of common gating to more positive voltages. Inhibited by 9-anthracene-carboxylic.
Features
Showing features for binding site, site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chloride channel complex | |
Cellular Component | plasma membrane | |
Cellular Component | T-tubule | |
Molecular Function | protein homodimerization activity | |
Molecular Function | voltage-gated chloride channel activity | |
Biological Process | chloride transmembrane transport | |
Biological Process | chloride transport | |
Biological Process | muscle contraction | |
Biological Process | neuronal action potential propagation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameChloride channel protein 1
- Short namesClC-1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP35523
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Cell membrane, sarcolemma ; Multi-pass membrane protein
Cell membrane, sarcolemma, T-tubule ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-118 | Cytoplasmic | ||||
Sequence: MEQSRSQQRGGEQSWWGSDPQYQYMPFEHCTSYGLPSENGGLQHRLRKDAGPRHNVHPTQIYGHHKEQFSDREQDIGMPKKTGSSSTVDSKDEDHYSKCQDCIHRLGQVVRRKLGEDG | ||||||
Transmembrane | 119-150 | Helical | ||||
Sequence: IFLVLLGLLMALVSWSMDYVSAKSLQAYKWSY | ||||||
Topological domain | 151-158 | Extracellular | ||||
Sequence: AQMQPSLP | ||||||
Transmembrane | 159-179 | Helical | ||||
Sequence: LQFLVWVTFPLVLILFSALFC | ||||||
Topological domain | 180-183 | Cytoplasmic | ||||
Sequence: HLIS | ||||||
Intramembrane | 184-189 | Note=Loop between two helices | ||||
Sequence: PQAVGS | ||||||
Intramembrane | 190-195 | Helical | ||||
Sequence: GIPEMK | ||||||
Topological domain | 196-208 | Cytoplasmic | ||||
Sequence: TILRGVVLKEYLT | ||||||
Intramembrane | 209-224 | Helical | ||||
Sequence: MKAFVAKVVALTAGLG | ||||||
Intramembrane | 225-230 | Note=Loop between two helices | ||||
Sequence: SGIPVG | ||||||
Intramembrane | 231-246 | Helical | ||||
Sequence: KEGPFVHIASICAAVL | ||||||
Topological domain | 247-268 | Cytoplasmic | ||||
Sequence: SKFMSVFCGVYEQPYYYSDILT | ||||||
Intramembrane | 269-280 | Helical | ||||
Sequence: VGCAVGVGCCFG | ||||||
Intramembrane | 281-290 | Helical | ||||
Sequence: TPLGGVLFSI | ||||||
Topological domain | 291-301 | Cytoplasmic | ||||
Sequence: EVTSTYFAVRN | ||||||
Transmembrane | 302-321 | Helical | ||||
Sequence: YWRGFFAATFSAFVFRVLAV | ||||||
Topological domain | 322-347 | Extracellular | ||||
Sequence: WNKDAVTITALFRTNFRMDFPFDLKE | ||||||
Transmembrane | 348-376 | Helical | ||||
Sequence: LPAFAAIGICCGLLGAVFVYLHRQVMLGV | ||||||
Topological domain | 377-390 | Cytoplasmic | ||||
Sequence: RKHKALSQFLAKHR | ||||||
Transmembrane | 391-408 | Helical | ||||
Sequence: LLYPGIVTFVIASFTFPP | ||||||
Topological domain | 409-414 | Extracellular | ||||
Sequence: GMGQFM | ||||||
Intramembrane | 415-418 | Note=Loop between two helices | ||||
Sequence: AGEL | ||||||
Intramembrane | 419-426 | Helical | ||||
Sequence: MPREAIST | ||||||
Topological domain | 427-457 | Extracellular | ||||
Sequence: LFDNNTWVKHAGDPESLGQSAVWIHPRVNVV | ||||||
Intramembrane | 458-475 | Helical | ||||
Sequence: IIIFLFFVMKFWMSIVAT | ||||||
Intramembrane | 476-482 | Note=Loop between two helices | ||||
Sequence: TMPIPCG | ||||||
Intramembrane | 483-498 | Helical | ||||
Sequence: GFMPVFVLGAAFGRLV | ||||||
Topological domain | 499-521 | Extracellular | ||||
Sequence: GEIMAMLFPDGILFDDIIYKILP | ||||||
Intramembrane | 522-538 | Helical | ||||
Sequence: GGYAVIGAAALTGAVSH | ||||||
Intramembrane | 539-540 | Note=Loop between two helices | ||||
Sequence: TV | ||||||
Intramembrane | 541-554 | Helical | ||||
Sequence: STAVICFELTGQIA | ||||||
Topological domain | 555-557 | Extracellular | ||||
Sequence: HIL | ||||||
Intramembrane | 558-571 | Helical | ||||
Sequence: PMMVAVILANMVAQ | ||||||
Intramembrane | 572-575 | Note=Loop between two helices | ||||
Sequence: SLQP | ||||||
Intramembrane | 576-578 | Helical | ||||
Sequence: SLY | ||||||
Topological domain | 579-988 | Cytoplasmic | ||||
Sequence: DSIIQVKKLPYLPDLGWNQLSKYTIFVEDIMVRDVKFVSASYTYGELRTLLQTTTVKTLPLVDSKDSMILLGSVERSELQALLQRHLCPERRLRAAQEMARKLSELPYDGKARLAGEGLPGAPPGRPESFAFVDEDEDEDLSGKSELPPSLALHPSTTAPLSPEEPNGPLPGHKQQPEAPEPAGQRPSIFQSLLHCLLGRARPTKKKTTQDSTDLVDNMSPEEIEAWEQEQLSQPVCFDSCCIDQSPFQLVEQTTLHKTHTLFSLLGLHLAYVTSMGKLRGVLALEELQKAIEGHTKSGVQLRPPLASFRNTTSTRKSTGAPPSSAENWNLPEDRPGATGTGDVIAASPETPVPSPSPEPPLSLAPGKVEGELEELELVESPGLEEELADILQGPSLRSTDEEDEDELIL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Myotonia congenita, autosomal dominant (MCAD)
- Note
- DescriptionA non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal dominant form (Thomsen disease) is less common and less severe than the autosomal recessive one (Becker disease). A milder form of autosomal dominant myotonia is characterized by isolated myotonia without muscle weakness, hypotrophy, or hypertrophy (myotonia levior).
- See alsoMIM:160800
Natural variants in MCAD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_075591 | 128 | M>V | in MCAD; dbSNP:rs80356699 | |
VAR_001586 | 161 | F>V | in MCAD and MCAR | |
VAR_075597 | 193 | E>K | in MCAD; dbSNP:rs80356686 | |
VAR_075599 | 198 | L>P | in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel; dbSNP:rs1347382107 | |
VAR_001589 | 200 | G>R | in MCAD and MCAR; dbSNP:rs1563074523 | |
VAR_001590 | 230 | G>E | in MCAD and MCAR; changed ion selectivity; loss of chloride transport; mild dominant effect; dbSNP:rs80356700 | |
VAR_001594 | 286 | V>A | in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel; dominant negative effect; dbSNP:rs80356689 | |
VAR_001595 | 290 | I>M | in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; decreased open probabilities of fast and slow gates; dominant negative effect; dbSNP:rs80356690 | |
VAR_001598 | 307 | F>S | in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; dominant negative effect; dbSNP:rs80356701 | |
VAR_001599 | 313 | A>T | in MCAD and MCAR; dbSNP:rs80356692 | |
VAR_001600 | 317 | R>Q | in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; dbSNP:rs80356702 | |
VAR_001603 | 338 | R>Q | in MCAD and MCAR; dbSNP:rs80356703 | |
VAR_077244 | 480 | P>H | in MCAD; decreased protein abundance; dbSNP:rs80356694 | |
VAR_001607 | 480 | P>L | in MCAD; loss of chloride transport; changed chloride channel activity; changed gating of the channel; dominant effect; dbSNP:rs80356694 | |
VAR_075605 | 484 | F>L | in MCAD; reduced chloride transport; changed calcium channel activity; changed channel gating; no dominant negative effect; dbSNP:rs1312002847 | |
VAR_001611 | 552 | Q>R | in MCAD and MCAR; also found in myotonia levior; reduced chloride transport; changed calcium channel activity; changed channel gating; weak dominant negative effect; dbSNP:rs80356696 | |
VAR_001612 | 556 | I>N | in MCAD and MCAR; mild form; reduced chloride transport; changed chloride channel activity; changed gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; partial dominant negative effect; dbSNP:rs80356697 | |
VAR_079520 | 950 | E>K | in MCAD; uncertain significance; dbSNP:rs201506176 |
Myotonia congenita, autosomal recessive (MCAR)
- Note
- DescriptionA non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal recessive form (Becker disease) is more severe than the autosomal dominant one (Thomsen disease).
- See alsoMIM:255700
Natural variants in MCAR
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_075588 | 43 | Q>R | in MCAR; decreased chloride transport; decreased localization to the plasma membrane; dominant negative effect on chloride transport and localization to the plasma membrane; no significant effect on chloride channel activity; no effect on homodimerization; dbSNP:rs868831424 | |
VAR_075589 | 70 | S>L | in MCAR; uncertain significance; no effect on chloride transport; dbSNP:rs769312894 | |
VAR_075590 | 82 | T>A | in MCAR; uncertain significance; no effect on chloride transport; dbSNP:rs772100356 | |
VAR_001582 | 105 | R>C | in MCAR; no effect on chloride transport; dbSNP:rs201509501 | |
VAR_001584 | 136 | D>G | in MCAR | |
VAR_075592 | 137 | Y>D | in MCAR; reduced chloride transport; decreased localization to the plasma membrane; no significant effect on chloride channel activity; dbSNP:rs748639603 | |
VAR_001585 | 150 | Y>C | in MCAR | |
VAR_075594 | 160 | Q>H | in MCAR; reduced chloride transport; decreased localization to the plasma membrane; no significant effect on chloride channel activity; dbSNP:rs771532474 | |
VAR_001586 | 161 | F>V | in MCAD and MCAR | |
VAR_075595 | 164 | W>R | in MCAR; altered chloride channel activity; dbSNP:rs1802429044 | |
VAR_001587 | 165 | V>G | in MCAR; dbSNP:rs1586485438 | |
VAR_001588 | 167 | F>L | in MCAR; no effect on chloride transport; dbSNP:rs149729531 | |
VAR_075596 | 190 | G>S | in MCAR; loss of chloride channel activity; dbSNP:rs797045032 | |
VAR_075598 | 197 | I>R | in MCAR; changed chloride channel activity | |
VAR_001589 | 200 | G>R | in MCAD and MCAR; dbSNP:rs1563074523 | |
VAR_001590 | 230 | G>E | in MCAD and MCAR; changed ion selectivity; loss of chloride transport; mild dominant effect; dbSNP:rs80356700 | |
VAR_001591 | 236 | V>L | in MCAR; loss of chloride transport; changed calcium channel activity; changed gating of the channel; dbSNP:rs776173406 | |
VAR_001592 | 261 | Y>C | in MCAR; dbSNP:rs200621976 | |
VAR_075600 | 270 | G>V | in MCAR; decreased chloride channel activity | |
VAR_075601 | 277 | C>R | in MCAR; reduced chloride transport; reduced open probabilities of both protopore and common gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; no effect on protein abundance; dbSNP:rs757109632 | |
VAR_075602 | 277 | C>Y | in MCAR; reduced chloride transport; reduced open probabilities of both protopore and common gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; changed ion selectivity; no effect on protein abundance; dbSNP:rs1802528255 | |
VAR_001593 | 285 | G>E | in MCAR; loss of chloride channel activity; dbSNP:rs150885084 | |
VAR_001596 | 291 | E>K | in MCAR; loss of calcium channel activity; no dominant negative effect; dbSNP:rs121912805 | |
VAR_001599 | 313 | A>T | in MCAD and MCAR; dbSNP:rs80356692 | |
VAR_001601 | 327 | V>I | in MCAR; due to a nucleotide substitution that can affect splicing or results in missense variant I-327; the missense variant does not affect chloride channel activity when expressed in Xenopus oocytes; dbSNP:rs774396430 | |
VAR_001602 | 329 | I>T | in MCAR | |
VAR_001603 | 338 | R>Q | in MCAD and MCAR; dbSNP:rs80356703 | |
VAR_075603 | 412 | Q>P | in MCAR; loss of chloride transport; decreased localization to the plasma membrane; loss of homodimerization; might be degraded; dbSNP:rs1279658001 | |
VAR_001604 | 413 | F>C | in MCAR; dbSNP:rs121912799 | |
VAR_001605 | 415 | A>V | in MCAR; dbSNP:rs2116854732 | |
VAR_075604 | 453 | R>W | in MCAR; uncertain significance; no effect on chloride channel activity; dbSNP:rs376026619 | |
VAR_001608 | 482 | G>R | in MCAR; dbSNP:rs746125212 | |
VAR_001609 | 485 | M>V | in MCAR; dbSNP:rs146457619 | |
VAR_001610 | 496 | R>S | in MCAR; loss of chloride channel activity; recessive; dbSNP:rs121912801 | |
VAR_075606 | 499 | G>R | in MCAR; reduced chloride transport; changed calcium channel activity; changed channel gating; dbSNP:rs121912807 | |
VAR_075607 | 527 | I>T | in MCAR; uncertain significance; dbSNP:rs1319653705 | |
VAR_075608 | 533 | T>I | in MCAR; uncertain significance | |
VAR_075609 | 536 | V>L | in MCAR; uncertain significance; dbSNP:rs777685454 | |
VAR_001611 | 552 | Q>R | in MCAD and MCAR; also found in myotonia levior; reduced chloride transport; changed calcium channel activity; changed channel gating; weak dominant negative effect; dbSNP:rs80356696 | |
VAR_001612 | 556 | I>N | in MCAD and MCAR; mild form; reduced chloride transport; changed chloride channel activity; changed gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; partial dominant negative effect; dbSNP:rs80356697 | |
VAR_001613 | 563 | V>I | in MCAR | |
VAR_075611 | 628 | L>P | in MCAR; uncertain significance; no effect on calcium channel activity | |
VAR_075612 | 640 | V>G | in MCAR; reduced calcium channel activity; dbSNP:rs1803111906 | |
VAR_001614 | 708 | F>L | in MCAR | |
VAR_075613 | 845 | G>S | in MCAR; uncertain significance; no effect on chloride channel activity; dbSNP:rs755433272 | |
VAR_075614 | 855 | G>E | in MCAR; uncertain significance; dbSNP:rs1554439879 | |
VAR_075615 | 932 | P>L | in MCAR; uncertain significance; dbSNP:rs80356706 | |
VAR_075616 | 947 | V>E | in MCAR; uncertain significance |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_075588 | 43 | in MCAR; decreased chloride transport; decreased localization to the plasma membrane; dominant negative effect on chloride transport and localization to the plasma membrane; no significant effect on chloride channel activity; no effect on homodimerization; dbSNP:rs868831424 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_075589 | 70 | in MCAR; uncertain significance; no effect on chloride transport; dbSNP:rs769312894 | |||
Sequence: S → L | ||||||
Natural variant | VAR_075590 | 82 | in MCAR; uncertain significance; no effect on chloride transport; dbSNP:rs772100356 | |||
Sequence: T → A | ||||||
Natural variant | VAR_001582 | 105 | in MCAR; no effect on chloride transport; dbSNP:rs201509501 | |||
Sequence: R → C | ||||||
Natural variant | VAR_001583 | 118 | in dbSNP:rs10282312 | |||
Sequence: G → W | ||||||
Natural variant | VAR_075591 | 128 | in MCAD; dbSNP:rs80356699 | |||
Sequence: M → V | ||||||
Natural variant | VAR_001584 | 136 | in MCAR | |||
Sequence: D → G | ||||||
Natural variant | VAR_075592 | 137 | in MCAR; reduced chloride transport; decreased localization to the plasma membrane; no significant effect on chloride channel activity; dbSNP:rs748639603 | |||
Sequence: Y → D | ||||||
Natural variant | VAR_001585 | 150 | in MCAR | |||
Sequence: Y → C | ||||||
Natural variant | VAR_075593 | 154 | no effect on chloride transport; dbSNP:rs111482384 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_075594 | 160 | in MCAR; reduced chloride transport; decreased localization to the plasma membrane; no significant effect on chloride channel activity; dbSNP:rs771532474 | |||
Sequence: Q → H | ||||||
Natural variant | VAR_001586 | 161 | in MCAD and MCAR | |||
Sequence: F → V | ||||||
Natural variant | VAR_075595 | 164 | in MCAR; altered chloride channel activity; dbSNP:rs1802429044 | |||
Sequence: W → R | ||||||
Natural variant | VAR_001587 | 165 | in MCAR; dbSNP:rs1586485438 | |||
Sequence: V → G | ||||||
Natural variant | VAR_001588 | 167 | in MCAR; no effect on chloride transport; dbSNP:rs149729531 | |||
Sequence: F → L | ||||||
Natural variant | VAR_075596 | 190 | in MCAR; loss of chloride channel activity; dbSNP:rs797045032 | |||
Sequence: G → S | ||||||
Natural variant | VAR_075597 | 193 | in MCAD; dbSNP:rs80356686 | |||
Sequence: E → K | ||||||
Natural variant | VAR_075598 | 197 | in MCAR; changed chloride channel activity | |||
Sequence: I → R | ||||||
Natural variant | VAR_075599 | 198 | in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel; dbSNP:rs1347382107 | |||
Sequence: L → P | ||||||
Natural variant | VAR_001589 | 200 | in MCAD and MCAR; dbSNP:rs1563074523 | |||
Sequence: G → R | ||||||
Natural variant | VAR_001590 | 230 | in MCAD and MCAR; changed ion selectivity; loss of chloride transport; mild dominant effect; dbSNP:rs80356700 | |||
Sequence: G → E | ||||||
Natural variant | VAR_001591 | 236 | in MCAR; loss of chloride transport; changed calcium channel activity; changed gating of the channel; dbSNP:rs776173406 | |||
Sequence: V → L | ||||||
Natural variant | VAR_001592 | 261 | in MCAR; dbSNP:rs200621976 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_075600 | 270 | in MCAR; decreased chloride channel activity | |||
Sequence: G → V | ||||||
Natural variant | VAR_075601 | 277 | in MCAR; reduced chloride transport; reduced open probabilities of both protopore and common gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; no effect on protein abundance; dbSNP:rs757109632 | |||
Sequence: C → R | ||||||
Natural variant | VAR_075602 | 277 | in MCAR; reduced chloride transport; reduced open probabilities of both protopore and common gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; changed ion selectivity; no effect on protein abundance; dbSNP:rs1802528255 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_001593 | 285 | in MCAR; loss of chloride channel activity; dbSNP:rs150885084 | |||
Sequence: G → E | ||||||
Natural variant | VAR_001594 | 286 | in MCAD; reduced chloride transport; changed calcium channel activity; changed gating of the channel; dominant negative effect; dbSNP:rs80356689 | |||
Sequence: V → A | ||||||
Natural variant | VAR_001595 | 290 | in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; decreased open probabilities of fast and slow gates; dominant negative effect; dbSNP:rs80356690 | |||
Sequence: I → M | ||||||
Mutagenesis | 290 | Changed chloride channel activity; changed gating of the channel. | ||||
Sequence: I → C, E, F, G, K, L, Q, T, V, or Y | ||||||
Natural variant | VAR_001596 | 291 | in MCAR; loss of calcium channel activity; no dominant negative effect; dbSNP:rs121912805 | |||
Sequence: E → K | ||||||
Mutagenesis | 291 | No effect on calcium channel activity. | ||||
Sequence: E → D | ||||||
Mutagenesis | 291 | Loss of calcium channel activity. | ||||
Sequence: E → L | ||||||
Natural variant | VAR_001597 | 300 | no effect on chloride transport; dbSNP:rs118066140 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_001598 | 307 | in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; dominant negative effect; dbSNP:rs80356701 | |||
Sequence: F → S | ||||||
Natural variant | VAR_001599 | 313 | in MCAD and MCAR; dbSNP:rs80356692 | |||
Sequence: A → T | ||||||
Natural variant | VAR_001600 | 317 | in MCAD; reduced chloride transport; changed chloride channel activity; changed gating of the channel; dbSNP:rs80356702 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_001601 | 327 | in MCAR; due to a nucleotide substitution that can affect splicing or results in missense variant I-327; the missense variant does not affect chloride channel activity when expressed in Xenopus oocytes; dbSNP:rs774396430 | |||
Sequence: V → I | ||||||
Natural variant | VAR_001602 | 329 | in MCAR | |||
Sequence: I → T | ||||||
Natural variant | VAR_001603 | 338 | in MCAD and MCAR; dbSNP:rs80356703 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_075603 | 412 | in MCAR; loss of chloride transport; decreased localization to the plasma membrane; loss of homodimerization; might be degraded; dbSNP:rs1279658001 | |||
Sequence: Q → P | ||||||
Natural variant | VAR_001604 | 413 | in MCAR; dbSNP:rs121912799 | |||
Sequence: F → C | ||||||
Natural variant | VAR_001605 | 415 | in MCAR; dbSNP:rs2116854732 | |||
Sequence: A → V | ||||||
Natural variant | VAR_001606 | 437 | in dbSNP:rs41276054 | |||
Sequence: A → T | ||||||
Natural variant | VAR_075604 | 453 | in MCAR; uncertain significance; no effect on chloride channel activity; dbSNP:rs376026619 | |||
Sequence: R → W | ||||||
Natural variant | VAR_077244 | 480 | in MCAD; decreased protein abundance; dbSNP:rs80356694 | |||
Sequence: P → H | ||||||
Natural variant | VAR_001607 | 480 | in MCAD; loss of chloride transport; changed chloride channel activity; changed gating of the channel; dominant effect; dbSNP:rs80356694 | |||
Sequence: P → L | ||||||
Natural variant | VAR_001608 | 482 | in MCAR; dbSNP:rs746125212 | |||
Sequence: G → R | ||||||
Natural variant | VAR_075605 | 484 | in MCAD; reduced chloride transport; changed calcium channel activity; changed channel gating; no dominant negative effect; dbSNP:rs1312002847 | |||
Sequence: F → L | ||||||
Natural variant | VAR_001609 | 485 | in MCAR; dbSNP:rs146457619 | |||
Sequence: M → V | ||||||
Natural variant | VAR_001610 | 496 | in MCAR; loss of chloride channel activity; recessive; dbSNP:rs121912801 | |||
Sequence: R → S | ||||||
Mutagenesis | 496 | Changed gating of the channel. | ||||
Sequence: R → K | ||||||
Natural variant | VAR_075606 | 499 | in MCAR; reduced chloride transport; changed calcium channel activity; changed channel gating; dbSNP:rs121912807 | |||
Sequence: G → R | ||||||
Mutagenesis | 499 | Changed gating of the channel. | ||||
Sequence: G → K or E | ||||||
Mutagenesis | 499 | No effect on gating of the channel. | ||||
Sequence: G → Q | ||||||
Mutagenesis | 500 | No effect on channel function. | ||||
Sequence: E → Q | ||||||
Natural variant | VAR_075607 | 527 | in MCAR; uncertain significance; dbSNP:rs1319653705 | |||
Sequence: I → T | ||||||
Natural variant | VAR_075608 | 533 | in MCAR; uncertain significance | |||
Sequence: T → I | ||||||
Natural variant | VAR_075609 | 536 | in MCAR; uncertain significance; dbSNP:rs777685454 | |||
Sequence: V → L | ||||||
Natural variant | VAR_036300 | 548 | in a breast cancer sample; somatic mutation; dbSNP:rs546411827 | |||
Sequence: E → K | ||||||
Natural variant | VAR_001611 | 552 | in MCAD and MCAR; also found in myotonia levior; reduced chloride transport; changed calcium channel activity; changed channel gating; weak dominant negative effect; dbSNP:rs80356696 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_001612 | 556 | in MCAD and MCAR; mild form; reduced chloride transport; changed chloride channel activity; changed gating of the channel; leads to a positive shift of the voltage dependence of channel conductance; partial dominant negative effect; dbSNP:rs80356697 | |||
Sequence: I → N | ||||||
Natural variant | VAR_001613 | 563 | in MCAR | |||
Sequence: V → I | ||||||
Natural variant | VAR_075610 | 614 | in dbSNP:rs140205115 | |||
Sequence: K → N | ||||||
Natural variant | VAR_075611 | 628 | in MCAR; uncertain significance; no effect on calcium channel activity | |||
Sequence: L → P | ||||||
Mutagenesis | 636 | Reduces the effect of adenosine nucleotides on common gate. | ||||
Sequence: T → A | ||||||
Mutagenesis | 638 | Reduces the effect of adenosine nucleotides on common gate. | ||||
Sequence: P → A | ||||||
Natural variant | VAR_075612 | 640 | in MCAR; reduced calcium channel activity; dbSNP:rs1803111906 | |||
Sequence: V → G | ||||||
Mutagenesis | 651 | Has normal sensitivity to adenosine nucleotides. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_001614 | 708 | in MCAR | |||
Sequence: F → L | ||||||
Natural variant | VAR_047779 | 727 | in dbSNP:rs13438232 | |||
Sequence: P → L | ||||||
Natural variant | VAR_075613 | 845 | in MCAR; uncertain significance; no effect on chloride channel activity; dbSNP:rs755433272 | |||
Sequence: G → S | ||||||
Mutagenesis | 847 | Reduces the effect of adenosine nucleotides on common gate. | ||||
Sequence: H → A | ||||||
Mutagenesis | 848 | Abrogates the effect of adenosine nucleotides on common gate. | ||||
Sequence: L → A | ||||||
Mutagenesis | 849 | Has normal sensitivity to adenosine nucleotides. | ||||
Sequence: A → V | ||||||
Natural variant | VAR_075614 | 855 | in MCAR; uncertain significance; dbSNP:rs1554439879 | |||
Sequence: G → E | ||||||
Natural variant | VAR_075615 | 932 | in MCAR; uncertain significance; dbSNP:rs80356706 | |||
Sequence: P → L | ||||||
Natural variant | VAR_075616 | 947 | in MCAR; uncertain significance | |||
Sequence: V → E | ||||||
Natural variant | VAR_079520 | 950 | in MCAD; uncertain significance; dbSNP:rs201506176 | |||
Sequence: E → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,417 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000094429 | 1-988 | UniProt | Chloride channel protein 1 | |||
Sequence: MEQSRSQQRGGEQSWWGSDPQYQYMPFEHCTSYGLPSENGGLQHRLRKDAGPRHNVHPTQIYGHHKEQFSDREQDIGMPKKTGSSSTVDSKDEDHYSKCQDCIHRLGQVVRRKLGEDGIFLVLLGLLMALVSWSMDYVSAKSLQAYKWSYAQMQPSLPLQFLVWVTFPLVLILFSALFCHLISPQAVGSGIPEMKTILRGVVLKEYLTMKAFVAKVVALTAGLGSGIPVGKEGPFVHIASICAAVLSKFMSVFCGVYEQPYYYSDILTVGCAVGVGCCFGTPLGGVLFSIEVTSTYFAVRNYWRGFFAATFSAFVFRVLAVWNKDAVTITALFRTNFRMDFPFDLKELPAFAAIGICCGLLGAVFVYLHRQVMLGVRKHKALSQFLAKHRLLYPGIVTFVIASFTFPPGMGQFMAGELMPREAISTLFDNNTWVKHAGDPESLGQSAVWIHPRVNVVIIIFLFFVMKFWMSIVATTMPIPCGGFMPVFVLGAAFGRLVGEIMAMLFPDGILFDDIIYKILPGGYAVIGAAALTGAVSHTVSTAVICFELTGQIAHILPMMVAVILANMVAQSLQPSLYDSIIQVKKLPYLPDLGWNQLSKYTIFVEDIMVRDVKFVSASYTYGELRTLLQTTTVKTLPLVDSKDSMILLGSVERSELQALLQRHLCPERRLRAAQEMARKLSELPYDGKARLAGEGLPGAPPGRPESFAFVDEDEDEDLSGKSELPPSLALHPSTTAPLSPEEPNGPLPGHKQQPEAPEPAGQRPSIFQSLLHCLLGRARPTKKKTTQDSTDLVDNMSPEEIEAWEQEQLSQPVCFDSCCIDQSPFQLVEQTTLHKTHTLFSLLGLHLAYVTSMGKLRGVLALEELQKAIEGHTKSGVQLRPPLASFRNTTSTRKSTGAPPSSAENWNLPEDRPGATGTGDVIAASPETPVPSPSPEPPLSLAPGKVEGELEELELVESPGLEEELADILQGPSLRSTDEEDEDELIL | |||||||
Modified residue | 886 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 886 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Predominantly expressed in skeletal muscles.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P35523 | APPBP2 Q92624 | 6 | EBI-10206780, EBI-743771 | |
BINARY | P35523 | CIDEB Q9UHD4 | 3 | EBI-10206780, EBI-7062247 | |
BINARY | P35523 | FAM9B Q8IZU0 | 3 | EBI-10206780, EBI-10175124 | |
BINARY | P35523 | PRDM5 Q9NQX1-2 | 3 | EBI-10206780, EBI-12859340 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 65-92 | Disordered | ||||
Sequence: HKEQFSDREQDIGMPKKTGSSSTVDSKD | ||||||
Motif | 188-192 | Selectivity filter part_1 | ||||
Sequence: GSGIP | ||||||
Motif | 230-234 | Selectivity filter part_2 | ||||
Sequence: GKEGP | ||||||
Motif | 482-486 | Selectivity filter part_3 | ||||
Sequence: GGFMP | ||||||
Domain | 609-668 | CBS 1 | ||||
Sequence: MVRDVKFVSASYTYGELRTLLQTTTVKTLPLVDSKDSMILLGSVERSELQALLQRHLCPE | ||||||
Region | 713-764 | Disordered | ||||
Sequence: EDEDEDLSGKSELPPSLALHPSTTAPLSPEEPNGPLPGHKQQPEAPEPAGQR | ||||||
Domain | 821-876 | CBS 2 | ||||
Sequence: IDQSPFQLVEQTTLHKTHTLFSLLGLHLAYVTSMGKLRGVLALEELQKAIEGHTKS | ||||||
Region | 880-988 | Disordered | ||||
Sequence: LRPPLASFRNTTSTRKSTGAPPSSAENWNLPEDRPGATGTGDVIAASPETPVPSPSPEPPLSLAPGKVEGELEELELVESPGLEEELADILQGPSLRSTDEEDEDELIL | ||||||
Compositional bias | 883-904 | Polar residues | ||||
Sequence: PLASFRNTTSTRKSTGAPPSSA |
Sequence similarities
Belongs to the chloride channel (TC 2.A.49) family. ClC-1/CLCN1 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length988
- Mass (Da)108,626
- Last updated2010-11-02 v3
- ChecksumCA838BCD2AF3CA68
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H7C1F4 | H7C1F4_HUMAN | CLCN1 | 100 | ||
H7C0N6 | H7C0N6_HUMAN | CLCN1 | 179 | ||
A0A3B3IU72 | A0A3B3IU72_HUMAN | CLCN1 | 988 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 697 | in Ref. 1; CAA80996/CAA81103 | ||||
Sequence: L → P | ||||||
Compositional bias | 883-904 | Polar residues | ||||
Sequence: PLASFRNTTSTRKSTGAPPSSA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z25587 EMBL· GenBank· DDBJ | CAA80996.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25884 EMBL· GenBank· DDBJ | CAA81103.1 EMBL· GenBank· DDBJ | mRNA | ||
CH236959 EMBL· GenBank· DDBJ | EAL23786.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC112156 EMBL· GenBank· DDBJ | AAI12157.1 EMBL· GenBank· DDBJ | mRNA | ||
BC113495 EMBL· GenBank· DDBJ | AAI13496.1 EMBL· GenBank· DDBJ | mRNA | ||
M97820 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
L08261 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
L08262 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
L08263 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
L08264 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
L08265 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
Z25753 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25754 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25755 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25756 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25757 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25758 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25759 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25760 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25761 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25762 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25763 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25764 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25765 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25766 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25767 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25752 EMBL· GenBank· DDBJ | CAB56792.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25768 EMBL· GenBank· DDBJ | CAB56814.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z25872 EMBL· GenBank· DDBJ | CAB56814.1 EMBL· GenBank· DDBJ | Genomic DNA |