Q8N6F1 · CLD19_HUMAN
- ProteinClaudin-19
- GeneCLDN19
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids224 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Forms paracellular channels: coassembles with CLDN16 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability (PubMed:18188451, PubMed:28028216).
Involved in the maintenance of ion gradients along the nephron. In the thick ascending limb (TAL) of Henle's loop, facilitates sodium paracellular permeability from the interstitial compartment to the lumen, contributing to the lumen-positive transepithelial potential that drives paracellular magnesium and calcium reabsorption (By similarity) (PubMed:17033971, PubMed:25555744).
Forms paracellular barriers on its own. In the peripheral nervous system, represents a major constituent of the tight junctions in Schwann cells and contributes to electrical sealing. During retinal neurogenesis, may regulate the barrier properties of tight junctions in retinal pigment epithelium, required for proper retinal tissue differentiation and vision (By similarity) (PubMed:17033971, PubMed:30937396).
Involved in the maintenance of ion gradients along the nephron. In the thick ascending limb (TAL) of Henle's loop, facilitates sodium paracellular permeability from the interstitial compartment to the lumen, contributing to the lumen-positive transepithelial potential that drives paracellular magnesium and calcium reabsorption (By similarity) (PubMed:17033971, PubMed:25555744).
Forms paracellular barriers on its own. In the peripheral nervous system, represents a major constituent of the tight junctions in Schwann cells and contributes to electrical sealing. During retinal neurogenesis, may regulate the barrier properties of tight junctions in retinal pigment epithelium, required for proper retinal tissue differentiation and vision (By similarity) (PubMed:17033971, PubMed:30937396).
Catalytic activity
- Mg2+(in) = Mg2+(out)
- Ca2+(in) = Ca2+(out)
- Na+(in) = Na+(out)
- K+(in) = K+(out)
- Rb+(in) = Rb+(out)
- Cs+(in) = Cs+(out)
- Li+(in) = Li+(out)
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameClaudin-19
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8N6F1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: Cotrafficks with CLDN16 from ER to tight junctions. Colocalizes with CLDN16 and CLDN3 in cell-cell contact areas of the TAL spatially separated from CLDN10b paracellular channels.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-7 | Cytoplasmic | ||||
Sequence: MANSGLQ | ||||||
Transmembrane | 8-28 | Helical | ||||
Sequence: LLGYFLALGGWVGIIASTALP | ||||||
Topological domain | 29-81 | Extracellular | ||||
Sequence: QWKQSSYAGDAIITAVGLYEGLWMSCASQSTGQVQCKLYDSLLALDGHIQSAR | ||||||
Transmembrane | 82-102 | Helical | ||||
Sequence: ALMVVAVLLGFVAMVLSVVGM | ||||||
Topological domain | 103-117 | Cytoplasmic | ||||
Sequence: KCTRVGDSNPIAKGR | ||||||
Transmembrane | 118-138 | Helical | ||||
Sequence: VAIAGGALFILAGLCTLTAVS | ||||||
Topological domain | 139-160 | Extracellular | ||||
Sequence: WYATLVTQEFFNPSTPVNARYE | ||||||
Transmembrane | 161-181 | Helical | ||||
Sequence: FGPALFVGWASAGLAVLGGSF | ||||||
Topological domain | 182-224 | Cytoplasmic | ||||
Sequence: LCCTCPEPERPNSSPQPYRPGPSAAAREPVVKLPASAKGPLGV |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Hypomagnesemia 5, renal, with or without ocular involvement (HOMG5)
- Note
- DescriptionA progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. The renal phenotype is virtually undistinguishable from that of patients with HOMG3.
- See alsoMIM:248190
Natural variants in HOMG5
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_031239 | 20 | G>D | in HOMG5; ER retention of the mutant protein; more than 90% decrease of homomeric interactions; loss of interaction with CLDN16; loss of cation-selective paracellular permeability; when overexpressed in the retina of PN0 mice, leads to retinal degeneration characterized by altered morphology of bipolar cells, shortened bipolar axon and dendrite lengths and decreased light response; no effect on interaction with CLDN18; dbSNP:rs118203979 | |
VAR_031240 | 57 | Q>E | in HOMG5; localizes throughout the apical part of polarized epithelia in a diffuse pattern; more than 90% decrease of homomeric interactions; loss of interaction with CLDN16; loss of cation-selective paracellular permeability; no effect on interaction with CLDN18; dbSNP:rs118203980 | |
VAR_089378 | 81 | R>W | in HOMG5; partial localization at the lateral membrane and partial intracellular; when overexpressed in the retina of PN0 mice, leads to retinal degeneration characterized by altered morphology of bipolar cells, shortened bipolar axon and dendrite lengths and decreased light response; dbSNP:rs1450421453 | |
VAR_031241 | 90 | L>P | in HOMG5; localizes at tight junctions; slight decrease of homomeric interactions; more than 70% decrease of interaction with CLDN16 associated with impaired functional synergistic effects on ion selectivity; partial loss of cation-selective paracellular permeability; no effect on interaction with CLDN18; dbSNP:rs118203981 | |
VAR_089379 | 123 | G>R | in HOMG5; localizes at tight junctions; slight decrease of homomeric interactions; more than 70% decrease of interaction with CLDN16 associated with impaired functional synergistic effects on ion selectivity; partial loss of cation-selective paracellular permeability; no effect on interaction with CLDN18 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_031238 | 13 | in dbSNP:rs12065961 | |||
Sequence: L → F | ||||||
Natural variant | VAR_031239 | 20 | in HOMG5; ER retention of the mutant protein; more than 90% decrease of homomeric interactions; loss of interaction with CLDN16; loss of cation-selective paracellular permeability; when overexpressed in the retina of PN0 mice, leads to retinal degeneration characterized by altered morphology of bipolar cells, shortened bipolar axon and dendrite lengths and decreased light response; no effect on interaction with CLDN18; dbSNP:rs118203979 | |||
Sequence: G → D | ||||||
Natural variant | VAR_031240 | 57 | in HOMG5; localizes throughout the apical part of polarized epithelia in a diffuse pattern; more than 90% decrease of homomeric interactions; loss of interaction with CLDN16; loss of cation-selective paracellular permeability; no effect on interaction with CLDN18; dbSNP:rs118203980 | |||
Sequence: Q → E | ||||||
Natural variant | VAR_089378 | 81 | in HOMG5; partial localization at the lateral membrane and partial intracellular; when overexpressed in the retina of PN0 mice, leads to retinal degeneration characterized by altered morphology of bipolar cells, shortened bipolar axon and dendrite lengths and decreased light response; dbSNP:rs1450421453 | |||
Sequence: R → W | ||||||
Natural variant | VAR_031241 | 90 | in HOMG5; localizes at tight junctions; slight decrease of homomeric interactions; more than 70% decrease of interaction with CLDN16 associated with impaired functional synergistic effects on ion selectivity; partial loss of cation-selective paracellular permeability; no effect on interaction with CLDN18; dbSNP:rs118203981 | |||
Sequence: L → P | ||||||
Natural variant | VAR_089379 | 123 | in HOMG5; localizes at tight junctions; slight decrease of homomeric interactions; more than 70% decrease of interaction with CLDN16 associated with impaired functional synergistic effects on ion selectivity; partial loss of cation-selective paracellular permeability; no effect on interaction with CLDN18 | |||
Sequence: G → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 245 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, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000144781 | 1-224 | Claudin-19 | |||
Sequence: MANSGLQLLGYFLALGGWVGIIASTALPQWKQSSYAGDAIITAVGLYEGLWMSCASQSTGQVQCKLYDSLLALDGHIQSARALMVVAVLLGFVAMVLSVVGMKCTRVGDSNPIAKGRVAIAGGALFILAGLCTLTAVSWYATLVTQEFFNPSTPVNARYEFGPALFVGWASAGLAVLGGSFLCCTCPEPERPNSSPQPYRPGPSAAAREPVVKLPASAKGPLGV | ||||||
Disulfide bond | 54↔64 | |||||
Sequence: CASQSTGQVQC |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Can form homo- and heteropolymeric tight junction strands. Interacts with other claudins including CLDN3, CLDN10, CLDN16 and CLDN18 with highest affinity for CLDN16 (PubMed:18188451, PubMed:19706394, PubMed:28028216, PubMed:36008380).
Interacts (via PDZ-binding motif TRV) with TJP1 (via PDZ domain) (By similarity).
Interacts (via PDZ-binding motif TRV) with TJP1 (via PDZ domain) (By similarity).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 191-224 | Disordered | ||||
Sequence: RPNSSPQPYRPGPSAAAREPVVKLPASAKGPLGV |
Sequence similarities
Belongs to the claudin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q8N6F1-1
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
- Length224
- Mass (Da)23,229
- Last updated2004-05-24 v2
- Checksum60E1A21902415219
Q8N6F1-2
- Name2
- Differences from canonical
- 210-224: PVVKLPASAKGPLGV → YV
Q8N6F1-3
- Name3
- Differences from canonical
- 131-224: LCTLTAVSWYATLVTQEFFNPSTPVNARYEFGPALFVGWASAGLAVLGGSFLCCTCPEPERPNSSPQPYRPGPSAAAREPVVKLPASAKGPLGV → MNLAQPCSWAGPQLAWPCWAAPSSAAHARSQRDPTAAHSPIGLDPLLLPESTSELRLPWPAPHPVAPLPSIQPASQHPGQGHWGIGWA
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 46 | in Ref. 2; BAC04691 | ||||
Sequence: L → P | ||||||
Alternative sequence | VSP_044839 | 131-224 | in isoform 3 | |||
Sequence: LCTLTAVSWYATLVTQEFFNPSTPVNARYEFGPALFVGWASAGLAVLGGSFLCCTCPEPERPNSSPQPYRPGPSAAAREPVVKLPASAKGPLGV → MNLAQPCSWAGPQLAWPCWAAPSSAAHARSQRDPTAAHSPIGLDPLLLPESTSELRLPWPAPHPVAPLPSIQPASQHPGQGHWGIGWA | ||||||
Sequence conflict | 186 | In isoform Q8N6F1-3; in Ref. 2; BAH12918 | ||||
Sequence: R → C | ||||||
Alternative sequence | VSP_010342 | 210-224 | in isoform 2 | |||
Sequence: PVVKLPASAKGPLGV → YV |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF497644 EMBL· GenBank· DDBJ | AAQ07256.1 EMBL· GenBank· DDBJ | mRNA | ||
AK096063 EMBL· GenBank· DDBJ | BAC04691.1 EMBL· GenBank· DDBJ | mRNA | ||
AK298992 EMBL· GenBank· DDBJ | BAH12918.1 EMBL· GenBank· DDBJ | mRNA | ||
AC098484 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471059 EMBL· GenBank· DDBJ | EAX07147.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC030524 EMBL· GenBank· DDBJ | AAH30524.1 EMBL· GenBank· DDBJ | mRNA |