Q53R12 · T4S20_HUMAN
- ProteinTransmembrane 4 L6 family member 20
- GeneTM4SF20
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids229 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Polytopic transmembrane protein that inhibits regulated intramembrane proteolysis (RIP) of CREB3L1, inhibiting its activation and the induction of collagen synthesis (PubMed:25310401, PubMed:27499293).
In response to ceramide, which alters TM4SF20 membrane topology, stimulates RIP activation of CREB3L1 (PubMed:27499293).
Ceramide reverses the direction through which transmembrane helices are translocated into the endoplasmic reticulum membrane during translation of TM4SF20, this mechanism is called 'regulated alternative translocation' (RAT) and regulates the function of the transmembrane protein (PubMed:27499293).
In response to ceramide, which alters TM4SF20 membrane topology, stimulates RIP activation of CREB3L1 (PubMed:27499293).
Ceramide reverses the direction through which transmembrane helices are translocated into the endoplasmic reticulum membrane during translation of TM4SF20, this mechanism is called 'regulated alternative translocation' (RAT) and regulates the function of the transmembrane protein (PubMed:27499293).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 13-14 | Cleavage | ||||
Sequence: FS |
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 | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | focal adhesion | |
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Biological Process | negative regulation of proteolysis |
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameTransmembrane 4 L6 family member 20
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ53R12
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Multi-pass membrane protein
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Note: Ceramide alters the direction through which transmembrane helices are translocated into the endoplasmic reticulum membrane during translation of TM4SF20.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-14 | Lumenal | ||||
Sequence: MTCCEGWTSCNGFS | ||||||
Transmembrane | 15-35 | Helical | ||||
Sequence: LLVLLLLGVVLNAIPLIVSLV | ||||||
Topological domain | 36-44 | Cytoplasmic | ||||
Sequence: EEDQFSQNP | ||||||
Transmembrane | 45-65 | Helical | ||||
Sequence: ISCFEWWFPGIIGAGLMAIPA | ||||||
Topological domain | 66-83 | Lumenal | ||||
Sequence: TTMSLTARKRACCNNRTG | ||||||
Transmembrane | 84-104 | Helical | ||||
Sequence: MFLSSLFSVITVIGALYCMLI | ||||||
Topological domain | 105-185 | Cytoplasmic | ||||
Sequence: SIQALLKGPLMCNSPSNSNANCEFSLKNISDIHPESFNLQWFFNDSCAPPTGFNKPTSNDTMASGWRASSFHFDSEENKHR | ||||||
Transmembrane | 186-206 | Helical | ||||
Sequence: LIHFSVFLGLLLVGILEVLFG | ||||||
Topological domain | 207-229 | Lumenal | ||||
Sequence: LSQIVIGFLGCLCGVSKRRSQIV |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Specific language impairment 5 (SLI5)
- Note
- DescriptionA disorder characterized by a delay in early speech acquisition. It is usually associated with cerebral white matter abnormalities on brain MRI. Some individuals may show disorders in communication, consistent with autism spectrum disorder, or global developmental delay, although others ultimately show normal cognitive function. Penetrance is incomplete and expressivity is variable.
- See alsoMIM:615432
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 12 | No effect on cleavage of the first 13 residues. | ||||
Sequence: G → P | ||||||
Mutagenesis | 13 | No effect on cleavage of the first 13 residues. | ||||
Sequence: F → P | ||||||
Mutagenesis | 14 | Abolishes cleavage of the first 13 residues. | ||||
Sequence: S → P | ||||||
Mutagenesis | 15 | No effect on cleavage of the first 13 residues. | ||||
Sequence: L → P | ||||||
Mutagenesis | 16 | No effect on cleavage of the first 13 residues. | ||||
Sequence: L → P | ||||||
Mutagenesis | 22 | Inverts transmembrane topology. Induces cleavage of CREB3L1. | ||||
Sequence: G → L | ||||||
Mutagenesis | 26 | Inverts transmembrane topology. | ||||
Sequence: N → L | ||||||
Natural variant | VAR_027673 | 27 | in dbSNP:rs7574414 | |||
Sequence: A → V | ||||||
Mutagenesis | 80 | No effect on glycosylation upon ceramide treatment. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 132 | Reduces glycosylation upon ceramide treatment. Abolishes glycosylation upon ceramide treatment; when associated with Q-132 and Q-163. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 148 | Reduces glycosylation upon ceramide treatment. Abolishes glycosylation upon ceramide treatment; when associated with Q-132 and Q-163. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 163 | Reduces glycosylation upon ceramide treatment. Abolishes glycosylation upon ceramide treatment; when associated with Q-132 and Q-148. | ||||
Sequence: N → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 272 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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000251228 | 1-229 | Transmembrane 4 L6 family member 20 | |||
Sequence: MTCCEGWTSCNGFSLLVLLLLGVVLNAIPLIVSLVEEDQFSQNPISCFEWWFPGIIGAGLMAIPATTMSLTARKRACCNNRTGMFLSSLFSVITVIGALYCMLISIQALLKGPLMCNSPSNSNANCEFSLKNISDIHPESFNLQWFFNDSCAPPTGFNKPTSNDTMASGWRASSFHFDSEENKHRLIHFSVFLGLLLVGILEVLFGLSQIVIGFLGCLCGVSKRRSQIV |
Post-translational modification
Glycosylated at Asn-132, Asn-148 and Asn-163 in presence of ceramide which inverts the orientation of TM4SF20 in membranes exposing these residues to the endoplasmic reticulum lumen.
Cleaved by signal peptidase at Ser-14 but the peptide does not act as a signal peptide. Cleavage is inhibited by ceramide which inverts the orientation of TM4SF20 in membranes exposing the N-terminus to the cytosol and not to the endoplasmic reticulum lumen.
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the brain, with high levels in the parietal lobe, hippocampus, pons, white matter and cerebellum.
Induction
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q53R12 | NINJ2 Q9NZG7 | 3 | EBI-1805798, EBI-10317425 | |
BINARY | Q53R12 | VAMP3 Q15836 | 3 | EBI-1805798, EBI-722343 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Domain
The first transmembrane helix plays a critical role for the insertion orientation in the endoplasmic reticulum membrane.
Sequence similarities
Belongs to the L6 tetraspanin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length229
- Mass (Da)25,075
- Last updated2005-05-24 v1
- Checksum1718E0594997A1A1
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9JES4 | C9JES4_HUMAN | TM4SF20 | 14 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 89 | in Ref. 1; AAQ89034 and 4; AAH35754 | ||||
Sequence: L → F |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY358671 EMBL· GenBank· DDBJ | AAQ89034.1 EMBL· GenBank· DDBJ | mRNA | ||
AK026453 EMBL· GenBank· DDBJ | BAB15488.1 EMBL· GenBank· DDBJ | mRNA | ||
AC097662 EMBL· GenBank· DDBJ | AAY24253.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC035754 EMBL· GenBank· DDBJ | AAH35754.1 EMBL· GenBank· DDBJ | mRNA | ||
BC137256 EMBL· GenBank· DDBJ | AAI37257.1 EMBL· GenBank· DDBJ | mRNA | ||
BC137257 EMBL· GenBank· DDBJ | AAI37258.1 EMBL· GenBank· DDBJ | mRNA |