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Protein

Transmembrane 4 L6 family member 20

Gene

TM4SF20

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).2 Publications

GO - Biological processi

  • negative regulation of proteolysis Source: UniProtKB

Protein family/group databases

TCDBi8.A.75.1.4. the transmembrane 4 superfamily 4 (tm4sf4) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane 4 L6 family member 20
Gene namesi
Name:TM4SF20
ORF Names:UNQ518/PRO994
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000168955.3.
HGNCiHGNC:26230. TM4SF20.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 14LumenalCuratedAdd BLAST14
Transmembranei15 – 35HelicalSequence analysisAdd BLAST21
Topological domaini36 – 44CytoplasmicCurated9
Transmembranei45 – 65HelicalSequence analysisAdd BLAST21
Topological domaini66 – 83LumenalCuratedAdd BLAST18
Transmembranei84 – 104HelicalSequence analysisAdd BLAST21
Topological domaini105 – 185CytoplasmicCuratedAdd BLAST81
Transmembranei186 – 206HelicalSequence analysisAdd BLAST21
Topological domaini207 – 229LumenalCuratedAdd BLAST23

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Specific language impairment 5 (SLI5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:615432

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi12G → P: No effect on cleavage of the first 13 residues. 1 Publication1
Mutagenesisi13F → P: No effect on cleavage of the first 13 residues. 1 Publication1
Mutagenesisi14S → P: Abolishes cleavage of the first 13 residues. 1 Publication1
Mutagenesisi15L → P: No effect on cleavage of the first 13 residues. 1 Publication1
Mutagenesisi16L → P: No effect on cleavage of the first 13 residues. 1 Publication1
Mutagenesisi22G → L: Inverts transmembrane topology. Induces cleavage of CREB3L1. 1 Publication1
Mutagenesisi26N → L: Inverts transmembrane topology. 1 Publication1
Mutagenesisi80N → Q: No effect on glycosylation upon ceramide treatment. 1 Publication1
Mutagenesisi132N → Q: Reduces glycosylation upon ceramide treatment. Abolishes glycosylation upon ceramide treatment; when associated with Q-132 and Q-163. 1 Publication1
Mutagenesisi148N → Q: Reduces glycosylation upon ceramide treatment. Abolishes glycosylation upon ceramide treatment; when associated with Q-132 and Q-163. 1 Publication1
Mutagenesisi163N → Q: Reduces glycosylation upon ceramide treatment. Abolishes glycosylation upon ceramide treatment; when associated with Q-132 and Q-148. 1 Publication1

Keywords - Diseasei

Autism spectrum disorder

Organism-specific databases

MalaCardsiTM4SF20.
MIMi615432. phenotype.
OpenTargetsiENSG00000168955.
PharmGKBiPA142670803.

Polymorphism and mutation databases

BioMutaiTM4SF20.
DMDMi74726514.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002512281 – 229Transmembrane 4 L6 family member 20Add BLAST229

Post-translational modificationi

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.1 Publication
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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei13 – 14Cleavage1 Publication2

Proteomic databases

MaxQBiQ53R12.
PaxDbiQ53R12.
PeptideAtlasiQ53R12.
PRIDEiQ53R12.

Expressioni

Tissue specificityi

Expressed in the brain, with high levels in the parietal lobe, hippocampus, pons, white matter and cerebellum.1 Publication

Inductioni

TGFB1 inhibits TM4SF20 expression to activate CREB3L1 (PubMed:25310401).1 Publication

Gene expression databases

BgeeiENSG00000168955.
CleanExiHS_TM4SF20.
ExpressionAtlasiQ53R12. baseline and differential.
GenevisibleiQ53R12. HS.

Organism-specific databases

HPAiHPA051838.
HPA063184.
HPA065531.

Interactioni

Protein-protein interaction databases

BioGridi122943. 12 interactors.
IntActiQ53R12. 1 interactor.

Structurei

3D structure databases

ProteinModelPortaliQ53R12.
SMRiQ53R12.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The first transmembrane helix plays a critical role for the insertion orientation in the endoplasmic reticulum membrane.1 Publication

Sequence similaritiesi

Belongs to the L6 tetraspanin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IH9I. Eukaryota.
ENOG410YJG8. LUCA.
GeneTreeiENSGT00640000091587.
HOGENOMiHOG000154492.
HOVERGENiHBG094021.
InParanoidiQ53R12.
OMAiMTCCEGW.
OrthoDBiEOG091G0L43.
PhylomeDBiQ53R12.
TreeFamiTF331371.

Family and domain databases

InterProiView protein in InterPro
IPR008661. L6_membrane.
PfamiView protein in Pfam
PF05805. L6_membrane. 1 hit.

Sequencei

Sequence statusi: Complete.

Q53R12-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTCCEGWTSC NGFSLLVLLL LGVVLNAIPL IVSLVEEDQF SQNPISCFEW
60 70 80 90 100
WFPGIIGAGL MAIPATTMSL TARKRACCNN RTGMFLSSLF SVITVIGALY
110 120 130 140 150
CMLISIQALL KGPLMCNSPS NSNANCEFSL KNISDIHPES FNLQWFFNDS
160 170 180 190 200
CAPPTGFNKP TSNDTMASGW RASSFHFDSE ENKHRLIHFS VFLGLLLVGI
210 220
LEVLFGLSQI VIGFLGCLCG VSKRRSQIV
Length:229
Mass (Da):25,075
Last modified:May 24, 2005 - v1
Checksum:i1718E0594997A1A1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti89L → F in AAQ89034 (PubMed:12975309).Curated1
Sequence conflicti89L → F in AAH35754 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02767327A → V2 PublicationsCorresponds to variant dbSNP:rs7574414Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358671 mRNA. Translation: AAQ89034.1.
AK026453 mRNA. Translation: BAB15488.1.
AC097662 Genomic DNA. Translation: AAY24253.1.
BC035754 mRNA. Translation: AAH35754.1.
BC137256 mRNA. Translation: AAI37257.1.
BC137257 mRNA. Translation: AAI37258.1.
CCDSiCCDS2466.1.
RefSeqiNP_079071.2. NM_024795.4.
UniGeneiHs.156652.

Genome annotation databases

EnsembliENST00000304568; ENSP00000303028; ENSG00000168955.
GeneIDi79853.
KEGGihsa:79853.
UCSCiuc002vpb.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiT4S20_HUMAN
AccessioniPrimary (citable) accession number: Q53R12
Secondary accession number(s): B2RP42
, Q5U609, Q6UWS1, Q9H5X9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: May 24, 2005
Last modified: September 27, 2017
This is version 88 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families