T4S5_HUMAN
ID T4S5_HUMAN Reviewed; 197 AA.
AC O14894; Q17RW9; Q6IB79;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Transmembrane 4 L6 family member 5;
DE AltName: Full=Tetraspan transmembrane protein L6H;
GN Name=TM4SF5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9479038; DOI=10.1016/s0378-1119(97)00633-1;
RA Mueller-Pillasch F., Wallrapp C., Lacher U., Friess H., Buchler M.,
RA Adler G., Gress T.M.;
RT "Identification of a new tumour-associated antigen TM4SF5 and its
RT expression in human cancer.";
RL Gene 208:25-30(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION.
RX PubMed=20399237; DOI=10.1016/j.bbamcr.2010.04.001;
RA Kim H., Kang M., Lee S.A., Kwak T.K., Jung O., Lee H.J., Kim S.H.,
RA Lee J.W.;
RT "TM4SF5 accelerates G1/S phase progression via cytosolic p27Kip1 expression
RT and RhoA activity.";
RL Biochim. Biophys. Acta 1803:975-982(2010).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MTOR; SLC38A9; CASTOR1 AND
RP SLC7A1, ARGININE-BINDING, AND MUTAGENESIS OF TRP-124; GLY-125; TYR-126;
RP HIS-127; PHE-128 AND GLU-129.
RX PubMed=30956113; DOI=10.1016/j.cmet.2019.03.005;
RA Jung J.W., Macalino S.J.Y., Cui M., Kim J.E., Kim H.J., Song D.G.,
RA Nam S.H., Kim S., Choi S., Lee J.W.;
RT "Transmembrane 4 L six family member 5 senses arginine for mTORC1
RT signaling.";
RL Cell Metab. 29:1306-1319(2019).
CC -!- FUNCTION: Acts as a lysosomal membrane arginine sensor
CC (PubMed:30956113). Forms a complex with MTOR and SLC38A9 on lysosomal
CC membranes in an arginine-regulated manner, leading to arginine efflux
CC which enables the activation of mTORC1 which subsequently leads to
CC RPS6KB1 and EIF4EBP1 phosphorylations (PubMed:30956113). Facilitates
CC cell cycle G1/S phase progression and the translocation of the CDK4-
CC CCND1 complex into the nucleus (PubMed:20399237). CDKN1B and RHOA/ROCK
CC signaling activity are involved in TM4SF5-mediated acceleration of G1/S
CC phase progression (PubMed:20399237). {ECO:0000269|PubMed:20399237,
CC ECO:0000269|PubMed:30956113}.
CC -!- SUBUNIT: Interacts with MTOR; the interaction is positively regulated
CC by arginine and is negatively regulated by leucine (PubMed:30956113).
CC Interacts with SLC38A9 (PubMed:30956113). Interacts with SLC7A1; the
CC interaction is negatively regulated by arginine (PubMed:30956113).
CC Interacts with CASTOR1; the interaction is positively regulated by
CC leucine and is negatively regulated by arginine (PubMed:30956113).
CC {ECO:0000269|PubMed:30956113}.
CC -!- INTERACTION:
CC O14894; Q86WK6: AMIGO1; NbExp=3; IntAct=EBI-19125949, EBI-19125216;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:30956113};
CC Multi-pass membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000269|PubMed:30956113}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localization to cell membrane increases during
CC conditions of arginine depletion and translocation to lysosome membrane
CC seen upon arginine repletion. {ECO:0000269|PubMed:30956113}.
CC -!- TISSUE SPECIFICITY: Intestine. Overexpressed in pancreatic cancers.
CC -!- SIMILARITY: Belongs to the L6 tetraspanin family. {ECO:0000305}.
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DR EMBL; AF027204; AAB82947.1; -; mRNA.
DR EMBL; CR456925; CAG33206.1; -; mRNA.
DR EMBL; BC069519; AAH69519.1; -; mRNA.
DR EMBL; BC093688; AAH93688.1; -; mRNA.
DR EMBL; BC117163; AAI17164.1; -; mRNA.
DR CCDS; CCDS11054.1; -.
DR PIR; JC6544; JC6544.
DR RefSeq; NP_003954.2; NM_003963.2.
DR AlphaFoldDB; O14894; -.
DR BioGRID; 114498; 31.
DR IntAct; O14894; 2.
DR STRING; 9606.ENSP00000270560; -.
DR ChEMBL; CHEMBL4523127; -.
DR TCDB; 8.A.75.1.5; the transmembrane 4 l6 (tm4l6) family.
DR GlyGen; O14894; 2 sites.
DR BioMuta; TM4SF5; -.
DR MassIVE; O14894; -.
DR PaxDb; O14894; -.
DR PeptideAtlas; O14894; -.
DR PRIDE; O14894; -.
DR ProteomicsDB; 48285; -.
DR ABCD; O14894; 3 sequenced antibodies.
DR Antibodypedia; 51548; 34 antibodies from 10 providers.
DR DNASU; 9032; -.
DR Ensembl; ENST00000270560.4; ENSP00000270560.3; ENSG00000142484.7.
DR GeneID; 9032; -.
DR KEGG; hsa:9032; -.
DR MANE-Select; ENST00000270560.4; ENSP00000270560.3; NM_003963.3; NP_003954.2.
DR UCSC; uc002fyw.1; human.
DR CTD; 9032; -.
DR DisGeNET; 9032; -.
DR GeneCards; TM4SF5; -.
DR HGNC; HGNC:11857; TM4SF5.
DR HPA; ENSG00000142484; Group enriched (intestine, liver).
DR MIM; 604657; gene.
DR neXtProt; NX_O14894; -.
DR OpenTargets; ENSG00000142484; -.
DR PharmGKB; PA36558; -.
DR VEuPathDB; HostDB:ENSG00000142484; -.
DR eggNOG; ENOG502RBE1; Eukaryota.
DR GeneTree; ENSGT01030000234590; -.
DR HOGENOM; CLU_087168_1_0_1; -.
DR InParanoid; O14894; -.
DR OMA; CVEPPGV; -.
DR OrthoDB; 922490at2759; -.
DR PhylomeDB; O14894; -.
DR TreeFam; TF331371; -.
DR PathwayCommons; O14894; -.
DR SignaLink; O14894; -.
DR BioGRID-ORCS; 9032; 9 hits in 1062 CRISPR screens.
DR ChiTaRS; TM4SF5; human.
DR GeneWiki; TM4SF5; -.
DR GenomeRNAi; 9032; -.
DR Pharos; O14894; Tbio.
DR PRO; PR:O14894; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O14894; protein.
DR Bgee; ENSG00000142484; Expressed in jejunal mucosa and 60 other tissues.
DR Genevisible; O14894; HS.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0034618; F:arginine binding; IMP:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IDA:UniProtKB.
DR InterPro; IPR008661; L6_membrane.
DR PANTHER; PTHR14198; PTHR14198; 1.
DR Pfam; PF05805; L6_membrane; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell membrane; Glycoprotein; Lysosome; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..197
FT /note="Transmembrane 4 L6 family member 5"
FT /id="PRO_0000219303"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..46
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 47..67
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..90
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 91..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..157
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..197
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 91..197
FT /note="Interaction with MTOR and CASTOR1"
FT /evidence="ECO:0000269|PubMed:30956113"
FT BINDING 124..129
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:30956113"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 124
FT /note="W->A: Disrupts arginine-binding."
FT /evidence="ECO:0000269|PubMed:30956113"
FT MUTAGEN 125
FT /note="G->A: Disrupts arginine-binding."
FT /evidence="ECO:0000269|PubMed:30956113"
FT MUTAGEN 126
FT /note="Y->S: Disrupts arginine-binding."
FT /evidence="ECO:0000269|PubMed:30956113"
FT MUTAGEN 127
FT /note="H->A: Disrupts arginine-binding."
FT /evidence="ECO:0000269|PubMed:30956113"
FT MUTAGEN 128
FT /note="F->S: Disrupts arginine-binding."
FT /evidence="ECO:0000269|PubMed:30956113"
FT MUTAGEN 129
FT /note="E->A: Disrupts arginine-binding."
FT /evidence="ECO:0000269|PubMed:30956113"
FT CONFLICT 19
FT /note="L -> F (in Ref. 1; AAB82947)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 197 AA; 20823 MW; 051AEB5ECCE1075C CRC64;
MCTGKCARCV GLSLITLCLV CIVANALLLV PNGETSWTNT NHLSLQVWLM GGFIGGGLMV
LCPGIAAVRA GGKGCCGAGC CGNRCRMLRS VFSSAFGVLG AIYCLSVSGA GLRNGPRCLM
NGEWGYHFED TAGAYLLNRT LWDRCEAPPR VVPWNVTLFS LLVAASCLEI VLCGIQLVNA
TIGVFCGDCR KKQDTPH
