TM6S2_HUMAN
ID TM6S2_HUMAN Reviewed; 377 AA.
AC Q9BZW4; Q0IJ64;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Transmembrane 6 superfamily member 2;
GN Name=TM6SF2;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-377 (ISOFORM 2).
RX PubMed=11124529; DOI=10.1159/000056784;
RA Carim-Todd L., Escarceller M., Estivill X., Sumoy L.;
RT "Cloning of the novel gene TM6SF1 reveals conservation of clusters of
RT paralogous genes between human chromosomes 15q24-q26 and 19p13.3-p12.";
RL Cytogenet. Cell Genet. 90:255-260(2000).
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 POSSIBLE FUNCTION AS STEROL ISOMERASE, AND IDENTIFICATION OF EXPERA DOMAIN.
RX PubMed=25566323; DOI=10.3389/fgene.2014.00439;
RA Sanchez-Pulido L., Ponting C.P.;
RT "TM6SF2 and MAC30, new enzyme homologs in sterol metabolism and common
RT metabolic disease.";
RL Front. Genet. 5:439-439(2014).
RN [5]
RP VARIANT LYS-167.
RX PubMed=24633158; DOI=10.1038/ng.2926;
RA Holmen O.L., Zhang H., Fan Y., Hovelson D.H., Schmidt E.M., Zhou W.,
RA Guo Y., Zhang J., Langhammer A., Lochen M.L., Ganesh S.K., Vatten L.,
RA Skorpen F., Dalen H., Zhang J., Pennathur S., Chen J., Platou C.,
RA Mathiesen E.B., Wilsgaard T., Njolstad I., Boehnke M., Chen Y.E.,
RA Abecasis G.R., Hveem K., Willer C.J.;
RT "Systematic evaluation of coding variation identifies a candidate causal
RT variant in TM6SF2 influencing total cholesterol and myocardial infarction
RT risk.";
RL Nat. Genet. 46:345-351(2014).
RN [6]
RP VARIANT LYS-167, CHARACTERIZATION OF VARIANT LYS-167, TISSUE SPECIFICITY,
RP AND FUNCTION.
RX PubMed=24531328; DOI=10.1038/ng.2901;
RA Kozlitina J., Smagris E., Stender S., Nordestgaard B.G., Zhou H.H.,
RA Tybjaerg-Hansen A., Vogt T.F., Hobbs H.H., Cohen J.C.;
RT "Exome-wide association study identifies a TM6SF2 variant that confers
RT susceptibility to nonalcoholic fatty liver disease.";
RL Nat. Genet. 46:352-356(2014).
RN [7]
RP VARIANT LYS-167.
RX PubMed=24978903; DOI=10.1038/ncomms5309;
RA Liu Y.L., Reeves H.L., Burt A.D., Tiniakos D., McPherson S., Leathart J.B.,
RA Allison M.E., Alexander G.J., Piguet A.C., Anty R., Donaldson P.,
RA Aithal G.P., Francque S., Van Gaal L., Clement K., Ratziu V., Dufour J.F.,
RA Day C.P., Daly A.K., Anstee Q.M.;
RT "TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with
RT non-alcoholic fatty liver disease.";
RL Nat. Commun. 5:4309-4309(2014).
RN [8]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=24927523; DOI=10.1073/pnas.1323785111;
RA Mahdessian H., Taxiarchis A., Popov S., Silveira A., Franco-Cereceda A.,
RA Hamsten A., Eriksson P., van't Hooft F.;
RT "TM6SF2 is a regulator of liver fat metabolism influencing triglyceride
RT secretion and hepatic lipid droplet content.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:8913-8918(2014).
CC -!- FUNCTION: Regulator of liver fat metabolism influencing triglyceride
CC secretion and hepatic lipid droplet content (PubMed:24531328,
CC PubMed:24927523). May function as sterol isomerase (PubMed:25566323).
CC {ECO:0000269|PubMed:24531328, ECO:0000269|PubMed:24927523,
CC ECO:0000303|PubMed:25566323}.
CC -!- INTERACTION:
CC Q9BZW4; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-13082040, EBI-11343438;
CC Q9BZW4; Q9BXK5: BCL2L13; NbExp=3; IntAct=EBI-13082040, EBI-747430;
CC Q9BZW4; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-13082040, EBI-18304435;
CC Q9BZW4; P31937: HIBADH; NbExp=3; IntAct=EBI-13082040, EBI-11427100;
CC Q9BZW4; P48051: KCNJ6; NbExp=3; IntAct=EBI-13082040, EBI-12017638;
CC Q9BZW4; P15941-11: MUC1; NbExp=3; IntAct=EBI-13082040, EBI-17263240;
CC Q9BZW4; P15151: PVR; NbExp=3; IntAct=EBI-13082040, EBI-3919694;
CC Q9BZW4; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-13082040, EBI-17247926;
CC Q9BZW4; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-13082040, EBI-17280858;
CC Q9BZW4; Q9BZW4: TM6SF2; NbExp=3; IntAct=EBI-13082040, EBI-13082040;
CC Q9BZW4; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-13082040, EBI-10982110;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:25566323}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum-Golgi intermediate compartment
CC membrane {ECO:0000269|PubMed:25566323}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BZW4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BZW4-2; Sequence=VSP_040282;
CC -!- TISSUE SPECIFICITY: Substantial expression in liver and intestine,
CC whereas all other tissues analyzed show low levels.
CC {ECO:0000269|PubMed:25566323}.
CC -!- SIMILARITY: Belongs to the TM6SF family. {ECO:0000305}.
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DR EMBL; AC003967; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF255923; AAG59700.1; -; mRNA.
DR EMBL; BC120986; AAI20987.1; -; mRNA.
DR EMBL; BC120987; AAI20988.1; -; mRNA.
DR CCDS; CCDS42528.1; -. [Q9BZW4-1]
DR RefSeq; NP_001001524.2; NM_001001524.2. [Q9BZW4-1]
DR AlphaFoldDB; Q9BZW4; -.
DR BioGRID; 119746; 12.
DR IntAct; Q9BZW4; 10.
DR STRING; 9606.ENSP00000374014; -.
DR TCDB; 8.A.93.2.1; the sigma2 receptor or tmem97 (s2r) family.
DR BioMuta; TM6SF2; -.
DR DMDM; 313104274; -.
DR MassIVE; Q9BZW4; -.
DR PaxDb; Q9BZW4; -.
DR PeptideAtlas; Q9BZW4; -.
DR PRIDE; Q9BZW4; -.
DR ProteomicsDB; 79909; -. [Q9BZW4-1]
DR ProteomicsDB; 79910; -. [Q9BZW4-2]
DR Antibodypedia; 67508; 63 antibodies from 13 providers.
DR DNASU; 53345; -.
DR Ensembl; ENST00000389363.5; ENSP00000374014.2; ENSG00000213996.13. [Q9BZW4-1]
DR GeneID; 53345; -.
DR KEGG; hsa:53345; -.
DR MANE-Select; ENST00000389363.5; ENSP00000374014.2; NM_001001524.3; NP_001001524.2.
DR UCSC; uc002nmd.2; human. [Q9BZW4-1]
DR CTD; 53345; -.
DR DisGeNET; 53345; -.
DR GeneCards; TM6SF2; -.
DR HGNC; HGNC:11861; TM6SF2.
DR HPA; ENSG00000213996; Group enriched (intestine, liver).
DR MIM; 606563; gene.
DR neXtProt; NX_Q9BZW4; -.
DR OpenTargets; ENSG00000213996; -.
DR PharmGKB; PA36562; -.
DR VEuPathDB; HostDB:ENSG00000213996; -.
DR eggNOG; ENOG502QRB2; Eukaryota.
DR GeneTree; ENSGT00390000012913; -.
DR HOGENOM; CLU_046717_0_0_1; -.
DR InParanoid; Q9BZW4; -.
DR OMA; TDSCFVY; -.
DR PhylomeDB; Q9BZW4; -.
DR TreeFam; TF333088; -.
DR PathwayCommons; Q9BZW4; -.
DR SignaLink; Q9BZW4; -.
DR BioGRID-ORCS; 53345; 16 hits in 1060 CRISPR screens.
DR GenomeRNAi; 53345; -.
DR Pharos; Q9BZW4; Tbio.
DR PRO; PR:Q9BZW4; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9BZW4; protein.
DR Bgee; ENSG00000213996; Expressed in ileal mucosa and 106 other tissues.
DR Genevisible; Q9BZW4; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IDA:UniProtKB.
DR InterPro; IPR033118; EXPERA.
DR PROSITE; PS51751; EXPERA; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..377
FT /note="Transmembrane 6 superfamily member 2"
FT /id="PRO_0000181835"
FT TRANSMEM 10..30
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..54
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT DOMAIN 61..186
FT /note="EXPERA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01087"
FT DOMAIN 217..351
FT /note="EXPERA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01087"
FT VAR_SEQ 327..353
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11124529"
FT /id="VSP_040282"
FT VARIANT 167
FT /note="E -> K (associated with higher circulating levels of
FT alanine transaminase with lower levels of low-density
FT lipoprotein-cholesterol (LDL-C), triglycerides and alkaline
FT phosphatase in 3 independent populations; reduces protein
FT expression by 46%; dbSNP:rs58542926)"
FT /evidence="ECO:0000269|PubMed:24531328,
FT ECO:0000269|PubMed:24633158, ECO:0000269|PubMed:24978903"
FT /id="VAR_062153"
SQ SEQUENCE 377 AA; 42554 MW; 56C2576367BBF2DF CRC64;
MDIPPLAGKI AALSLSALPV SYALNHVSAL SHPLWVALMS ALILGLLFVA VYSLSHGEVS
YDPLYAVFAV FAFTSVVDLI IALQEDSYVV GFMEFYTKEG EPYLRTAHGV FICYWDGTVH
YLLYLAMAGA ICRRKRYRNF GLYWLGSFAM SILVFLTGNI LGKYSSEIRP AFFLTIPYLL
VPCWAGMKVF SQPRALTRCT ANMVQEEQRK GLLQRPADLA LVIYLILAGF FTLFRGLVVL
DCPTDACFVY IYQYEPYLRD PVAYPKVQML MYMFYVLPFC GLAAYALTFP GCSWLPDWAL
VFAGGIGQAQ FSHMGASMHL RTPFTYRVPE DTWGCFFVCN LLYALGPHLL AYRCLQWPAF
FHQPPPSDPL ALHKKQH
