(data stored in ACNUC10409 zone)

SWISSPROT: 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   11-DEC-2019, entry version 119.
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   -!- 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}.
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   IntAct; Q9BZW4; 11.
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   PaxDb; Q9BZW4; -.
DR   PeptideAtlas; Q9BZW4; -.
DR   PRIDE; Q9BZW4; -.
DR   ProteomicsDB; 79909; -. [Q9BZW4-1]
DR   ProteomicsDB; 79910; -. [Q9BZW4-2]
DR   DNASU; 53345; -.
DR   Ensembl; ENST00000389363; ENSP00000374014; ENSG00000213996. [Q9BZW4-1]
DR   GeneID; 53345; -.
DR   KEGG; hsa:53345; -.
DR   UCSC; uc002nmd.2; human. [Q9BZW4-1]
DR   CTD; 53345; -.
DR   DisGeNET; 53345; -.
DR   EuPathDB; HostDB:ENSG00000213996.12; -.
DR   GeneCards; TM6SF2; -.
DR   HGNC; HGNC:11861; TM6SF2.
DR   HPA; HPA066026; -.
DR   MIM; 606563; gene.
DR   neXtProt; NX_Q9BZW4; -.
DR   OpenTargets; ENSG00000213996; -.
DR   PharmGKB; PA36562; -.
DR   eggNOG; ENOG410IJ78; Eukaryota.
DR   eggNOG; ENOG41113JR; LUCA.
DR   GeneTree; ENSGT00390000012913; -.
DR   HOGENOM; HOG000035128; -.
DR   InParanoid; Q9BZW4; -.
DR   OMA; VGFMEFY; -.
DR   OrthoDB; 784438at2759; -.
DR   PhylomeDB; Q9BZW4; -.
DR   TreeFam; TF333088; -.
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 97 organ(s), highest expression level in small intestine Peyer's patch.
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: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;
DR   PRODOM; Q9BZW4.
DR   SWISS-2DPAGE; Q9BZW4.
KW   Alternative splicing; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW   Polymorphism; Reference proteome; Repeat; Transmembrane;
KW   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 (common polymorphism; associated with higher
FT                   circulating levels of alanine transaminase with lower
FT                   levels of low-density lipoprotein-cholesterol (LDL-C),
FT                   triglycerides and alkaline phosphatase in 3 independent
FT                   populations; reduces protein expression by 46%;
FT                   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
//

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