VSTM1_HUMAN
ID VSTM1_HUMAN Reviewed; 236 AA.
AC Q6UX27; B6A8C6; D2DJS3; D2DJS4; Q496B6; Q496B7;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=V-set and transmembrane domain-containing protein 1;
DE AltName: Full=Signal inhibitory receptor on leukocytes-1;
DE Short=SIRL-1;
DE Flags: Precursor;
GN Name=VSTM1; ORFNames=UNQ3033/PRO9835;
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] (ISOFORMS 1 AND 2), FUNCTION (ISOFORM 2),
RP SUBCELLULAR LOCATION (ISOFORM 2), AND VARIANT GLY-163.
RC TISSUE=Granulocyte, and Spleen;
RX PubMed=22960280; DOI=10.1016/j.cellimm.2012.07.009;
RA Guo X., Zhang Y., Wang P., Li T., Fu W., Mo X., Shi T., Zhang Z., Chen Y.,
RA Ma D., Han W.;
RT "VSTM1-v2, a novel soluble glycoprotein, promotes the differentiation and
RT activation of Th17 cells.";
RL Cell. Immunol. 278:136-142(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1), ITIM MOTIF,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Peripheral blood monocyte;
RX PubMed=20375307; DOI=10.4049/jimmunol.0902039;
RA Steevels T.A., Lebbink R.J., Westerlaken G.H., Coffer P.J., Meyaard L.;
RT "Signal inhibitory receptor on leukocytes-1 is a novel functional
RT inhibitory immune receptor expressed on human phagocytes.";
RL J. Immunol. 184:4741-4748(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLY-163.
RC TISSUE=Bone marrow;
RA Barrow A.D., de Bono B., Trowsdale J.;
RT "OSCAR-like transcript-1 (OLT-1) mRNA.";
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-163.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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 [7]
RP PROTEIN SEQUENCE OF 17-31.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
CC -!- FUNCTION: [Isoform 2]: Behaves as a cytokine, promoting IL17A secretion
CC by CD4+ T-cells, and differentiation and activation of IL17 producing
CC helper T-cells (TH17).
CC -!- FUNCTION: [Isoform 1]: Inhibitory immune receptor involved in the
CC regulation of phagocytes.
CC -!- INTERACTION:
CC Q6UX27-3; Q86Y34: ADGRG3; NbExp=3; IntAct=EBI-12190699, EBI-17979264;
CC Q6UX27-3; Q8WW43: APH1B; NbExp=3; IntAct=EBI-12190699, EBI-2606497;
CC Q6UX27-3; Q13520: AQP6; NbExp=3; IntAct=EBI-12190699, EBI-13059134;
CC Q6UX27-3; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-12190699, EBI-11343438;
CC Q6UX27-3; P19397: CD53; NbExp=3; IntAct=EBI-12190699, EBI-6657396;
CC Q6UX27-3; O95471: CLDN7; NbExp=3; IntAct=EBI-12190699, EBI-740744;
CC Q6UX27-3; O95484: CLDN9; NbExp=3; IntAct=EBI-12190699, EBI-18341636;
CC Q6UX27-3; Q8IUN9: CLEC10A; NbExp=3; IntAct=EBI-12190699, EBI-2873246;
CC Q6UX27-3; O75208: COQ9; NbExp=3; IntAct=EBI-12190699, EBI-724524;
CC Q6UX27-3; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-12190699, EBI-781551;
CC Q6UX27-3; Q969F0: FATE1; NbExp=3; IntAct=EBI-12190699, EBI-743099;
CC Q6UX27-3; Q9UK22: FBXO2; NbExp=3; IntAct=EBI-12190699, EBI-4287196;
CC Q6UX27-3; P12314: FCGR1A; NbExp=3; IntAct=EBI-12190699, EBI-2869867;
CC Q6UX27-3; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-12190699, EBI-12142257;
CC Q6UX27-3; O95377: GJB5; NbExp=3; IntAct=EBI-12190699, EBI-3909454;
CC Q6UX27-3; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-12190699, EBI-712073;
CC Q6UX27-3; Q8TED1: GPX8; NbExp=3; IntAct=EBI-12190699, EBI-11721746;
CC Q6UX27-3; Q9UBK5: HCST; NbExp=3; IntAct=EBI-12190699, EBI-2801937;
CC Q6UX27-3; P48051: KCNJ6; NbExp=3; IntAct=EBI-12190699, EBI-12017638;
CC Q6UX27-3; P11279: LAMP1; NbExp=3; IntAct=EBI-12190699, EBI-2805407;
CC Q6UX27-3; Q9HCJ2: LRRC4C; NbExp=3; IntAct=EBI-12190699, EBI-3925442;
CC Q6UX27-3; Q9H8J5: MANSC1; NbExp=3; IntAct=EBI-12190699, EBI-2830042;
CC Q6UX27-3; Q5TF39: MFSD4B; NbExp=3; IntAct=EBI-12190699, EBI-11922631;
CC Q6UX27-3; Q6IN84: MRM1; NbExp=3; IntAct=EBI-12190699, EBI-5454865;
CC Q6UX27-3; O43688: PLPP2; NbExp=3; IntAct=EBI-12190699, EBI-722017;
CC Q6UX27-3; Q9H169-2: STMN4; NbExp=3; IntAct=EBI-12190699, EBI-20117546;
CC Q6UX27-3; Q9NWD8: TMEM248; NbExp=3; IntAct=EBI-12190699, EBI-10314986;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane {ECO:0000305}; Single-pass
CC membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted
CC {ECO:0000269|PubMed:22960280}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6UX27-1; Sequence=Displayed;
CC Name=2; Synonyms=VSTM1-v2;
CC IsoId=Q6UX27-2; Sequence=VSP_022381;
CC Name=3;
CC IsoId=Q6UX27-3; Sequence=VSP_022382, VSP_022383;
CC -!- TISSUE SPECIFICITY: Expressed on myeloid (neutrophils, eosinophils and
CC monocytes) but not on lymphoid cells. {ECO:0000269|PubMed:20375307}.
CC -!- DOMAIN: Contains 2 copies of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC Both motives are required for full inhibition of FCER1A-mediated
CC degranulation.
CC -!- PTM: Isoform 2 is N-glycosylated.
CC -!- MISCELLANEOUS: [Isoform 2]: Mainly detected in immune tissues and
CC cells. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
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DR EMBL; FJ584316; ACU00108.1; -; mRNA.
DR EMBL; FJ584317; ACU00109.1; -; mRNA.
DR EMBL; FJ584318; ACU00110.1; -; mRNA.
DR EMBL; FN398145; CAZ61324.1; -; mRNA.
DR EMBL; DQ479397; ABF19807.1; -; mRNA.
DR EMBL; AY358542; AAQ88906.1; -; mRNA.
DR EMBL; AC012314; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC100942; AAI00943.1; -; mRNA.
DR EMBL; BC100943; AAI00944.1; -; mRNA.
DR CCDS; CCDS12872.1; -. [Q6UX27-1]
DR CCDS; CCDS74442.1; -. [Q6UX27-2]
DR RefSeq; NP_001275720.1; NM_001288791.1.
DR RefSeq; NP_001275721.1; NM_001288792.1. [Q6UX27-2]
DR RefSeq; NP_001275722.1; NM_001288793.1.
DR RefSeq; NP_940883.2; NM_198481.3. [Q6UX27-1]
DR RefSeq; XP_016882155.1; XM_017026666.1. [Q6UX27-3]
DR AlphaFoldDB; Q6UX27; -.
DR SMR; Q6UX27; -.
DR BioGRID; 129868; 60.
DR IntAct; Q6UX27; 27.
DR STRING; 9606.ENSP00000343366; -.
DR GlyGen; Q6UX27; 2 sites.
DR BioMuta; VSTM1; -.
DR DMDM; 296452860; -.
DR MassIVE; Q6UX27; -.
DR PaxDb; Q6UX27; -.
DR PeptideAtlas; Q6UX27; -.
DR PRIDE; Q6UX27; -.
DR Antibodypedia; 71979; 30 antibodies from 11 providers.
DR DNASU; 284415; -.
DR Ensembl; ENST00000338372.7; ENSP00000343366.2; ENSG00000189068.11. [Q6UX27-1]
DR Ensembl; ENST00000376626.5; ENSP00000365813.1; ENSG00000189068.11. [Q6UX27-2]
DR Ensembl; ENST00000447872.5; ENSP00000401926.1; ENSG00000189068.11. [Q6UX27-3]
DR Ensembl; ENST00000610629.4; ENSP00000482197.1; ENSG00000274953.4. [Q6UX27-1]
DR Ensembl; ENST00000610794.4; ENSP00000478582.1; ENSG00000276159.4. [Q6UX27-1]
DR Ensembl; ENST00000610804.4; ENSP00000480533.1; ENSG00000274887.4. [Q6UX27-1]
DR Ensembl; ENST00000611293.4; ENSP00000482555.1; ENSG00000275330.4. [Q6UX27-1]
DR Ensembl; ENST00000612105.4; ENSP00000483412.1; ENSG00000275577.4. [Q6UX27-1]
DR Ensembl; ENST00000612436.4; ENSP00000482985.1; ENSG00000276066.4. [Q6UX27-1]
DR Ensembl; ENST00000612864.4; ENSP00000481977.1; ENSG00000275962.4. [Q6UX27-3]
DR Ensembl; ENST00000613042.4; ENSP00000479748.1; ENSG00000275577.4. [Q6UX27-2]
DR Ensembl; ENST00000615235.4; ENSP00000479198.1; ENSG00000277607.4. [Q6UX27-2]
DR Ensembl; ENST00000615508.4; ENSP00000484886.1; ENSG00000276066.4. [Q6UX27-2]
DR Ensembl; ENST00000616717.4; ENSP00000480383.1; ENSG00000274953.4. [Q6UX27-2]
DR Ensembl; ENST00000617115.4; ENSP00000481140.1; ENSG00000275330.4. [Q6UX27-2]
DR Ensembl; ENST00000617281.4; ENSP00000480547.1; ENSG00000277607.4. [Q6UX27-1]
DR Ensembl; ENST00000617776.4; ENSP00000484699.1; ENSG00000275962.4. [Q6UX27-2]
DR Ensembl; ENST00000617862.4; ENSP00000484844.1; ENSG00000276363.4. [Q6UX27-1]
DR Ensembl; ENST00000619024.4; ENSP00000483411.1; ENSG00000276159.4. [Q6UX27-2]
DR Ensembl; ENST00000619921.4; ENSP00000483797.1; ENSG00000276363.4. [Q6UX27-2]
DR Ensembl; ENST00000620474.4; ENSP00000484806.1; ENSG00000275962.4. [Q6UX27-1]
DR Ensembl; ENST00000622762.4; ENSP00000483104.1; ENSG00000274887.4. [Q6UX27-2]
DR GeneID; 284415; -.
DR KEGG; hsa:284415; -.
DR MANE-Select; ENST00000338372.7; ENSP00000343366.2; NM_198481.4; NP_940883.2.
DR UCSC; uc002qcw.5; human. [Q6UX27-1]
DR CTD; 284415; -.
DR DisGeNET; 284415; -.
DR GeneCards; VSTM1; -.
DR HGNC; HGNC:29455; VSTM1.
DR HPA; ENSG00000189068; Tissue enriched (bone).
DR neXtProt; NX_Q6UX27; -.
DR OpenTargets; ENSG00000189068; -.
DR PharmGKB; PA147357166; -.
DR VEuPathDB; HostDB:ENSG00000189068; -.
DR eggNOG; ENOG502SXQ3; Eukaryota.
DR GeneTree; ENSGT01050000244944; -.
DR HOGENOM; CLU_103389_0_0_1; -.
DR InParanoid; Q6UX27; -.
DR OMA; QEWSGES; -.
DR OrthoDB; 1327293at2759; -.
DR PhylomeDB; Q6UX27; -.
DR TreeFam; TF336644; -.
DR PathwayCommons; Q6UX27; -.
DR SignaLink; Q6UX27; -.
DR BioGRID-ORCS; 284415; 6 hits in 1056 CRISPR screens.
DR ChiTaRS; VSTM1; human.
DR GenomeRNAi; 284415; -.
DR Pharos; Q6UX27; Tbio.
DR PRO; PR:Q6UX27; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q6UX27; protein.
DR Bgee; ENSG00000189068; Expressed in monocyte and 85 other tissues.
DR ExpressionAtlas; Q6UX27; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR Pfam; PF13895; Ig_2; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytokine; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Membrane;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 17..236
FT /note="V-set and transmembrane domain-containing protein 1"
FT /id="PRO_0000272269"
FT TOPO_DOM 17..135
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..236
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..114
FT /note="Ig-like V-type"
FT REGION 166..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 215..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 204..209
FT /note="ITIM motif 1"
FT MOTIF 229..234
FT /note="ITIM motif 2"
FT COMPBIAS 168..182
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..96
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 132..163
FT /note="DTRTIFVAIFSCISILLLFLSVFIIYRCSQHS -> G (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:22960280"
FT /id="VSP_022381"
FT VAR_SEQ 164..174
FT /note="SSSEESTKRTS -> ELRERKGREGE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022382"
FT VAR_SEQ 175..236
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022383"
FT VARIANT 163
FT /note="S -> G (in dbSNP:rs2433724)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:22960280, ECO:0000269|Ref.3"
FT /id="VAR_030034"
SQ SEQUENCE 236 AA; 26109 MW; 508E7881ADF6E1A5 CRC64;
MTAEFLSLLC LGLCLGYEDE KKNEKPPKPS LHAWPSSVVE AESNVTLKCQ AHSQNVTFVL
RKVNDSGYKQ EQSSAENEAE FPFTDLKPKD AGRYFCAYKT TASHEWSESS EHLQLVVTDK
HDELEAPSMK TDTRTIFVAI FSCISILLLF LSVFIIYRCS QHSSSSEEST KRTSHSKLPE
QEAAEADLSN MERVSLSTAD PQGVTYAELS TSALSEAASD TTQEPPGSHE YAALKV
