ID   TSLP_HUMAN              Reviewed;         159 AA.
AC   Q969D9; G3XAM8; Q8IW99; Q96AU7;
DT   11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 129.
DE   RecName: Full=Thymic stromal lymphopoietin;
DE   Flags: Precursor;
GN   Name=TSLP;
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] (ISOFORM 1), SUBCELLULAR LOCATION, AND FUNCTION
RP   (ISOFORM 1).
RX   PubMed=11418668; DOI=10.4049/jimmunol.167.1.336;
RA   Reche P.A., Soumelis V., Gorman D.M., Clifford T., Liu M.-R., Travis M.,
RA   Zurawski S.M., Johnston J., Liu Y.-J., Spits H., de Waal Malefyt R.,
RA   Kastelein R.A., Bazan J.F.;
RT   "Human thymic stromal lymphopoietin preferentially stimulates myeloid
RT   cells.";
RL   J. Immunol. 167:336-343(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1), AND TISSUE
RP   SPECIFICITY.
RX   PubMed=11480573; DOI=10.1038/sj.leu.2402175;
RA   Quentmeier H., Drexler H.G., Fleckenstein D., Zaborski M., Armstrong A.,
RA   Sims J.E., Lyman S.D.;
RT   "Cloning of human thymic stromal lymphopoietin (TSLP) and signaling
RT   mechanisms leading to proliferation.";
RL   Leukemia 15:1286-1292(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, Lung, and Testis;
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   [6]
RP   FUNCTION IN ALLERGIC INFLAMMATION (ISOFORM 1), AND INDUCTION.
RX   PubMed=17242164; DOI=10.1084/jem.20062211;
RA   Allakhverdi Z., Comeau M.R., Jessup H.K., Yoon B.R., Brewer A.,
RA   Chartier S., Paquette N., Ziegler S.F., Sarfati M., Delespesse G.;
RT   "Thymic stromal lymphopoietin is released by human epithelial cells in
RT   response to microbes, trauma, or inflammation and potently activates mast
RT   cells.";
RL   J. Exp. Med. 204:253-258(2007).
RN   [7]
RP   TISSUE SPECIFICITY (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 2), AND
RP   FUNCTION (ISOFORM 2).
RX   PubMed=24850429; DOI=10.1038/mi.2014.41;
RA   Bjerkan L., Schreurs O., Engen S.A., Jahnsen F.L., Baekkevold E.S.,
RA   Blix I.J., Schenck K.;
RT   "The short form of TSLP is constitutively translated in human keratinocytes
RT   and has characteristics of an antimicrobial peptide.";
RL   Mucosal Immunol. 8:49-56(2015).
CC   -!- FUNCTION: [Isoform 1]: Cytokine that induces the release of T-cell-
CC       attracting chemokines from monocytes and, in particular, enhances the
CC       maturation of CD11c(+) dendritic cells. Can induce allergic
CC       inflammation by directly activating mast cells.
CC       {ECO:0000269|PubMed:11418668, ECO:0000269|PubMed:11480573,
CC       ECO:0000269|PubMed:17242164}.
CC   -!- FUNCTION: [Isoform 2]: May act as an antimicrobial peptide in the oral
CC       cavity and on the skin. {ECO:0000269|PubMed:24850429}.
CC   -!- SUBUNIT: Interacts with a receptor composed of CRLF2 and IL7R. Binding
CC       of TSLP to CRLF2/TSLPR is a mechanistic prerequisite for recruitment of
CC       IL7R to the high-affinity ternary complex.
CC       {ECO:0000250|UniProtKB:Q9JIE6}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11418668}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=lfTSLP;
CC         IsoId=Q969D9-1; Sequence=Displayed;
CC       Name=2; Synonyms=sfTSLP;
CC         IsoId=Q969D9-2; Sequence=VSP_057462;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is expressed in a number of tissues
CC       including heart, liver and prostate. Isoform 2 is the predominant form
CC       in keratinocytes of oral mucosa, skin and in salivary glands. It is
CC       secreted into saliva. {ECO:0000269|PubMed:11480573,
CC       ECO:0000269|PubMed:24850429}.
CC   -!- INDUCTION: Released by primary epithelial cells in response to certain
CC       microbial products, physical injury, or inflammatory cytokines.
CC       {ECO:0000269|PubMed:17242164}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH16720.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAH22894.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AY037115; AAK67490.1; -; mRNA.
DR   EMBL; AF338732; AAK60617.1; -; mRNA.
DR   EMBL; AC008572; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471086; EAW49038.1; -; Genomic_DNA.
DR   EMBL; BC016720; AAH16720.1; ALT_INIT; mRNA.
DR   EMBL; BC022894; AAH22894.1; ALT_INIT; mRNA.
DR   EMBL; BC040592; AAH40592.1; -; mRNA.
DR   CCDS; CCDS4101.1; -. [Q969D9-1]
DR   RefSeq; NP_149024.1; NM_033035.4. [Q969D9-1]
DR   RefSeq; NP_612561.2; NM_138551.4. [Q969D9-2]
DR   RefSeq; XP_011542000.1; XM_011543698.1. [Q969D9-2]
DR   PDB; 5J11; X-ray; 2.56 A; A=36-159.
DR   PDB; 5J12; X-ray; 3.55 A; A=1-159.
DR   PDB; 5J13; X-ray; 2.30 A; A=29-159.
DR   PDBsum; 5J11; -.
DR   PDBsum; 5J12; -.
DR   PDBsum; 5J13; -.
DR   AlphaFoldDB; Q969D9; -.
DR   SASBDB; Q969D9; -.
DR   SMR; Q969D9; -.
DR   BioGRID; 124555; 4.
DR   IntAct; Q969D9; 2.
DR   STRING; 9606.ENSP00000339804; -.
DR   ChEMBL; CHEMBL3712931; -.
DR   DrugBank; DB15090; Tezepelumab.
DR   GlyCosmos; Q969D9; 2 sites, No reported glycans.
DR   GlyGen; Q969D9; 2 sites.
DR   PhosphoSitePlus; Q969D9; -.
DR   BioMuta; TSLP; -.
DR   MassIVE; Q969D9; -.
DR   PaxDb; 9606-ENSP00000339804; -.
DR   ABCD; Q969D9; 5 sequenced antibodies.
DR   Antibodypedia; 25309; 886 antibodies from 42 providers.
DR   DNASU; 85480; -.
DR   Ensembl; ENST00000344895.4; ENSP00000339804.3; ENSG00000145777.15. [Q969D9-1]
DR   Ensembl; ENST00000379706.4; ENSP00000427827.1; ENSG00000145777.15. [Q969D9-2]
DR   GeneID; 85480; -.
DR   KEGG; hsa:85480; -.
DR   MANE-Select; ENST00000344895.4; ENSP00000339804.3; NM_033035.5; NP_149024.1.
DR   UCSC; uc003kpb.3; human. [Q969D9-1]
DR   UCSC; uc031skq.1; human.
DR   AGR; HGNC:30743; -.
DR   CTD; 85480; -.
DR   DisGeNET; 85480; -.
DR   GeneCards; TSLP; -.
DR   HGNC; HGNC:30743; TSLP.
DR   HPA; ENSG00000145777; Tissue enhanced (liver, urinary bladder).
DR   MIM; 607003; gene.
DR   neXtProt; NX_Q969D9; -.
DR   OpenTargets; ENSG00000145777; -.
DR   PharmGKB; PA162407159; -.
DR   VEuPathDB; HostDB:ENSG00000145777; -.
DR   eggNOG; ENOG502TEM0; Eukaryota.
DR   GeneTree; ENSGT00390000012541; -.
DR   HOGENOM; CLU_2885173_0_0_1; -.
DR   InParanoid; Q969D9; -.
DR   OMA; CLEQVSY; -.
DR   OrthoDB; 4835294at2759; -.
DR   PhylomeDB; Q969D9; -.
DR   TreeFam; TF338216; -.
DR   PathwayCommons; Q969D9; -.
DR   Reactome; R-HSA-1266695; Interleukin-7 signaling.
DR   SignaLink; Q969D9; -.
DR   SIGNOR; Q969D9; -.
DR   BioGRID-ORCS; 85480; 15 hits in 1147 CRISPR screens.
DR   GeneWiki; Thymic_stromal_lymphopoietin; -.
DR   GenomeRNAi; 85480; -.
DR   Pharos; Q969D9; Tclin.
DR   PRO; PR:Q969D9; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q969D9; Protein.
DR   Bgee; ENSG00000145777; Expressed in epithelial cell of pancreas and 114 other cell types or tissues.
DR   ExpressionAtlas; Q969D9; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProt.
DR   GO; GO:0005125; F:cytokine activity; IDA:UniProtKB.
DR   GO; GO:0005139; F:interleukin-7 receptor binding; IMP:UniProtKB.
DR   GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR   GO; GO:0050832; P:defense response to fungus; IDA:UniProtKB.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR   GO; GO:0071654; P:positive regulation of chemokine (C-C motif) ligand 1 production; IMP:UniProtKB.
DR   GO; GO:0032722; P:positive regulation of chemokine production; IDA:UniProtKB.
DR   GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IDA:UniProtKB.
DR   GO; GO:0071657; P:positive regulation of granulocyte colony-stimulating factor production; IMP:UniProtKB.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB.
DR   GO; GO:0032733; P:positive regulation of interleukin-10 production; IMP:UniProtKB.
DR   GO; GO:0032736; P:positive regulation of interleukin-13 production; IMP:UniProtKB.
DR   GO; GO:0032754; P:positive regulation of interleukin-5 production; IMP:UniProtKB.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
DR   GO; GO:0033005; P:positive regulation of mast cell activation; IMP:UniProtKB.
DR   GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; IDA:UniProtKB.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:UniProtKB.
DR   Gene3D; 1.20.1250.90; Thymic stromal lymphopoietin; 1.
DR   InterPro; IPR029189; TSLP.
DR   InterPro; IPR038329; TSLP_sf.
DR   PANTHER; PTHR38003; THYMIC STROMAL LYMPHOPOIETIN; 1.
DR   PANTHER; PTHR38003:SF1; THYMIC STROMAL LYMPHOPOIETIN; 1.
DR   Pfam; PF15216; TSLP; 1.
DR   Genevisible; Q969D9; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytokine; Disulfide bond; Glycoprotein;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..159
FT                   /note="Thymic stromal lymphopoietin"
FT                   /id="PRO_0000300873"
FT   CARBOHYD        64
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        119
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        34..110
FT                   /evidence="ECO:0000250|UniProtKB:Q9JIE6"
FT   DISULFID        69..75
FT                   /evidence="ECO:0000250|UniProtKB:Q9JIE6"
FT   DISULFID        90..137
FT                   /evidence="ECO:0000250|UniProtKB:Q9JIE6"
FT   VAR_SEQ         1..96
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_057462"
FT   CONFLICT        1..11
FT                   /note="MFPFALLYVLS -> MKCLGQSKKEE (in Ref. 3; AAH40592)"
FT                   /evidence="ECO:0000305"
FT   HELIX           31..33
FT                   /evidence="ECO:0007829|PDB:5J13"
FT   HELIX           36..45
FT                   /evidence="ECO:0007829|PDB:5J13"
FT   HELIX           47..54
FT                   /evidence="ECO:0007829|PDB:5J13"
FT   HELIX           60..62
FT                   /evidence="ECO:0007829|PDB:5J11"
FT   HELIX           72..84
FT                   /evidence="ECO:0007829|PDB:5J13"
FT   HELIX           97..109
FT                   /evidence="ECO:0007829|PDB:5J13"
FT   HELIX           135..151
FT                   /evidence="ECO:0007829|PDB:5J13"
SQ   SEQUENCE   159 AA;  18141 MW;  FE158129406E3963 CRC64;
     MFPFALLYVL SVSFRKIFIL QLVGLVLTYD FTNCDFEKIK AAYLSTISKD LITYMSGTKS
     TEFNNTVSCS NRPHCLTEIQ SLTFNPTAGC ASLAKEMFAM KTKAALAIWC PGYSETQINA
     TQAMKKRRKR KVTTNKCLEQ VSQLQGLWRR FNRPLLKQQ
//