TSLP_HUMAN
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 03-AUG-2022, entry version 120.
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 GlyGen; Q969D9; 2 sites.
DR PhosphoSitePlus; Q969D9; -.
DR BioMuta; TSLP; -.
DR MassIVE; Q969D9; -.
DR PaxDb; Q969D9; -.
DR PRIDE; Q969D9; -.
DR ABCD; Q969D9; 5 sequenced antibodies.
DR Antibodypedia; 25309; 676 antibodies from 41 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 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; NPTPRCA; -.
DR OrthoDB; 1389326at2759; -.
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; 14 hits in 1069 CRISPR screens.
DR GeneWiki; Thymic_stromal_lymphopoietin; -.
DR GenomeRNAi; 85480; -.
DR Pharos; Q969D9; Tbio.
DR PRO; PR:Q969D9; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q969D9; protein.
DR Bgee; ENSG00000145777; Expressed in epithelial cell of pancreas and 113 other tissues.
DR ExpressionAtlas; Q969D9; baseline and differential.
DR Genevisible; Q969D9; HS.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
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; -; 1.
DR InterPro; IPR029189; TSLP.
DR InterPro; IPR038329; TSLP_sf.
DR PANTHER; PTHR38003; PTHR38003; 1.
DR Pfam; PF15216; TSLP; 1.
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
