ID IL19_HUMAN Reviewed; 177 AA. AC Q9UHD0; B6VEV9; Q5VUT3; Q96QR4; Q9NUA0; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2007, sequence version 2. DT 27-MAR-2024, entry version 185. DE RecName: Full=Interleukin-19; DE Short=IL-19; DE AltName: Full=Melanoma differentiation-associated protein-like protein; DE AltName: Full=NG.1; DE Flags: Precursor; GN Name=IL19; Synonyms=ZMDA1; 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 [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP SER-175. RX PubMed=11196675; DOI=10.1038/sj.gene.6363714; RA Gallagher G., Dickensheets H., Eskdale J., Izotova L.S., RA Mirochnitchenko O.V., Peat J.D., Vasquez N., Pestka S., Donnelly R.P., RA Kotenko S.V.; RT "Cloning, expression and initial characterization of interleukin-19 (IL- RT 19), a novel homolog of human interleukin-10 (IL-10)."; RL Genes Immun. 1:442-450(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-175. RX PubMed=12370360; DOI=10.4049/jimmunol.169.8.4288; RA Liao Y.-C., Liang W.G., Chen F.W., Hsu J.H., Yang J.J., Chang M.-S.; RT "IL-19 induces production of IL-6 and TNF-alpha and results in cell RT apoptosis through TNF-alpha."; RL J. Immunol. 169:4288-4297(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=19906316; DOI=10.1186/1471-2164-10-518; RA Wang P., Yu P., Gao P., Shi T., Ma D.; RT "Discovery of novel human transcript variants by analysis of intronic RT single-block EST with polyadenylation site."; RL BMC Genomics 10:518-518(2009). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-175. RA Conklin D., Petersen J., Loften-Day C., Whitmore T., Muerer M., Sexson S., RA Smith D., Lok S., Pownder T., O'Hara P.; RT "Homo sapiens homolog of melanoma differentiation associated gene."; RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-175. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP FUNCTION. RX PubMed=11564763; DOI=10.4049/jimmunol.167.7.3545; RA Dumoutier L., Leemans C., Lejeune D., Kotenko S.V., Renauld J.-C.; RT "STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes RT of two types."; RL J. Immunol. 167:3545-3549(2001). RN [8] RP FUNCTION. RX PubMed=12351624; DOI=10.1074/jbc.m205114200; RA Parrish-Novak J., Xu W., Brender T., Yao L., Jones C., West J., Brandt C., RA Jelinek L., Madden K., McKernan P.A., Foster D.C., Jaspers S., RA Chandrasekher Y.A.; RT "Interleukins 19, 20, and 24 signal through two distinct receptor RT complexes. Differences in receptor-ligand interactions mediate unique RT biological functions."; RL J. Biol. Chem. 277:47517-47523(2002). RN [9] RP PROTEIN SEQUENCE OF 25-39. 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). RN [10] RP FUNCTION. RX PubMed=16365913; DOI=10.1002/eji.200425523; RA Oral H.B., Kotenko S.V., Yilmaz M., Mani O., Zumkehr J., Blaser K., RA Akdis C.A., Akdis M.; RT "Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family RT cytokines IL-19, IL-20, IL-22, IL-24 and IL-26."; RL Eur. J. Immunol. 36:380-388(2006). RN [11] RP FUNCTION, AND INDUCTION BY DNA DAMAGE. RX PubMed=34932373; DOI=10.1126/scisignal.aba2611; RA Small S.H., Tang E.J., Ragland R.L., Ruzankina Y., Schoppy D.W., RA Mandal R.S., Glineburg M.R., Ustelenca Z., Powell D.J., Simpkins F., RA Johnson F.B., Brown E.J.; RT "Induction of IL19 expression through JNK and cGAS-STING modulates DNA RT damage-induced cytokine production."; RL Sci. Signal. 14:eaba2611-eaba2611(2021). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 19-177, AND DISULFIDE BONDS. RX PubMed=12403790; DOI=10.1074/jbc.m208602200; RA Chang C., Magracheva E., Kozlov S., Fong S., Tobin G., Kotenko S., RA Wlodawer A., Zdanov A.; RT "Crystal structure of interleukin-19 defines a new subfamily of helical RT cytokines."; RL J. Biol. Chem. 278:3308-3313(2003). CC -!- FUNCTION: Cytokine that functions as an anti-inflammatory and CC proangiogenic factor (PubMed:34932373). Polarizes adaptive immunity to CC an anti-inflammatory phenotype through induction of T-helper 2 CC responses by both down-regulation of IFN-gamma and up-regulation of IL4 CC and IL13 (PubMed:16365913). Produced by osteocytes, stimulates CC granulopoiesis and neutrophil formation (By similarity). Exerts its CC biological effect through a receptor complex consisting of a CC heterodimer of IL20RA and IL20RB (PubMed:12351624). In turn, activates CC the Janus kinase (JAK) and signal transducer and activator of CC transcription (STAT) pathway, and importantly, STAT3 (PubMed:11564763). CC {ECO:0000250|UniProtKB:Q8CJ70, ECO:0000269|PubMed:11564763, CC ECO:0000269|PubMed:12351624, ECO:0000269|PubMed:16365913, CC ECO:0000269|PubMed:34932373}. CC -!- INTERACTION: CC PRO_0000015379; Q6UXL0: IL20RB; NbExp=4; IntAct=EBI-14023330, EBI-14022792; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9UHD0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UHD0-2; Sequence=VSP_046253; CC Name=3; CC IsoId=Q9UHD0-3; Sequence=VSP_057193; CC -!- INDUCTION: by DNA damage through pathways mediated by JUN and cGAS- CC STING leading to production of the cytokines IL1, IL6, and IL8. CC {ECO:0000269|PubMed:34932373}. CC -!- SIMILARITY: Belongs to the IL-10 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/il19/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF276915; AAG16755.1; -; Genomic_DNA. DR EMBL; AY040367; AAK91776.1; -; mRNA. DR EMBL; AF453946; AAN40906.1; -; mRNA. DR EMBL; FJ380053; ACJ06540.1; -; mRNA. DR EMBL; AF192498; AAF06663.1; -; mRNA. DR EMBL; AF390905; AAK64498.1; -; Genomic_DNA. DR EMBL; AL513315; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL049615; CAB72342.1; -; Genomic_DNA. DR CCDS; CCDS1469.1; -. [Q9UHD0-1] DR RefSeq; NP_037503.2; NM_013371.3. [Q9UHD0-1] DR RefSeq; NP_715639.1; NM_153758.2. [Q9UHD0-1] DR RefSeq; XP_011507752.1; XM_011509450.2. [Q9UHD0-3] DR PDB; 1N1F; X-ray; 1.95 A; A=19-177. DR PDBsum; 1N1F; -. DR AlphaFoldDB; Q9UHD0; -. DR SMR; Q9UHD0; -. DR BioGRID; 118986; 3. DR IntAct; Q9UHD0; 2. DR STRING; 9606.ENSP00000499459; -. DR GlyCosmos; Q9UHD0; 2 sites, No reported glycans. DR GlyGen; Q9UHD0; 2 sites. DR BioMuta; IL19; -. DR DMDM; 146345440; -. DR MassIVE; Q9UHD0; -. DR PaxDb; 9606-ENSP00000343000; -. DR PeptideAtlas; Q9UHD0; -. DR ProteomicsDB; 84320; -. [Q9UHD0-1] DR Antibodypedia; 34588; 452 antibodies from 31 providers. DR DNASU; 29949; -. DR Ensembl; ENST00000270218.10; ENSP00000270218.6; ENSG00000142224.18. [Q9UHD0-1] DR Ensembl; ENST00000340758.7; ENSP00000343000.3; ENSG00000142224.18. [Q9UHD0-1] DR Ensembl; ENST00000656872.2; ENSP00000499487.2; ENSG00000142224.18. [Q9UHD0-1] DR Ensembl; ENST00000659997.3; ENSP00000499459.2; ENSG00000142224.18. [Q9UHD0-1] DR GeneID; 29949; -. DR KEGG; hsa:29949; -. DR MANE-Select; ENST00000659997.3; ENSP00000499459.2; NM_153758.5; NP_715639.2. DR UCSC; uc001heo.3; human. [Q9UHD0-1] DR AGR; HGNC:5990; -. DR CTD; 29949; -. DR DisGeNET; 29949; -. DR GeneCards; IL19; -. DR HGNC; HGNC:5990; IL19. DR HPA; ENSG00000142224; Group enriched (cervix, salivary gland). DR MIM; 605687; gene. DR neXtProt; NX_Q9UHD0; -. DR OpenTargets; ENSG00000142224; -. DR PharmGKB; PA29806; -. DR VEuPathDB; HostDB:ENSG00000142224; -. DR eggNOG; ENOG502SRCR; Eukaryota. DR GeneTree; ENSGT00950000183124; -. DR HOGENOM; CLU_098690_0_0_1; -. DR InParanoid; Q9UHD0; -. DR OMA; FLYMQKA; -. DR OrthoDB; 5219752at2759; -. DR PhylomeDB; Q9UHD0; -. DR TreeFam; TF333253; -. DR PathwayCommons; Q9UHD0; -. DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. DR SignaLink; Q9UHD0; -. DR SIGNOR; Q9UHD0; -. DR BioGRID-ORCS; 29949; 9 hits in 1147 CRISPR screens. DR ChiTaRS; IL19; human. DR EvolutionaryTrace; Q9UHD0; -. DR GenomeRNAi; 29949; -. DR Pharos; Q9UHD0; Tbio. DR PRO; PR:Q9UHD0; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9UHD0; Protein. DR Bgee; ENSG00000142224; Expressed in nasal cavity epithelium and 78 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW. DR GO; GO:0005125; F:cytokine activity; TAS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0006955; P:immune response; NAS:UniProtKB. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IEA:Ensembl. DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR020443; IL-10/19/20/22/24/26_fam. DR InterPro; IPR020423; IL-10_CS. DR InterPro; IPR020421; IL-19. DR PANTHER; PTHR48394:SF5; INTERLEUKIN-19; 1. DR PANTHER; PTHR48394; INTERLEUKIN-19-RELATED; 1. DR Pfam; PF00726; IL10; 1. DR PRINTS; PR01934; INTRLEUKIN19. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR PROSITE; PS00520; INTERLEUKIN_10; 1. DR Genevisible; Q9UHD0; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Cytokine; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 25..177 FT /note="Interleukin-19" FT /id="PRO_0000015379" FT CARBOHYD 56 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 135 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 28..121 FT /evidence="ECO:0000269|PubMed:12403790" FT DISULFID 75..127 FT /evidence="ECO:0000269|PubMed:12403790" FT DISULFID 76..129 FT /evidence="ECO:0000269|PubMed:12403790" FT VAR_SEQ 1 FT /note="M -> MCTEGAFPHRSACSLPLTHVHTHIHVCVPVLWGSVPRGM (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:11196675" FT /id="VSP_046253" FT VAR_SEQ 122..177 FT /note="QEQRQCHCRQEATNATRVIHDNYDQLEVHAAAIKSLGELDVFLAWINKNHEV FT MFSA -> VSHWVRIPASAPCLPKERPGSAGPHRPPDMVLGVKGNSLRTSTGRTVENLS FT QWPLLPQGSLPADNSSDGLLLDNPPGVTNLCQHIP (in isoform 3)" FT /evidence="ECO:0000303|PubMed:19906316" FT /id="VSP_057193" FT VARIANT 175 FT /note="F -> S (in dbSNP:rs2243191)" FT /evidence="ECO:0000269|PubMed:11196675, FT ECO:0000269|PubMed:12370360, ECO:0000269|Ref.4, FT ECO:0000269|Ref.5" FT /id="VAR_013077" FT HELIX 23..26 FT /evidence="ECO:0007829|PDB:1N1F" FT TURN 28..31 FT /evidence="ECO:0007829|PDB:1N1F" FT HELIX 34..49 FT /evidence="ECO:0007829|PDB:1N1F" FT HELIX 61..64 FT /evidence="ECO:0007829|PDB:1N1F" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:1N1F" FT HELIX 71..87 FT /evidence="ECO:0007829|PDB:1N1F" FT HELIX 89..92 FT /evidence="ECO:0007829|PDB:1N1F" FT HELIX 98..121 FT /evidence="ECO:0007829|PDB:1N1F" FT HELIX 131..146 FT /evidence="ECO:0007829|PDB:1N1F" FT HELIX 149..158 FT /evidence="ECO:0007829|PDB:1N1F" FT HELIX 160..170 FT /evidence="ECO:0007829|PDB:1N1F" SQ SEQUENCE 177 AA; 20452 MW; 7CCFB052177DE408 CRC64; MKLQCVSLWL LGTILILCSV DNHGLRRCLI STDMHHIEES FQEIKRAIQA KDTFPNVTIL STLETLQIIK PLDVCCVTKN LLAFYVDRVF KDHQEPNPKI LRKISSIANS FLYMQKTLRQ CQEQRQCHCR QEATNATRVI HDNYDQLEVH AAAIKSLGEL DVFLAWINKN HEVMFSA //