UniProtKB - Q9NZH6 (IL37_HUMAN)
Interleukin-37
IL37
Functioni
Suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. Suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation.
2 PublicationsGO - Molecular functioni
- cytokine activity Source: GO_Central
- interleukin-1 receptor binding Source: UniProtKB
GO - Biological processi
- cellular response to lipopolysaccharide Source: GO_Central
- cytokine-mediated signaling pathway Source: GO_Central
- immune response Source: UniProtKB
- inflammatory response Source: GO_Central
- inflammatory response to antigenic stimulus Source: GO_Central
- negative regulation of interleukin-6 production Source: ARUK-UCL
- negative regulation of tumor necrosis factor production Source: ARUK-UCL
- positive regulation of gene expression Source: GO_Central
- regulation of inflammatory response Source: ARUK-UCL
Keywordsi
Molecular function | Cytokine |
Enzyme and pathway databases
PathwayCommonsi | Q9NZH6 |
Reactomei | R-HSA-9008059, Interleukin-37 signaling R-HSA-9012546, Interleukin-18 signaling |
SignaLinki | Q9NZH6 |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-37Short name: IL-37 Alternative name(s): FIL1 zeta IL-1X Interleukin-1 family member 7 Short name: IL-1F7 Interleukin-1 homolog 4 Short name: IL-1H Short name: IL-1H4 Interleukin-1 zeta Short name: IL-1 zeta Interleukin-1-related protein Short name: IL-1RP1 Interleukin-23 Short name: IL-23 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:15563, IL37 |
MIMi | 605510, gene |
neXtProti | NX_Q9NZH6 |
VEuPathDBi | HostDB:ENSG00000125571 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Extracellular region or secreted
- Secreted 2 Publications
Cytoplasm and Cytosol
- cytosol 2 Publications
Note: Stimulation with IL1B leads to colocalization with SMAD3 mostly in perinuclear regions (PubMed:20935647). Only the CASP1-cleaved mature form translocates into the nucleus upon LPS stimulation (PubMed:18390730). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059).1 Publication
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular region Source: UniProtKB
- extracellular space Source: GO_Central
Nucleus
- nucleoplasm Source: HPA
Other locations
- intracellular membrane-bounded organelle Source: HPA
Keywords - Cellular componenti
Cytoplasm, Nucleus, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 27178 |
OpenTargetsi | ENSG00000125571 |
PharmGKBi | PA38390 |
Miscellaneous databases
Pharosi | Q9NZH6, Tbio |
Genetic variation databases
BioMutai | IL37 |
DMDMi | 25008593 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
PropeptideiPRO_0000015335 | 1 – 45 | Removed in mature form1 PublicationAdd BLAST | 45 | |
ChainiPRO_0000015336 | 46 – 218 | Interleukin-37Add BLAST | 173 |
Post-translational modificationi
Proteomic databases
MassIVEi | Q9NZH6 |
PaxDbi | Q9NZH6 |
PeptideAtlasi | Q9NZH6 |
PRIDEi | Q9NZH6 |
ProteomicsDBi | 83390 [Q9NZH6-1] 83391 [Q9NZH6-2] 83392 [Q9NZH6-3] 83393 [Q9NZH6-4] 83394 [Q9NZH6-5] |
PTM databases
iPTMneti | Q9NZH6 |
PhosphoSitePlusi | Q9NZH6 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000125571, Expressed in skin of leg and 158 other tissues |
Genevisiblei | Q9NZH6, HS |
Organism-specific databases
HPAi | ENSG00000125571, Tissue enriched (skin) |
Interactioni
Subunit structurei
Interacts with SMAD3. Binds IL18R1, but not to IL1R1, with lower affinity than IL18, and does not seem to act as a receptor antagonist for IL18.
Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059).
3 PublicationsBinary interactionsi
Q9NZH6
GO - Molecular functioni
- cytokine activity Source: GO_Central
- interleukin-1 receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 118054, 27 interactors |
IntActi | Q9NZH6, 14 interactors |
STRINGi | 9606.ENSP00000263326 |
Miscellaneous databases
RNActi | Q9NZH6, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9NZH6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 40 | DisorderedSequence analysisAdd BLAST | 40 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502TCXA, Eukaryota |
GeneTreei | ENSGT00950000182943 |
HOGENOMi | CLU_095373_0_0_1 |
InParanoidi | Q9NZH6 |
OMAi | DCEDWER |
OrthoDBi | 1142952at2759 |
PhylomeDBi | Q9NZH6 |
TreeFami | TF300203 |
Family and domain databases
InterProi | View protein in InterPro IPR000975, IL-1_fam IPR003297, IL-1RA/IL-36 IPR008996, IL1/FGF |
PANTHERi | PTHR10078, PTHR10078, 1 hit |
Pfami | View protein in Pfam PF00340, IL1, 1 hit |
PRINTSi | PR00264, INTERLEUKIN1 PR01360, INTRLEUKIN1X |
SUPFAMi | SSF50353, SSF50353, 1 hit |
s (5)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSFVGENSGV KMGSEDWEKD EPQCCLEDPA GSPLEPGPSL PTMNFVHTSP
60 70 80 90 100
KVKNLNPKKF SIHDQDHKVL VLDSGNLIAV PDKNYIRPEI FFALASSLSS
110 120 130 140 150
ASAEKGSPIL LGVSKGEFCL YCDKDKGQSH PSLQLKKEKL MKLAAQKESA
160 170 180 190 200
RRPFIFYRAQ VGSWNMLESA AHPGWFICTS CNCNEPVGVT DKFENRKHIE
210
FSFQPVCKAE MSPSEVSD
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014260 | 31 | G → V3 PublicationsCorresponds to variant dbSNP:rs3811046Ensembl. | 1 | |
Natural variantiVAR_014261 | 42 | T → A3 PublicationsCorresponds to variant dbSNP:rs3811047EnsemblClinVar. | 1 | |
Natural variantiVAR_049574 | 50 | P → R. Corresponds to variant dbSNP:rs2708943Ensembl. | 1 | |
Natural variantiVAR_049575 | 54 | N → S. Corresponds to variant dbSNP:rs2723183Ensembl. | 1 | |
Natural variantiVAR_023334 | 108 | P → L1 PublicationCorresponds to variant dbSNP:rs2723187Ensembl. | 1 | |
Natural variantiVAR_023335 | 152 | R → W1 PublicationCorresponds to variant dbSNP:rs28947200EnsemblClinVar. | 1 | |
Natural variantiVAR_023336 | 164 | W → R1 PublicationCorresponds to variant dbSNP:rs2708947Ensembl. | 1 | |
Natural variantiVAR_023337 | 218 | D → N1 PublicationCorresponds to variant dbSNP:rs2723192Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_002653 | 1 – 49 | MSFVG…FVHTS → MSGCDRRETETKGKNSFKKR LRG in isoform A. 1 PublicationAdd BLAST | 49 | |
Alternative sequenceiVSP_002655 | 28 – 88 | Missing in isoform E. 1 PublicationAdd BLAST | 61 | |
Alternative sequenceiVSP_002654 | 28 – 49 | DPAGS…FVHTS → G in isoform D. 2 PublicationsAdd BLAST | 22 | |
Alternative sequenceiVSP_002656 | 49 – 89 | SPKVK…YIRPE → K in isoform C. 1 PublicationAdd BLAST | 41 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF200496 mRNA Translation: AAF69252.1 AF167368 mRNA Translation: AAG29344.1 AF251118 mRNA Translation: AAG14420.1 AF251119 mRNA Translation: AAG14421.1 AF251120 mRNA Translation: AAG14422.1 AF201832 mRNA Translation: AAF25212.1 AY071840 mRNA Translation: AAL67151.1 AY071841 mRNA Translation: AAL67154.1 AY973625 Genomic DNA Translation: AAX59036.1 AB451333 mRNA Translation: BAG70147.1 AB451478 mRNA Translation: BAG70292.1 AC079753 Genomic DNA Translation: AAX88889.1 CH471217 Genomic DNA Translation: EAW73609.1 BC020637 mRNA Translation: AAH20637.1 |
CCDSi | CCDS2103.1 [Q9NZH6-1] CCDS2104.1 [Q9NZH6-4] CCDS2105.1 [Q9NZH6-5] CCDS2106.1 [Q9NZH6-3] CCDS2107.1 [Q9NZH6-2] |
RefSeqi | NP_055254.2, NM_014439.3 [Q9NZH6-1] NP_775294.1, NM_173202.1 [Q9NZH6-4] NP_775295.1, NM_173203.1 [Q9NZH6-5] NP_775296.1, NM_173204.1 [Q9NZH6-3] NP_775297.1, NM_173205.1 [Q9NZH6-2] XP_011509265.1, XM_011510963.2 [Q9NZH6-1] XP_011509266.1, XM_011510964.2 [Q9NZH6-3] |
Genome annotation databases
Ensembli | ENST00000263326; ENSP00000263326; ENSG00000125571 ENST00000311328; ENSP00000309883; ENSG00000125571 [Q9NZH6-2] ENST00000349806; ENSP00000263328; ENSG00000125571 [Q9NZH6-5] ENST00000352179; ENSP00000263327; ENSG00000125571 [Q9NZH6-4] ENST00000353225; ENSP00000309208; ENSG00000125571 [Q9NZH6-3] |
GeneIDi | 27178 |
KEGGi | hsa:27178 |
MANE-Selecti | ENST00000263326.8; ENSP00000263326.3; NM_014439.4; NP_055254.2 |
UCSCi | uc002tij.4, human [Q9NZH6-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Interleukin-1 entry |
SeattleSNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF200496 mRNA Translation: AAF69252.1 AF167368 mRNA Translation: AAG29344.1 AF251118 mRNA Translation: AAG14420.1 AF251119 mRNA Translation: AAG14421.1 AF251120 mRNA Translation: AAG14422.1 AF201832 mRNA Translation: AAF25212.1 AY071840 mRNA Translation: AAL67151.1 AY071841 mRNA Translation: AAL67154.1 AY973625 Genomic DNA Translation: AAX59036.1 AB451333 mRNA Translation: BAG70147.1 AB451478 mRNA Translation: BAG70292.1 AC079753 Genomic DNA Translation: AAX88889.1 CH471217 Genomic DNA Translation: EAW73609.1 BC020637 mRNA Translation: AAH20637.1 |
CCDSi | CCDS2103.1 [Q9NZH6-1] CCDS2104.1 [Q9NZH6-4] CCDS2105.1 [Q9NZH6-5] CCDS2106.1 [Q9NZH6-3] CCDS2107.1 [Q9NZH6-2] |
RefSeqi | NP_055254.2, NM_014439.3 [Q9NZH6-1] NP_775294.1, NM_173202.1 [Q9NZH6-4] NP_775295.1, NM_173203.1 [Q9NZH6-5] NP_775296.1, NM_173204.1 [Q9NZH6-3] NP_775297.1, NM_173205.1 [Q9NZH6-2] XP_011509265.1, XM_011510963.2 [Q9NZH6-1] XP_011509266.1, XM_011510964.2 [Q9NZH6-3] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5HN1 | X-ray | 2.25 | A/B | 46-218 | [»] | |
6NCU | X-ray | 3.50 | A/B | 53-206 | [»] | |
SMRi | Q9NZH6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 118054, 27 interactors |
IntActi | Q9NZH6, 14 interactors |
STRINGi | 9606.ENSP00000263326 |
PTM databases
iPTMneti | Q9NZH6 |
PhosphoSitePlusi | Q9NZH6 |
Genetic variation databases
BioMutai | IL37 |
DMDMi | 25008593 |
Proteomic databases
MassIVEi | Q9NZH6 |
PaxDbi | Q9NZH6 |
PeptideAtlasi | Q9NZH6 |
PRIDEi | Q9NZH6 |
ProteomicsDBi | 83390 [Q9NZH6-1] 83391 [Q9NZH6-2] 83392 [Q9NZH6-3] 83393 [Q9NZH6-4] 83394 [Q9NZH6-5] |
Protocols and materials databases
Antibodypediai | 33300, 331 antibodies from 33 providers |
DNASUi | 27178 |
Genome annotation databases
Ensembli | ENST00000263326; ENSP00000263326; ENSG00000125571 ENST00000311328; ENSP00000309883; ENSG00000125571 [Q9NZH6-2] ENST00000349806; ENSP00000263328; ENSG00000125571 [Q9NZH6-5] ENST00000352179; ENSP00000263327; ENSG00000125571 [Q9NZH6-4] ENST00000353225; ENSP00000309208; ENSG00000125571 [Q9NZH6-3] |
GeneIDi | 27178 |
KEGGi | hsa:27178 |
MANE-Selecti | ENST00000263326.8; ENSP00000263326.3; NM_014439.4; NP_055254.2 |
UCSCi | uc002tij.4, human [Q9NZH6-1] |
Organism-specific databases
CTDi | 27178 |
DisGeNETi | 27178 |
GeneCardsi | IL37 |
HGNCi | HGNC:15563, IL37 |
HPAi | ENSG00000125571, Tissue enriched (skin) |
MIMi | 605510, gene |
neXtProti | NX_Q9NZH6 |
OpenTargetsi | ENSG00000125571 |
PharmGKBi | PA38390 |
VEuPathDBi | HostDB:ENSG00000125571 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502TCXA, Eukaryota |
GeneTreei | ENSGT00950000182943 |
HOGENOMi | CLU_095373_0_0_1 |
InParanoidi | Q9NZH6 |
OMAi | DCEDWER |
OrthoDBi | 1142952at2759 |
PhylomeDBi | Q9NZH6 |
TreeFami | TF300203 |
Enzyme and pathway databases
PathwayCommonsi | Q9NZH6 |
Reactomei | R-HSA-9008059, Interleukin-37 signaling R-HSA-9012546, Interleukin-18 signaling |
SignaLinki | Q9NZH6 |
Miscellaneous databases
BioGRID-ORCSi | 27178, 6 hits in 1032 CRISPR screens |
GeneWikii | IL1F7 |
GenomeRNAii | 27178 |
Pharosi | Q9NZH6, Tbio |
PROi | PR:Q9NZH6 |
RNActi | Q9NZH6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000125571, Expressed in skin of leg and 158 other tissues |
Genevisiblei | Q9NZH6, HS |
Family and domain databases
InterProi | View protein in InterPro IPR000975, IL-1_fam IPR003297, IL-1RA/IL-36 IPR008996, IL1/FGF |
PANTHERi | PTHR10078, PTHR10078, 1 hit |
Pfami | View protein in Pfam PF00340, IL1, 1 hit |
PRINTSi | PR00264, INTERLEUKIN1 PR01360, INTRLEUKIN1X |
SUPFAMi | SSF50353, SSF50353, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IL37_HUMAN | |
Accessioni | Q9NZH6Primary (citable) accession number: Q9NZH6 Secondary accession number(s): B5BU97 Q9UHA6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 8, 2002 |
Last sequence update: | October 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 174 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families