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Protein

Interleukin-37

Gene

IL37

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 Publications

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • interleukin-1 receptor binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

ReactomeiR-HSA-9008059 Interleukin-37 signaling
R-HSA-9012546 Interleukin-18 signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-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-37
Gene namesi
Name:IL37
Synonyms:FIL1Z, IL1F7, IL1H4, IL1RP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000125571.9
HGNCiHGNC:15563 IL37
MIMi605510 gene
neXtProtiNX_Q9NZH6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi27178
OpenTargetsiENSG00000125571
PharmGKBiPA38390

Polymorphism and mutation databases

BioMutaiIL37
DMDMi25008593

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000153351 – 45Removed in mature form1 PublicationAdd BLAST45
ChainiPRO_000001533646 – 218Interleukin-37Add BLAST173

Post-translational modificationi

Proteolytically converted to the mature form by CASP1.

Proteomic databases

PaxDbiQ9NZH6
PeptideAtlasiQ9NZH6
PRIDEiQ9NZH6
ProteomicsDBi83390
83391 [Q9NZH6-2]
83392 [Q9NZH6-3]
83393 [Q9NZH6-4]
83394 [Q9NZH6-5]

PTM databases

iPTMnetiQ9NZH6
PhosphoSitePlusiQ9NZH6

Miscellaneous databases

PMAP-CutDBiQ9NZH6

Expressioni

Tissue specificityi

In general, low constitutive expression, if any, in healthy tissues; high expression in inflammatory counterparts, including in synovial tissues from individuals with active rheumatoid arthritis. Isoform A, isoform B and isoform C are expressed in testis, colon, placenta, lung and lymph node. Isoform D and isoform E were found only in testis and bone marrow. Whereas only isoform A is found in brain, only isoform B in kidney and only isoform C in heart.2 Publications

Inductioni

Highly induced by bacterial lipopolysaccharides (LPS) and TGFB1, more moderately by IFNG, IL18, IL1B, TNF and the dinucleotide CpG (at protein level). Constitutive expression in bone marrow macrophages is down-regulated in the presence of IL4 and CSF2. Induced by phorbol myristate acetate (PMA) in different cell lines.2 Publications

Gene expression databases

BgeeiENSG00000125571 Expressed in 143 organ(s), highest expression level in skin of leg
CleanExiHS_IL1F7
GenevisibleiQ9NZH6 HS

Organism-specific databases

HPAiHPA054371
HPA057950

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 IL18.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118054, 12 interactors
IntActiQ9NZH6, 3 interactors
STRINGi9606.ENSP00000263326

Structurei

Secondary structure

1218
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9NZH6
SMRiQ9NZH6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGiENOG410J8RD Eukaryota
ENOG41118IW LUCA
GeneTreeiENSGT00900000141014
HOVERGENiHBG052101
InParanoidiQ9NZH6
KOiK05485
OMAiRKHTEFS
OrthoDBiEOG091G0J3H
PhylomeDBiQ9NZH6
TreeFamiTF300203

Family and domain databases

InterProiView protein in InterPro
IPR000975 IL-1_fam
IPR003297 IL-1RA/IL-36
IPR008996 IL1/FGF
PfamiView protein in Pfam
PF00340 IL1, 1 hit
PRINTSiPR00264 INTERLEUKIN1
PR01360 INTRLEUKIN1X
SUPFAMiSSF50353 SSF50353, 1 hit

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform B (identifier: Q9NZH6-1) [UniParc]FASTAAdd to basket
Also known as: IL-1F7b, IL-HLa

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Note: The name IL-HL refers to isoform B containing polymorphisms Val-31 and Ala-42.1 Publication
Length:218
Mass (Da):24,126
Last modified:October 1, 2000 - v1
Checksum:i96E089310D2CEA68
GO
Isoform A (identifier: Q9NZH6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: MSFVGENSGVKMGSEDWEKDEPQCCLEDPAGSPLEPGPSLPTMNFVHTS → MSGCDRRETETKGKNSFKKRLRG

Show »
Length:192
Mass (Da):21,543
Checksum:i4AF584C81802F612
GO
Isoform C (identifier: Q9NZH6-3) [UniParc]FASTAAdd to basket
Also known as: IL-HS

The sequence of this isoform differs from the canonical sequence as follows:
     49-89: SPKVKNLNPKKFSIHDQDHKVLVLDSGNLIAVPDKNYIRPE → K

Show »
Length:178
Mass (Da):19,604
Checksum:iD9BE1DD4858C4932
GO
Isoform D (identifier: Q9NZH6-4) [UniParc]FASTAAdd to basket
Also known as: IL1F7d

The sequence of this isoform differs from the canonical sequence as follows:
     28-49: DPAGSPLEPGPSLPTMNFVHTS → G

Show »
Length:197
Mass (Da):21,950
Checksum:i55BEA6540008B67A
GO
Isoform E (identifier: Q9NZH6-5) [UniParc]FASTAAdd to basket
Also known as: IL1F7e

The sequence of this isoform differs from the canonical sequence as follows:
     28-88: Missing.

Show »
Length:157
Mass (Da):17,459
Checksum:i5EA5EA10CF309086
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01426031G → V3 PublicationsCorresponds to variant dbSNP:rs3811046Ensembl.1
Natural variantiVAR_01426142T → A3 PublicationsCorresponds to variant dbSNP:rs3811047Ensembl.1
Natural variantiVAR_04957450P → R. Corresponds to variant dbSNP:rs2708943Ensembl.1
Natural variantiVAR_04957554N → S. Corresponds to variant dbSNP:rs2723183Ensembl.1
Natural variantiVAR_023334108P → L1 PublicationCorresponds to variant dbSNP:rs2723187Ensembl.1
Natural variantiVAR_023335152R → W1 PublicationCorresponds to variant dbSNP:rs28947200Ensembl.1
Natural variantiVAR_023336164W → R1 PublicationCorresponds to variant dbSNP:rs2708947Ensembl.1
Natural variantiVAR_023337218D → N1 PublicationCorresponds to variant dbSNP:rs2723192Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0026531 – 49MSFVG…FVHTS → MSGCDRRETETKGKNSFKKR LRG in isoform A. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_00265528 – 88Missing in isoform E. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_00265428 – 49DPAGS…FVHTS → G in isoform D. 2 PublicationsAdd BLAST22
Alternative sequenceiVSP_00265649 – 89SPKVK…YIRPE → K in isoform C. 1 PublicationAdd BLAST41

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
CCDSiCCDS2103.1 [Q9NZH6-1]
CCDS2104.1 [Q9NZH6-4]
CCDS2105.1 [Q9NZH6-5]
CCDS2106.1 [Q9NZH6-3]
CCDS2107.1 [Q9NZH6-2]
RefSeqiNP_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]
UniGeneiHs.166371

Genome annotation databases

EnsembliENST00000263326; ENSP00000263326; ENSG00000125571 [Q9NZH6-1]
ENST00000311328; ENSP00000309883; ENSG00000125571 [Q9NZH6-2]
ENST00000349806; ENSP00000263328; ENSG00000125571 [Q9NZH6-5]
ENST00000352179; ENSP00000263327; ENSG00000125571 [Q9NZH6-4]
ENST00000353225; ENSP00000309208; ENSG00000125571 [Q9NZH6-3]
GeneIDi27178
KEGGihsa:27178
UCSCiuc002tij.4 human [Q9NZH6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS2103.1 [Q9NZH6-1]
CCDS2104.1 [Q9NZH6-4]
CCDS2105.1 [Q9NZH6-5]
CCDS2106.1 [Q9NZH6-3]
CCDS2107.1 [Q9NZH6-2]
RefSeqiNP_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]
UniGeneiHs.166371

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5HN1X-ray2.25A/B46-218[»]
ProteinModelPortaliQ9NZH6
SMRiQ9NZH6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118054, 12 interactors
IntActiQ9NZH6, 3 interactors
STRINGi9606.ENSP00000263326

PTM databases

iPTMnetiQ9NZH6
PhosphoSitePlusiQ9NZH6

Polymorphism and mutation databases

BioMutaiIL37
DMDMi25008593

Proteomic databases

PaxDbiQ9NZH6
PeptideAtlasiQ9NZH6
PRIDEiQ9NZH6
ProteomicsDBi83390
83391 [Q9NZH6-2]
83392 [Q9NZH6-3]
83393 [Q9NZH6-4]
83394 [Q9NZH6-5]

Protocols and materials databases

DNASUi27178
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263326; ENSP00000263326; ENSG00000125571 [Q9NZH6-1]
ENST00000311328; ENSP00000309883; ENSG00000125571 [Q9NZH6-2]
ENST00000349806; ENSP00000263328; ENSG00000125571 [Q9NZH6-5]
ENST00000352179; ENSP00000263327; ENSG00000125571 [Q9NZH6-4]
ENST00000353225; ENSP00000309208; ENSG00000125571 [Q9NZH6-3]
GeneIDi27178
KEGGihsa:27178
UCSCiuc002tij.4 human [Q9NZH6-1]

Organism-specific databases

CTDi27178
DisGeNETi27178
EuPathDBiHostDB:ENSG00000125571.9
GeneCardsiIL37
HGNCiHGNC:15563 IL37
HPAiHPA054371
HPA057950
MIMi605510 gene
neXtProtiNX_Q9NZH6
OpenTargetsiENSG00000125571
PharmGKBiPA38390
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J8RD Eukaryota
ENOG41118IW LUCA
GeneTreeiENSGT00900000141014
HOVERGENiHBG052101
InParanoidiQ9NZH6
KOiK05485
OMAiRKHTEFS
OrthoDBiEOG091G0J3H
PhylomeDBiQ9NZH6
TreeFamiTF300203

Enzyme and pathway databases

ReactomeiR-HSA-9008059 Interleukin-37 signaling
R-HSA-9012546 Interleukin-18 signaling

Miscellaneous databases

GeneWikiiIL1F7
GenomeRNAii27178
PMAP-CutDBiQ9NZH6
PROiPR:Q9NZH6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125571 Expressed in 143 organ(s), highest expression level in skin of leg
CleanExiHS_IL1F7
GenevisibleiQ9NZH6 HS

Family and domain databases

InterProiView protein in InterPro
IPR000975 IL-1_fam
IPR003297 IL-1RA/IL-36
IPR008996 IL1/FGF
PfamiView protein in Pfam
PF00340 IL1, 1 hit
PRINTSiPR00264 INTERLEUKIN1
PR01360 INTRLEUKIN1X
SUPFAMiSSF50353 SSF50353, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIL37_HUMAN
AccessioniPrimary (citable) accession number: Q9NZH6
Secondary accession number(s): B5BU97
, Q56AP9, Q8TD04, Q8TD05, Q9HBF2, Q9HBF3, Q9UHA6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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