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Q9NZH6 (IL37_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:IL37
Synonyms:FIL1Z, IL1F7, IL1H4, IL1RP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length218 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11 Ref.12

Subunit structure

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. Ref.3 Ref.12

Subcellular location

Cytoplasmcytosol. Nucleus. Secreted. Note: Stimulation with IL1B leads to colocalization with SMAD3 mostly in perinuclear regions. Only the CASP1-cleaved mature form translocates into the nucleus upon LPS stimulation. Ref.3 Ref.11 Ref.12

Tissue specificity

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. Ref.3 Ref.12

Induction

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. Ref.11 Ref.12

Post-translational modification

Proteolytically converted to the mature form by CASP1.

Sequence similarities

Belongs to the IL-1 family.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   Molecular functionCytokine
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processimmune response

Non-traceable author statement Ref.4Ref.1. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Non-traceable author statement Ref.4. Source: UniProtKB

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioninterleukin-1 receptor binding

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform B (identifier: Q9NZH6-1)

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.
Note: The name IL-HL refers to isoform B containing polymorphisms Val-31 and Ala-42 (PubMed:11145836).
Isoform A (identifier: Q9NZH6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: MSFVGENSGVKMGSEDWEKDEPQCCLEDPAGSPLEPGPSLPTMNFVHTS → MSGCDRRETETKGKNSFKKRLRG
Isoform C (identifier: Q9NZH6-3)

Also known as: IL-HS;

The sequence of this isoform differs from the canonical sequence as follows:
     49-89: SPKVKNLNPKKFSIHDQDHKVLVLDSGNLIAVPDKNYIRPE → K
Isoform D (identifier: Q9NZH6-4)

Also known as: IL1F7d;

The sequence of this isoform differs from the canonical sequence as follows:
     28-49: DPAGSPLEPGPSLPTMNFVHTS → G
Isoform E (identifier: Q9NZH6-5)

Also known as: IL1F7e;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 4545Removed in mature form
PRO_0000015335
Chain46 – 218173Interleukin-37
PRO_0000015336

Natural variations

Alternative sequence1 – 4949MSFVG…FVHTS → MSGCDRRETETKGKNSFKKR LRG in isoform A.
VSP_002653
Alternative sequence28 – 8861Missing in isoform E.
VSP_002655
Alternative sequence28 – 4922DPAGS…FVHTS → G in isoform D.
VSP_002654
Alternative sequence49 – 8941SPKVK…YIRPE → K in isoform C.
VSP_002656
Natural variant311G → V. Ref.3 Ref.6 Ref.10
Corresponds to variant rs3811046 [ dbSNP | Ensembl ].
VAR_014260
Natural variant421T → A. Ref.3 Ref.6 Ref.10
Corresponds to variant rs3811047 [ dbSNP | Ensembl ].
VAR_014261
Natural variant501P → R.
Corresponds to variant rs2708943 [ dbSNP | Ensembl ].
VAR_049574
Natural variant541N → S.
Corresponds to variant rs2723183 [ dbSNP | Ensembl ].
VAR_049575
Natural variant1081P → L. Ref.6
Corresponds to variant rs2723187 [ dbSNP | Ensembl ].
VAR_023334
Natural variant1521R → W. Ref.6
Corresponds to variant rs28947200 [ dbSNP | Ensembl ].
VAR_023335
Natural variant1641W → R. Ref.6
Corresponds to variant rs2708947 [ dbSNP | Ensembl ].
VAR_023336
Natural variant2181D → N. Ref.6
Corresponds to variant rs2723192 [ dbSNP | Ensembl ].
VAR_023337

Sequences

Sequence LengthMass (Da)Tools
Isoform B (IL-1F7b) (IL-HLa) [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 96E089310D2CEA68

FASTA21824,126
        10         20         30         40         50         60 
MSFVGENSGV KMGSEDWEKD EPQCCLEDPA GSPLEPGPSL PTMNFVHTSP KVKNLNPKKF 

        70         80         90        100        110        120 
SIHDQDHKVL VLDSGNLIAV PDKNYIRPEI FFALASSLSS ASAEKGSPIL LGVSKGEFCL 

       130        140        150        160        170        180 
YCDKDKGQSH PSLQLKKEKL MKLAAQKESA RRPFIFYRAQ VGSWNMLESA AHPGWFICTS 

       190        200        210 
CNCNEPVGVT DKFENRKHIE FSFQPVCKAE MSPSEVSD 

« Hide

Isoform A [UniParc].

Checksum: 4AF584C81802F612
Show »

FASTA19221,543
Isoform C (IL-HS) [UniParc].

Checksum: D9BE1DD4858C4932
Show »

FASTA17819,604
Isoform D (IL1F7d) [UniParc].

Checksum: 55BEA6540008B67A
Show »

FASTA19721,950
Isoform E (IL1F7e) [UniParc].

Checksum: 5EA5EA10CF309086
Show »

FASTA15717,459

References

« Hide 'large scale' references
[1]"Identification and initial characterization of four novel members of the interleukin-1 family."
Kumar S., McDonnell P.C., Lehr R., Tierney L., Tzimas M.N., Griswold D.E., Capper E.A., Tal-Singer R., Wells G.I., Doyle M.L., Young P.R.
J. Biol. Chem. 275:10308-10314(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
Tissue: Fetal B-cell, Fetal colon, Fetal lung and Fetal testis.
[2]Manoj P.P., Mantovani A., Muzio M.
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
Tissue: Colon carcinoma.
[3]"IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp."
Pan G., Risser P., Mao W., Baldwin D.T., Zhong A.W., Filvaroff E., Yansura D., Lewis L., Eigenbrot C., Henzel W.J., Vandlen R.
Cytokine 13:1-7(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), PROTEIN SEQUENCE OF 46-54, INTERACTION WITH IL18R1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS VAL-31 AND ALA-42.
[4]"Four new members expand the IL-1 superfamily."
Smith D.E., Renshaw B.R., Ketchem R.R., Kubin M., Garka K.E., Sims J.E.
J. Biol. Chem. 275:1169-1175(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[5]"Genomic organization of the interleukin-1 locus."
Taylor S.L., Renshaw B.R., Garka K.E., Smith D.E., Sims J.E.
Genomics 79:726-733(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS D AND E).
[6]SeattleSNPs variation discovery resource
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-31; ALA-42; LEU-108; TRP-152; ARG-164 AND ASN-218.
[7]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D).
[8]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B), VARIANTS VAL-31 AND ALA-42.
Tissue: Placenta.
[11]"The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines."
Sharma S., Kulk N., Nold M.F., Graf R., Kim S.H., Reinhardt D., Dinarello C.A., Bufler P.
J. Immunol. 180:5477-5482(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MATURATION BY CASP1, INDUCTION.
[12]"IL-37 is a fundamental inhibitor of innate immunity."
Nold M.F., Nold-Petry C.A., Zepp J.A., Palmer B.E., Bufler P., Dinarello C.A.
Nat. Immunol. 11:1014-1022(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SMAD3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
+Additional computationally mapped references.

Web resources

Wikipedia

Interleukin-1 entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_055254.2. NM_014439.3.
NP_775294.1. NM_173202.1.
NP_775295.1. NM_173203.1.
NP_775296.1. NM_173204.1.
NP_775297.1. NM_173205.1.
UniGeneHs.166371.

3D structure databases

ProteinModelPortalQ9NZH6.
SMRQ9NZH6. Positions 60-192.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118054. 4 interactions.
IntActQ9NZH6. 1 interaction.
MINTMINT-1208512.
STRING9606.ENSP00000263326.

Polymorphism databases

DMDM25008593.

Proteomic databases

PaxDbQ9NZH6.
PRIDEQ9NZH6.

Protocols and materials databases

DNASU27178.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263326; ENSP00000263326; ENSG00000125571. [Q9NZH6-1]
ENST00000311328; ENSP00000309883; ENSG00000125571. [Q9NZH6-2]
ENST00000349806; ENSP00000263328; ENSG00000125571. [Q9NZH6-5]
ENST00000352179; ENSP00000263327; ENSG00000125571. [Q9NZH6-4]
ENST00000353225; ENSP00000309208; ENSG00000125571. [Q9NZH6-3]
GeneID27178.
KEGGhsa:27178.
UCSCuc002tij.3. human. [Q9NZH6-1]
uc002tik.3. human. [Q9NZH6-4]
uc002til.3. human. [Q9NZH6-3]
uc002tim.3. human. [Q9NZH6-5]
uc002tin.3. human. [Q9NZH6-2]

Organism-specific databases

CTD27178.
GeneCardsGC02P113672.
HGNCHGNC:15563. IL37.
HPAHPA054371.
HPA057950.
MIM605510. gene.
neXtProtNX_Q9NZH6.
PharmGKBPA38390.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG78218.
HOVERGENHBG052101.
InParanoidQ9NZH6.
KOK05485.
OMASCNSGEP.
OrthoDBEOG7RRF8N.
PhylomeDBQ9NZH6.
TreeFamTF300203.

Gene expression databases

BgeeQ9NZH6.
CleanExHS_IL1F7.
GenevestigatorQ9NZH6.

Family and domain databases

InterProIPR008996. Cytokine_IL1-like.
IPR000975. IL-1.
IPR003297. IL-1RA/IL-36.
IPR027169. IL-37.
[Graphical view]
PANTHERPTHR10078:SF9. PTHR10078:SF9. 1 hit.
PfamPF00340. IL1. 1 hit.
[Graphical view]
PRINTSPR00264. INTERLEUKIN1.
PR01360. INTRLEUKIN1X.
SMARTSM00125. IL1. 1 hit.
[Graphical view]
SUPFAMSSF50353. SSF50353. 1 hit.
ProtoNetSearch...

Other

GeneWikiIL1F7.
GenomeRNAi27178.
NextBio49992.
PMAP-CutDBQ9NZH6.
PROQ9NZH6.
SOURCESearch...

Entry information

Entry nameIL37_HUMAN
AccessionPrimary (citable) accession number: Q9NZH6
Secondary accession number(s): B5BU97 expand/collapse secondary AC list , Q56AP9, Q8TD04, Q8TD05, Q9HBF2, Q9HBF3, Q9UHA6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: October 1, 2000
Last modified: March 19, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM