Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
6  structures 46  species 2  interactions 128  sequences 6  architectures

Family: IL28A (PF15177)

Summary: Interleukin-28A

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Interleukin 28". More...

Interleukin 28 Edit Wikipedia article

Interleukin 28A
Identifiers
Symbol IL28A
Alt. symbols IFNL2
Entrez 282616
HUGO 18364
OMIM 607401
RefSeq NM_172138
UniProt Q8IZJ0
Other data
Locus Chr. 19 q13.13
Interleukin 28B
Identifiers
Symbol IL28B
Alt. symbols IFNL3
Entrez 282617
HUGO 18365
OMIM 607402
RefSeq NM_172139
UniProt Q8IZI9
Other data
Locus Chr. 19 q13.13

Interleukin-28 (IL-28) is a cytokine that comes in two isoforms, IL-28A and IL-28B, and plays a role in immune defense against viruses, including the induction of an "antiviral state" by turning on Mx proteins, 2',5'-oligoadenylate synthetase as well as ISGF3G (Interferon Stimulated Gene Factor 3).[1] IL-28A and IL-28B belong to the type III interferon family of cytokines and are highly similar (in amino acid sequence) to IL-29. Their classification as Interferons is due to their ability to induce an antiviral state, while their additional classification as cytokines is due to their chromosomal location as well as the fact that they are encoded by multiple exons, as opposed to a single exon, as most type-I IFNs are.

Discovery

IL-28 was discovered in 2002 by Zymogenetics[2] using a genomic screening process in which the entire human genome was scanned for putative genes. Once these genes were found, a second scan was performed to look specifically for cytokines. Both IL-28 and IL-29 were found in humans using this type of analysis.

Structure

IL-28 genes are located near IL-29 on chromosome 19 in humans. The two isoforms of IL-28 (IL-28A and IL-28B) are 96% homologous. Differences in function between the two forms remains unclear.

The receptor for IL-28 is composed of a unique IL-28 Receptor Alpha chain which pairs with the IL-10 Receptor Beta chain, leading many to classify IL-28 as an IL-10-like family member.

Function

IL-28 has also been shown to play a role in the adaptive immune response, as its inclusion as an immunoadjuvant during small animal vaccination lead to augmented antigen-specific Interferon Gamma release as well as an increased cytotoxic potential in CD8+ T cells.[3]

Clinical significance

Addition of IL-28 to vaccination results in 100% protection from a lethal H1N1 Influenza challenge in a small animal model when it was paired with an Influenza vaccine that protected only 50% of the time without IL-28.[3]

Studies of IL-28B in non-human primate models of vaccination confirmed the small animal models, leading to an increase in Interferon Gamma production and CD8+ T cell activity in the form of cytotoxicity in an HIV vaccine study.[4] Scientists have credited this link to explain why some people infected with HSV-1 experience cold sores, while others do not.

A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to hepatitis C treatment with interferon and ribavirin.[5][6] The SNP was identified in a genome-wide association study (GWAS) and is to date the best example of a successful GWAS hit that is clinically relevant.[7]

References

  1. ^ Kempuraj D, Donelan J, Frydas S, Iezzi T, Conti F, Boucher W, Papadopoulou NG, Madhappan B, Letourneau L, Cao J, Sabatino G, Meneghini F, Stellin L, Verna N, Riccioni G, Theoharides TC (2004). "Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral activities". Int J Immunopathol Pharmacol. 17 (2): 103–6. PMID 15171810. 
  2. ^ Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM (January 2003). "IL-28, IL-29 and their class II cytokine receptor IL-28R". Nat. Immunol. 4 (1): 63–8. PMID 12469119. doi:10.1038/ni873. 
  3. ^ a b Morrow MP, Pankhong P, Laddy DJ, Schoenly KA, Yan J, Cisper N, Weiner DB (June 2009). "Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity". Blood. 113 (23): 5868–77. PMC 2700323Freely accessible. PMID 19304955. doi:10.1182/blood-2008-11-190520. 
  4. ^ Morrow MP, Yan J, Pankhong P, Shedlock DJ, Lewis MG, Talbott K, Toporovski R, Khan AS, Sardesai NY, Weiner DB (Sep 2010). "IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques". Molecular Therapy. 18 (9): 1714–23. PMC 2956930Freely accessible. PMID 20571540. doi:10.1038/mt.2010.118. 
  5. ^ PGxNews.Org (August 2009). "New biomarker predicts response to hepatitis C treatment". PGxNews.Org. Archived from the original on November 21, 2009. Retrieved 2009-08-17. 
  6. ^ Ge D; Fellay j; Thompson A; et al. (2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature. 461 (7262): 399–401. PMID 19684573. doi:10.1038/nature08309. 
  7. ^ Maxmen, Amy. "Pharmacogenomics: Playing the odds". Nature. 474 (7350): S9–S10. PMID 21666735. doi:10.1038/474S9a. 

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Interleukin-28A Provide feedback

The protein family, Interleukin-28A, plays an important role in modulating the immune system. This protein family is induced by viral infection and interacts with a class II receptor [1]. This family of proteins is found in eukaryotes. Proteins in this family are typically between 145 and 195 amino acids in length.

Literature references

  1. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM;, Nat Immunol. 2003;4:63-68.: IL-28, IL-29 and their class II cytokine receptor IL-28R. PUBMED:12469119 EPMC:12469119


This tab holds annotation information from the InterPro database.

InterPro entry IPR029177

Interferon (IFN)-lambda proteins belong to the new type III IFN group. In contrast to type I or type II IFNs, the response to type III IFN is cell-type specific. Only epithelial-like cells and some immune cells respond to IFN-lambda [PUBMED:22190970]. In human,four distinct proteins called IFN-lambda1 (interleukin-29, IL-29), IFN-lambda2 (IL-28A), IFN_lambda3 (IL-28B) and IFNL4 have been identified [PUBMED:20712453, PUBMED:12469119, PUBMED:23291588]. IFN-lambda proteins activate IFN-stimulated gene factor 3 (ISGF3), and are capable of inducing antiviral protection and MHC class I antigen expression [PUBMED:22190970].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan 4H_Cytokine (CL0053), which has the following description:

Cytokines are regulatory peptides that can be produced by various cells for communicating and orchestrating the large multicellular system. Cytokines are key mediators of hematopoiesis, immunity, allergy, inflammation, tissue remodeling, angiogenesis, and embryonic development [2]. This superfamily includes both the long and short chain helical cytokines.

The clan contains the following 29 members:

CNTF CSF-1 EPO_TPO Flt3_lig GCSF GM_CSF Hormone_1 IFN-gamma IL10 IL11 IL12 IL13 IL15 IL2 IL22 IL23 IL28A IL3 IL34 IL4 IL5 IL6 IL7 Interferon Leptin LIF_OSM PRF SCF TSLP

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(29)
Full
(128)
Representative proteomes UniProt
(175)
NCBI
(526)
Meta
(0)
RP15
(12)
RP35
(41)
RP55
(73)
RP75
(114)
Jalview View  View  View  View  View  View  View  View   
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(29)
Full
(128)
Representative proteomes UniProt
(175)
NCBI
(526)
Meta
(0)
RP15
(12)
RP35
(41)
RP55
(73)
RP75
(114)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(29)
Full
(128)
Representative proteomes UniProt
(175)
NCBI
(526)
Meta
(0)
RP15
(12)
RP35
(41)
RP55
(73)
RP75
(114)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Jackhmmer:Q8IZJ0
Previous IDs: none
Type: Domain
Author: Eberhardt RY, Coggill P, Hetherington K
Number in seed: 29
Number in full: 128
Average length of the domain: 133.70 aa
Average identity of full alignment: 50 %
Average coverage of the sequence by the domain: 76.72 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 43.1 27.0
Noise cut-off 25.5 26.4
Model length: 157
Family (HMM) version: 5
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 2 interactions for this family. More...

Tissue_fac IL28A

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IL28A domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...