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UniProtKB - P05231 (IL6_HUMAN)

Entry version 238 (23 Feb 2022)
Sequence version 1 (13 Aug 1987)
Previous versions | rss
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Protein

Interleukin-6

Gene

IL6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable).

1 Publication

IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (Probable). In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4+ T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4+ T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells (By similarity).

By similarity1 Publication

Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability (PubMed:17075861, PubMed:12794819).

Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF (PubMed:12794819).

Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (PubMed:20823453).

'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis (By similarity).

Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (By similarity).

Also acts as a myokine (Probable). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity).

Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection (PubMed:15124018).

Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).

By similarity1 Publication4 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionCytokine, Growth factor
Biological processAcute phase

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P05231

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1059683, Interleukin-6 signaling
R-HSA-110056, MAPK3 (ERK1) activation
R-HSA-112411, MAPK1 (ERK2) activation
R-HSA-2559582, Senescence-Associated Secretory Phenotype (SASP)
R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-6783783, Interleukin-10 signaling
R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling
R-HSA-8853884, Transcriptional Regulation by VENTX
R-HSA-8957275, Post-translational protein phosphorylation
R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9662834, CD163 mediating an anti-inflammatory response

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P05231

SIGNOR Signaling Network Open Resource

More...SIGNORi		P05231

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Interleukin-6Curated
Short name:
IL-6
Alternative name(s):
B-cell stimulatory factor 2
Short name:
BSF-2
CTL differentiation factor
Short name:
CDF
Hybridoma growth factor
Interferon beta-2
Short name:
IFN-beta-2
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:IL6Imported
Synonyms:IFNB2
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 7

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:6018, IL6

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		147620, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P05231

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000136244

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Rheumatoid arthritis systemic juvenile (RASJ)1 Publication
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionAn inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.
Related information in OMIM
A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi173A → V: Almost no loss of activity. 1 Publication1
Mutagenesisi185W → R: No loss of activity. 1 Publication1
Mutagenesisi204S → P: 87% loss of activity. 1 Publication1
Mutagenesisi210R → K, E, Q, T, A or P: Loss of activity. 1 Publication1
Mutagenesisi212M → T, N, S or R: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		3569

MalaCards human disease database

More...MalaCardsi		IL6
MIMi148000, phenotype
604302, phenotype

Open Targets

More...OpenTargetsi		ENSG00000136244

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		206, NON RARE IN EUROPE: Crohn disease
85414, Systemic-onset juvenile idiopathic arthritis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA198

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P05231, Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL1795129

Drug and drug target database

More...DrugBanki		DB05767, Andrographolide
DB05513, Atiprimod
DB11967, Binimetinib
DB05744, CRx-139
DB12140, Dilmapimod
DB10770, Foreskin fibroblast (neonatal)
DB10772, Foreskin keratinocyte (neonatal)
DB01404, Ginseng
DB09221, Polaprezinc
DB09036, Siltuximab
DB06083, Tapinarof
DB05470, VX-702
DB05017, YSIL6

DrugCentral

More...DrugCentrali		P05231

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		IL6

Domain mapping of disease mutations (DMDM)

More...DMDMi		124347

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 293 PublicationsAdd BLAST29
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001558230 – 212Interleukin-6Add BLAST183

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi72 ↔ 781 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi73N-linked (GlcNAc...) asparagine1 Publication1
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei81Phosphoserine; by FAM20C1 Publication1
Disulfide bondi101 ↔ 1111 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

N- and O-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P05231

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P05231

PeptideAtlas

More...PeptideAtlasi		P05231

PRoteomics IDEntifications database

More...PRIDEi		P05231

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		51828

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P05231, 1 site

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P05231

MetOSite database of methionine sulfoxide sites

More...MetOSitei		P05231

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P05231

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Produced by skeletal muscle.1 Publication

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Plasma levels are highly increased upon exercise, due to enhanced production by contracting skeletal muscles.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000136244, Expressed in left coronary artery and 160 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P05231, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P05231, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000136244, Tissue enhanced (urinary)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6R to associate with the signaling subunit IL6ST (PubMed:12829785).

Interacts with IL6R (via the N-terminal ectodomain); this interaction may be affected by IL6R-binding with SORL1, hence decreasing IL6 cis signaling (PubMed:28265003).

Interacts with SORL1 (via the N-terminal ectodomain); this interaction leads to IL6 internalization and lysosomal degradation (PubMed:28265003). May form a trimeric complex with the soluble SORL1 ectodomain and soluble IL6R receptor; this interaction might stabilize circulating IL6, hence promoting IL6 trans signaling (PubMed:28265003).

2 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		109783, 10 interactors

Database of interacting proteins

More...DIPi		DIP-482N

Protein interaction database and analysis system

More...IntActi		P05231, 8 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000385675

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P05231

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P05231, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1212
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P05231

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P05231

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the IL-6 superfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		ENOG502S7Q4, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00390000000878

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P05231

Identification of Orthologs from Complete Genome Data

More...OMAi		YDKCENS

Database for complete collections of gene phylogenies

More...PhylomeDBi		P05231

TreeFam database of animal gene trees

More...TreeFami		TF335984

Family and domain databases

Database of protein disorder

More...DisProti		DP02745

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.20.1250.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR009079, 4_helix_cytokine-like_core
IPR003574, IL-6
IPR030474, IL-6/GCSF/MGF
IPR030473, IL6/GCSF/MGF_CS

The PANTHER Classification System

More...PANTHERi		PTHR10511, PTHR10511, 1 hit
PTHR10511:SF3, PTHR10511:SF3, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00489, IL6, 1 hit

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF001935, IL6_MGF_GCSF, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00433, IL6GCSFMGF

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00126, IL6, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF47266, SSF47266, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00254, INTERLEUKIN_6, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P05231-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNSFSTSAFG PVAFSLGLLL VLPAAFPAPV PPGEDSKDVA APHRQPLTSS 
        60         70         80         90        100
ERIDKQIRYI LDGISALRKE TCNKSNMCES SKEALAENNL NLPKMAEKDG 
       110        120        130        140        150
CFQSGFNEET CLVKIITGLL EFEVYLEYLQ NRFESSEEQA RAVQMSTKVL 
       160        170        180        190        200
IQFLQKKAKN LDAITTPDPT TNASLLTKLQ AQNQWLQDMT THLILRSFKE 
       210 
FLQSSLRALR QM
Length:212
Mass (Da):23,718
Last modified:August 13, 1987 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i1F1ED1FE1B734079
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B5MCZ3B5MCZ3_HUMAN
Interleukin-6
IL6
189Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
C9J5B0C9J5B0_HUMAN
Interleukin-6
IL6
152Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
B5MC14B5MC14_HUMAN
Interleukin-6
IL6
198Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
B5MC21B5MC21_HUMAN
Interleukin-6
IL6
136Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
B4DNV3B4DNV3_HUMAN
Interleukin-6
IL6
122Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Genetic variations in IL6 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_01307532P → S1 PublicationCorresponds to variant dbSNP:rs2069830EnsemblClinVar.1
Natural variantiVAR_029266162D → E. Corresponds to variant dbSNP:rs13306435Ensembl.1
Natural variantiVAR_013076162D → V1 PublicationCorresponds to variant dbSNP:rs2069860EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
X04430 mRNA Translation: CAA28026.1
M14584 mRNA Translation: AAA52728.1
X04602 mRNA Translation: CAA28268.1
Y00081 Genomic DNA Translation: CAA68278.1
M18403 mRNA Translation: AAA52729.1
M29150 mRNA Translation: AAA59154.1
X04402 Genomic DNA Translation: CAA27990.1
X04403 mRNA Translation: CAA27991.1
M54894 mRNA Translation: AAC41704.1
S56892 mRNA Translation: AAD13886.1
AF372214 Genomic DNA Translation: AAK48987.1
BC015511 mRNA Translation: AAH15511.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS5375.1

Protein sequence database of the Protein Information Resource

More...PIRi		A32648, IVHUB2

NCBI Reference Sequences

More...RefSeqi		NP_000591.1, NM_000600.4
XP_011513692.1, XM_011515390.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000258743; ENSP00000258743; ENSG00000136244
ENST00000404625; ENSP00000385675; ENSG00000136244

Database of genes from NCBI RefSeq genomes

More...GeneIDi		3569

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:3569

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000258743.10; ENSP00000258743.5; NM_000600.5; NP_000591.1

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Wikipedia

Interleukin-6 entry

SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04430 mRNA Translation: CAA28026.1
M14584 mRNA Translation: AAA52728.1
X04602 mRNA Translation: CAA28268.1
Y00081 Genomic DNA Translation: CAA68278.1
M18403 mRNA Translation: AAA52729.1
M29150 mRNA Translation: AAA59154.1
X04402 Genomic DNA Translation: CAA27990.1
X04403 mRNA Translation: CAA27991.1
M54894 mRNA Translation: AAC41704.1
S56892 mRNA Translation: AAD13886.1
AF372214 Genomic DNA Translation: AAK48987.1
BC015511 mRNA Translation: AAH15511.1
CCDSiCCDS5375.1
PIRiA32648, IVHUB2
RefSeqiNP_000591.1, NM_000600.4
XP_011513692.1, XM_011515390.2

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ALUX-ray1.90A28-212[»]
1IL6NMR-A28-212[»]
1P9MX-ray3.65B29-212[»]
2IL6NMR-A28-212[»]
4CNIX-ray2.20C/D42-212[»]
4J4LX-ray2.30C/D47-212[»]
4NI7X-ray2.40A28-212[»]
4NI9X-ray2.55A/C28-212[»]
4O9HX-ray2.42A28-212[»]
4ZS7X-ray2.93A42-212[»]
5FUCX-ray2.70A/B49-212[»]
7NXZX-ray2.00AAA30-212[»]
SMRiP05231
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi109783, 10 interactors
DIPiDIP-482N
IntActiP05231, 8 interactors
STRINGi9606.ENSP00000385675

Chemistry databases

BindingDBiP05231
ChEMBLiCHEMBL1795129
DrugBankiDB05767, Andrographolide
DB05513, Atiprimod
DB11967, Binimetinib
DB05744, CRx-139
DB12140, Dilmapimod
DB10770, Foreskin fibroblast (neonatal)
DB10772, Foreskin keratinocyte (neonatal)
DB01404, Ginseng
DB09221, Polaprezinc
DB09036, Siltuximab
DB06083, Tapinarof
DB05470, VX-702
DB05017, YSIL6
DrugCentraliP05231

PTM databases

GlyGeniP05231, 1 site
iPTMnetiP05231
MetOSiteiP05231
PhosphoSitePlusiP05231

Genetic variation databases

BioMutaiIL6
DMDMi124347

Proteomic databases

MassIVEiP05231
PaxDbiP05231
PeptideAtlasiP05231
PRIDEiP05231
ProteomicsDBi51828

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		P05231, 186 sequenced antibodies

Antibodypedia a portal for validated antibodies

More...Antibodypediai		12025, 3040 antibodies from 50 providers

The CPTC Antibody Portal

More...CPTCi		P05231, 3 antibodies

The DNASU plasmid repository

More...DNASUi		3569

Genome annotation databases

EnsembliENST00000258743; ENSP00000258743; ENSG00000136244
ENST00000404625; ENSP00000385675; ENSG00000136244
GeneIDi3569
KEGGihsa:3569
MANE-SelectiENST00000258743.10; ENSP00000258743.5; NM_000600.5; NP_000591.1

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		3569
DisGeNETi3569

GeneCards: human genes, protein and diseases

More...GeneCardsi		IL6
HGNCiHGNC:6018, IL6
HPAiENSG00000136244, Tissue enhanced (urinary)
MalaCardsiIL6
MIMi147620, gene
148000, phenotype
604302, phenotype
neXtProtiNX_P05231
OpenTargetsiENSG00000136244
Orphaneti206, NON RARE IN EUROPE: Crohn disease
85414, Systemic-onset juvenile idiopathic arthritis
PharmGKBiPA198
VEuPathDBiHostDB:ENSG00000136244

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiENOG502S7Q4, Eukaryota
GeneTreeiENSGT00390000000878
InParanoidiP05231
OMAiYDKCENS
PhylomeDBiP05231
TreeFamiTF335984

Enzyme and pathway databases

PathwayCommonsiP05231
ReactomeiR-HSA-1059683, Interleukin-6 signaling
R-HSA-110056, MAPK3 (ERK1) activation
R-HSA-112411, MAPK1 (ERK2) activation
R-HSA-2559582, Senescence-Associated Secretory Phenotype (SASP)
R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-6783783, Interleukin-10 signaling
R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling
R-HSA-8853884, Transcriptional Regulation by VENTX
R-HSA-8957275, Post-translational protein phosphorylation
R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9662834, CD163 mediating an anti-inflammatory response
SignaLinkiP05231
SIGNORiP05231

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		3569, 5 hits in 1045 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		IL6, human
EvolutionaryTraceiP05231

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Interleukin_6

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		3569
PharosiP05231, Tclin

Protein Ontology

More...PROi		PR:P05231
RNActiP05231, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000136244, Expressed in left coronary artery and 160 other tissues
ExpressionAtlasiP05231, baseline and differential
GenevisibleiP05231, HS

Family and domain databases

DisProtiDP02745
Gene3Di1.20.1250.10, 1 hit
InterProiView protein in InterPro
IPR009079, 4_helix_cytokine-like_core
IPR003574, IL-6
IPR030474, IL-6/GCSF/MGF
IPR030473, IL6/GCSF/MGF_CS
PANTHERiPTHR10511, PTHR10511, 1 hit
PTHR10511:SF3, PTHR10511:SF3, 1 hit
PfamiView protein in Pfam
PF00489, IL6, 1 hit
PIRSFiPIRSF001935, IL6_MGF_GCSF, 1 hit
PRINTSiPR00433, IL6GCSFMGF
SMARTiView protein in SMART
SM00126, IL6, 1 hit
SUPFAMiSSF47266, SSF47266, 1 hit
PROSITEiView protein in PROSITE
PS00254, INTERLEUKIN_6, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiIL6_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P05231
Secondary accession number(s): Q9UCU2, Q9UCU3, Q9UCU4
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: February 23, 2022
This is version 238 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families
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