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Q9Y6W8 (ICOS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:
Inducible T-cell costimulator
Alternative name(s):
Activation-inducible lymphocyte immunomediatory molecule
CD_antigen=CD278
Gene names
Name:ICOS
Synonyms:AILIM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length199 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes By similarity. Ref.1 Ref.8

Subunit structure

Homodimer; disulfide-linked. Ref.1 Ref.8

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein Potential.

Isoform 2: Secreted Potential.

Tissue specificity

Activated T-cells. Highly expressed on tonsillar T-cells, which are closely associated with B-cells in the apical light zone of germinal centers, the site of terminal B-cell maturation. Expressed at lower levels in thymus, lung, lymph node and peripheral blood leukocytes. Expressed in the medulla of fetal and newborn thymus. Ref.1 Ref.2 Ref.8

Induction

By phorbol myristate acetate (PMA) and ionomycin. Up-regulated early on T-cells and continues to be expressed into the later phases of T-cell activation. Ref.8

Post-translational modification

N-glycosylated. Ref.8

Involvement in disease

Immunodeficiency, common variable, 1 (CVID1) [MIM:607594]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y6W8-1)

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.
Isoform 2 (identifier: Q9Y6W8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     168-199: KYSSSVHDPNGEYMFMRAVNTAKKSRLTDVTL → M
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 199179Inducible T-cell costimulator
PRO_0000014806

Regions

Topological domain21 – 140120Extracellular Potential
Transmembrane141 – 16121Helical; Potential
Topological domain162 – 19938Cytoplasmic Potential
Domain30 – 132103Ig-like V-type

Amino acid modifications

Glycosylation231N-linked (GlcNAc...) Potential
Glycosylation891N-linked (GlcNAc...) Potential
Glycosylation1101N-linked (GlcNAc...) Potential
Disulfide bond42 ↔ 109 By similarity
Disulfide bond63 ↔ 83 By similarity

Natural variations

Alternative sequence168 – 19932KYSSS…TDVTL → M in isoform 2.
VSP_010788

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 214EC741C9BDC9FC

FASTA19922,625
        10         20         30         40         50         60 
MKSGLWYFFL FCLRIKVLTG EINGSANYEM FIFHNGGVQI LCKYPDIVQQ FKMQLLKGGQ 

        70         80         90        100        110        120 
ILCDLTKTKG SGNTVSIKSL KFCHSQLSNN SVSFFLYNLD HSHANYYFCN LSIFDPPPFK 

       130        140        150        160        170        180 
VTLTGGYLHI YESQLCCQLK FWLPIGCAAF VVVCILGCIL ICWLTKKKYS SSVHDPNGEY 

       190 
MFMRAVNTAK KSRLTDVTL 

« Hide

Isoform 2 [UniParc].

Checksum: 499CFB5E6860A365
Show »

FASTA16819,127

References

« Hide 'large scale' references
[1]"ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28."
Hutloff A., Dittrich A.M., Beier K.C., Eljaschewitsch B., Kraft R., Anagnostopoulos I., Kroczek R.A.
Nature 397:263-266(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), PROTEIN SEQUENCE OF 192-198, FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
[2]"Identification and characterization of rat AILIM/ICOS, a novel T-cell costimulatory molecule, related to the CD28/CTLA4 family."
Tezuka K., Tsuji T., Hirano D., Tamatani T., Sakamaki K., Kobayashi Y., Kamada M.
Biochem. Biophys. Res. Commun. 276:335-345(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Blood.
[3]"Characterization of human inducible costimulator ligand expression and function."
Aicher A., Hayden-Ledbetter M., Brady W.A., Pezzutto A., Richter G., Magaletti D., Buckwalter S., Ledbetter J.A., Clark E.A.
J. Immunol. 164:4689-4696(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
Tissue: Thymus.
[4]"Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches."
Ling V., Wu P.W., Finnerty H.F., Agostino M.J., Graham J.R., Chen S., Jussiff J.M., Fisk G.J., Miller C.P., Collins M.
Genomics 78:155-168(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]"Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation."
Haaning Andersen A.D., Lange M., Lillevang S.T.
Tissue Antigens 61:276-285(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[6]Todd J.A.
Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[7]"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] (ISOFORMS 1 AND 2).
Tissue: Blood.
[8]"Induction, binding specificity and function of human ICOS."
Beier K.C., Hutloff A., Dittrich A.M., Heuck C., Rauch A., Buechner K., Ludewig B., Ochs H.D., Mages H.W., Kroczek R.A.
Eur. J. Immunol. 30:3707-3717(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, GLYCOSYLATION, SUBUNIT, INDUCTION, TISSUE SPECIFICITY.
[9]"Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency."
Grimbacher B., Hutloff A., Schlesier M., Glocker E., Warnatz K., Draeger R., Eibel H., Fischer B., Schaeffer A.A., Mages H.W., Kroczek R.A., Peter H.H.
Nat. Immunol. 4:261-268(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CVID1.
+Additional computationally mapped references.

Web resources

ICOSbase

ICOS mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ277832 mRNA. Translation: CAC06612.1.
AB023135 mRNA. Translation: BAA82129.1.
AF218312 mRNA. Translation: AAF71301.1.
AF411058 Genomic DNA. Translation: AAL40933.1.
AF411059 Genomic DNA. Translation: AAL40934.1.
AF488347, AF488346 Genomic DNA. Translation: AAM00909.1.
AJ535718 Genomic DNA. Translation: CAD59742.1.
BC028006 mRNA. Translation: AAH28006.1.
BC028210 mRNA. Translation: AAH28210.1.
CCDSCCDS2363.1. [Q9Y6W8-1]
PIRS78540.
RefSeqNP_036224.1. NM_012092.3. [Q9Y6W8-1]
UniGeneHs.56247.

3D structure databases

ProteinModelPortalQ9Y6W8.
SMRQ9Y6W8. Positions 25-115.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118933. 4 interactions.
IntActQ9Y6W8. 1 interaction.
STRING9606.ENSP00000319476.

PTM databases

PhosphoSiteQ9Y6W8.

Polymorphism databases

DMDM50400701.

Proteomic databases

PaxDbQ9Y6W8.
PRIDEQ9Y6W8.

Protocols and materials databases

DNASU29851.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316386; ENSP00000319476; ENSG00000163600. [Q9Y6W8-1]
ENST00000435193; ENSP00000415951; ENSG00000163600. [Q9Y6W8-2]
GeneID29851.
KEGGhsa:29851.
UCSCuc002vam.3. human. [Q9Y6W8-1]
uc010fua.3. human. [Q9Y6W8-2]

Organism-specific databases

CTD29851.
GeneCardsGC02P204765.
GeneReviewsICOS.
HGNCHGNC:5351. ICOS.
HPACAB032575.
MIM604558. gene.
607594. phenotype.
neXtProtNX_Q9Y6W8.
Orphanet1572. Common variable immunodeficiency.
PharmGKBPA29599.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG69972.
HOGENOMHOG000112996.
HOVERGENHBG052079.
InParanoidQ9Y6W8.
KOK06713.
OMAHSHANYY.
OrthoDBEOG7JMGFN.
PhylomeDBQ9Y6W8.
TreeFamTF335679.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9Y6W8.
BgeeQ9Y6W8.
CleanExHS_ICOS.
GenevestigatorQ9Y6W8.

Family and domain databases

ProtoNetSearch...

Other

GeneWikiCD278.
GenomeRNAi29851.
NextBio52391.
PROQ9Y6W8.
SOURCESearch...

Entry information

Entry nameICOS_HUMAN
AccessionPrimary (citable) accession number: Q9Y6W8
Secondary accession number(s): Q8N6W8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 111 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 chromosome 2

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

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries