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Q9Y6W8

- ICOS_HUMAN

UniProt

Q9Y6W8 - ICOS_HUMAN

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Protein

Inducible T-cell costimulator

Gene

ICOS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Biological processi

  1. immune response Source: UniProtKB
  2. single organismal cell-cell adhesion Source: Ensembl
  3. T cell costimulation Source: Reactome
  4. T cell tolerance induction Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_19344. Costimulation by the CD28 family.

Names & Taxonomyi

Protein namesi
Recommended name:
Inducible T-cell costimulator
Alternative name(s):
Activation-inducible lymphocyte immunomediatory molecule
CD_antigen: CD278
Gene namesi
Name:ICOS
Synonyms:AILIM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:5351. ICOS.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 140120ExtracellularSequence AnalysisAdd
BLAST
Transmembranei141 – 16121HelicalSequence AnalysisAdd
BLAST
Topological domaini162 – 19938CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. external side of plasma membrane Source: Ensembl
  2. extracellular region Source: UniProtKB-KW
  3. integral component of plasma membrane Source: Ensembl
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.

Organism-specific databases

MIMi607594. phenotype.
Orphaneti1572. Common variable immunodeficiency.
PharmGKBiPA29599.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence AnalysisAdd
BLAST
Chaini21 – 199179Inducible T-cell costimulatorPRO_0000014806Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi23 – 231N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi42 ↔ 109By similarity
Disulfide bondi63 ↔ 83By similarity
Glycosylationi89 – 891N-linked (GlcNAc...)Sequence Analysis
Glycosylationi110 – 1101N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Y6W8.
PRIDEiQ9Y6W8.

PTM databases

PhosphoSiteiQ9Y6W8.

Expressioni

Tissue specificityi

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.3 Publications

Inductioni

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.1 Publication

Gene expression databases

BgeeiQ9Y6W8.
CleanExiHS_ICOS.
ExpressionAtlasiQ9Y6W8. baseline and differential.
GenevestigatoriQ9Y6W8.

Organism-specific databases

HPAiCAB032575.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.2 Publications

Protein-protein interaction databases

BioGridi118933. 6 interactions.
IntActiQ9Y6W8. 1 interaction.
STRINGi9606.ENSP00000319476.

Structurei

3D structure databases

ProteinModelPortaliQ9Y6W8.
SMRiQ9Y6W8. Positions 25-115.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 132103Ig-like V-typeAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG69972.
GeneTreeiENSGT00390000000801.
HOGENOMiHOG000112996.
HOVERGENiHBG052079.
InParanoidiQ9Y6W8.
KOiK06713.
OMAiHSHANYY.
OrthoDBiEOG7JMGFN.
PhylomeDBiQ9Y6W8.
TreeFamiTF335679.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9Y6W8-1) [UniParc]FASTAAdd to Basket

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
MKSGLWYFFL FCLRIKVLTG EINGSANYEM FIFHNGGVQI LCKYPDIVQQ
60 70 80 90 100
FKMQLLKGGQ ILCDLTKTKG SGNTVSIKSL KFCHSQLSNN SVSFFLYNLD
110 120 130 140 150
HSHANYYFCN LSIFDPPPFK VTLTGGYLHI YESQLCCQLK FWLPIGCAAF
160 170 180 190
VVVCILGCIL ICWLTKKKYS SSVHDPNGEY MFMRAVNTAK KSRLTDVTL
Length:199
Mass (Da):22,625
Last modified:November 1, 1999 - v1
Checksum:i214EC741C9BDC9FC
GO
Isoform 2 (identifier: Q9Y6W8-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     168-199: KYSSSVHDPNGEYMFMRAVNTAKKSRLTDVTL → M

Note: No experimental confirmation available.

Show »
Length:168
Mass (Da):19,127
Checksum:i499CFB5E6860A365
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei168 – 19932KYSSS…TDVTL → M in isoform 2. 1 PublicationVSP_010788Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2363.1. [Q9Y6W8-1]
PIRiS78540.
RefSeqiNP_036224.1. NM_012092.3. [Q9Y6W8-1]
UniGeneiHs.56247.

Genome annotation databases

EnsembliENST00000316386; ENSP00000319476; ENSG00000163600. [Q9Y6W8-1]
ENST00000435193; ENSP00000415951; ENSG00000163600. [Q9Y6W8-2]
GeneIDi29851.
KEGGihsa:29851.
UCSCiuc002vam.3. human. [Q9Y6W8-1]
uc010fua.3. human. [Q9Y6W8-2]

Polymorphism databases

DMDMi50400701.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

ICOSbase

ICOS mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS2363.1. [Q9Y6W8-1 ]
PIRi S78540.
RefSeqi NP_036224.1. NM_012092.3. [Q9Y6W8-1 ]
UniGenei Hs.56247.

3D structure databases

ProteinModelPortali Q9Y6W8.
SMRi Q9Y6W8. Positions 25-115.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 118933. 6 interactions.
IntActi Q9Y6W8. 1 interaction.
STRINGi 9606.ENSP00000319476.

PTM databases

PhosphoSitei Q9Y6W8.

Polymorphism databases

DMDMi 50400701.

Proteomic databases

PaxDbi Q9Y6W8.
PRIDEi Q9Y6W8.

Protocols and materials databases

DNASUi 29851.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000316386 ; ENSP00000319476 ; ENSG00000163600 . [Q9Y6W8-1 ]
ENST00000435193 ; ENSP00000415951 ; ENSG00000163600 . [Q9Y6W8-2 ]
GeneIDi 29851.
KEGGi hsa:29851.
UCSCi uc002vam.3. human. [Q9Y6W8-1 ]
uc010fua.3. human. [Q9Y6W8-2 ]

Organism-specific databases

CTDi 29851.
GeneCardsi GC02P204765.
GeneReviewsi ICOS.
HGNCi HGNC:5351. ICOS.
HPAi CAB032575.
MIMi 604558. gene.
607594. phenotype.
neXtProti NX_Q9Y6W8.
Orphaneti 1572. Common variable immunodeficiency.
PharmGKBi PA29599.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG69972.
GeneTreei ENSGT00390000000801.
HOGENOMi HOG000112996.
HOVERGENi HBG052079.
InParanoidi Q9Y6W8.
KOi K06713.
OMAi HSHANYY.
OrthoDBi EOG7JMGFN.
PhylomeDBi Q9Y6W8.
TreeFami TF335679.

Enzyme and pathway databases

Reactomei REACT_19344. Costimulation by the CD28 family.

Miscellaneous databases

GeneWikii CD278.
GenomeRNAii 29851.
NextBioi 52391.
PROi Q9Y6W8.
SOURCEi Search...

Gene expression databases

Bgeei Q9Y6W8.
CleanExi HS_ICOS.
ExpressionAtlasi Q9Y6W8. baseline and differential.
Genevestigatori Q9Y6W8.

Family and domain databases

ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: FUNCTION, GLYCOSYLATION, SUBUNIT, INDUCTION, TISSUE SPECIFICITY.
  9. Cited for: INVOLVEMENT IN CVID1.

Entry informationi

Entry nameiICOS_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6W8
Secondary accession number(s): Q8N6W8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: November 1, 1999
Last modified: November 26, 2014
This is version 115 of the entry and version 1 of the sequence. [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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3