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Protein

Inducible T-cell costimulator

Gene

ICOS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 similarity2 Publications

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-1257604 PIP3 activates AKT signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-388841 Costimulation by the CD28 family
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

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
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000163600.12
HGNCiHGNC:5351 ICOS
MIMi604558 gene
neXtProtiNX_Q9Y6W8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 140ExtracellularSequence analysisAdd BLAST120
Transmembranei141 – 161HelicalSequence analysisAdd BLAST21
Topological domaini162 – 199CytoplasmicSequence analysisAdd BLAST38

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency, common variable, 1 (CVID1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:607594

Organism-specific databases

DisGeNETi29851
GeneReviewsiICOS
MalaCardsiICOS
MIMi607594 phenotype
OpenTargetsiENSG00000163600
Orphaneti1572 Common variable immunodeficiency
PharmGKBiPA29599

Polymorphism and mutation databases

BioMutaiICOS
DMDMi50400701

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001480621 – 199Inducible T-cell costimulatorAdd BLAST179

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi42 ↔ 109By similarity
Disulfide bondi63 ↔ 83By similarity
Glycosylationi89N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi110N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Y6W8
PeptideAtlasiQ9Y6W8
PRIDEiQ9Y6W8

PTM databases

iPTMnetiQ9Y6W8
PhosphoSitePlusiQ9Y6W8

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

BgeeiENSG00000163600
CleanExiHS_ICOS
ExpressionAtlasiQ9Y6W8 baseline and differential
GenevisibleiQ9Y6W8 HS

Organism-specific databases

HPAiCAB032575

Interactioni

Subunit structurei

Homodimer; disulfide-linked.2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi118933, 10 interactors
IntActiQ9Y6W8, 12 interactors
STRINGi9606.ENSP00000319476

Structurei

3D structure databases

ProteinModelPortaliQ9Y6W8
SMRiQ9Y6W8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 132Ig-like V-typeAdd BLAST103

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J005 Eukaryota
ENOG41117EH LUCA
GeneTreeiENSGT00390000000801
HOGENOMiHOG000112996
HOVERGENiHBG052079
InParanoidiQ9Y6W8
KOiK06713
OMAiYNLDSSH
OrthoDBiEOG091G0IRJ
PhylomeDBiQ9Y6W8
TreeFamiTF335679

Family and domain databases

Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR013783 Ig-like_fold
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF15910 V-set_2, 1 hit

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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010788168 – 199KYSSS…TDVTL → M in isoform 2. 1 PublicationAdd BLAST32

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.4 human [Q9Y6W8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiICOS_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6W8
Secondary accession number(s): Q8N6W8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: November 1, 1999
Last modified: May 23, 2018
This is version 144 of the entry and version 1 of the sequence. See 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

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