Q9Y6W8 (ICOS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inducible T-cell costimulator

Alternative name(s):
Activation-inducible lymphocyte immunomediatory molecule
CD_antigen=CD278

Gene names

Name:	ICOS
Synonyms:	AILIM

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	199 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Traceable author statement. Source: Reactome T cell tolerance induction Inferred from electronic annotation. Source: Compara cell-cell adhesion Inferred from electronic annotation. Source: Compara immune response Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Non-traceable author statement. Source: UniProtKB integral to plasma membrane Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 199	179	Inducible T-cell costimulator		PRO_0000014806
Regions
	Topological domain	21 – 140	120	Extracellular Potential
	Transmembrane	141 – 161	21	Helical; Potential
	Topological domain	162 – 199	38	Cytoplasmic Potential
	Domain	30 – 132	103	Ig-like V-type
Amino acid modifications
	Glycosylation	23	1	N-linked (GlcNAc...) Potential
	Glycosylation	89	1	N-linked (GlcNAc...) Potential
	Glycosylation	110	1	N-linked (GlcNAc...) Potential
	Disulfide bond	42 ↔ 109		By similarity
	Disulfide bond	63 ↔ 83		By similarity
Natural variations
	Alternative sequence	168 – 199	32	KYSSS…TDVTL → M in isoform 2.		VSP_010788

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 214EC741C9BDC9FC	FASTA	199	22,625
	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
	Isoform 2 [UniParc]. Checksum: 499CFB5E6860A365	FASTA	168	19,127
	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 VTLTGGYLHI YESQLCCQLK FWLPIGCAAF VVVCILGCIL ICWLTKKM

References

	« Hide 'large scale' referencesShow '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

GeneReviews

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.
IPI	IPI00424030. IPI00424031.
PIR	S78540.
RefSeq	NP_036224.1. NM_012092.3.
UniGene	Hs.56247.
3D structure databases
ProteinModelPortal	Q9Y6W8.
SMR	Q9Y6W8. Positions 21-131.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y6W8. 1 interaction.
STRING	9606.ENSP00000319476.
PTM databases
PhosphoSite	Q9Y6W8.
Polymorphism databases
DMDM	50400701.
Proteomic databases
PaxDb	Q9Y6W8.
PRIDE	Q9Y6W8.
Protocols and materials databases
DNASU	29851.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000316386; ENSP00000319476; ENSG00000163600. ENST00000435193; ENSP00000415951; ENSG00000163600.
GeneID	29851.
KEGG	hsa:29851.
UCSC	uc002vam.3. human. uc010fua.3. human.
Organism-specific databases
CTD	29851.
GeneCards	GC02P204765.
HGNC	HGNC:5351. ICOS.
HPA	CAB032575.
MIM	604558. gene. 607594. phenotype.
neXtProt	NX_Q9Y6W8.
Orphanet	99831. Common variable immunodeficiency due to an intrinsic T cell defect.
PharmGKB	PA29599.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG69972.
HOGENOM	HOG000112996.
HOVERGEN	HBG052079.
InParanoid	Q9Y6W8.
KO	K06713.
OMA	FDPPPFQ.
OrthoDB	EOG4Q58QW.
PhylomeDB	Q9Y6W8.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9Y6W8.
Bgee	Q9Y6W8.
CleanEx	HS_ICOS.
Genevestigator	Q9Y6W8.
GermOnline	ENSG00000163600. Homo sapiens.
Family and domain databases
PROSITE	PS50835. IG_LIKE. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	29851.
NextBio	52391.
SOURCE	Search...

Entry information

Entry name

ICOS_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.