Reviewed, UniProtKB/Swiss-Prot O75144 (ICOSL_HUMAN)

Names and origin

Protein names

Recommended name:
    ICOS ligand
Alternative name(s):
    B7 homolog 2
      Short name=B7-H2
    B7-like protein Gl50
    B7-related protein 1
      Short name=B7RP-1
    CD_antigen=CD275

Gene names

Name:	ICOSLG
Synonyms:	B7H2, B7RP1, ICOSL, KIAA0653

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	302 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	Ligand for the T-cell-specific cell surface receptor ICOS. Acts as a costimulatory signal for T-cell proliferation and cytokine secretion; induces also B-cell proliferation and differentiation into plasma cells. Could play an important role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T-cell function By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein By similarity.
Tissue specificity	Isoform 1 is widely expressed (brain, heart, kidney, liver, lung, pancreas, placenta, skeletal muscle, bone marrow, colon, ovary, prostate, testis, lymph nodes, leukocytes, spleen, thymus and tonsil), while isoform 2 is detected only in lymph nodes, leukocytes and spleen. Expressed on activated monocytes and dendritic cells. Ref.7
Induction	Constitutive expression is further enhanced by treatment with TNF-alpha in peripheral blood B-cells and monocytes, while it is decreased in dendritic cells.
Sequence similarities	Belongs to the immunoglobulin superfamily. BTN/MOG family. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 Ig-like V-type (immunoglobulin-like) domain.
Sequence caution	The sequence BAA31628.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAA31628.1 differs from that shown. Reason: Miscellaneous discrepancy. The sequence differs from that shown in position 300 onward for unknown reason.

Ontologies

Keywords
Biological process	B-cell activation Immune response
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Signal Transmembrane
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	B cell activation Inferred from electronic annotation. Source: UniProtKB-KW T cell activation Non-traceable author statement. Source: UniProtKB defense response Non-traceable author statement. Source: UniProtKB hyperosmotic response Non-traceable author statement. Source: UniProtKB immune response Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of activated T cell proliferation Traceable author statement. Source: UniProtKB signal transduction Non-traceable author statement. Source: UniProtKB
Cellular component	integral to membrane Non-traceable author statement. Source: UniProtKB
Molecular function	receptor binding Traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: O75144-1)

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: O75144-2)

The sequence of this isoform differs from the canonical sequence as follows:
     300-302: GHV → ESWNLLLLLS

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 302	284	ICOS ligand		PRO_0000014803
Regions
	Topological domain	19 – 256	238	Extracellular Potential
	Transmembrane	257 – 277	21	Potential
	Topological domain	278 – 302	25	Cytoplasmic Potential
	Domain	19 – 129	111	Ig-like V-type
	Domain	141 – 227	87	Ig-like C2-type
Amino acid modifications
	Glycosylation	70	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	102	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	137	1	N-linked (GlcNAc...) Potential
	Glycosylation	173	1	N-linked (GlcNAc...) Potential
	Glycosylation	186	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	225	1	N-linked (GlcNAc...) Potential
	Disulfide bond	37 ↔ 113		Potential
	Disulfide bond	158 ↔ 216		Potential
Natural variations
	Alternative sequence	300 – 302	3	GHV → ESWNLLLLLS in isoform 2.		VSP_002520
	Natural variant	128	1	V → I: dbSNP rs11558819.		VAR_049880

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 14, 2001. Version 2. Checksum: 647934E21B55E34A	FASTA	302	33,349
	10 20 30 40 50 60 MRLGSPGLLF LLFSSLRADT QEKEVRAMVG SDVELSCACP EGSRFDLNDV YVYWQTSESK 70 80 90 100 110 120 TVVTYHIPQN SSLENVDSRY RNRALMSPAG MLRGDFSLRL FNVTPQDEQK FHCLVLSQSL 130 140 150 160 170 180 GFQEVLSVEV TLHVAANFSV PVVSAPHSPS QDELTFTCTS INGYPRPNVY WINKTDNSLL 190 200 210 220 230 240 DQALQNDTVF LNMRGLYDVV SVLRIARTPS VNIGCCIENV LLQQNLTVGS QTGNDIGERD 250 260 270 280 290 300 KITENPVSTG EKNAATWSIL AVLCLLVVVA VAIGWVCRDR CLQHSYAGAW AVSPETELTG HV
	Isoform 2. Checksum: D019EC5307D796A5	FASTA	309	34,225
	10 20 30 40 50 60 MRLGSPGLLF LLFSSLRADT QEKEVRAMVG SDVELSCACP EGSRFDLNDV YVYWQTSESK 70 80 90 100 110 120 TVVTYHIPQN SSLENVDSRY RNRALMSPAG MLRGDFSLRL FNVTPQDEQK FHCLVLSQSL 130 140 150 160 170 180 GFQEVLSVEV TLHVAANFSV PVVSAPHSPS QDELTFTCTS INGYPRPNVY WINKTDNSLL 190 200 210 220 230 240 DQALQNDTVF LNMRGLYDVV SVLRIARTPS VNIGCCIENV LLQQNLTVGS QTGNDIGERD 250 260 270 280 290 300 KITENPVSTG EKNAATWSIL AVLCLLVVVA VAIGWVCRDR CLQHSYAGAW AVSPETELTE SWNLLLLLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS." Wang S., Zhu G., Chapoval A.I., Dong H., Tamada K., Ni J., Chen L. Blood 96:2808-2813(2000) [PubMed: 11023515] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Dendritic cell.
[2]	"Characterization of a new human B7-related protein: B7RP-1 is the ligand to the co-stimulatory protein ICOS." Yoshinaga S.K., Zhang M., Pistillo J., Horan T., Khare S.D., Miner K., Sonnenberg M., Boone T., Brankow D., Dai T., Delaney J., Han H., Hui A., Kohno T., Manoukian R., Whoriskey J.S., Coccia M.A. Int. Immunol. 12:1439-1447(2000) [PubMed: 11007762] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION. Tissue: Peripheral blood lymphocyte.
[3]	"Identification of GL50, a novel B7-like protein that functionally binds to ICOS receptor." Ling V., Wu P.W., Finnerty H.F., Bean K.M., Spaulding V., Fouser L.A., Leonard J.P., Hunter S.E., Zollner R., Thomas J.L., Miyashiro J.S., Jacobs K.A., Collins M. J. Immunol. 164:1653-1657(2000) [PubMed: 10657606] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Leukocyte.
[4]	"GL50 molecules and uses therefor." Ling V., Dunussi-Joannopolulos K. Patent number WO0121796, 29-MAR-2001 Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2).
[5]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed: 9734811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon.
[7]	"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: 10779774] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-102 AND ASN-186, MASS SPECTROMETRY. Tissue: Plasma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF199028 mRNA. Translation: AAF34739.1. AF289028 mRNA. Translation: AAG01176.1. AF216749 mRNA. Translation: AAK16241.1. AX100595 Unassigned DNA. Translation: CAC36465.1. AB014553 mRNA. Translation: BAA31628.1. Sequence problems. BC064637 mRNA. Translation: AAH64637.1.
IPI	IPI00219131. IPI00414888.
RefSeq	NP_056074.1.
UniGene	Hs.14155
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	O75144.
Genome annotation databases
Ensembl	ENSG00000160223. Homo sapiens. [Contig view]
GeneID	23308.
KEGG	hsa:23308.
NMPDR	fig|9606.3.peg.21062.
Organism-specific databases
GeneCards	GC21M044468.
H-InvDB	HIX0016164.
HGNC	HGNC:17087. ICOSLG.
MIM	605717. gene.
PharmGKB	PA134977297.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O75144.
HOVERGEN	O75144.
Gene expression databases
ArrayExpress	O75144.
Bgee	O75144.
CleanEx	HS_ICOSLG.
GermOnline	ENSG00000160223. Homo sapiens.
Family and domain databases
InterPro	IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
Pfam	PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	45170.
SOURCE	Search...

Entry information

Entry name

ICOSL_HUMAN

Accession

Primary (citable) accession number: O75144
Secondary accession number(s): Q9HD18, Q9NRQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	August 14, 2001
Last modified:	June 16, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)