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O75144 (ICOSL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length302 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 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: The sequence differs from that shown in position 300 onward for unknown reason.

Ontologies

Keywords
   Biological processAdaptive immunity
B-cell activation
Immunity
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainImmunoglobulin domain
Signal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell activation

Inferred from electronic annotation. Source: UniProtKB-KW

T cell activation

Non-traceable author statement PubMed 11983910. Source: UniProtKB

T cell costimulation

Traceable author statement. Source: Reactome

defense response

Non-traceable author statement PubMed 11983910. Source: UniProtKB

hyperosmotic response

Non-traceable author statement PubMed 12145647. Source: UniProtKB

positive regulation of activated T cell proliferation

Traceable author statement PubMed 11429535. Source: UniProtKB

positive regulation of interleukin-4 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement PubMed 12145647. Source: UniProtKB

   Cellular_componentexternal side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Non-traceable author statement PubMed 12145647. Source: UniProtKB

integral component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionreceptor binding

Traceable author statement PubMed 11429535. 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 302284ICOS ligand
PRO_0000014803

Regions

Topological domain19 – 256238Extracellular Potential
Transmembrane257 – 27721Helical; Potential
Topological domain278 – 30225Cytoplasmic Potential
Domain19 – 129111Ig-like V-type
Domain141 – 22787Ig-like C2-type

Amino acid modifications

Glycosylation701N-linked (GlcNAc...) Ref.8
Glycosylation1021N-linked (GlcNAc...) Ref.8
Glycosylation1371N-linked (GlcNAc...) Potential
Glycosylation1731N-linked (GlcNAc...) Potential
Glycosylation1861N-linked (GlcNAc...) Ref.8
Glycosylation2251N-linked (GlcNAc...) Potential
Disulfide bond37 ↔ 113 Potential
Disulfide bond158 ↔ 216 Potential

Natural variations

Alternative sequence300 – 3023GHV → ESWNLLLLLS in isoform 2.
VSP_002520
Natural variant1281V → I.
Corresponds to variant rs11558819 [ dbSNP | Ensembl ].
VAR_049880

Sequences

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

Last modified August 14, 2001. Version 2.
Checksum: 647934E21B55E34A

FASTA30233,349
        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 

« Hide

Isoform 2 [UniParc].

Checksum: D019EC5307D796A5
Show »

FASTA30934,225

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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 [MRNA] (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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-102 AND ASN-186.
Tissue: Plasma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF199028 mRNA. Translation: AAF34739.1.
AF289028 mRNA. Translation: AAG01176.1.
AF216749 mRNA. Translation: AAK16241.1.
AX100595 mRNA. Translation: CAC36465.1.
AB014553 mRNA. Translation: BAA31628.1. Sequence problems.
BC064637 mRNA. Translation: AAH64637.1.
RefSeqNP_001269979.1. NM_001283050.1.
NP_056074.1. NM_015259.5.
UniGeneHs.14155.

3D structure databases

ProteinModelPortalO75144.
SMRO75144. Positions 22-225.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116900. 1 interaction.
STRING9606.ENSP00000384432.

Proteomic databases

PaxDbO75144.
PRIDEO75144.

Protocols and materials databases

DNASU23308.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344330; ENSP00000339477; ENSG00000160223. [O75144-2]
ENST00000407780; ENSP00000384432; ENSG00000160223. [O75144-1]
GeneID23308.
KEGGhsa:23308.
UCSCuc002zee.3. human. [O75144-1]

Organism-specific databases

CTD23308.
GeneCardsGC21M045642.
H-InvDBHIX0016164.
HGNCHGNC:17087. ICOSLG.
HPACAB026037.
MIM605717. gene.
neXtProtNX_O75144.
PharmGKBPA134977297.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43300.
HOGENOMHOG000036913.
HOVERGENHBG106483.
KOK06710.
OrthoDBEOG79KPFZ.
TreeFamTF331083.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressO75144.
BgeeO75144.
CleanExHS_ICOSLG.
GenevestigatorO75144.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamPF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiICOSLG.
GenomeRNAi23308.
NextBio45170.
PROO75144.
SOURCESearch...

Entry information

Entry nameICOSL_HUMAN
AccessionPrimary (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: March 19, 2014
This is version 129 of the entry and version 2 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM

Human cell differentiation molecules

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