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Protein

ICOS ligand

Gene

ICOSLG

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

Functioni

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).By similarity

GO - Molecular functioni

  • receptor binding Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • B cell activation Source: UniProtKB-KW
  • defense response Source: UniProtKB
  • hyperosmotic response Source: UniProtKB
  • positive regulation of activated T cell proliferation Source: UniProtKB
  • signal transduction Source: UniProtKB
  • T cell activation Source: UniProtKB
  • T cell costimulation Source: Reactome
Complete GO annotation...

Keywordsi

Biological processAdaptive immunity, B-cell activation, Immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160223-MONOMER.
ReactomeiR-HSA-388841. Costimulation by the CD28 family.

Names & Taxonomyi

Protein namesi
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 namesi
Name:ICOSLG
Synonyms:B7H2, B7RP1, ICOSL, KIAA0653
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:17087. ICOSLG.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 256ExtracellularSequence analysisAdd BLAST238
Transmembranei257 – 277HelicalSequence analysisAdd BLAST21
Topological domaini278 – 302CytoplasmicSequence analysisAdd BLAST25

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • plasma membrane Source: Reactome

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi102723996.
23308.
OpenTargetsiENSG00000160223.
ENSG00000277117.
PharmGKBiPA134977297.

Polymorphism and mutation databases

BioMutaiICOSLG.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001480319 – 302ICOS ligandAdd BLAST284

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi37 ↔ 113PROSITE-ProRule annotation
Glycosylationi70N-linked (GlcNAc...)1 Publication1
Glycosylationi102N-linked (GlcNAc...)1 Publication1
Glycosylationi137N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi158 ↔ 216PROSITE-ProRule annotation
Glycosylationi173N-linked (GlcNAc...)Sequence analysis1
Glycosylationi186N-linked (GlcNAc...)1 Publication1
Glycosylationi225N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO75144.
PaxDbiO75144.
PeptideAtlasiO75144.
PRIDEiO75144.
TopDownProteomicsiO75144-2. [O75144-2]

PTM databases

iPTMnetiO75144.
PhosphoSitePlusiO75144.
SwissPalmiO75144.
UniCarbKBiO75144.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

Constitutive expression is further enhanced by treatment with TNF in peripheral blood B-cells and monocytes, while it is decreased in dendritic cells.

Gene expression databases

BgeeiENSG00000160223.
CleanExiHS_ICOSLG.
ExpressionAtlasiO75144. baseline and differential.
GenevisibleiO75144. HS.

Organism-specific databases

HPAiCAB026037.

Interactioni

GO - Molecular functioni

  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116900. 7 interactors.
STRINGi9606.ENSP00000384432.

Structurei

3D structure databases

ProteinModelPortaliO75144.
SMRiO75144.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 129Ig-like V-typeAdd BLAST111
Domaini141 – 227Ig-like C2-typeAdd BLAST87

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IYI6. Eukaryota.
ENOG410Z67K. LUCA.
GeneTreeiENSGT00830000128435.
HOGENOMiHOG000015302.
HOVERGENiHBG106483.
InParanoidiO75144.
KOiK06710.
OMAiTELTESW.
OrthoDBiEOG091G0IEZ.
PhylomeDBiO75144.
TreeFamiTF331083.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O75144-1) [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
MRLGSPGLLF LLFSSLRADT QEKEVRAMVG SDVELSCACP EGSRFDLNDV
60 70 80 90 100
YVYWQTSESK TVVTYHIPQN SSLENVDSRY RNRALMSPAG MLRGDFSLRL
110 120 130 140 150
FNVTPQDEQK FHCLVLSQSL GFQEVLSVEV TLHVAANFSV PVVSAPHSPS
160 170 180 190 200
QDELTFTCTS INGYPRPNVY WINKTDNSLL DQALQNDTVF LNMRGLYDVV
210 220 230 240 250
SVLRIARTPS VNIGCCIENV LLQQNLTVGS QTGNDIGERD KITENPVSTG
260 270 280 290 300
EKNAATWSIL AVLCLLVVVA VAIGWVCRDR CLQHSYAGAW AVSPETELTG

HV
Length:302
Mass (Da):33,349
Last modified:August 14, 2001 - v2
Checksum:i647934E21B55E34A
GO
Isoform 2 (identifier: O75144-2) [UniParc]FASTAAdd to basket

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

Show »
Length:309
Mass (Da):34,225
Checksum:iD019EC5307D796A5
GO
Isoform 3 (identifier: O75144-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-134: Missing.

Show »
Length:185
Mass (Da):20,120
Checksum:i0DAD5D52E6DE5F5F
GO

Sequence cautioni

The sequence BAA31628 differs from that shown. The sequence differs from that shown in position 300 onward for unknown reason.Curated
The sequence BAA31628 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049880128V → I. Corresponds to variant dbSNP:rs11558819Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05471818 – 134Missing in isoform 3. 1 PublicationAdd BLAST117
Alternative sequenceiVSP_002520300 – 302GHV → ESWNLLLLLS in isoform 2. 2 Publications3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK090492 mRNA. Translation: BAG52170.1.
AP001058 Genomic DNA. No translation available.
AP001059 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09446.1.
BC064637 mRNA. Translation: AAH64637.1.
CCDSiCCDS42952.1. [O75144-1]
CCDS63377.1. [O75144-3]
CCDS63379.1. [O75144-2]
RefSeqiNP_001269979.1. NM_001283050.1. [O75144-2]
NP_001269980.1. NM_001283051.1. [O75144-3]
NP_056074.1. NM_015259.5. [O75144-1]
XP_006723963.1. XM_006723900.2. [O75144-1]
UniGeneiHs.14155.

Genome annotation databases

EnsembliENST00000344330; ENSP00000339477; ENSG00000160223. [O75144-2]
ENST00000400377; ENSP00000383228; ENSG00000160223. [O75144-3]
ENST00000407780; ENSP00000384432; ENSG00000160223. [O75144-1]
GeneIDi102723996.
23308.
KEGGihsa:102723996.
hsa:23308.
UCSCiuc002zee.5. human. [O75144-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK090492 mRNA. Translation: BAG52170.1.
AP001058 Genomic DNA. No translation available.
AP001059 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09446.1.
BC064637 mRNA. Translation: AAH64637.1.
CCDSiCCDS42952.1. [O75144-1]
CCDS63377.1. [O75144-3]
CCDS63379.1. [O75144-2]
RefSeqiNP_001269979.1. NM_001283050.1. [O75144-2]
NP_001269980.1. NM_001283051.1. [O75144-3]
NP_056074.1. NM_015259.5. [O75144-1]
XP_006723963.1. XM_006723900.2. [O75144-1]
UniGeneiHs.14155.

3D structure databases

ProteinModelPortaliO75144.
SMRiO75144.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116900. 7 interactors.
STRINGi9606.ENSP00000384432.

PTM databases

iPTMnetiO75144.
PhosphoSitePlusiO75144.
SwissPalmiO75144.
UniCarbKBiO75144.

Polymorphism and mutation databases

BioMutaiICOSLG.

Proteomic databases

MaxQBiO75144.
PaxDbiO75144.
PeptideAtlasiO75144.
PRIDEiO75144.
TopDownProteomicsiO75144-2. [O75144-2]

Protocols and materials databases

DNASUi23308.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344330; ENSP00000339477; ENSG00000160223. [O75144-2]
ENST00000400377; ENSP00000383228; ENSG00000160223. [O75144-3]
ENST00000407780; ENSP00000384432; ENSG00000160223. [O75144-1]
GeneIDi102723996.
23308.
KEGGihsa:102723996.
hsa:23308.
UCSCiuc002zee.5. human. [O75144-1]

Organism-specific databases

CTDi23308.
DisGeNETi102723996.
23308.
GeneCardsiICOSLG.
H-InvDBHIX0016164.
HGNCiHGNC:17087. ICOSLG.
HPAiCAB026037.
MIMi605717. gene.
neXtProtiNX_O75144.
OpenTargetsiENSG00000160223.
ENSG00000277117.
PharmGKBiPA134977297.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IYI6. Eukaryota.
ENOG410Z67K. LUCA.
GeneTreeiENSGT00830000128435.
HOGENOMiHOG000015302.
HOVERGENiHBG106483.
InParanoidiO75144.
KOiK06710.
OMAiTELTESW.
OrthoDBiEOG091G0IEZ.
PhylomeDBiO75144.
TreeFamiTF331083.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160223-MONOMER.
ReactomeiR-HSA-388841. Costimulation by the CD28 family.

Miscellaneous databases

ChiTaRSiICOSLG. human.
GeneWikiiICOSLG.
PROiO75144.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160223.
CleanExiHS_ICOSLG.
ExpressionAtlasiO75144. baseline and differential.
GenevisibleiO75144. HS.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiICOSL_HUMAN
AccessioniPrimary (citable) accession number: O75144
Secondary accession number(s): A8MUZ1, Q9HD18, Q9NRQ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: August 14, 2001
Last modified: November 2, 2016
This is version 155 of the entry and version 2 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, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.