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Protein

Cytotoxic T-lymphocyte protein 4

Gene

Ctla4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28 (By similarity).By similarity

GO - Biological processi

  1. B cell receptor signaling pathway Source: MGI
  2. cellular response to DNA damage stimulus Source: MGI
  3. immune response Source: InterPro
  4. negative regulation of B cell proliferation Source: MGI
  5. negative regulation of regulatory T cell differentiation Source: MGI
  6. positive regulation of apoptotic process Source: MGI
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Cytotoxic T-lymphocyte protein 4
Alternative name(s):
Cytotoxic T-lymphocyte-associated antigen 4
Short name:
CTLA-4
CD_antigen: CD152
Gene namesi
Name:Ctla4
Synonyms:Cd152
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:88556. Ctla4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini36 – 161126ExtracellularSequence AnalysisAdd
BLAST
Transmembranei162 – 18221HelicalSequence AnalysisAdd
BLAST
Topological domaini183 – 22341CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. clathrin-coated endocytic vesicle Source: MGI
  2. external side of plasma membrane Source: MGI
  3. Golgi apparatus Source: MGI
  4. integral component of membrane Source: UniProtKB-KW
  5. perinuclear region of cytoplasm Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3535Sequence AnalysisAdd
BLAST
Chaini36 – 223188Cytotoxic T-lymphocyte protein 4PRO_0000014735Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi58 ↔ 129
Disulfide bondi85 ↔ 103
Glycosylationi108 – 1081N-linked (GlcNAc...)Sequence Analysis
Glycosylationi113 – 1131N-linked (GlcNAc...)Sequence Analysis
Glycosylationi145 – 1451N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi157 – 157InterchainPROSITE-ProRule annotation
Modified residuei201 – 2011Phosphotyrosine; by TXK and JAK2By similarity

Post-translational modificationi

N-glycosylation is important for dimerization.By similarity
Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiP09793.

PTM databases

PhosphoSiteiP09793.

Expressioni

Tissue specificityi

Widely expressed with highest levels in lymphoid tissues.1 Publication

Gene expression databases

CleanExiMM_CTLA4.
GenevestigatoriP09793.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2 (By similarity).By similarity

Protein-protein interaction databases

BioGridi198575. 1 interaction.
IntActiP09793. 1 interaction.
MINTiMINT-8019867.

Structurei

Secondary structure

1
223
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi39 – 413Combined sources
Beta strandi44 – 474Combined sources
Beta strandi54 – 629Combined sources
Beta strandi68 – 769Combined sources
Beta strandi81 – 899Combined sources
Beta strandi91 – 966Combined sources
Beta strandi103 – 1086Combined sources
Beta strandi111 – 1166Combined sources
Helixi121 – 1233Combined sources
Beta strandi125 – 13814Combined sources
Beta strandi140 – 1434Combined sources
Beta strandi147 – 1504Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DQTX-ray2.00A/B/C/D38-154[»]
SMRiP09793. Positions 38-154.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09793.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini36 – 145110Ig-like V-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni46 – 505HomodimerizationBy similarity
Regioni150 – 1556HomodimerizationBy similarity

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42442.
HOGENOMiHOG000112047.
HOVERGENiHBG057978.
InParanoidiP09793.
KOiK06538.
PhylomeDBiP09793.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR008096. CTLA4.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
PRINTSiPR01720. CTLANTIGEN4.
SMARTiSM00409. IG. 1 hit.
[Graphical view]
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P09793-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MACLGLRRYK AQLQLPSRTW PFVALLTLLF IPVFSEAIQV TQPSVVLASS
60 70 80 90 100
HGVASFPCEY SPSHNTDEVR VTVLRQTNDQ MTEVCATTFT EKNTVGFLDY
110 120 130 140 150
PFCSGTFNES RVNLTIQGLR AVDTGLYLCK VELMYPPPYF VGMGNGTQIY
160 170 180 190 200
VIDPEPCPDS DFLLWILVAV SLGLFFYSFL VSAVSLSKML KKRSPLTTGV
210 220
YVKMPPTEPE CEKQFQPYFI PIN
Length:223
Mass (Da):24,993
Last modified:July 1, 1989 - v1
Checksum:i5318FAAF416F4685
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti182 – 1821S → T in AAF01489 (PubMed:10493833).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05719 mRNA. Translation: CAA29191.1.
AF142145 Genomic DNA. Translation: AAF01489.1.
M74362 Genomic DNA. Translation: AAA37489.1.
CCDSiCCDS14993.1.
PIRiA29063.
RefSeqiNP_033973.2. NM_009843.4.
UniGeneiMm.390.

Genome annotation databases

GeneIDi12477.
KEGGimmu:12477.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05719 mRNA. Translation: CAA29191.1.
AF142145 Genomic DNA. Translation: AAF01489.1.
M74362 Genomic DNA. Translation: AAA37489.1.
CCDSiCCDS14993.1.
PIRiA29063.
RefSeqiNP_033973.2. NM_009843.4.
UniGeneiMm.390.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DQTX-ray2.00A/B/C/D38-154[»]
SMRiP09793. Positions 38-154.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198575. 1 interaction.
IntActiP09793. 1 interaction.
MINTiMINT-8019867.

PTM databases

PhosphoSiteiP09793.

Proteomic databases

PRIDEiP09793.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi12477.
KEGGimmu:12477.

Organism-specific databases

CTDi1493.
MGIiMGI:88556. Ctla4.

Phylogenomic databases

eggNOGiNOG42442.
HOGENOMiHOG000112047.
HOVERGENiHBG057978.
InParanoidiP09793.
KOiK06538.
PhylomeDBiP09793.

Miscellaneous databases

EvolutionaryTraceiP09793.
NextBioi281362.
PROiP09793.
SOURCEiSearch...

Gene expression databases

CleanExiMM_CTLA4.
GenevestigatoriP09793.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR008096. CTLA4.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
PRINTSiPR01720. CTLANTIGEN4.
SMARTiSM00409. IG. 1 hit.
[Graphical view]
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Complete sequence determination of the mouse and human CTLA4 gene loci: cross-species DNA sequence similarity beyond exon borders."
    Ling V., Wu P.W., Finnerty H.F., Sharpe A.H., Gray G.S., Collins M.
    Genomics 60:341-355(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
    Strain: 129/SvJ.
  3. "CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location."
    Harper K., Balzano C., Rouvier E., Mattei M.-G., Luciani M.-F., Golstein P.
    J. Immunol. 147:1037-1044(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE OF 1-36.
  4. "Structure of murine CTLA-4 and its role in modulating T cell responsiveness."
    Ostrov D.A., Shi W., Schwartz J.-C., Almo S.C., Nathenson S.G.
    Science 290:816-819(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 38-154.

Entry informationi

Entry nameiCTLA4_MOUSE
AccessioniPrimary (citable) accession number: P09793
Secondary accession number(s): Q9QZZ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 1, 2015
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.