P09793 (CTLA4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytotoxic T-lymphocyte protein 4

Alternative name(s):
Cytotoxic T-lymphocyte-associated antigen 4
Short name=CTLA-4
CD_antigen=CD152

Gene names

Name:	Ctla4
Synonyms:	Cd152

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	223 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	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.
Subunit structure	Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity.
Tissue specificity	Widely expressed with highest levels in lymphoid tissues. Ref.2
Post-translational modification	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.
Sequence similarities	Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Membrane
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	immune response Inferred from electronic annotation. Source: InterPro
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 16227984. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 35

35

Potential

Chain

36 – 223

188

Cytotoxic T-lymphocyte protein 4

PRO_0000014735

Regions

Topological domain

36 – 161

126

Extracellular Potential

Transmembrane

162 – 182

21

Helical; Potential

Topological domain

183 – 223

41

Cytoplasmic Potential

Domain

36 – 145

110

Ig-like V-type

Region

46 – 50

5

Homodimerization By similarity

Region

150 – 155

6

Homodimerization By similarity

Amino acid modifications

Modified residue

201

1

Phosphotyrosine; by TXK and JAK2 By similarity

Glycosylation

108

1

N-linked (GlcNAc...) Potential

Glycosylation

113

1

N-linked (GlcNAc...) Potential

Glycosylation

145

1

N-linked (GlcNAc...) Potential

Disulfide bond

58 ↔ 129

Disulfide bond

85 ↔ 103

Disulfide bond

157

Interchain By similarity

Experimental info

Sequence conflict

182

1

S → T in AAF01489. Ref.2

Secondary structure

1

.

.

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223

Helix Strand Turn

Details...

Beta strand

39 – 41

3

Beta strand

44 – 47

4

Beta strand

54 – 62

9

Beta strand

68 – 76

9

Beta strand

81 – 89

9

Beta strand

91 – 96

6

Beta strand

103 – 108

6

Beta strand

111 – 116

6

Helix

121 – 123

3

Beta strand

125 – 138

14

Beta strand

140 – 143

4

Beta strand

147 – 150

4

Sequences

	Sequence		Length	Mass (Da)
	P09793 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 5318FAAF416F4685	FASTA	223	24,993
	10 20 30 40 50 60 MACLGLRRYK AQLQLPSRTW PFVALLTLLF IPVFSEAIQV TQPSVVLASS HGVASFPCEY 70 80 90 100 110 120 SPSHNTDEVR VTVLRQTNDQ MTEVCATTFT EKNTVGFLDY PFCSGTFNES RVNLTIQGLR 130 140 150 160 170 180 AVDTGLYLCK VELMYPPPYF VGMGNGTQIY VIDPEPCPDS DFLLWILVAV SLGLFFYSFL 190 200 210 220 VSAVSLSKML KKRSPLTTGV YVKMPPTEPE CEKQFQPYFI PIN

References

[1]	"A new member of the immunoglobulin superfamily -- CTLA-4." Brunet J.-F., Denizot F., Luciani M.-F., Roux-Dosseto M., Suzan M., Mattei M.-G., Golstein P. Nature 328:267-270(1987) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X05719 mRNA. Translation: CAA29191.1.
AF142145 Genomic DNA. Translation: AAF01489.1.
M74362 Genomic DNA. Translation: AAA37489.1.

IPI

IPI00110378.

PIR

A29063.

RefSeq

NP_033973.2. NM_009843.3.

UniGene

Mm.390.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DQT	X-ray	2.00	A/B/C/D	38-154	[»]

ProteinModelPortal

P09793.

SMR

P09793. Positions 38-154.

ModBase

Search...

PTM databases

PhosphoSite

P09793.

Proteomic databases

PRIDE

P09793.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

12477.

KEGG

mmu:12477.

Organism-specific databases

CTD

1493.

MGI

MGI:88556. Ctla4.

Phylogenomic databases

eggNOG

NOG42442.

HOGENOM

HOG000112047.

HOVERGEN

HBG057978.

InParanoid

P09793.

KO

K06538.

OrthoDB

EOG4Q58QK.

Gene expression databases

CleanEx

MM_CTLA4.

Genevestigator

P09793.

GermOnline

ENSMUSG00000026011. Mus musculus.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR008096. CTLA4.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]

Pfam

PF07686. V-set. 1 hit.
[Graphical view]

PRINTS

PR01720. CTLANTIGEN4.

SMART

SM00409. IG. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P09793.

NextBio

281362.

SOURCE

Search...

Entry information

Entry name

CTLA4_MOUSE

Accession

Primary (citable) accession number: P09793
Secondary accession number(s): Q9QZZ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	April 3, 2013
This is version 119 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program