Human Gene CTLA4 (ENST00000648405.2) from GENCODE V44
  Description: Homo sapiens cytotoxic T-lymphocyte associated protein 4 (CTLA4), transcript variant 1, mRNA. (from RefSeq NM_005214)
RefSeq Summary (NM_005214): This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000648405.2
Gencode Gene: ENSG00000163599.18
Transcript (Including UTRs)
   Position: hg38 chr2:203,867,771-203,873,965 Size: 6,195 Total Exon Count: 4 Strand: +
Coding Region
   Position: hg38 chr2:203,867,943-203,872,812 Size: 4,870 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:203,867,771-203,873,965)mRNA (may differ from genome)Protein (223 aa)
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neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: CTLA4_HUMAN
DESCRIPTION: RecName: Full=Cytotoxic T-lymphocyte protein 4; AltName: Full=Cytotoxic T-lymphocyte-associated antigen 4; Short=CTLA-4; AltName: CD_antigen=CD152; Flags: Precursor;
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.
SUBUNIT: Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2.
INTERACTION: P33681:CD80; NbExp=3; IntAct=EBI-1030991, EBI-1031024; P42081:CD86; NbExp=2; IntAct=EBI-1030991, EBI-1030956;
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Note=Exists primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalisation;.
TISSUE SPECIFICITY: Widely expressed with highest levels in lymphoid tissues. Detected in activated T-cells where expression levels are 30- to 50-fold less than CD28, the stimulatory coreceptor, on the cell surface following activation.
PTM: N-glycosylation is important for dimerization.
PTM: Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface.
POLYMORPHISM: Genetic variations in CTLA4 are associated with susceptibility to several autoimmune disorders. They influence responsiveness to hepatitis B virus (HBV) infection [MIM:610424].
DISEASE: Genetic variation in CTLA4 influences susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. SLE is thought to represent a failure of the regulatory mechanisms of the autoimmune system.
DISEASE: Note=Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism.
DISEASE: Genetic variation in CTLA4 is the cause of susceptibility to diabetes mellitus insulin-dependent type 12 (IDDM12) [MIM:601388]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
DISEASE: Genetic variation in CTLA4 is the cause of susceptibility to celiac disease type 3 (CELIAC3) [MIM:609755]. It is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. In its classic form, celiac disease is characterized in children by malabsorption and failure to thrive.
PHARMACEUTICAL: Engineered fusion proteins consisting of the extracellular domain of CTLA4 and the IgG Fc region (Ctla4-Ig), inhibit T-cell-dependent antibody responses, and are used as immunosuppressive agents. They are soluble, have an enhanced affinity for B7 ligands and act as a competitive inhibitor of CD28.
SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like) domain.
WEB RESOURCE: Name=Wikipedia; Note=CLTA-4 entry; URL="http://en.wikipedia.org/wiki/CTLA-4";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: CTLA4
Diseases sorted by gene-association score: autoimmune lymphoproliferative syndrome, type v* (1650), celiac disease 3* (603), hashimoto thyroiditis* (595), diabetes mellitus, insulin-dependent, 12* (577), autoimmune lymphoproliferative syndrome due to ctla4 haploinsuffiency* (400), systemic lupus erythematosus* (358), sezary's disease* (250), mycosis fungoides* (207), graves' disease (48), celiac disease (42), wegener granulomatosis* (30), lupus erythematosus (28), thyroiditis (23), paracoccidioidomycosis (19), hypersensitivity reaction type ii disease (17), hyperthyroidism (16), adult-onset myasthenia gravis* (14), diabetes mellitus, insulin-dependent (14), anca-associated vasculitis (13), autoimmune hepatitis (13), autoimmune lymphoproliferative syndrome (12), alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity (12), autoinflammation with infantile enterocolitis (11), addison's disease (11), lymphoproliferative syndrome (11), autoimmune addison disease (11), myasthenia gravis (10), sympathetic ophthalmia (10), myxedema (10), uveitis (8), autoimmune disease of endocrine system (8), primary biliary cirrhosis (7), anterior uveitis (7), orbital plasma cell granuloma (7), chronic orbital inflammation (7), autoimmune pancreatitis (7), alopecia areata (7), filariasis (7), vitiligo-associated multiple autoimmune disease susceptibility 1 (6), thymoma (6), diabetes mellitus, insulin-dependent, 2 (6), severe hemophilia a (6), diabetes mellitus, ketosis-prone (6), urinary schistosomiasis (6), diabetes mellitus, insulin-dependent, 5 (6), rheumatoid arthritis (6), myasthenic syndrome, congenital, 7, presynaptic (6), chronic active epstein-barr virus infection (6), diabetes mellitus, insulin-dependent, 17 (6), spotted fever (6), hematopoietic stem cell transplantation (5), diabetes mellitus, insulin-dependent, 11 (5), chorioangioma (5), hepatitis b (5), autoimmune disease of gastrointestinal tract (4), diabetes mellitus, insulin-dependent, 13 (4), type 1 diabetes mellitus 10 (4), malignant skin fibrous histiocytoma (4), hemangioma of intra-abdominal structure (4), malignant dermis tumor (4), multiple sclerosis, disease progression, modifier of (3), common variable immunodeficiency (2), hypersensitivity reaction disease (2), malaria (1), cell type cancer (1), behcet syndrome (1), immune system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 2.82 RPKM in Spleen
Total median expression: 16.77 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -36.60172-0.213 Picture PostScript Text
3' UTR -318.101153-0.276 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008096 - CTLA4
IPR013783 - Ig-like_fold
IPR013106 - Ig_V-set
IPR003596 - Ig_V-set_subgr

Pfam Domains:
PF07686 - Immunoglobulin V-set domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1AH1 - NMR MuPIT 1H6E - X-ray MuPIT 1I85 - X-ray MuPIT 1I8L - X-ray MuPIT 2X44 - X-ray MuPIT 3BX7 - X-ray MuPIT 3OSK - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P16410
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding

Biological Process:
GO:0002250 adaptive immune response
GO:0002376 immune system process
GO:0006955 immune response
GO:0006974 cellular response to DNA damage stimulus
GO:0030889 negative regulation of B cell proliferation
GO:0031295 T cell costimulation
GO:0042130 negative regulation of T cell proliferation
GO:0043065 positive regulation of apoptotic process
GO:0045589 regulation of regulatory T cell differentiation
GO:0045590 negative regulation of regulatory T cell differentiation
GO:0050777 negative regulation of immune response
GO:0050853 B cell receptor signaling pathway

Cellular Component:
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009897 external side of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0045334 clathrin-coated endocytic vesicle
GO:0048471 perinuclear region of cytoplasm
GO:0098636 protein complex involved in cell adhesion


-  Descriptions from all associated GenBank mRNAs
  BC070162 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4, mRNA (cDNA clone MGC:88142 IMAGE:30417685), complete cds.
JD165112 - Sequence 146136 from Patent EP1572962.
AF414120 - Homo sapiens CTLA4 (CTLA4) mRNA, complete cds.
LQ882888 - Sequence 37 from Patent WO2018160841.
LQ927248 - Sequence 25 from Patent WO2018191660.
AK313732 - Homo sapiens cDNA, FLJ94332, highly similar to Homo sapiens cytotoxic T-lymphocyte-associated protein 4 (CTLA4), mRNA.
BC069566 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4, mRNA (cDNA clone MGC:97034 IMAGE:7262243), complete cds.
JD254540 - Sequence 235564 from Patent EP1572962.
BC074893 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4, mRNA (cDNA clone MGC:103865 IMAGE:30915247), complete cds.
BC074842 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4, mRNA (cDNA clone MGC:104099 IMAGE:30915552), complete cds.
AB590653 - Synthetic construct DNA, clone: pFN21AB6904, Homo sapiens CTLA4 gene for cytotoxic T-lymphocyte-associated protein 4, without stop codon, in Flexi system.
KJ890998 - Synthetic construct Homo sapiens clone ccsbBroadEn_00392 CTLA4 gene, encodes complete protein.
KR712092 - Synthetic construct Homo sapiens clone CCSBHm_00035703 CTLA4 (CTLA4) mRNA, encodes complete protein.
AF486806 - Homo sapiens CTLA4 mRNA, partial cds.
AY209009 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4 (CTLA4) mRNA, complete cds.
AY792514 - Homo sapiens ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4 (CTLA4) mRNA, complete cds.
AY999702 - Homo sapiens cytotoxic T lymphocyte associated antigen 4 short spliced form mRNA, complete cds, alternatively spliced.
DQ785106 - Homo sapiens CD152 isoform (CTLA4) mRNA, partial cds, alternatively spliced.
L15006 - Homo sapiens Ig superfamily CTLA-4 mRNA, complete cds.
U90273 - Homo sapiens CTLA-4 mRNA, partial cds.
JD171964 - Sequence 152988 from Patent EP1572962.
JD313936 - Sequence 294960 from Patent EP1572962.
JD410559 - Sequence 391583 from Patent EP1572962.
JD533758 - Sequence 514782 from Patent EP1572962.
JD314154 - Sequence 295178 from Patent EP1572962.
JD181456 - Sequence 162480 from Patent EP1572962.
JD119576 - Sequence 100600 from Patent EP1572962.
JD102564 - Sequence 83588 from Patent EP1572962.
JD074755 - Sequence 55779 from Patent EP1572962.
JD302934 - Sequence 283958 from Patent EP1572962.
MP216602 - Sequence 26 from Patent WO2019161400.
MP584538 - Sequence 37 from Patent WO2020081767.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04514 - Cell adhesion molecules (CAMs)
hsa04660 - T cell receptor signaling pathway
hsa05320 - Autoimmune thyroid disease

BioCarta from NCI Cancer Genome Anatomy Project
h_ctla4Pathway - The Co-Stimulatory Signal During T-cell Activation

Reactome (by CSHL, EBI, and GO)

Protein P16410 (Reactome details) participates in the following event(s):

R-HSA-389532 PP2A binds CTLA4 homodimer
R-HSA-388809 CTLA-4 binds B7-1/B7-2
R-HSA-388833 Phosphorylation of CTLA-4
R-HSA-388829 SHP2 phosphatase binds CTLA-4
R-HSA-8877330 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-8878171 Transcriptional regulation by RUNX1
R-HSA-388841 Costimulation by the CD28 family
R-HSA-212436 Generic Transcription Pathway
R-HSA-1280218 Adaptive Immune System
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-168256 Immune System
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A0N1S0, CD152, CTLA4_HUMAN, E9PDH0, ENST00000648405.1, NM_005214, P16410, Q0PP65, Q52MC1, Q53TD5, Q5S005, Q8WXJ1, Q96P43, Q9UKN9, uc002vak.1, uc002vak.2, uc002vak.3, uc002vak.4, uc002vak.5
UCSC ID: ENST00000648405.2
RefSeq Accession: NM_005214
Protein: P16410 (aka CTLA4_HUMAN or CTL4_HUMAN)
CCDS: CCDS2362.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.