P79184 · CD4_MACFU
- ProteinT-cell surface glycoprotein CD4
- GeneCD4
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids458 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score4/5
Function
function
Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | external side of plasma membrane | |
Cellular Component | membrane raft | |
Molecular Function | coreceptor activity | |
Molecular Function | MHC class II protein binding | |
Molecular Function | MHC class II protein complex binding | |
Molecular Function | protein tyrosine kinase binding | |
Biological Process | adaptive immune response | |
Biological Process | cell adhesion | |
Biological Process | interleukin-15-mediated signaling pathway | |
Biological Process | positive regulation of ERK1 and ERK2 cascade | |
Biological Process | T cell differentiation | |
Biological Process | T cell selection |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameT-cell surface glycoprotein CD4
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca
Accessions
- Primary accessionP79184
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Note: Localizes to lipid rafts.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 26-396 | Extracellular | ||||
Sequence: KKVVLGKKGDTVELTCNASQKKNTQFHWKNSNQIKILGIQGSFLTKGPSKLSDRADSRKSLWDQGCFSMIIKNLKIEDSDTYICEVENKKEEVELLVFGLTANSDTHLLEGQSLTLTLESPPGSSPSVKCRSPGGKNIQGGRTISVPQLERQDSGTWTCTVSQDQKTVEFKIDIVVLAFQKASSTVYKKEGEQVEFSFPLAFTLEKLTGSGELWWQAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLALEAKTGKLHQEVNLVVMRAAQFQENLTCEVWGPTSPKLTLSLKLENKGATVSKQAKAVWVLNPEAGMWQCLLSDSGQVLLESNIKVVPTWPTPVQP | ||||||
Transmembrane | 397-418 | Helical | ||||
Sequence: MALIVLGGVAGLLLFTGLGIFF | ||||||
Topological domain | 419-458 | Cytoplasmic | ||||
Sequence: CVRCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, lipidation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-25 | |||||
Sequence: MNRGIPFRHLLLVLQLALLPAVTQG | ||||||
Chain | PRO_0000014623 | 26-458 | T-cell surface glycoprotein CD4 | |||
Sequence: KKVVLGKKGDTVELTCNASQKKNTQFHWKNSNQIKILGIQGSFLTKGPSKLSDRADSRKSLWDQGCFSMIIKNLKIEDSDTYICEVENKKEEVELLVFGLTANSDTHLLEGQSLTLTLESPPGSSPSVKCRSPGGKNIQGGRTISVPQLERQDSGTWTCTVSQDQKTVEFKIDIVVLAFQKASSTVYKKEGEQVEFSFPLAFTLEKLTGSGELWWQAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLALEAKTGKLHQEVNLVVMRAAQFQENLTCEVWGPTSPKLTLSLKLENKGATVSKQAKAVWVLNPEAGMWQCLLSDSGQVLLESNIKVVPTWPTPVQPMALIVLGGVAGLLLFTGLGIFFCVRCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI | ||||||
Disulfide bond | 41↔109 | |||||
Sequence: CNASQKKNTQFHWKNSNQIKILGIQGSFLTKGPSKLSDRADSRKSLWDQGCFSMIIKNLKIEDSDTYIC | ||||||
Glycosylation | 42 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 155↔184 | |||||
Sequence: CRSPGGKNIQGGRTISVPQLERQDSGTWTC | ||||||
Glycosylation | 296 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 325 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 328↔370 | |||||
Sequence: CEVWGPTSPKLTLSLKLENKGATVSKQAKAVWVLNPEAGMWQC | ||||||
Lipidation | 419 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Lipidation | 422 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 433 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 440 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 456 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts.
Phosphorylated by PKC; phosphorylation plays an important role for CD4 internalization.
Keywords
- PTM
PTM databases
Interaction
Subunit
Forms disulfide-linked homodimers at the cell surface. Interacts with LCK. Interacts with PTK2/FAK1. Binds to P4HB/PDI. Interacts with IL16; this interaction induces a CD4-dependent signaling in lymphocytes. Interacts (via Ig-like V-type domain) with MHCII alpha chain (via alpha-2 domain) and beta chain (via beta-2 domain); this interaction increases the affinity of TCR for peptide-MHCII. CD4 oligomerization via Ig-like C2-type 2 and 3 domains appears to be required for stable binding to MHCII and adhesion between T cells and APCs.
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 26-125 | Ig-like V-type | ||||
Sequence: KKVVLGKKGDTVELTCNASQKKNTQFHWKNSNQIKILGIQGSFLTKGPSKLSDRADSRKSLWDQGCFSMIIKNLKIEDSDTYICEVENKKEEVELLVFGL | ||||||
Domain | 126-203 | Ig-like C2-type 1 | ||||
Sequence: TANSDTHLLEGQSLTLTLESPPGSSPSVKCRSPGGKNIQGGRTISVPQLERQDSGTWTCTVSQDQKTVEFKIDIVVLA | ||||||
Domain | 204-317 | Ig-like C2-type 2 | ||||
Sequence: FQKASSTVYKKEGEQVEFSFPLAFTLEKLTGSGELWWQAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLALEAKTGKLHQEVNLVVM | ||||||
Domain | 318-374 | Ig-like C2-type 3 | ||||
Sequence: RAAQFQENLTCEVWGPTSPKLTLSLKLENKGATVSKQAKAVWVLNPEAGMWQCLLSD |
Domain
The Ig-like V-type domain mediates the interaction with MHCII.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length458
- Mass (Da)50,828
- Last updated1997-05-01 v1
- Checksum76B3E7EF08185535