UniProtKB - Q08338 (CD4_CHLAE)
T-cell surface glycoprotein CD4
CD4
Functioni
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.
By similarityGO - Molecular functioni
- coreceptor activity Source: InterPro
- MHC class II protein complex binding Source: UniProtKB
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- cell adhesion Source: InterPro
- T cell differentiation Source: UniProtKB
- T cell selection Source: UniProtKB
Keywordsi
Biological process | Adaptive immunity, Immunity |
Names & Taxonomyi
Protein namesi | Recommended name: T-cell surface glycoprotein CD4Alternative name(s): T-cell surface antigen T4/Leu-3 CD_antigen: CD4 |
Gene namesi | Name:CD4 |
Organismi | Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops) |
Taxonomic identifieri | 9534 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Chlorocebus |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein By similarity
Note: Localizes to lipid rafts.By similarity
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 26 – 396 | ExtracellularSequence analysisAdd BLAST | 371 | |
Transmembranei | 397 – 418 | HelicalSequence analysisAdd BLAST | 22 | |
Topological domaini | 419 – 458 | CytoplasmicSequence analysisAdd BLAST | 40 |
Keywords - Cellular componenti
Cell membrane, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 25 | By similarityAdd BLAST | 25 | |
ChainiPRO_0000014620 | 26 – 458 | T-cell surface glycoprotein CD4Add BLAST | 433 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 41 ↔ 109 | PROSITE-ProRule annotation | ||
Glycosylationi | 42 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 155 ↔ 184 | PROSITE-ProRule annotation | ||
Glycosylationi | 281 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 296 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 325 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 328 ↔ 370 | PROSITE-ProRule annotation | ||
Lipidationi | 419 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 422 | S-palmitoyl cysteineBy similarity | 1 | |
Modified residuei | 433 | PhosphoserineBy similarity | 1 | |
Modified residuei | 440 | PhosphoserineBy similarity | 1 | |
Modified residuei | 456 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, PhosphoproteinInteractioni
Subunit structurei
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.
By similarityFamily & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 125 | Ig-like V-typeAdd BLAST | 100 | |
Domaini | 126 – 203 | Ig-like C2-type 1Add BLAST | 78 | |
Domaini | 204 – 317 | Ig-like C2-type 2Add BLAST | 114 | |
Domaini | 318 – 374 | Ig-like C2-type 3Add BLAST | 57 |
Domaini
Keywords - Domaini
Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helixFamily and domain databases
Gene3Di | 2.60.40.10, 4 hits |
InterProi | View protein in InterPro IPR000973, CD4 IPR015274, CD4-extracel IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR008424, Ig_C2-set IPR003599, Ig_sub IPR003598, Ig_sub2 IPR013106, Ig_V-set IPR013151, Immunoglobulin IPR021963, Tcell_CD4_Cterm |
PANTHERi | PTHR11422:SF0, PTHR11422:SF0, 1 hit |
Pfami | View protein in Pfam PF05790, C2-set, 2 hits PF09191, CD4-extracel, 1 hit PF00047, ig, 1 hit PF12104, Tcell_CD4_C, 1 hit |
PRINTSi | PR00692, CD4TCANTIGEN |
SMARTi | View protein in SMART SM00409, IG, 3 hits SM00408, IGc2, 2 hits SM00406, IGv, 1 hit |
SUPFAMi | SSF48726, SSF48726, 4 hits |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MNWGIPFRHL LLVLQLALLP AVTQGKKVVL GKKGDTVELT CNASQKTTTQ
60 70 80 90 100
FHWKNSNQIK ILGKQGSFLT KGSSKLRDRI DSRKSLWDQG CFSMIIKNLK
110 120 130 140 150
IEDSETYICE VENKKEEVEL LVFGLTANSD THLLQGQSLT LTLESPPGSS
160 170 180 190 200
PSVKCRSPRG KNIQGGRTLS VPQLERQDSG TWTCTVSQDQ NTVEFKIDIM
210 220 230 240 250
VLAFQKASST VYKKEGEQVE FSFPLAFTLE KLTGSGELWW QAERASSSKS
260 270 280 290 300
WITFDLKNKE VSVKQVTQDP KLQMGKKLPL NLTLPQALPQ YAGSGNLTLA
310 320 330 340 350
LEAKTGKLHQ EVNLVVMRAT QFQENLTCEV WGPTSPKLML SLKLENKAAT
360 370 380 390 400
VSKQAKAVWV LNPEEGMWQC LLSDSGQVLL ESNIKVLPTW PTPVQPMALI
410 420 430 440 450
VLGGVAGLLL FTGLGIFFCV RCRHRRRQAQ RMSQIKRLLS EKKTCQCPHR
FQKTCSPI
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 46 | K → N in CAA51748 (PubMed:1425921).Curated | 1 | |
Sequence conflicti | 46 | K → N in AAB60875 (PubMed:9379478).Curated | 1 | |
Sequence conflicti | 59 | I → T in AAB60873 (PubMed:9379478).Curated | 1 | |
Sequence conflicti | 115 | K → E in BAA13132 (Ref. 1) Curated | 1 | |
Sequence conflicti | 165 | G → V in AAB60873 (PubMed:9379478).Curated | 1 | |
Sequence conflicti | 165 | G → V in AAC25124 (PubMed:9656488).Curated | 1 | |
Sequence conflicti | 200 | M → V (PubMed:1425921).Curated | 1 | |
Sequence conflicti | 200 | M → V (PubMed:9379478).Curated | 1 | |
Sequence conflicti | 227 | F → L in AAB60873 (PubMed:9379478).Curated | 1 | |
Sequence conflicti | 271 | K → E in AAB60873 (PubMed:9379478).Curated | 1 | |
Sequence conflicti | 281 | N → H in AAB60873 (PubMed:9379478).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D86589 mRNA Translation: BAA13132.1 X73322 mRNA Translation: CAA51748.1 AF001226 mRNA Translation: AAB60873.1 AF001228 mRNA Translation: AAB60875.1 AF057380 Genomic DNA Translation: AAC25124.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D86589 mRNA Translation: BAA13132.1 X73322 mRNA Translation: CAA51748.1 AF001226 mRNA Translation: AAB60873.1 AF001228 mRNA Translation: AAB60875.1 AF057380 Genomic DNA Translation: AAC25124.1 |
3D structure databases
AlphaFoldDBi | Q08338 |
SMRi | Q08338 |
ModBasei | Search... |
Family and domain databases
Gene3Di | 2.60.40.10, 4 hits |
InterProi | View protein in InterPro IPR000973, CD4 IPR015274, CD4-extracel IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR008424, Ig_C2-set IPR003599, Ig_sub IPR003598, Ig_sub2 IPR013106, Ig_V-set IPR013151, Immunoglobulin IPR021963, Tcell_CD4_Cterm |
PANTHERi | PTHR11422:SF0, PTHR11422:SF0, 1 hit |
Pfami | View protein in Pfam PF05790, C2-set, 2 hits PF09191, CD4-extracel, 1 hit PF00047, ig, 1 hit PF12104, Tcell_CD4_C, 1 hit |
PRINTSi | PR00692, CD4TCANTIGEN |
SMARTi | View protein in SMART SM00409, IG, 3 hits SM00408, IGc2, 2 hits SM00406, IGv, 1 hit |
SUPFAMi | SSF48726, SSF48726, 4 hits |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CD4_CHLAE | |
Accessioni | Q08338Primary (citable) accession number: Q08338 Secondary accession number(s): O02805, O77593, Q28217 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | November 21, 2003 | |
Last modified: | May 25, 2022 | |
This is version 111 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |