CD4_RABIT
ID CD4_RABIT Reviewed; 459 AA.
AC P46630;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=T-cell surface glycoprotein CD4;
DE AltName: Full=T-cell surface antigen T4/Leu-3;
DE AltName: CD_antigen=CD4;
DE Flags: Precursor;
GN Name=CD4;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1518821; DOI=10.1073/pnas.89.17.7963;
RA Hague B.F., Sawasdikosol S., Brown T.J., Lee K., Recker D.P., Kindt T.J.;
RT "CD4 and its role in infection of rabbit cell lines by human
RT immunodeficiency virus type 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7963-7967(1992).
CC -!- FUNCTION: Integral membrane glycoprotein that plays an essential role
CC in the immune response and serves multiple functions in responses
CC against both external and internal offenses. In T-cells, functions
CC primarily as a coreceptor for MHC class II molecule:peptide complex.
CC The antigens presented by class II peptides are derived from
CC extracellular proteins while class I peptides are derived from
CC cytosolic proteins. Interacts simultaneously with the T-cell receptor
CC (TCR) and the MHC class II presented by antigen presenting cells
CC (APCs). In turn, recruits the Src kinase LCK to the vicinity of the
CC TCR-CD3 complex. LCK then initiates different intracellular signaling
CC pathways by phosphorylating various substrates ultimately leading to
CC lymphokine production, motility, adhesion and activation of T-helper
CC cells. In other cells such as macrophages or NK cells, plays a role in
CC differentiation/activation, cytokine expression and cell migration in a
CC TCR/LCK-independent pathway. Participates in the development of T-
CC helper cells in the thymus and triggers the differentiation of
CC monocytes into functional mature macrophages.
CC {ECO:0000250|UniProtKB:P01730}.
CC -!- SUBUNIT: Forms disulfide-linked homodimers at the cell surface.
CC Interacts with LCK. Interacts with PTK2/FAK1. Binds to P4HB/PDI.
CC Interacts with IL16; this interaction induces a CD4-dependent signaling
CC in lymphocytes. Interacts (via Ig-like V-type domain) with MHCII alpha
CC chain (via alpha-2 domain) and beta chain (via beta-2 domain); this
CC interaction increases the affinity of TCR for peptide-MHCII. CD4
CC oligomerization via Ig-like C2-type 2 and 3 domains appears to be
CC required for stable binding to MHCII and adhesion between T cells and
CC APCs. {ECO:0000250|UniProtKB:P01730}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P01730};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P01730}.
CC Note=Localizes to lipid rafts. {ECO:0000250|UniProtKB:P01730}.
CC -!- DOMAIN: The Ig-like V-type domain mediates the interaction with MHCII.
CC {ECO:0000250|UniProtKB:P01730}.
CC -!- PTM: Palmitoylation and association with LCK contribute to the
CC enrichment of CD4 in lipid rafts. {ECO:0000250|UniProtKB:P01730}.
CC -!- PTM: Phosphorylated by PKC; phosphorylation plays an important role for
CC CD4 internalization. {ECO:0000250|UniProtKB:P01730}.
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DR EMBL; M92840; AAA31198.1; -; mRNA.
DR PIR; A46254; A46254.
DR RefSeq; NP_001075782.1; NM_001082313.2.
DR AlphaFoldDB; P46630; -.
DR SMR; P46630; -.
DR STRING; 9986.ENSOCUP00000011113; -.
DR GeneID; 100009152; -.
DR KEGG; ocu:100009152; -.
DR CTD; 920; -.
DR eggNOG; ENOG502S0W5; Eukaryota.
DR InParanoid; P46630; -.
DR OrthoDB; 652984at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0009986; C:cell surface; IEA:UniProt.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro.
DR GO; GO:0023026; F:MHC class II protein complex binding; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045058; P:T cell selection; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR000973; CD4.
DR InterPro; IPR015274; CD4-extracel.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR008424; Ig_C2-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR021963; Tcell_CD4_Cterm.
DR PANTHER; PTHR11422:SF0; PTHR11422:SF0; 1.
DR Pfam; PF05790; C2-set; 2.
DR Pfam; PF09191; CD4-extracel; 1.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF12104; Tcell_CD4_C; 1.
DR PRINTS; PR00692; CD4TCANTIGEN.
DR SMART; SM00409; IG; 3.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 2: Evidence at transcript level;
KW Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..459
FT /note="T-cell surface glycoprotein CD4"
FT /id="PRO_0000014628"
FT TOPO_DOM 26..396
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 397..419
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 420..459
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..129
FT /note="Ig-like V-type"
FT DOMAIN 130..208
FT /note="Ig-like C2-type 1"
FT DOMAIN 209..318
FT /note="Ig-like C2-type 2"
FT DOMAIN 319..374
FT /note="Ig-like C2-type 3"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT LIPID 420
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 423
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 41..113
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 329..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 459 AA; 50886 MW; B323311CBD40013D CRC64;
MNRRIYFQCL LLVLPLALLP AATWGKTVVR GKAGAIVELP CQSSQKRNSV FNWKHANQVK
ILGNQGSSSS SFWLKGNSPL SNRVESKKNM WDQGSFPLVI KDLRMDDSGT YICEVGDKKM
EVELLVFRLT ANPNTRLLHG QSLTLTLEGP SVGSPSVQWK SPENKIIETG PTCSMPKLRL
QDSGTWSCHL SFQDQNKLEL DIKIIVLGFP KASATVYKKE GEQVEFSFPL NFEDESLSGE
LMWQVDGASS AQSWVSFSLE DRKVSVQKIL PDLKIQMSKG LPLSLTLPQA LHRYAGSGNL
SLTLDKGKLH QQVSLVMLKV TQVKNKLTCE VLGPIDPKMK LSLKLEDQEA KVSTQKMVQV
LDPKAGTWQC LLSSGDQVLL ESKADVLATG LSHQQPTLLA GALGGTAGLV LFAGLCIYCC
VKCRHRRHQA QRMSQIKKLL SEKKTCQCPH RLQKTYNLL
