CD4_CHLAE
ID CD4_CHLAE Reviewed; 458 AA.
AC Q08338; O02805; O77593; Q28217;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 21-NOV-2003, sequence version 3.
DT 03-AUG-2022, entry version 112.
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 Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RA Hashimoto O., Tatsumi M.;
RT "Molecular cloning and expression of African green monkey CD4.";
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE OF 28-424.
RC TISSUE=Blood;
RX PubMed=1425921; DOI=10.1002/eji.1830221132;
RA Fomsgaard A., Hirsch V.M., Johnson P.R.;
RT "Cloning and sequences of primate CD4 molecules: diversity of the cellular
RT receptor for simian immunodeficiency virus/human immunodeficiency virus.";
RL Eur. J. Immunol. 22:2973-2981(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE OF 28-424.
RC TISSUE=Peripheral blood;
RX PubMed=9379478; DOI=10.1111/j.1600-0684.1997.tb00043.x;
RA Fomsgaard A., Mueller-Trutwin M.C., Diop O., Hansen J., Mathiot C.,
RA Corbet S., Barre-Sinoussi F., Allan J.S.;
RT "Relation between phylogeny of African green monkey CD4 genes and their
RT respective simian immunodeficiency virus genes.";
RL J. Med. Primatol. 26:120-128(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE OF 107-192.
RX PubMed=9656488; DOI=10.1093/oxfordjournals.molbev.a025993;
RA Harris E.E., Disotell T.R.;
RT "Nuclear gene trees and the phylogenetic relationships of the mangabeys
RT (Primates: Papionini).";
RL Mol. Biol. Evol. 15:892-900(1998).
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; D86589; BAA13132.1; -; mRNA.
DR EMBL; X73322; CAA51748.1; -; mRNA.
DR EMBL; AF001226; AAB60873.1; -; mRNA.
DR EMBL; AF001228; AAB60875.1; -; mRNA.
DR EMBL; AF057380; AAC25124.1; -; Genomic_DNA.
DR AlphaFoldDB; Q08338; -.
DR SMR; Q08338; -.
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; IPR003598; Ig_sub2.
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; SM00408; IGc2; 2.
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 Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000250"
FT CHAIN 26..458
FT /note="T-cell surface glycoprotein CD4"
FT /id="PRO_0000014620"
FT TOPO_DOM 26..396
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 397..418
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 419..458
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..125
FT /note="Ig-like V-type"
FT DOMAIN 126..203
FT /note="Ig-like C2-type 1"
FT DOMAIN 204..317
FT /note="Ig-like C2-type 2"
FT DOMAIN 318..374
FT /note="Ig-like C2-type 3"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT LIPID 419
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 422
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 41..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 155..184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 328..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 46
FT /note="K -> N (in Ref. 2; CAA51748 and 3; AAB60875)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="I -> T (in Ref. 3; AAB60873)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="K -> E (in Ref. 1; BAA13132)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="G -> V (in Ref. 3; AAB60873 and 4; AAC25124)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="M -> V (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="F -> L (in Ref. 3; AAB60873)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="K -> E (in Ref. 3; AAB60873)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="N -> H (in Ref. 3; AAB60873)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 458 AA; 51158 MW; FC523D2EDD1F72E7 CRC64;
MNWGIPFRHL LLVLQLALLP AVTQGKKVVL GKKGDTVELT CNASQKTTTQ FHWKNSNQIK
ILGKQGSFLT KGSSKLRDRI DSRKSLWDQG CFSMIIKNLK IEDSETYICE VENKKEEVEL
LVFGLTANSD THLLQGQSLT LTLESPPGSS PSVKCRSPRG KNIQGGRTLS VPQLERQDSG
TWTCTVSQDQ NTVEFKIDIM VLAFQKASST VYKKEGEQVE FSFPLAFTLE KLTGSGELWW
QAERASSSKS WITFDLKNKE VSVKQVTQDP KLQMGKKLPL NLTLPQALPQ YAGSGNLTLA
LEAKTGKLHQ EVNLVVMRAT QFQENLTCEV WGPTSPKLML SLKLENKAAT VSKQAKAVWV
LNPEEGMWQC LLSDSGQVLL ESNIKVLPTW PTPVQPMALI VLGGVAGLLL FTGLGIFFCV
RCRHRRRQAQ RMSQIKRLLS EKKTCQCPHR FQKTCSPI
