CD4_PANTR
ID CD4_PANTR Reviewed; 458 AA.
AC P16004;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 146.
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 Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2107024; DOI=10.1016/0092-8674(90)90089-w;
RA Camerini D., Seed B.;
RT "A CD4 domain important for HIV-mediated syncytium formation lies outside
RT the virus binding site.";
RL Cell 60:747-754(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-424.
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).
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; M31135; AAA35407.1; -; mRNA.
DR EMBL; X73323; CAA51749.1; -; mRNA.
DR PIR; B32722; RWCZT4.
DR RefSeq; NP_001009043.1; NM_001009043.1.
DR RefSeq; XP_016777999.1; XM_016922510.1.
DR RefSeq; XP_016778000.1; XM_016922511.1.
DR AlphaFoldDB; P16004; -.
DR SMR; P16004; -.
DR STRING; 9598.ENSPTRP00000054833; -.
DR PaxDb; P16004; -.
DR Ensembl; ENSPTRT00000062277; ENSPTRP00000054833; ENSPTRG00000004590.
DR GeneID; 450124; -.
DR KEGG; ptr:450124; -.
DR CTD; 920; -.
DR VGNC; VGNC:5330; CD4.
DR eggNOG; ENOG502S0W5; Eukaryota.
DR GeneTree; ENSGT00390000001745; -.
DR InParanoid; P16004; -.
DR OMA; KTCQCSH; -.
DR OrthoDB; 652984at2759; -.
DR Proteomes; UP000002277; Chromosome 12.
DR Bgee; ENSPTRG00000004590; Expressed in thymus and 18 other tissues.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro.
DR GO; GO:0042011; F:interleukin-16 binding; IEA:Ensembl.
DR GO; GO:0042012; F:interleukin-16 receptor activity; IEA:Ensembl.
DR GO; GO:0042289; F:MHC class II protein binding; IBA:GO_Central.
DR GO; GO:0023026; F:MHC class II protein complex binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IEA:Ensembl.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl.
DR GO; GO:0035397; P:helper T cell enhancement of adaptive immune response; IEA:Ensembl.
DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl.
DR GO; GO:0032507; P:maintenance of protein location in cell; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0050870; P:positive regulation of T cell activation; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0042110; P:T cell activation; IBA:GO_Central.
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 Reference proteome; 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_0000014626"
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 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
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 42
FT /note="T -> N (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="L -> S (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="K -> N (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 458 AA; 51057 MW; A7C3AC8A5257D3AD CRC64;
MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGDTVELT CTASQKKSIQ FHWKNSNQTK
ILGNQGSFLT KGPSKLNDRV DSRRSLWDQG NFTLIIKNLK IEDSDTYICE VGDQKEEVQL
LVFGLTANSD THLLQGQSLT LTLESPPGSS PSVQCRSPRG KNIQGGKTLS VSQLELQDSG
TWTCTVLQNQ KKVEFKIDIV VLAFQKASSI VYKKEGEQVE FSFPLAFTVE KLTGSGELWW
QAERASSSKS WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA
LEAKTGKLHQ EVNLVVMRAT QLQKNLTCEV WGPTSPKLML SLKLENKEAK VSKREKAVWV
LNPEAGMWQC LLSDSGQVLL ESNIKVLPTW STPVQPMALI VLGGVAGLLL FIGLGIFFCV
RCRHRRRQAQ RMSQIKRLLS EKKTCQCPHR FQKTCSPI
