CD4_MACMU
ID CD4_MACMU Reviewed; 458 AA.
AC P16003; Q29617;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2002, sequence version 2.
DT 25-MAY-2022, entry version 148.
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 Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE.
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 [GENOMIC DNA].
RC TISSUE=Thymocyte;
RA Hashimoto O., Tatsumi M.;
RT "Molecular cloning and expression of macaque CD4s.";
RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] 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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] 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; M31134; AAA36838.1; -; mRNA.
DR EMBL; D63347; BAA09671.1; -; mRNA.
DR EMBL; X73326; CAA51752.1; -; mRNA.
DR EMBL; AF057385; AAC25129.1; -; Genomic_DNA.
DR PIR; C32722; RWMQT4.
DR RefSeq; NP_001036127.1; NM_001042662.1.
DR PDB; 6TYB; X-ray; 2.30 A; C=26-203.
DR PDBsum; 6TYB; -.
DR AlphaFoldDB; P16003; -.
DR SMR; P16003; -.
DR STRING; 9544.ENSMMUP00000017342; -.
DR ABCD; P16003; 5 sequenced antibodies.
DR GeneID; 713807; -.
DR KEGG; mcc:713807; -.
DR CTD; 920; -.
DR eggNOG; ENOG502S0W5; Eukaryota.
DR InParanoid; P16003; -.
DR OrthoDB; 652984at2759; -.
DR Proteomes; UP000006718; Unplaced.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro.
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:1990782; F:protein tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
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; 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 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Lipoprotein; Membrane;
KW Palmitate; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT CHAIN 26..458
FT /note="T-cell surface glycoprotein CD4"
FT /id="PRO_0000014624"
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="N -> T (in Ref. 1; AAA36838)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="L -> S (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="L -> S (in Ref. 2; BAA09671 and 3; CAA51752)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="I -> L (in Ref. 2; BAA09671 and 4; AAC25129)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="K -> N (in Ref. 3; CAA51752)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="S -> P (in Ref. 2; BAA09671)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="R -> Q (in Ref. 3; CAA51752)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="A -> T (in Ref. 2; BAA09671)"
FT /evidence="ECO:0000305"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:6TYB"
FT HELIX 75..79
FT /evidence="ECO:0007829|PDB:6TYB"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:6TYB"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:6TYB"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 114..125
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 162..173
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 180..188
FT /evidence="ECO:0007829|PDB:6TYB"
FT STRAND 191..199
FT /evidence="ECO:0007829|PDB:6TYB"
SQ SEQUENCE 458 AA; 50884 MW; 8BB80339FAFEC808 CRC64;
MNRGIPFRHL LLVLQLALLP AVTQGKKVVL GKKGDTVELT CNASQKKNTQ FHWKNSNQIK
ILGIQGLFLT KGPSKLSDRA DSRKSLWDQG CFSMIIKNLK IEDSDTYICE VENKKEEVEL
LVFGLTANSD THLLEGQSLT LTLESPPGSS PSVKCRSPGG KNIQGGRTIS VPQLERQDSG
TWTCTVSQDQ KTVEFKIDIV VLAFQKASST VYKKEGEQVE FSFPLAFTLE KLTGSGELWW
QAERASSSKS WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA
LEAKTGKLHQ EVNLVVMRAT QFQENLTCEV WGPTSPKLTL SLKLENKGAT VSKQAKAVWV
LNPEAGMWQC LLSDSGQVLL ESNIKVVPTW PTPVQPMALI VLGGVAGLLL FTGLGIFFCV
RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI
