CD4_RAT
ID CD4_RAT Reviewed; 457 AA.
AC P05540;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=T-cell surface glycoprotein CD4;
DE AltName: Full=T-cell surface antigen T4/Leu-3;
DE AltName: Full=W3/25 antigen;
DE AltName: CD_antigen=CD4;
DE Flags: Precursor;
GN Name=Cd4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=3104900; DOI=10.1073/pnas.84.6.1649;
RA Clark S.J., Jefferies W.A., Barclay A.N., Gagnon J., Williams A.F.;
RT "Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for
RT derivation from a structure with four immunoglobulin-related domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:1649-1653(1987).
RN [2]
RP PROTEIN SEQUENCE OF 42-51; 83-88; 95-101; 109-112; 146-164; 178-192;
RP 256-273; 292-300; 327-329 AND 368-371, DISULFIDE BONDS, GLYCOSYLATION AT
RP ASN-186 AND ASN-297, AND MUTAGENESIS OF ASN-186 AND ASN-297.
RX PubMed=2113054; DOI=10.1016/s0021-9258(18)86961-7;
RA Davis S.J., Ward H.A., Puklavec M.J., Willis A.C., Williams A.F.,
RA Barclay A.N.;
RT "High level expression in Chinese hamster ovary cells of soluble forms of
RT CD4 T lymphocyte glycoprotein including glycosylation variants.";
RL J. Biol. Chem. 265:10410-10418(1990).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 210-393.
RX PubMed=8493535; DOI=10.1126/science.8493535;
RA Brady R.L., Dodson E.J., Dodson G.G., Lange G., Davis S.J., Williams A.F.,
RA Barclay A.N.;
RT "Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-
RT terminal domains.";
RL Science 260:979-983(1993).
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; M15768; AAA40901.1; -; mRNA.
DR PIR; A27449; A27449.
DR RefSeq; NP_036837.1; NM_012705.1.
DR RefSeq; XP_006237393.1; XM_006237331.3.
DR RefSeq; XP_008761502.1; XM_008763280.2.
DR PDB; 1CID; X-ray; 2.80 A; A=210-386.
DR PDBsum; 1CID; -.
DR AlphaFoldDB; P05540; -.
DR SMR; P05540; -.
DR STRING; 10116.ENSRNOP00000021915; -.
DR GlyConnect; 588; 10 N-Linked glycans.
DR GlyGen; P05540; 4 sites, 19 N-linked glycans (1 site).
DR iPTMnet; P05540; -.
DR PhosphoSitePlus; P05540; -.
DR PaxDb; P05540; -.
DR PRIDE; P05540; -.
DR GeneID; 24932; -.
DR KEGG; rno:24932; -.
DR UCSC; RGD:2306; rat.
DR CTD; 920; -.
DR RGD; 2306; Cd4.
DR eggNOG; ENOG502S0W5; Eukaryota.
DR HOGENOM; CLU_047414_0_0_1; -.
DR InParanoid; P05540; -.
DR OMA; KTCQCSH; -.
DR OrthoDB; 652984at2759; -.
DR PhylomeDB; P05540; -.
DR TreeFam; TF335974; -.
DR Reactome; R-RNO-1462054; Alpha-defensins.
DR Reactome; R-RNO-202424; Downstream TCR signaling.
DR Reactome; R-RNO-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-RNO-202430; Translocation of ZAP-70 to Immunological synapse.
DR Reactome; R-RNO-202433; Generation of second messenger molecules.
DR Reactome; R-RNO-389948; PD-1 signaling.
DR Reactome; R-RNO-449836; Other interleukin signaling.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR EvolutionaryTrace; P05540; -.
DR PRO; PR:P05540; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000016294; Expressed in thymus and 18 other tissues.
DR Genevisible; P05540; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0019865; F:immunoglobulin binding; IDA:RGD.
DR GO; GO:0042011; F:interleukin-16 binding; ISO:RGD.
DR GO; GO:0042012; F:interleukin-16 receptor activity; ISO:RGD.
DR GO; GO:0042289; F:MHC class II protein binding; ISO:RGD.
DR GO; GO:0023026; F:MHC class II protein complex binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IDA:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISO:RGD.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:RGD.
DR GO; GO:0035397; P:helper T cell enhancement of adaptive immune response; ISO:RGD.
DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; ISO:RGD.
DR GO; GO:0030225; P:macrophage differentiation; ISO:RGD.
DR GO; GO:0032507; P:maintenance of protein location in cell; ISO:RGD.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; IDA:RGD.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0050870; P:positive regulation of T cell activation; ISO:RGD.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:RGD.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:RGD.
DR GO; GO:0050863; P:regulation of T cell activation; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0033280; P:response to vitamin D; IEP:RGD.
DR GO; GO:0042110; P:T cell activation; IMP:RGD.
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; 3.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT CHAIN 28..457
FT /note="T-cell surface glycoprotein CD4"
FT /id="PRO_0000014629"
FT TOPO_DOM 28..394
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..417
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 418..457
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..127
FT /note="Ig-like V-type"
FT DOMAIN 128..206
FT /note="Ig-like C2-type 1"
FT DOMAIN 207..316
FT /note="Ig-like C2-type 2"
FT DOMAIN 317..374
FT /note="Ig-like C2-type 3"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT LIPID 418
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 421
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2113054"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2113054"
FT CARBOHYD 392
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 43..111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:2113054"
FT DISULFID 158..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:2113054"
FT DISULFID 328..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:2113054"
FT MUTAGEN 186
FT /note="N->T: No change in secretion; when associated with
FT S-297."
FT /evidence="ECO:0000269|PubMed:2113054"
FT MUTAGEN 297
FT /note="N->S: No change in secretion; when associated with
FT T-186."
FT /evidence="ECO:0000269|PubMed:2113054"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 235..245
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 252..258
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 261..266
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 282..285
FT /evidence="ECO:0007829|PDB:1CID"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 294..301
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 303..319
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 321..332
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 336..344
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 349..362
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 365..374
FT /evidence="ECO:0007829|PDB:1CID"
FT STRAND 377..385
FT /evidence="ECO:0007829|PDB:1CID"
SQ SEQUENCE 457 AA; 51438 MW; 477BE157D30954C1 CRC64;
MCRGFSFRHL LPLLLLQLSK LLVVTQGKTV VLGKEGGSAE LPCESTSRRS ASFAWKSSDQ
KTILGYKNKL LIKGSLELYS RFDSRKNAWE RGSFPLIINK LRMEDSQTYV CELENKKEEV
ELWVFRVTFN PGTRLLQGQS LTLILDSNPK VSDPPIECKH KSSNIVKDSK AFSTHSLRIQ
DSGIWNCTVT LNQKKHSFDM KLSVLGFAST SITAYKSEGE SAEFSFPLNL GEESLQGELR
WKAEKAPSSQ SWITFSLKNQ KVSVQKSTSN PKFQLSETLP LTLQIPQVSL QFAGSGNLTL
TLDRGILYQE VNLVVMKVTQ PDSNTLTCEV MGPTSPKMRL ILKQENQEAR VSRQEKVIQV
QAPEAGVWQC LLSEGEEVKM DSKIQVLSKG LNQTMFLAVV LGSAFSFLVF TGLCILFCVR
CRHQQRQAAR MSQIKRLLSE KKTCQCSHRM QKSHNLI
