CD4_MOUSE
ID CD4_MOUSE Reviewed; 457 AA.
AC P06332;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=T-cell surface glycoprotein CD4;
DE AltName: Full=T-cell differentiation antigen L3T4;
DE AltName: Full=T-cell surface antigen T4/Leu-3;
DE AltName: CD_antigen=CD4;
DE Flags: Precursor;
GN Name=Cd4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3094146; DOI=10.1126/science.3094146;
RA Tourvieille B., Gorman S.D., Field E.H., Hunkapiller T., Parnes J.R.;
RT "Isolation and sequence of L3T4 complementary DNA clones: expression in T
RT cells and brain.";
RL Science 234:610-614(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3027575; DOI=10.1038/325453a0;
RA Littman D.R., Gettner S.N.;
RT "Unusual intron in the immunoglobulin domain of the newly isolated murine
RT CD4 (L3T4) gene.";
RL Nature 325:453-455(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Brain;
RX PubMed=3326818; DOI=10.1111/j.1600-065x.1987.tb00529.x;
RA Parnes J.R., Hunkapiller T.;
RT "L3T4 and the immunoglobulin gene superfamily: new relationships between
RT the immune system and the nervous system.";
RL Immunol. Rev. 100:109-127(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=2823269; DOI=10.1073/pnas.84.21.7644;
RA Gorman S.D., Tourvieille B., Parnes J.R.;
RT "Structure of the mouse gene encoding CD4 and an unusual transcript in
RT brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7644-7648(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9445485;
RA Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., Lu J.,
RA Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A.;
RT "Comparative sequence analysis of a gene-rich cluster at human chromosome
RT 12p13 and its syntenic region in mouse chromosome 6.";
RL Genome Res. 8:29-40(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 27-43.
RX PubMed=3082751; DOI=10.1007/bf00377974;
RA Classon B.J., Tsagaratos J., Kirszbaum L., Maddox J., McKay C.R.,
RA Brandon M., McKenzie I.F.C., Walker I.D.;
RT "The L3T4 antigen in mouse and the sheep equivalent are immunoglobulin-
RT like.";
RL Immunogenetics 23:129-132(1986).
RN [8]
RP DISULFIDE BONDS.
RX PubMed=3086886; DOI=10.1073/pnas.83.12.4499;
RA Classon B.J., Tsagaratos J., McKenzie I.F.C., Walker I.D.;
RT "Partial primary structure of the T4 antigens of mouse and sheep:
RT assignment of intrachain disulfide bonds.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:4499-4503(1986).
RN [9]
RP FUNCTION, INTERACTION WITH LCK, AND SUBCELLULAR LOCATION.
RX PubMed=3262426; DOI=10.1016/0092-8674(88)90053-0;
RA Veillette A., Bookman M.A., Horak E.M., Bolen J.B.;
RT "The CD4 and CD8 T cell surface antigens are associated with the internal
RT membrane tyrosine-protein kinase p56lck.";
RL Cell 55:301-308(1988).
RN [10]
RP FUNCTION.
RX PubMed=2784195; DOI=10.1038/338257a0;
RA Veillette A., Bookman M.A., Horak E.M., Samelson L.E., Bolen J.B.;
RT "Signal transduction through the CD4 receptor involves the activation of
RT the internal membrane tyrosine-protein kinase p56lck.";
RL Nature 338:257-259(1989).
RN [11]
RP PHOSPHORYLATION.
RX PubMed=2512251; DOI=10.1007/bf02421181;
RA DiSanto J.P., Klein J.S., Flomenberg N.;
RT "Phosphorylation and down-regulation of CD4 and CD8 in human CTLs and mouse
RT L cells.";
RL Immunogenetics 30:494-501(1989).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=1832488; DOI=10.1038/353180a0;
RA Rahemtulla A., Fung-Leung W.P., Schilham M.W., Kuendig T.M., Sambhara S.R.,
RA Narendran A., Arabian A., Wakeham A., Paige C.J., Zinkernagel R.M.;
RT "Normal development and function of CD8+ cells but markedly decreased
RT helper cell activity in mice lacking CD4.";
RL Nature 353:180-184(1991).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=10706685; DOI=10.4049/jimmunol.164.6.2978;
RA Vremec D., Pooley J., Hochrein H., Wu L., Shortman K.;
RT "CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and
RT spleen.";
RL J. Immunol. 164:2978-2986(2000).
RN [14]
RP FUNCTION, AND SUBUNIT.
RX PubMed=16709847; DOI=10.4049/jimmunol.176.11.6873;
RA Maekawa A., Schmidt B., Fazekas de St Groth B., Sanejouand Y.H., Hogg P.J.;
RT "Evidence for a domain-swapped CD4 dimer as the coreceptor for binding to
RT class II MHC.";
RL J. Immunol. 176:6873-6878(2006).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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, ECO:0000269|PubMed:16709847,
CC ECO:0000269|PubMed:1832488, ECO:0000269|PubMed:2784195,
CC ECO:0000269|PubMed:3262426}.
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 -!- INTERACTION:
CC P06332; P06240: Lck; NbExp=3; IntAct=EBI-1404, EBI-1401;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P01730};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P01730}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P06332-1; Sequence=Displayed;
CC Name=2; Synonyms=Brain-specific;
CC IsoId=P06332-2; Sequence=VSP_002489;
CC -!- TISSUE SPECIFICITY: Highly expressed in T-helper cells. The presence of
CC CD4 is a hallmark of T-helper cells which are specialized in the
CC activation and growth of cytotoxic T-cells, regulation of B cells, or
CC activation of phagocytes. CD4 is also present in other immune cells
CC such as macrophages, dendritic cells or NK cells.
CC {ECO:0000269|PubMed:10706685}.
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:0000269|PubMed:2512251}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Cd4 display markedly decreased T-
CC helper cell activity. {ECO:0000269|PubMed:1832488}.
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DR EMBL; M36850; AAA39401.1; -; mRNA.
DR EMBL; M13816; AAA37267.1; -; mRNA.
DR EMBL; X04836; CAA28539.1; -; mRNA.
DR EMBL; M36851; AAA39402.1; -; Genomic_DNA.
DR EMBL; M17080; AAA37403.1; -; Genomic_DNA.
DR EMBL; M17078; AAA37403.1; JOINED; Genomic_DNA.
DR EMBL; M17079; AAA37403.1; JOINED; Genomic_DNA.
DR EMBL; AC002397; AAC36010.1; -; Genomic_DNA.
DR EMBL; BC039137; AAH39137.1; -; mRNA.
DR CCDS; CCDS20535.1; -. [P06332-1]
DR PIR; A02110; RWMST4.
DR RefSeq; NP_038516.1; NM_013488.2. [P06332-1]
DR AlphaFoldDB; P06332; -.
DR SMR; P06332; -.
DR BioGRID; 198599; 1.
DR IntAct; P06332; 5.
DR MINT; P06332; -.
DR STRING; 10090.ENSMUSP00000024044; -.
DR GlyGen; P06332; 4 sites.
DR iPTMnet; P06332; -.
DR PhosphoSitePlus; P06332; -.
DR MaxQB; P06332; -.
DR PaxDb; P06332; -.
DR PRIDE; P06332; -.
DR ProteomicsDB; 279984; -. [P06332-1]
DR ProteomicsDB; 279985; -. [P06332-2]
DR ABCD; P06332; 7 sequenced antibodies.
DR Antibodypedia; 1341; 6513 antibodies from 59 providers.
DR DNASU; 12504; -.
DR Ensembl; ENSMUST00000024044; ENSMUSP00000024044; ENSMUSG00000023274. [P06332-1]
DR GeneID; 12504; -.
DR KEGG; mmu:12504; -.
DR UCSC; uc009dsi.1; mouse. [P06332-1]
DR UCSC; uc012esr.1; mouse. [P06332-2]
DR CTD; 920; -.
DR MGI; MGI:88335; Cd4.
DR VEuPathDB; HostDB:ENSMUSG00000023274; -.
DR eggNOG; ENOG502S0W5; Eukaryota.
DR GeneTree; ENSGT00390000001745; -.
DR HOGENOM; CLU_047414_0_0_1; -.
DR InParanoid; P06332; -.
DR OMA; KTCQCSH; -.
DR OrthoDB; 652984at2759; -.
DR PhylomeDB; P06332; -.
DR TreeFam; TF335974; -.
DR Reactome; R-MMU-1462054; Alpha-defensins.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-MMU-202430; Translocation of ZAP-70 to Immunological synapse.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-389948; PD-1 signaling.
DR Reactome; R-MMU-449836; Other interleukin signaling.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 12504; 7 hits in 75 CRISPR screens.
DR PRO; PR:P06332; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P06332; protein.
DR Bgee; ENSMUSG00000023274; Expressed in thymus and 123 other tissues.
DR ExpressionAtlas; P06332; baseline and differential.
DR Genevisible; P06332; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019865; F:immunoglobulin binding; ISO:MGI.
DR GO; GO:0042011; F:interleukin-16 binding; ISO:MGI.
DR GO; GO:0042012; F:interleukin-16 receptor activity; ISO:MGI.
DR GO; GO:0042289; F:MHC class II protein binding; ISO:MGI.
DR GO; GO:0023026; F:MHC class II protein complex binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:MGI.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISO:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:MGI.
DR GO; GO:0035397; P:helper T cell enhancement of adaptive immune response; IMP:UniProtKB.
DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; ISO:MGI.
DR GO; GO:0030225; P:macrophage differentiation; ISO:MGI.
DR GO; GO:0032507; P:maintenance of protein location in cell; ISO:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; ISO:MGI.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IDA:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0050870; P:positive regulation of T cell activation; IDA:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:MGI.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0050863; P:regulation of T cell activation; ISO:MGI.
DR GO; GO:0042110; P:T cell activation; IDA:MGI.
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 Adaptive immunity; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:3082751"
FT CHAIN 27..457
FT /note="T-cell surface glycoprotein CD4"
FT /id="PRO_0000014627"
FT TOPO_DOM 27..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 27..128
FT /note="Ig-like V-type"
FT DOMAIN 129..207
FT /note="Ig-like C2-type 1"
FT DOMAIN 208..317
FT /note="Ig-like C2-type 2"
FT DOMAIN 318..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 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 392
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..112
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:3086886"
FT DISULFID 159..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:3086886"
FT DISULFID 328..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:3086886"
FT VAR_SEQ 1..240
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_002489"
SQ SEQUENCE 457 AA; 51297 MW; 1B1DA7527CB00F33 CRC64;
MCRAISLRRL LLLLLQLSQL LAVTQGKTLV LGKEGESAEL PCESSQKKIT VFTWKFSDQR
KILGQHGKGV LIRGGSPSQF DRFDSKKGAW EKGSFPLIIN KLKMEDSQTY ICELENRKEE
VELWVFKVTF SPGTSLLQGQ SLTLTLDSNS KVSNPLTECK HKKGKVVSGS KVLSMSNLRV
QDSDFWNCTV TLDQKKNWFG MTLSVLGFQS TAITAYKSEG ESAEFSFPLN FAEENGWGEL
MWKAEKDSFF QPWISFSIKN KEVSVQKSTK DLKLQLKETL PLTLKIPQVS LQFAGSGNLT
LTLDKGTLHQ EVNLVVMKVA QLNNTLTCEV MGPTSPKMRL TLKQENQEAR VSEEQKVVQV
VAPETGLWQC LLSEGDKVKM DSRIQVLSRG VNQTVFLACV LGGSFGFLGF LGLCILCCVR
CRHQQRQAAR MSQIKRLLSE KKTCQCPHRM QKSHNLI
