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 02-SEP-2026, entry version 224. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_013488.3. [P06332-1] DR AlphaFoldDB; P06332; -. DR SMR; P06332; -. DR BioGRID; 198599; 1. DR FunCoup; P06332; 720. DR IntAct; P06332; 5. DR MINT; P06332; -. DR STRING; 10090.ENSMUSP00000024044; -. DR GlyCosmos; P06332; 4 sites, No reported glycans. DR GlyGen; P06332; 5 sites. DR iPTMnet; P06332; -. DR PhosphoSitePlus; P06332; -. DR PaxDb; 10090-ENSMUSP00000024044; -. DR ProteomicsDB; 279984; -. [P06332-1] DR ProteomicsDB; 279985; -. [P06332-2] DR Antibodypedia; 1341; 7225 antibodies from 65 providers. DR DNASU; 12504; -. DR Ensembl; ENSMUST00000024044.7; ENSMUSP00000024044.7; ENSMUSG00000023274.15. [P06332-1] DR GeneID; 12504; -. DR KEGG; mmu:12504; -. DR UCSC; uc009dsi.1; mouse. [P06332-1] DR UCSC; uc012esr.1; mouse. [P06332-2] DR AGR; MGI:88335; -. 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; 8657369at2759; -. DR PhylomeDB; P06332; -. 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; Co-inhibition by PD-1. 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 80 CRISPR screens. DR PRO; PR:P06332; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; P06332; protein. DR Bgee; ENSMUSG00000023274; Expressed in thymus and 123 other cell types or tissues. DR ExpressionAtlas; P06332; baseline and differential. 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:0045121; C:membrane raft; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0015026; F:coreceptor activity; ISO:GO_Central. DR GO; GO:0019899; F:enzyme binding; ISO:GO_Central. DR GO; GO:0042802; F:identical protein binding; ISO:GO_Central. DR GO; GO:0019865; F:immunoglobulin binding; ISO:GO_Central. DR GO; GO:0042011; F:interleukin-16 binding; ISO:GO_Central. DR GO; GO:0042012; F:interleukin-16 receptor activity; ISO:GO_Central. DR GO; GO:0008289; F:lipid binding; ISO:GO_Central. DR GO; GO:0042289; F:MHC class II protein binding; ISO:GO_Central. DR GO; GO:0023026; F:MHC class II protein complex binding; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISO:GO_Central. DR GO; GO:0019901; F:protein kinase binding; ISO:GO_Central. DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; ISO:GO_Central. DR GO; GO:0001618; F:virus receptor activity; ISO:GO_Central. DR GO; GO:0008270; F:zinc ion binding; ISO:GO_Central. 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:GO_Central. 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:0006955; P:immune response; IEA:InterPro. DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; ISO:GO_Central. DR GO; GO:0030225; P:macrophage differentiation; ISO:GO_Central. DR GO; GO:0032507; P:maintenance of protein location in cell; ISO:MGI. DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; ISO:GO_Central. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IDA:MGI. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:GO_Central. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:GO_Central. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:GO_Central. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:GO_Central. DR GO; GO:0045657; P:positive regulation of monocyte differentiation; ISO:GO_Central. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA: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:GO_Central. DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:GO_Central. DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:GO_Central. DR GO; GO:0050863; P:regulation of T cell activation; ISO:GO_Central. DR GO; GO:0046718; P:symbiont entry into host cell; ISO: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:0050852; P:T cell receptor signaling pathway; ISO:GO_Central. DR GO; GO:0045058; P:T cell selection; ISS:UniProtKB. DR CDD; cd22570; CD4_CD; 1. DR FunFam; 1.20.5.900:FF:000001; T-cell surface glycoprotein CD4; 1. DR FunFam; 2.60.40.10:FF:001105; T-cell surface glycoprotein CD4; 1. DR FunFam; 2.60.40.10:FF:001221; T-cell surface glycoprotein CD4; 1. DR FunFam; 2.60.40.10:FF:001253; T-cell surface glycoprotein CD4; 1. DR FunFam; 2.60.40.10:FF:002969; T-cell surface glycoprotein CD4; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 4. DR Gene3D; 1.20.5.900; transmembrane domain of human cd4; 1. 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_dom. DR InterPro; IPR021963; Tcell_CD4_Cterm. DR PANTHER; PTHR11422; T-CELL SURFACE GLYCOPROTEIN CD4; 1. DR PANTHER; PTHR11422:SF0; T-CELL SURFACE GLYCOPROTEIN CD4; 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; Immunoglobulin; 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 //