ID:CD4_HUMAN DESCRIPTION: RecName: Full=T-cell surface glycoprotein CD4; AltName: Full=T-cell surface antigen T4/Leu-3; AltName: CD_antigen=CD4; Flags: Precursor; FUNCTION: Accessory protein for MHC class-II antigen/T-cell receptor interaction. May regulate T-cell activation. Induces the aggregation of lipid rafts. SUBUNIT: Associates with LCK. Binds to HIV-1 gp120 and to P4HB/PDI and upon HIV-1 binding to the cell membrane, is part of P4HB/PDI- CD4-CXCR4-gp120 complex. Interacts with HIV-1 Envelope polyprotein gp160 and protein Vpu. Interacts with Human Herpes virus 7 capsid proteins. Interacts with PTK2/FAK1; this interaction requires the presence of HIV-1 gp120. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Note=Localizes to lipid rafts. Removed from plasma membrane by HIV-1 Nef protein that increases clathrin-dependent endocytosis of this antigen to target it to lysosomal degradation. Cell surface expression is also down-modulated by HIV-1 Envelope polyprotein gp160 that interacts with, and sequesters CD4 in the endoplasmic reticulum. PTM: Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts. POLYMORPHISM: The OKT monoclonal antibodies are widely used for the analysis of human peripheral blood T-lymphocytes. OKT4 reacts with T-helper/inducer lymphocytes. The OKT4 epitope of the CD4 cell-surface protein is polymorphic in white, black, and Japanese populations. The variable phenotypic expression is due a CD4 polymorphism. OKT4 positive individuals carry Arg-265 and OKT4 negative individuals carry Trp-265 [MIM:613949]. MISCELLANEOUS: Primary receptor for HIV-1. SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like) domains. SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like) domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cd4/"; WEB RESOURCE: Name=Wikipedia; Note=CD4 entry; URL="http://en.wikipedia.org/wiki/CD4";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P01730
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001816 cytokine production GO:0001934 positive regulation of protein phosphorylation GO:0002250 adaptive immune response GO:0002376 immune system process GO:0006948 induction by virus of host cell-cell fusion GO:0006955 immune response GO:0007155 cell adhesion GO:0007165 signal transduction GO:0007166 cell surface receptor signaling pathway GO:0007167 enzyme linked receptor protein signaling pathway GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway GO:0010524 positive regulation of calcium ion transport into cytosol GO:0016032 viral process GO:0019064 fusion of virus membrane with host plasma membrane GO:0019221 cytokine-mediated signaling pathway GO:0030217 T cell differentiation GO:0030260 entry into host cell GO:0032355 response to estradiol GO:0032507 maintenance of protein location in cell GO:0033280 response to vitamin D GO:0033674 positive regulation of kinase activity GO:0035397 helper T cell enhancement of adaptive immune response GO:0035723 interleukin-15-mediated signaling pathway GO:0042102 positive regulation of T cell proliferation GO:0042110 T cell activation GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043410 positive regulation of MAPK cascade GO:0045058 T cell selection GO:0045086 positive regulation of interleukin-2 biosynthetic process GO:0045657 positive regulation of monocyte differentiation GO:0045860 positive regulation of protein kinase activity GO:0045893 positive regulation of transcription, DNA-templated GO:0046598 positive regulation of viral entry into host cell GO:0050690 regulation of defense response to virus by virus GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0050829 defense response to Gram-negative bacterium GO:0050850 positive regulation of calcium-mediated signaling GO:0050852 T cell receptor signaling pathway GO:0050863 regulation of T cell activation GO:0050870 positive regulation of T cell activation GO:0051924 regulation of calcium ion transport GO:0061024 membrane organization GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus
AK316461 - Homo sapiens cDNA, FLJ79360 complete cds, highly similar to T-cell surface glycoprotein CD4 precursor. AK310750 - Homo sapiens cDNA, FLJ17792. AK310652 - Homo sapiens cDNA, FLJ17694. AK311495 - Homo sapiens cDNA, FLJ18537. AK315898 - Homo sapiens cDNA, FLJ79547 complete cds, highly similar to T-cell surface glycoprotein CD4 precursor. AK312828 - Homo sapiens cDNA, FLJ93265, Homo sapiens CD4 antigen (p55) (CD4), mRNA. AK316462 - Homo sapiens cDNA, FLJ79361 complete cds, highly similar to T-cell surface glycoprotein CD4 precursor. AK310687 - Homo sapiens cDNA, FLJ17729. AK300052 - Homo sapiens cDNA FLJ50658 complete cds, highly similar to T-cell surface glycoprotein CD4 precursor. AK308344 - Homo sapiens cDNA, FLJ98292. BC025782 - Homo sapiens CD4 molecule, mRNA (cDNA clone MGC:34241 IMAGE:5226427), complete cds. M12807 - Human T-cell surface glycoprotein T4 mRNA, complete cds. JD543045 - Sequence 524069 from Patent EP1572962. DQ892052 - Synthetic construct clone IMAGE:100004682; FLH182726.01X; RZPDo839B07140D CD4 molecule (CD4) gene, encodes complete protein. DQ895246 - Synthetic construct Homo sapiens clone IMAGE:100009706; FLH182722.01L; RZPDo839B07139D CD4 molecule (CD4) gene, encodes complete protein. CU693068 - Synthetic construct Homo sapiens gateway clone IMAGE:100019492 5' read CD4 mRNA. AB590293 - Synthetic construct DNA, clone: pFN21AE2271, Homo sapiens CD4 gene for CD4 molecule, without stop codon, in Flexi system. BT019791 - Homo sapiens CD4 antigen (p55) mRNA, complete cds. BT019811 - Homo sapiens CD4 antigen (p55) mRNA, complete cds. KJ896560 - Synthetic construct Homo sapiens clone ccsbBroadEn_05954 CD4 gene, encodes complete protein. AK303968 - Homo sapiens cDNA FLJ52390 complete cds, highly similar to T-cell surface glycoprotein CD4 precursor. AK310677 - Homo sapiens cDNA, FLJ17719. U40625 - Human surface glycoprotein variant (CD4) mRNA, partial cds. JD447856 - Sequence 428880 from Patent EP1572962. JD085825 - Sequence 66849 from Patent EP1572962. JD255225 - Sequence 236249 from Patent EP1572962. JD411124 - Sequence 392148 from Patent EP1572962. JD120194 - Sequence 101218 from Patent EP1572962. JD562356 - Sequence 543380 from Patent EP1572962. JD351029 - Sequence 332053 from Patent EP1572962. JD521989 - Sequence 503013 from Patent EP1572962. JD298429 - Sequence 279453 from Patent EP1572962. JD420334 - Sequence 401358 from Patent EP1572962. JD288080 - Sequence 269104 from Patent EP1572962. JD288081 - Sequence 269105 from Patent EP1572962. JD216346 - Sequence 197370 from Patent EP1572962. JD378591 - Sequence 359615 from Patent EP1572962. JD401465 - Sequence 382489 from Patent EP1572962. JD341315 - Sequence 322339 from Patent EP1572962. JD158576 - Sequence 139600 from Patent EP1572962. JD201061 - Sequence 182085 from Patent EP1572962. JD103408 - Sequence 84432 from Patent EP1572962. JD096727 - Sequence 77751 from Patent EP1572962. JD316588 - Sequence 297612 from Patent EP1572962. JD352700 - Sequence 333724 from Patent EP1572962. JD288937 - Sequence 269961 from Patent EP1572962. JD536916 - Sequence 517940 from Patent EP1572962. JD469727 - Sequence 450751 from Patent EP1572962. JD248358 - Sequence 229382 from Patent EP1572962. JD248359 - Sequence 229383 from Patent EP1572962. JD533997 - Sequence 515021 from Patent EP1572962. JD466320 - Sequence 447344 from Patent EP1572962. JD071613 - Sequence 52637 from Patent EP1572962. JD167454 - Sequence 148478 from Patent EP1572962. JD175314 - Sequence 156338 from Patent EP1572962. JD341704 - Sequence 322728 from Patent EP1572962. JD132254 - Sequence 113278 from Patent EP1572962. JD447916 - Sequence 428940 from Patent EP1572962. JD390724 - Sequence 371748 from Patent EP1572962. JD239905 - Sequence 220929 from Patent EP1572962. JD402420 - Sequence 383444 from Patent EP1572962. JD493570 - Sequence 474594 from Patent EP1572962. JD126627 - Sequence 107651 from Patent EP1572962. JD244920 - Sequence 225944 from Patent EP1572962. MK170450 - Homo sapiens cell line Jurkat CD4 (CD4) mRNA, complete cds.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_CSKPathway - Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor h_inflamPathway - Cytokines and Inflammatory Response h_nktPathway - Selective expression of chemokine receptors during T-cell polarization h_thelperPathway - T Helper Cell Surface Molecules h_bbcellPathway - Bystander B Cell Activation h_tcraPathway - Lck and Fyn tyrosine kinases in initiation of TCR Activation h_asbcellPathway - Antigen Dependent B Cell Activation h_il17Pathway - IL 17 Signaling Pathway h_stemPathway - Regulation of hematopoiesis by cytokines h_tcapoptosisPathway - HIV Induced T Cell Apoptosis h_no2il12Pathway - NO2-dependent IL 12 Pathway in NK cells h_vifPathway - HIV-1 defeats host-mediated resistance by CEM15 h_il5Pathway - IL 5 Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P01730 (Reactome details) participates in the following event(s):
R-HSA-164509 Binding of gp120 of ENV oligomer to the host CD4 R-HSA-200879 Formation of a Nef:ARF1:CD4 complex R-HSA-449087 CD4 binds Interleukin-16 R-HSA-1471314 HNP1-3 bind CD4 R-HSA-180606 Association of Vpu with CD4 R-HSA-167566 Nef mediated disruption of CD4:Lck Complex R-HSA-167537 Formation of CD4:Nef:AP-2 Complex:v-ATPase Complex R-HSA-202214 Dephosphorylation of Lck-pY505 by CD45 R-HSA-202233 Inactivation of Lck by Csk R-HSA-202291 Activation of Lck R-HSA-8852200 Inactivation of LCK by PTPN22 R-HSA-202165 Phosphorylation of ITAM motifs in CD3 complexes R-HSA-202344 Recruitment of ZAP-70 to phosphorylated ITAMs R-HSA-389758 Dephosphorylation of CD3-zeta by PD-1 bound phosphatases R-HSA-180591 Vpu:CD4 associates with beta-TrCP R-HSA-167597 Internalization of the CD4:Nef:AP-2 Complex:v-ATPase Complex R-HSA-164510 Conformational change in gp120 of Env oligomer R-HSA-164507 CD4:gp120 binds to chemokine co-receptor CCR5/CXCR4 R-HSA-164524 Fusion of viral membrane with host cell membrane R-HSA-202168 Phosphorylation of ZAP-70 by Lck R-HSA-202307 Change of PKC theta conformation R-HSA-202174 Activation of ZAP-70 R-HSA-8855381 PTPN22 dephosphorylates ZAP70 R-HSA-8866277 AP-2 directly binds some endocytic cargo R-HSA-180599 The Vpu:CD4:beta-TrCP complex recruits SKP1 R-HSA-164508 N and C terminal heptad repeat helices of gp41 form six-helix bundle R-HSA-164521 Insertion of gp41 fusion peptide into the target membrane R-HSA-164515 Fusogenic activation of gp41 R-HSA-164500 Conformational changes in gp120 exposes gp41 R-HSA-202216 Phosphorylation of SLP-76 R-HSA-202245 Phosphorylation of TBSMs in LAT R-HSA-180597 Ubiquitination of CD4 by Vpu:CD4:beta-TrCP:SKP1 complex R-HSA-202248 Phosphorylation of PLC-gamma1 R-HSA-8867756 CLASP proteins and cargo are recruited to the nascent clathrin-coated pit R-HSA-8868071 Clathrin recruits PIK3C2A R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission R-HSA-8868648 SYNJ hydrolyze PI(4,5)P2 to PI(4)P R-HSA-8871194 RAB5 and GAPVD1 bind AP-2 R-HSA-8868658 HSPA8-mediated ATP hydrolysis promotes vesicle uncoating R-HSA-8868659 Clathrin recruits auxilins to the clathrin-coated vesicle R-HSA-8868660 Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle R-HSA-8867754 F- and N- BAR domain proteins bind the clathrin-coated pit R-HSA-8868230 SNX9 recruits components of the actin polymerizing machinery R-HSA-8868072 Clathrin-associated PIK3C2A phosphorylates PI(4)P to PI(3,4)P2 R-HSA-8868236 BAR domain proteins recruit dynamin R-HSA-8868651 Endophilins recruit synaptojanins to the clathrin-coated pit R-HSA-173107 Binding and entry of HIV virion R-HSA-167590 Nef Mediated CD4 Down-regulation R-HSA-449836 Other interleukin signaling R-HSA-1462054 Alpha-defensins R-HSA-180534 Vpu mediated degradation of CD4 R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains R-HSA-202430 Translocation of ZAP-70 to Immunological synapse R-HSA-389948 PD-1 signaling R-HSA-162594 Early Phase of HIV Life Cycle R-HSA-164938 Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters R-HSA-449147 Signaling by Interleukins R-HSA-1461973 Defensins R-HSA-162909 Host Interactions of HIV factors R-HSA-202403 TCR signaling R-HSA-202424 Downstream TCR signaling R-HSA-388841 Costimulation by the CD28 family R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis R-HSA-162587 HIV Life Cycle R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-6803157 Antimicrobial peptides R-HSA-162906 HIV Infection R-HSA-1280218 Adaptive Immune System R-HSA-202433 Generation of second messenger molecules R-HSA-8856828 Clathrin-mediated endocytosis R-HSA-168256 Immune System R-HSA-168249 Innate Immune System R-HSA-5663205 Infectious disease R-HSA-199991 Membrane Trafficking R-HSA-1643685 Disease R-HSA-5653656 Vesicle-mediated transport
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
