Human Gene CD4 (ENST00000011653.9) from GENCODE V44
Description: Homo sapiens CD4 molecule (CD4), transcript variant 9, mRNA. (from RefSeq NM_001382714) RefSeq Summary (NM_000616): This gene encodes the CD4 membrane glycoprotein of T lymphocytes. The CD4 antigen acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class II MHC molecules. The CD4 antigen is also a primary receptor for entry of the human immunodeficiency virus through interactions with the HIV Env gp120 subunit. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, granulocytes, as well as in various regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, May 2020]. Gencode Transcript: ENST00000011653.9 Gencode Gene: ENSG00000010610.10 Transcript (Including UTRs) Position: hg38 chr12:6,789,528-6,820,799 Size: 31,272 Total Exon Count: 10 Strand: + Coding Region Position: hg38 chr12:6,800,139-6,819,329 Size: 19,191 Coding Exon Count: 9
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
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
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. 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. 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. MK170450 - Homo sapiens cell line Jurkat CD4 (CD4) mRNA, complete cds. AK310750 - Homo sapiens cDNA, FLJ17792. JD543045 - Sequence 524069 from Patent EP1572962. 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. 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.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04514 - Cell adhesion molecules (CAMs) hsa04612 - Antigen processing and presentation hsa04640 - Hematopoietic cell lineage hsa04660 - T cell receptor signaling pathway hsa05340 - Primary immunodeficiency
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 
Microarray Expression Data 
