CD4_HUMAN
ID CD4_HUMAN Reviewed; 458 AA.
AC P01730; B2R737; D3DUS5; Q4ZGK2; Q5U066; Q9UDE5;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=T-cell surface glycoprotein CD4;
DE AltName: Full=T-cell surface antigen T4/Leu-3;
DE AltName: CD_antigen=CD4;
DE Flags: Precursor;
GN Name=CD4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=2990730; DOI=10.1016/s0092-8674(85)80105-7;
RA Maddon P.J., Littman D.R., Godfrey M., Maddon D.E., Chess L., Axel R.;
RT "The isolation and nucleotide sequence of a cDNA encoding the T cell
RT surface protein T4: a new member of the immunoglobulin gene family.";
RL Cell 42:93-104(1985).
RN [2]
RP SEQUENCE REVISION TO 26.
RX PubMed=3263213; DOI=10.1016/0092-8674(88)90211-5;
RA Littman D.R., Maddon P.J., Axel R.;
RT "Corrected CD4 sequence.";
RL Cell 55:541-541(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8723724; DOI=10.1101/gr.6.4.314;
RA Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S.,
RA Malley T., Gibbs R.A.;
RT "A gene-rich cluster between the CD4 and triosephosphate isomerase genes at
RT human chromosome 12p13.";
RL Genome Res. 6:314-326(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=9074930; DOI=10.1101/gr.7.3.268;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], POLYMORPHISM, VARIANT TRP-265, AND TOPOLOGY.
RX PubMed=1708753; DOI=10.1016/0198-8859(91)90077-m;
RA Hodge T.W., Sasso D.R., McDougal J.S.;
RT "Humans with OKT4-epitope deficiency have a single nucleotide base change
RT in the CD4 gene, resulting in substitution of TRP240 for ARG240.";
RL Hum. Immunol. 30:99-104(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-191; SER-227 AND
RP TRP-265.
RG NIEHS SNPs program;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 28-424.
RC TISSUE=Blood;
RX PubMed=1425921; DOI=10.1002/eji.1830221132;
RA Fomsgaard A., Hirsch V.M., Johnson P.R.;
RT "Cloning and sequences of primate CD4 molecules: diversity of the cellular
RT receptor for simian immunodeficiency virus/human immunodeficiency virus.";
RL Eur. J. Immunol. 22:2973-2981(1992).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2823150; DOI=10.1038/330256a0;
RA Doyle C., Strominger J.L.;
RT "Interaction between CD4 and class II MHC molecules mediates cell
RT adhesion.";
RL Nature 330:256-259(1987).
RN [13]
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, DISULFIDE BOND, AND GLYCOSYLATION AT
RP ASN-296 AND ASN-325.
RX PubMed=2592374; DOI=10.1016/s0021-9258(19)30077-8;
RA Carr S.A., Hemling M.E., Folena-Wasserman G., Sweet R.W., Anumula K.,
RA Barr J.R., Huddleston M.J., Taylor P.;
RT "Protein and carbohydrate structural analysis of a recombinant soluble CD4
RT receptor by mass spectrometry.";
RL J. Biol. Chem. 264:21286-21295(1989).
RN [15]
RP PROTEIN SEQUENCE OF 26-40, AND TOPOLOGY.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 250-280, POLYMORPHISM, AND VARIANT TRP-265.
RX PubMed=1961196; DOI=10.1016/0161-5890(91)90003-3;
RA Lederman S., DeMartino J.A., Daugherty B.L., Foeldvari I., Yellin M.J.,
RA Cleary A.M., Berkowitz N., Lowy I., Braunstein N.S., Mark G.E.;
RT "A single amino acid substitution in a common African allele of the CD4
RT molecule ablates binding of the monoclonal antibody, OKT4.";
RL Mol. Immunol. 28:1171-1181(1991).
RN [17]
RP PHOSPHORYLATION AT SER-433; SER-440 AND SER-456, AND MUTAGENESIS OF
RP SER-433.
RX PubMed=2105883; DOI=10.1002/j.1460-2075.1990.tb08127.x;
RA Shin J., Doyle C., Yang Z., Kappes D., Strominger J.L.;
RT "Structural features of the cytoplasmic region of CD4 required for
RT internalization.";
RL EMBO J. 9:425-434(1990).
RN [18]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HIV-1 ENVELOPE POLYPROTEIN
RP GP160 (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION (MICROBIAL
RP INFECTION).
RX PubMed=2214026; DOI=10.1128/jvi.64.11.5585-5593.1990;
RA Crise B., Buonocore L., Rose J.K.;
RT "CD4 is retained in the endoplasmic reticulum by the human immunodeficiency
RT virus type 1 glycoprotein precursor.";
RL J. Virol. 64:5585-5593(1990).
RN [19]
RP GLYCOSYLATION AT ASN-296 AND ASN-325.
RX PubMed=2001369; DOI=10.1021/bi00223a015;
RA Spellman M.W., Leonard C.K., Basa L.J., Gelineo I., van Halbeek H.;
RT "Carbohydrate structures of recombinant soluble human CD4 expressed in
RT Chinese hamster ovary cells.";
RL Biochemistry 30:2395-2406(1991).
RN [20]
RP INTERACTION WITH IL16.
RX PubMed=1673145;
RA Cruikshank W.W., Greenstein J.L., Theodore A.C., Center D.M.;
RT "Lymphocyte chemoattractant factor induces CD4-dependent intracytoplasmic
RT signaling in lymphocytes.";
RL J. Immunol. 146:2928-2934(1991).
RN [21]
RP PALMITOYLATION AT CYS-419 AND CYS-422.
RX PubMed=1618861; DOI=10.1016/s0021-9258(18)42253-3;
RA Crise B., Rose J.K.;
RT "Identification of palmitoylation sites on CD4, the human immunodeficiency
RT virus receptor.";
RL J. Biol. Chem. 267:13593-13597(1992).
RN [22]
RP SUBCELLULAR LOCATION (MICROBIAL INFECTION) AND MUTAGENESIS OF MET-432;
RP SER-433; 438-LEU-LEU-439 AND SER-440.
RX PubMed=8124721; DOI=10.1016/0092-8674(94)90360-3;
RA Aiken C., Konner J., Landau N.R., Lenburg M.E., Trono D.;
RT "Nef induces CD4 endocytosis: requirement for a critical dileucine motif in
RT the membrane-proximal CD4 cytoplasmic domain.";
RL Cell 76:853-864(1994).
RN [23]
RP TISSUE SPECIFICITY.
RX PubMed=8088877; DOI=10.1016/0165-2478(94)90178-3;
RA Winkel K., Sotzik F., Vremec D., Cameron P.U., Shortman K.;
RT "CD4 and CD8 expression by human and mouse thymic dendritic cells.";
RL Immunol. Lett. 40:93-99(1994).
RN [24]
RP FUNCTION, INTERACTION WITH MHCII, INTERACTION WITH HIV-1 SURFACE PROTEIN
RP GP120 (MICROBIAL INFECTION), MUTAGENESIS OF PHE-68 AND ARG-265, AND DOMAIN.
RX PubMed=7604010; DOI=10.1073/pnas.92.14.6444;
RA Sakihama T., Smolyar A., Reinherz E.L.;
RT "Oligomerization of CD4 is required for stable binding to class II major
RT histocompatibility complex proteins but not for interaction with human
RT immunodeficiency virus gp120.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:6444-6448(1995).
RN [25]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN HERPESVIRUS 7
RP SURFACE PROTEINS.
RX PubMed=7909607; DOI=10.1073/pnas.91.9.3872;
RA Lusso P., Secchiero P., Crowley R.W., Garzino-Demo A., Berneman Z.N.,
RA Gallo R.C.;
RT "CD4 is a critical component of the receptor for human herpesvirus 7:
RT interference with human immunodeficiency virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:3872-3876(1994).
RN [26]
RP INTERACTION WITH SPG21, AND MUTAGENESIS OF 457-PRO-ILE-458.
RX PubMed=11113139; DOI=10.1074/jbc.m009270200;
RA Zeitlmann L., Sirim P., Kremmer E., Kolanus W.;
RT "Cloning of ACP33 as a novel intracellular ligand of CD4.";
RL J. Biol. Chem. 276:9123-9132(2001).
RN [27]
RP FUNCTION (MICROBIAL INFECTION), SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=12089508; DOI=10.1038/ni815;
RA Matthias L.J., Yam P.T., Jiang X.M., Vandegraaff N., Li P., Poumbourios P.,
RA Donoghue N., Hogg P.J.;
RT "Disulfide exchange in domain 2 of CD4 is required for entry of HIV-1.";
RL Nat. Immunol. 3:727-732(2002).
RN [28]
RP SUBCELLULAR LOCATION, INTERACTION WITH LCK, AND TOPOLOGY.
RX PubMed=12517957; DOI=10.4049/jimmunol.170.2.913;
RA Fragoso R., Ren D., Zhang X., Su M.W., Burakoff S.J., Jin Y.J.;
RT "Lipid raft distribution of CD4 depends on its palmitoylation and
RT association with Lck, and evidence for CD4-induced lipid raft aggregation
RT as an additional mechanism to enhance CD3 signaling.";
RL J. Immunol. 170:913-921(2003).
RN [29]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 SURFACE PROTEIN
RP GP120 (MICROBIAL INFECTION).
RX PubMed=16331979; DOI=10.1021/bi051120s;
RA Sharma D., Balamurali M.M., Chakraborty K., Kumaran S., Jeganathan S.,
RA Rashid U., Ingallinella P., Varadarajan R.;
RT "Protein minimization of the gp120 binding region of human CD4.";
RL Biochemistry 44:16192-16202(2005).
RN [30]
RP INTERACTION WITH LCK.
RX PubMed=16888650; DOI=10.1038/sj.embor.7400775;
RA Loewenberg M., Verhaar A.P., Bilderbeek J., Marle J.V., Buttgereit F.,
RA Peppelenbosch M.P., van Deventer S.J., Hommes D.W.;
RT "Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated
RT protein complex containing LCK and FYN.";
RL EMBO Rep. 7:1023-1029(2006).
RN [31]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16951326; DOI=10.4049/jimmunol.177.6.3669;
RA Bernstein H.B., Plasterer M.C., Schiff S.E., Kitchen C.M., Kitchen S.,
RA Zack J.A.;
RT "CD4 expression on activated NK cells: ligation of CD4 induces cytokine
RT expression and cell migration.";
RL J. Immunol. 177:3669-3676(2006).
RN [32]
RP FUNCTION (MICROBIAL INFECTION), AND REVIEW.
RX PubMed=17346169; DOI=10.2174/156652407780059177;
RA Lindwasser O.W., Chaudhuri R., Bonifacino J.S.;
RT "Mechanisms of CD4 downregulation by the Nef and Vpu proteins of primate
RT immunodeficiency viruses.";
RL Curr. Mol. Med. 7:171-184(2007).
RN [33]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-296.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [34]
RP REVIEW ON FUNCTION.
RX PubMed=24696433; DOI=10.1128/cmr.00097-13;
RA Tubo N.J., Jenkins M.K.;
RT "CD4+ T Cells: guardians of the phagosome.";
RL Clin. Microbiol. Rev. 27:200-213(2014).
RN [35]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24942581; DOI=10.1128/jvi.00616-14;
RA Zhen A., Krutzik S.R., Levin B.R., Kasparian S., Zack J.A., Kitchen S.G.;
RT "CD4 ligation on human blood monocytes triggers macrophage differentiation
RT and enhances HIV infection.";
RL J. Virol. 88:9934-9946(2014).
RN [36]
RP INTERACTION WITH MHCII.
RX PubMed=27114505; DOI=10.1073/pnas.1513918113;
RA Joensson P., Southcombe J.H., Santos A.M., Huo J., Fernandes R.A.,
RA McColl J., Lever M., Evans E.J., Hudson A., Chang V.T., Hanke T.,
RA Godkin A., Dunne P.D., Horrocks M.H., Palayret M., Screaton G.R.,
RA Petersen J., Rossjohn J., Fugger L., Dushek O., Xu X.N., Davis S.J.,
RA Klenerman D.;
RT "Remarkably low affinity of CD4/peptide-major histocompatibility complex
RT class II protein interactions.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:5682-5687(2016).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 26-208.
RX PubMed=1701030; DOI=10.1038/348411a0;
RA Wang J., Yan Y., Garrett T.P., Liu J., Rodgers D.W., Garlick R.L.,
RA Tarr G.E., Husain Y., Reinherz E.L., Harrison S.C.;
RT "Atomic structure of a fragment of human CD4 containing two immunoglobulin-
RT like domains.";
RL Nature 348:411-418(1990).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 26-208.
RX PubMed=2247146; DOI=10.1038/348419a0;
RA Ryu S.-E., Kwong P.D., Truneh A., Porter T.G., Arthos J., Rosenberg M.,
RA Dai X., Xuong N.-H., Axel R., Sweet R.W., Hendrickson W.A.;
RT "Crystal structure of an HIV-binding recombinant fragment of human CD4.";
RL Nature 348:419-426(1990).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (3.9 ANGSTROMS) OF 26-388, HOMODIMERIZATION,
RP INTERACTION WITH CD81, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-445 AND
RP CYS-447.
RX PubMed=9168119; DOI=10.1038/387527a0;
RA Wu H., Kwong P.D., Hendrickson W.A.;
RT "Dimeric association and segmental variability in the structure of human
RT CD4.";
RL Nature 387:527-530(1997).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 26-208 IN COMPLEX WITH HIV SURFACE
RP PROTEIN GP120 (MICROBIAL INFECTION), AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=9641677; DOI=10.1038/31405;
RA Kwong P.D., Wyatt R., Robinson J., Sweet R.W., Sodroski J.,
RA Hendrickson W.A.;
RT "Structure of an HIV gp120 envelope glycoprotein in complex with the CD4
RT receptor and a neutralizing human antibody.";
RL Nature 393:648-659(1998).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 428-450 IN COMPLEX WITH
RP PTK2/FAK1, AND INTERACTION WITH PTK2/FAK1.
RX PubMed=18078954; DOI=10.1016/j.jmb.2007.11.040;
RA Garron M.L., Arthos J., Guichou J.F., McNally J., Cicala C., Arold S.T.;
RT "Structural basis for the interaction between focal adhesion kinase and
RT CD4.";
RL J. Mol. Biol. 375:1320-1328(2008).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 26-203, INTERACTION WITH MHCII,
RP MUTAGENESIS OF GLN-65; THR-70; SER-85 AND ASP-88, AND DOMAIN.
RX PubMed=21900604; DOI=10.1073/pnas.1109438108;
RA Wang X.X., Li Y., Yin Y., Mo M., Wang Q., Gao W., Wang L., Mariuzza R.A.;
RT "Affinity maturation of human CD4 by yeast surface display and crystal
RT structure of a CD4-HLA-DR1 complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15960-15965(2011).
RN [43]
RP INVOLVEMENT IN IMD79.
RX PubMed=31781092; DOI=10.3389/fimmu.2019.02502;
RA Fernandes R.A., Perez-Andres M., Blanco E., Jara-Acevedo M., Criado I.,
RA Almeida J., Botafogo V., Coutinho I., Paiva A., van Dongen J.J.M.,
RA Orfao A., Faria E.;
RT "Complete Multilineage CD4 Expression Defect Associated With Warts Due to
RT an Inherited Homozygous CD4 Gene Mutation.";
RL Front. Immunol. 10:2502-2502(2019).
RN [44]
RP INVOLVEMENT IN IMD79.
RX PubMed=33471124; DOI=10.1093/infdis/jiab025;
RA Lisco A., Ye P., Wong C.S., Pei L., Hsu A.P., Mace E.M., Orange J.S.,
RA Lage S.L., Ward A.J., Migueles S.A., Connors M., Anderson M.V.,
RA Buckner C.M., Moir S., Rupert A., Dulau-Florea A., Ogbogu P.,
RA Timberlake D., Notarangelo L.D., Pittaluga S., Abraham R.S., Sereti I.;
RT "Lost in Translation: Lack of CD4 Expression due to a Novel Genetic
RT Defect.";
RL J. Infect. Dis. 223:645-654(2021).
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:0000269|PubMed:16951326, ECO:0000269|PubMed:24942581,
CC ECO:0000269|PubMed:2823150, ECO:0000269|PubMed:7604010}.
CC -!- FUNCTION: (Microbial infection) Primary receptor for human
CC immunodeficiency virus-1 (HIV-1) (PubMed:2214026, PubMed:16331979,
CC PubMed:9641677, PubMed:12089508). Down-regulated by HIV-1 Vpu
CC (PubMed:17346169). Acts as a receptor for Human Herpes virus 7/HHV-7
CC (PubMed:7909607). {ECO:0000269|PubMed:12089508,
CC ECO:0000269|PubMed:16331979, ECO:0000269|PubMed:17346169,
CC ECO:0000269|PubMed:2214026, ECO:0000269|PubMed:7909607,
CC ECO:0000269|PubMed:9641677}.
CC -!- SUBUNIT: Forms disulfide-linked homodimers at the cell surface.
CC Interacts with LCK (PubMed:16888650). Interacts with PTK2/FAK1
CC (PubMed:18078954). Binds to P4HB/PDI. Interacts with IL16; this
CC interaction induces a CD4-dependent signaling in lymphocytes
CC (PubMed:1673145). Interacts (via Ig-like V-type domain) with MHCII
CC alpha chain (via alpha-2 domain) and beta chain (via beta-2 domain);
CC this 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 (PubMed:27114505, PubMed:21900604, PubMed:7604010).
CC {ECO:0000269|PubMed:11113139, ECO:0000269|PubMed:12089508,
CC ECO:0000269|PubMed:1673145, ECO:0000269|PubMed:16888650,
CC ECO:0000269|PubMed:18078954, ECO:0000269|PubMed:21900604,
CC ECO:0000269|PubMed:27114505, ECO:0000269|PubMed:7604010}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Envelope
CC polyprotein gp160 and protein Vpu (PubMed:2214026, PubMed:16331979,
CC PubMed:9641677, PubMed:7604010). {ECO:0000269|PubMed:16331979,
CC ECO:0000269|PubMed:2214026, ECO:0000269|PubMed:7604010,
CC ECO:0000269|PubMed:9641677}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Human Herpes virus 7
CC surface proteins. {ECO:0000269|PubMed:7909607}.
CC -!- INTERACTION:
CC P01730; P51681: CCR5; NbExp=3; IntAct=EBI-353826, EBI-489374;
CC P01730; P01730: CD4; NbExp=2; IntAct=EBI-353826, EBI-353826;
CC P01730; P13473-2: LAMP2; NbExp=3; IntAct=EBI-353826, EBI-21591415;
CC P01730; P06239: LCK; NbExp=2; IntAct=EBI-353826, EBI-1348;
CC P01730; P04150: NR3C1; NbExp=2; IntAct=EBI-353826, EBI-493507;
CC P01730; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-353826, EBI-2623095;
CC P01730; P04578: env; Xeno; NbExp=2; IntAct=EBI-353826, EBI-6163496;
CC P01730; PRO_0000038427 [P04578]: env; Xeno; NbExp=3; IntAct=EBI-353826, EBI-6179761;
CC P01730; Q1PHM6: env; Xeno; NbExp=2; IntAct=EBI-353826, EBI-15845606;
CC P01730; Q2N0S6: env; Xeno; NbExp=3; IntAct=EBI-353826, EBI-16080048;
CC P01730; P03407: nef; Xeno; NbExp=2; IntAct=EBI-353826, EBI-7355020;
CC P01730; P05919: vpu; Xeno; NbExp=3; IntAct=EBI-353826, EBI-6248147;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12089508,
CC ECO:0000269|PubMed:12517957, ECO:0000269|PubMed:2823150,
CC ECO:0000269|PubMed:2990730}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:12517957, ECO:0000269|PubMed:15340161,
CC ECO:0000269|PubMed:1708753}. Note=Localizes to lipid rafts
CC (PubMed:12517957, PubMed:9168119). Removed from plasma membrane by HIV-
CC 1 Nef protein that increases clathrin-dependent endocytosis of this
CC antigen to target it to lysosomal degradation. Cell surface expression
CC is also down-modulated by HIV-1 Envelope polyprotein gp160 that
CC interacts with, and sequesters CD4 in the endoplasmic reticulum.
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:16951326, ECO:0000269|PubMed:24942581,
CC ECO:0000269|PubMed:8088877}.
CC -!- DOMAIN: The Ig-like V-type domain mediates the interaction with MHCII.
CC {ECO:0000269|PubMed:21900604, ECO:0000269|PubMed:7604010}.
CC -!- PTM: Palmitoylation and association with LCK contribute to the
CC enrichment of CD4 in lipid rafts. {ECO:0000269|PubMed:1618861}.
CC -!- PTM: Phosphorylated by PKC; phosphorylation at Ser-433 plays an
CC important role for CD4 internalization. {ECO:0000269|PubMed:2105883,
CC ECO:0000269|PubMed:2512251}.
CC -!- POLYMORPHISM: The OKT monoclonal antibodies are widely used for the
CC analysis of human peripheral blood T-lymphocytes. OKT4 reacts with T-
CC helper/inducer lymphocytes. The OKT4 epitope of the CD4 cell-surface
CC protein is polymorphic in white, black, and Japanese populations. The
CC variable phenotypic expression is due a CD4 polymorphism. OKT4 positive
CC individuals carry Arg-265 and OKT4 negative individuals carry Trp-265
CC [MIM:613949]. {ECO:0000269|PubMed:1708753, ECO:0000269|PubMed:1961196}.
CC -!- DISEASE: Immunodeficiency 79 (IMD79) [MIM:619238]: An autosomal
CC recessive disorder characterized by childhood onset of recurrent and
CC recalcitrant skin warts due to uncontrolled viral infection with human
CC papillomavirus (HPV). Some patients may also have recurrent respiratory
CC infections. Laboratory studies show a complete absence of CD4+ T cells.
CC {ECO:0000269|PubMed:31781092, ECO:0000269|PubMed:33471124}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cd4/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CD4 entry;
CC URL="https://en.wikipedia.org/wiki/CD4";
CC ---------------------------------------------------------------------------
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DR EMBL; M12807; AAA35572.1; -; mRNA.
DR EMBL; U47924; AAB51309.1; -; Genomic_DNA.
DR EMBL; M35160; AAA16069.1; -; mRNA.
DR EMBL; BT019791; AAV38594.1; -; mRNA.
DR EMBL; BT019811; AAV38614.1; -; mRNA.
DR EMBL; DQ012936; AAY22175.1; -; Genomic_DNA.
DR EMBL; AK312828; BAG35684.1; -; mRNA.
DR EMBL; CH471116; EAW88738.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88739.1; -; Genomic_DNA.
DR EMBL; BC025782; AAH25782.1; -; mRNA.
DR CCDS; CCDS8562.1; -.
DR PIR; A90872; RWHUT4.
DR RefSeq; NP_000607.1; NM_000616.4.
DR PDB; 1CDH; X-ray; 2.30 A; A=26-203.
DR PDB; 1CDI; X-ray; 2.90 A; A=26-203.
DR PDB; 1CDJ; X-ray; 2.50 A; A=26-203.
DR PDB; 1CDU; X-ray; 2.70 A; A=26-203.
DR PDB; 1CDY; X-ray; 2.00 A; A=26-203.
DR PDB; 1G9M; X-ray; 2.20 A; C=26-208.
DR PDB; 1G9N; X-ray; 2.90 A; C=26-208.
DR PDB; 1GC1; X-ray; 2.50 A; C=26-206.
DR PDB; 1JL4; X-ray; 4.30 A; D=26-203.
DR PDB; 1Q68; NMR; -; A=421-458.
DR PDB; 1RZJ; X-ray; 2.20 A; C=26-208.
DR PDB; 1RZK; X-ray; 2.90 A; C=26-208.
DR PDB; 1WBR; NMR; -; A=428-444.
DR PDB; 1WIO; X-ray; 3.90 A; A/B=26-388.
DR PDB; 1WIP; X-ray; 4.00 A; A/B=26-388.
DR PDB; 1WIQ; X-ray; 5.00 A; A/B=26-388.
DR PDB; 2B4C; X-ray; 3.30 A; C=26-206.
DR PDB; 2JKR; X-ray; 2.98 A; P/Q=431-441.
DR PDB; 2JKT; X-ray; 3.40 A; P/Q=435-441.
DR PDB; 2KLU; NMR; -; A=397-458.
DR PDB; 2NXY; X-ray; 2.00 A; B=26-208.
DR PDB; 2NXZ; X-ray; 2.04 A; B=26-208.
DR PDB; 2NY0; X-ray; 2.20 A; B=26-208.
DR PDB; 2NY1; X-ray; 1.99 A; B=26-208.
DR PDB; 2NY2; X-ray; 2.00 A; B=26-208.
DR PDB; 2NY3; X-ray; 2.00 A; B=26-208.
DR PDB; 2NY4; X-ray; 2.00 A; B=26-208.
DR PDB; 2NY5; X-ray; 2.50 A; C=26-208.
DR PDB; 2NY6; X-ray; 2.80 A; B=26-208.
DR PDB; 2QAD; X-ray; 3.30 A; B/F=26-206.
DR PDB; 3B71; X-ray; 2.82 A; D/E/F=428-450.
DR PDB; 3CD4; X-ray; 2.20 A; A=26-207.
DR PDB; 3J70; EM; -; C/O/T=26-208.
DR PDB; 3JCB; EM; -; D=26-200.
DR PDB; 3JCC; EM; -; D=26-200.
DR PDB; 3JWD; X-ray; 2.61 A; C/D=26-208.
DR PDB; 3JWO; X-ray; 3.51 A; C=26-208.
DR PDB; 3LQA; X-ray; 3.40 A; C=26-207.
DR PDB; 3O2D; X-ray; 2.19 A; A=26-207.
DR PDB; 3S4S; X-ray; 2.40 A; G/H=26-203.
DR PDB; 3S5L; X-ray; 2.10 A; G/H=26-203.
DR PDB; 3T0E; X-ray; 4.00 A; E=26-388.
DR PDB; 4H8W; X-ray; 1.85 A; C=26-208.
DR PDB; 4JM2; X-ray; 3.10 A; F=26-208.
DR PDB; 4P9H; X-ray; 3.00 A; C=26-207.
DR PDB; 4Q6I; X-ray; 3.65 A; C/I/J/K=1-208.
DR PDB; 4R2G; X-ray; 3.28 A; B/F/H/L=26-208.
DR PDB; 4R4H; X-ray; 4.28 A; B=26-203.
DR PDB; 4RQS; X-ray; 4.49 A; B=26-208.
DR PDB; 5A7X; EM; 17.00 A; B/F/J=26-206.
DR PDB; 5A8H; EM; 23.00 A; B/H/N=26-208.
DR PDB; 5CAY; X-ray; 3.00 A; B=26-208.
DR PDB; 5THR; EM; 8.90 A; G/H/I=26-207.
DR PDB; 5U1F; EM; 6.80 A; M=26-388.
DR PDB; 5VN3; EM; 3.70 A; C/E/F=26-208.
DR PDB; 6CM3; EM; 3.54 A; G/H/I=26-207.
DR PDB; 6EDU; EM; 4.06 A; G/H/I=26-208.
DR PDB; 6L1Y; X-ray; 2.47 A; C=26-202.
DR PDB; 6MEO; EM; 3.90 A; A=26-201.
DR PDB; 6MET; EM; 4.50 A; A=26-388.
DR PDB; 6OPN; EM; 3.50 A; C/F/I=25-203.
DR PDB; 6OPO; EM; 3.50 A; C/G/N=25-203.
DR PDB; 6OPP; EM; 3.70 A; C/F/M=25-203.
DR PDB; 6OPQ; EM; 3.80 A; C/I/J=25-203.
DR PDB; 6QH6; X-ray; 5.00 A; Q=431-440.
DR PDB; 6QH7; X-ray; 3.40 A; Q=431-440.
DR PDB; 6U0L; EM; 3.30 A; D/E/F=26-207.
DR PDB; 6U0N; EM; 3.50 A; D/E/F=26-207.
DR PDB; 6URI; X-ray; 3.00 A; D=419-444.
DR PDB; 6X5B; EM; 3.60 A; C/G/N=25-203.
DR PDB; 6X5C; EM; 4.04 A; C/I/J=25-203.
DR PDB; 7T0O; EM; 8.70 A; H/L/M=26-389.
DR PDB; 7T0R; X-ray; 3.65 A; A/D=26-389.
DR PDBsum; 1CDH; -.
DR PDBsum; 1CDI; -.
DR PDBsum; 1CDJ; -.
DR PDBsum; 1CDU; -.
DR PDBsum; 1CDY; -.
DR PDBsum; 1G9M; -.
DR PDBsum; 1G9N; -.
DR PDBsum; 1GC1; -.
DR PDBsum; 1JL4; -.
DR PDBsum; 1Q68; -.
DR PDBsum; 1RZJ; -.
DR PDBsum; 1RZK; -.
DR PDBsum; 1WBR; -.
DR PDBsum; 1WIO; -.
DR PDBsum; 1WIP; -.
DR PDBsum; 1WIQ; -.
DR PDBsum; 2B4C; -.
DR PDBsum; 2JKR; -.
DR PDBsum; 2JKT; -.
DR PDBsum; 2KLU; -.
DR PDBsum; 2NXY; -.
DR PDBsum; 2NXZ; -.
DR PDBsum; 2NY0; -.
DR PDBsum; 2NY1; -.
DR PDBsum; 2NY2; -.
DR PDBsum; 2NY3; -.
DR PDBsum; 2NY4; -.
DR PDBsum; 2NY5; -.
DR PDBsum; 2NY6; -.
DR PDBsum; 2QAD; -.
DR PDBsum; 3B71; -.
DR PDBsum; 3CD4; -.
DR PDBsum; 3J70; -.
DR PDBsum; 3JCB; -.
DR PDBsum; 3JCC; -.
DR PDBsum; 3JWD; -.
DR PDBsum; 3JWO; -.
DR PDBsum; 3LQA; -.
DR PDBsum; 3O2D; -.
DR PDBsum; 3S4S; -.
DR PDBsum; 3S5L; -.
DR PDBsum; 3T0E; -.
DR PDBsum; 4H8W; -.
DR PDBsum; 4JM2; -.
DR PDBsum; 4P9H; -.
DR PDBsum; 4Q6I; -.
DR PDBsum; 4R2G; -.
DR PDBsum; 4R4H; -.
DR PDBsum; 4RQS; -.
DR PDBsum; 5A7X; -.
DR PDBsum; 5A8H; -.
DR PDBsum; 5CAY; -.
DR PDBsum; 5THR; -.
DR PDBsum; 5U1F; -.
DR PDBsum; 5VN3; -.
DR PDBsum; 6CM3; -.
DR PDBsum; 6EDU; -.
DR PDBsum; 6L1Y; -.
DR PDBsum; 6MEO; -.
DR PDBsum; 6MET; -.
DR PDBsum; 6OPN; -.
DR PDBsum; 6OPO; -.
DR PDBsum; 6OPP; -.
DR PDBsum; 6OPQ; -.
DR PDBsum; 6QH6; -.
DR PDBsum; 6QH7; -.
DR PDBsum; 6U0L; -.
DR PDBsum; 6U0N; -.
DR PDBsum; 6URI; -.
DR PDBsum; 6X5B; -.
DR PDBsum; 6X5C; -.
DR PDBsum; 7T0O; -.
DR PDBsum; 7T0R; -.
DR AlphaFoldDB; P01730; -.
DR SMR; P01730; -.
DR BioGRID; 107358; 97.
DR DIP; DIP-617N; -.
DR ELM; P01730; -.
DR IntAct; P01730; 38.
DR MINT; P01730; -.
DR STRING; 9606.ENSP00000011653; -.
DR BindingDB; P01730; -.
DR ChEMBL; CHEMBL2754; -.
DR DrugBank; DB00098; Antithymocyte immunoglobulin (rabbit).
DR DrugBank; DB06241; Clenoliximab.
DR DrugBank; DB12698; Ibalizumab.
DR DrugCentral; P01730; -.
DR TCDB; 8.A.23.2.1; the basigin (basigin) family.
DR GlyConnect; 587; 31 N-Linked glycans (2 sites).
DR GlyGen; P01730; 4 sites, 54 N-linked glycans (3 sites).
DR iPTMnet; P01730; -.
DR PhosphoSitePlus; P01730; -.
DR SwissPalm; P01730; -.
DR BioMuta; CD4; -.
DR DMDM; 116013; -.
DR jPOST; P01730; -.
DR MassIVE; P01730; -.
DR MaxQB; P01730; -.
DR PaxDb; P01730; -.
DR PeptideAtlas; P01730; -.
DR PRIDE; P01730; -.
DR ProteomicsDB; 51451; -.
DR ABCD; P01730; 46 sequenced antibodies.
DR Antibodypedia; 1341; 6513 antibodies from 59 providers.
DR CPTC; P01730; 5 antibodies.
DR DNASU; 920; -.
DR Ensembl; ENST00000011653.9; ENSP00000011653.4; ENSG00000010610.10.
DR GeneID; 920; -.
DR KEGG; hsa:920; -.
DR MANE-Select; ENST00000011653.9; ENSP00000011653.4; NM_000616.5; NP_000607.1.
DR UCSC; uc001qqv.3; human.
DR CTD; 920; -.
DR DisGeNET; 920; -.
DR GeneCards; CD4; -.
DR HGNC; HGNC:1678; CD4.
DR HPA; ENSG00000010610; Tissue enhanced (liver, lymphoid tissue, parathyroid gland).
DR MalaCards; CD4; -.
DR MIM; 186940; gene.
DR MIM; 613949; phenotype.
DR MIM; 619238; phenotype.
DR neXtProt; NX_P01730; -.
DR OpenTargets; ENSG00000010610; -.
DR PharmGKB; PA26220; -.
DR VEuPathDB; HostDB:ENSG00000010610; -.
DR eggNOG; ENOG502S0W5; Eukaryota.
DR GeneTree; ENSGT00390000001745; -.
DR HOGENOM; CLU_047414_0_0_1; -.
DR InParanoid; P01730; -.
DR OMA; KTCQCSH; -.
DR OrthoDB; 652984at2759; -.
DR PhylomeDB; P01730; -.
DR TreeFam; TF335974; -.
DR PathwayCommons; P01730; -.
DR Reactome; R-HSA-1462054; Alpha-defensins.
DR Reactome; R-HSA-167590; Nef Mediated CD4 Down-regulation.
DR Reactome; R-HSA-173107; Binding and entry of HIV virion.
DR Reactome; R-HSA-180534; Vpu mediated degradation of CD4.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-HSA-202430; Translocation of ZAP-70 to Immunological synapse.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-389948; PD-1 signaling.
DR Reactome; R-HSA-449836; Other interleukin signaling.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; P01730; -.
DR SIGNOR; P01730; -.
DR BioGRID-ORCS; 920; 19 hits in 1072 CRISPR screens.
DR ChiTaRS; CD4; human.
DR EvolutionaryTrace; P01730; -.
DR GeneWiki; CD4; -.
DR GenomeRNAi; 920; -.
DR Pharos; P01730; Tclin.
DR PRO; PR:P01730; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P01730; protein.
DR Bgee; ENSG00000010610; Expressed in granulocyte and 166 other tissues.
DR ExpressionAtlas; P01730; baseline and differential.
DR Genevisible; P01730; HS.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:CAFA.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042101; C:T cell receptor complex; NAS:UniProtKB.
DR GO; GO:0015026; F:coreceptor activity; TAS:ProtInc.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0005201; F:extracellular matrix structural constituent; NAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042011; F:interleukin-16 binding; IPI:CAFA.
DR GO; GO:0042012; F:interleukin-16 receptor activity; IDA:CAFA.
DR GO; GO:0042289; F:MHC class II protein binding; IDA:UniProtKB.
DR GO; GO:0023026; F:MHC class II protein complex binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IDA:CAFA.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; TAS:ProtInc.
DR GO; GO:0035397; P:helper T cell enhancement of adaptive immune response; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; IDA:CAFA.
DR GO; GO:0030225; P:macrophage differentiation; IMP:ARUK-UCL.
DR GO; GO:0032507; P:maintenance of protein location in cell; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:CAFA.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:CAFA.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; NAS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IDA:CAFA.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:CAFA.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; IDA:CAFA.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:CAFA.
DR GO; GO:0050870; P:positive regulation of T cell activation; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:CAFA.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IDA:CAFA.
DR GO; GO:0051924; P:regulation of calcium ion transport; IDA:CAFA.
DR GO; GO:0050863; P:regulation of T cell activation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0042110; P:T cell activation; IBA:GO_Central.
DR GO; GO:0030217; P:T cell differentiation; IDA:UniProtKB.
DR GO; GO:0045058; P:T cell selection; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; NAS: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; IPR003598; Ig_sub2.
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; SM00408; IGc2; 2.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
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; Host cell receptor for virus entry;
KW Host-virus interaction; Immunity; Immunoglobulin domain; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:2592374"
FT CHAIN 26..458
FT /note="T-cell surface glycoprotein CD4"
FT /id="PRO_0000014621"
FT TOPO_DOM 26..396
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 397..418
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 419..458
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..125
FT /note="Ig-like V-type"
FT DOMAIN 126..203
FT /note="Ig-like C2-type 1"
FT DOMAIN 204..317
FT /note="Ig-like C2-type 2"
FT DOMAIN 318..374
FT /note="Ig-like C2-type 3"
FT REGION 427..455
FT /note="HIV-1 Vpu-susceptibility domain"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2105883"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2105883"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2105883"
FT LIPID 419
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:1618861"
FT LIPID 422
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:1618861"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:2001369, ECO:0000269|PubMed:2592374"
FT /id="CAR_000053"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2001369,
FT ECO:0000269|PubMed:2592374"
FT /id="CAR_000054"
FT DISULFID 41..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:2592374"
FT DISULFID 155..184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:2592374"
FT DISULFID 328..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:2592374"
FT VARIANT 191
FT /note="K -> E (in dbSNP:rs28917504)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_023459"
FT VARIANT 227
FT /note="F -> S (in dbSNP:rs11064419)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_023460"
FT VARIANT 265
FT /note="R -> W (in OKT4-negative populations;
FT dbSNP:rs28919570)"
FT /evidence="ECO:0000269|PubMed:1708753,
FT ECO:0000269|PubMed:1961196, ECO:0000269|Ref.8"
FT /id="VAR_003906"
FT MUTAGEN 65
FT /note="Q->Y: Increases the affinity for MHCII; when
FT associated with W-70; R-85 and R-88."
FT /evidence="ECO:0000269|PubMed:21900604"
FT MUTAGEN 68
FT /note="F->I: Abrogates the interaction with MHCII and T
FT cell activation."
FT /evidence="ECO:0000269|PubMed:7604010"
FT MUTAGEN 70
FT /note="T->W: Increases the affinity for MHCII; when
FT associated with Y-65; R-85 and R-88."
FT /evidence="ECO:0000269|PubMed:21900604"
FT MUTAGEN 85
FT /note="S->R: Increases the affinity for MHCII; when
FT associated with Y-65; W-70 and R-88."
FT /evidence="ECO:0000269|PubMed:21900604"
FT MUTAGEN 88
FT /note="D->R: Increases the affinity for MHCII; when
FT associated with Y-65; W-70 and R-85."
FT /evidence="ECO:0000269|PubMed:21900604"
FT MUTAGEN 265
FT /note="R->A: Has no effect on the interaction with MHCII.
FT Impairs recognition by OKT4 antibody."
FT /evidence="ECO:0000269|PubMed:7604010"
FT MUTAGEN 432
FT /note="M->T: No effect."
FT /evidence="ECO:0000269|PubMed:8124721"
FT MUTAGEN 433
FT /note="S->A: About 75% loss of internalization."
FT /evidence="ECO:0000269|PubMed:2105883"
FT MUTAGEN 433
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:8124721"
FT MUTAGEN 438..439
FT /note="LL->AA: Loss of Nef-induced CD4 down-modulation."
FT /evidence="ECO:0000269|PubMed:8124721"
FT MUTAGEN 440
FT /note="S->L: No effect."
FT /evidence="ECO:0000269|PubMed:8124721"
FT MUTAGEN 445
FT /note="C->A: Loss of homodimerization; when associated with
FT A-447."
FT /evidence="ECO:0000269|PubMed:9168119"
FT MUTAGEN 447
FT /note="C->A: Loss of homodimerization; when associated with
FT A-445."
FT /evidence="ECO:0000269|PubMed:9168119"
FT MUTAGEN 457..458
FT /note="Missing: Abolished interaction with SPG21 and
FT induced T-cell activation."
FT /evidence="ECO:0000269|PubMed:11113139"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:3LQA"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:2NY6"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:4H8W"
FT HELIX 84..89
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:4H8W"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 114..129
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:2NY1"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:1G9N"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:1CDJ"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:4H8W"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 180..188
FT /evidence="ECO:0007829|PDB:4H8W"
FT STRAND 191..200
FT /evidence="ECO:0007829|PDB:4H8W"
FT HELIX 398..421
FT /evidence="ECO:0007829|PDB:2KLU"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:2KLU"
FT HELIX 432..438
FT /evidence="ECO:0007829|PDB:3B71"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:1WBR"
SQ SEQUENCE 458 AA; 51111 MW; 20ED893F9E56D236 CRC64;
MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGDTVELT CTASQKKSIQ FHWKNSNQIK
ILGNQGSFLT KGPSKLNDRA DSRRSLWDQG NFPLIIKNLK IEDSDTYICE VEDQKEEVQL
LVFGLTANSD THLLQGQSLT LTLESPPGSS PSVQCRSPRG KNIQGGKTLS VSQLELQDSG
TWTCTVLQNQ KKVEFKIDIV VLAFQKASSI VYKKEGEQVE FSFPLAFTVE KLTGSGELWW
QAERASSSKS WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA
LEAKTGKLHQ EVNLVVMRAT QLQKNLTCEV WGPTSPKLML SLKLENKEAK VSKREKAVWV
LNPEAGMWQC LLSDSGQVLL ESNIKVLPTW STPVQPMALI VLGGVAGLLL FIGLGIFFCV
RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI
