CD28_HUMAN
ID CD28_HUMAN Reviewed; 220 AA.
AC P10747; A8KAC1; Q13964; Q52M23; Q70WG0; Q8NI54; Q8NI55; Q8NI56; Q8WXJ2;
AC Q9BYV0;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=T-cell-specific surface glycoprotein CD28;
DE AltName: Full=TP44;
DE AltName: CD_antigen=CD28;
DE Flags: Precursor;
GN Name=CD28;
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] (ISOFORM 1).
RX PubMed=2825196; DOI=10.1073/pnas.84.23.8573;
RA Aruffo A., Seed B.;
RT "Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression
RT system.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8573-8577(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3), AND ALTERNATIVE
RP SPLICING.
RX PubMed=2162892;
RA Lee K.P., Taylor C., Petryniak B., Turka L.A., June C.H., Thompson C.B.;
RT "The genomic organization of the CD28 gene. Implications for the regulation
RT of CD28 mRNA expression and heterogeneity.";
RL J. Immunol. 145:344-352(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RX PubMed=11916166; DOI=10.1016/s0198-8859(01)00354-8;
RA Deshpande M., Venuprasad K., Parab P.B., Saha B., Mitra D.;
RT "A novel CD28 mRNA variant and simultaneous presence of various CD28 mRNA
RT isoforms in human T lymphocytes.";
RL Hum. Immunol. 63:20-23(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 4 AND 6), AND CHARACTERIZATION
RP (ISOFORM 3).
RC TISSUE=Peripheral blood T-cell;
RX PubMed=11877290; DOI=10.1182/blood.v99.6.2138;
RA Hanawa H., Ma Y., Mikolajczak S.A., Charles M.L., Yoshida T., Yoshida R.,
RA Strathdee C.A., Litchfield D.W., Ochi A.;
RT "A novel costimulatory signaling in human T lymphocytes by a splice variant
RT of CD28.";
RL Blood 99:2138-2145(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7).
RA Gan S.U., Hare J., Krivoshchapov L., Hui K.M., Galea-Lauri J., Farzaneh F.,
RA Darling D.;
RT "New human CD28 isoforms generated by a novel splicing event in the
RT 5'UTR.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium, and Trachea;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [GENOMIC DNA] OF 1-178 (ISOFORM 1).
RX PubMed=11735222; DOI=10.1006/geno.2001.6655;
RA Ling V., Wu P.W., Finnerty H.F., Agostino M.J., Graham J.R., Chen S.,
RA Jussiff J.M., Fisk G.J., Miller C.P., Collins M.;
RT "Assembly and annotation of human chromosome 2q33 sequence containing the
RT CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative,
RT and microarray approaches.";
RL Genomics 78:155-168(2001).
RN [12]
RP FUNCTION.
RX PubMed=8617933;
RA Blotta M.H., Marshall J.D., DeKruyff R.H., Umetsu D.T.;
RT "Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a
RT costimulatory signal that up-regulates IL-4 synthesis.";
RL J. Immunol. 156:3133-3140(1996).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-209, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [14]
RP FUNCTION (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM 3), INTERACTION WITH
RP CD40LG (ISOFORM 3), AND PHOSPHORYLATION (ISOFORM 3).
RX PubMed=15067037; DOI=10.1084/jem.20031705;
RA Mikolajczak S.A., Ma B.Y., Yoshida T., Yoshida R., Kelvin D.J., Ochi A.;
RT "The modulation of CD40 ligand signaling by transmembrane CD28 splice
RT variant in human T cells.";
RL J. Exp. Med. 199:1025-1031(2004).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-71 AND ASN-129.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-189 AND TYR-191, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 17-152 IN COMPLEX WITH THE FAB
RP FRAGMENT OF A MITOGENIC ANTIBODY, DISULFIDE BONDS, AND GLYCOSYLATION AT
RP ASN-37 AND ASN-105.
RX PubMed=15696168; DOI=10.1038/ni1170;
RA Evans E.J., Esnouf R.M., Manso-Sancho R., Gilbert R.J., James J.R., Yu C.,
RA Fennelly J.A., Vowles C., Hanke T., Walse B., Hunig T., Sorensen P.,
RA Stuart D.I., Davis S.J.;
RT "Crystal structure of a soluble CD28-Fab complex.";
RL Nat. Immunol. 6:271-279(2005).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 189-196 IN COMPLEX WITH GRB2, AND
RP INTERACTION WITH GRB2.
RX PubMed=24098653; DOI=10.1371/journal.pone.0074482;
RA Higo K., Ikura T., Oda M., Morii H., Takahashi J., Abe R., Ito N.;
RT "High resolution crystal structure of the Grb2 SH2 domain with a
RT phosphopeptide derived from CD28.";
RL PLoS ONE 8:E74482-E74482(2013).
CC -!- FUNCTION: Involved in T-cell activation, the induction of cell
CC proliferation and cytokine production and promotion of T-cell survival.
CC Enhances the production of IL4 and IL10 in T-cells in conjunction with
CC TCR/CD3 ligation and CD40L costimulation (PubMed:8617933). Isoform 3
CC enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and
CC PAK2 in T-cells (PubMed:15067037). {ECO:0000269|PubMed:15067037,
CC ECO:0000269|PubMed:8617933}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with DUSP14. Binds to
CC CD80/B7-1 and CD86/B7-2/B70. Interacts with GRB2. Isoform 3 interacts
CC with CD40LG (PubMed:15067037). {ECO:0000269|PubMed:15067037,
CC ECO:0000269|PubMed:15696168, ECO:0000269|PubMed:24098653}.
CC -!- INTERACTION:
CC P10747; P27986: PIK3R1; NbExp=10; IntAct=EBI-4314301, EBI-79464;
CC P10747-1; P01552: entB; Xeno; NbExp=5; IntAct=EBI-15945088, EBI-1027464;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell surface
CC {ECO:0000269|PubMed:15067037}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=P10747-1; Sequence=Displayed;
CC Name=2; Synonyms=CD28-S2;
CC IsoId=P10747-2; Sequence=VSP_002494;
CC Name=3; Synonyms=CD28i;
CC IsoId=P10747-3; Sequence=VSP_002495;
CC Name=4; Synonyms=CD28-S1;
CC IsoId=P10747-4; Sequence=VSP_002496;
CC Name=5;
CC IsoId=P10747-5; Sequence=VSP_002495, VSP_002497, VSP_002498;
CC Name=6; Synonyms=CD28-S3;
CC IsoId=P10747-6; Sequence=VSP_002495, VSP_002499;
CC Name=7;
CC IsoId=P10747-7; Sequence=VSP_047701;
CC -!- TISSUE SPECIFICITY: Expressed in T-cells and plasma cells, but not in
CC less mature B-cells.
CC -!- PTM: CD40LG induces tyrosine phosphorylation of isoform 3.
CC {ECO:0000269|PubMed:15067037}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CD28 entry;
CC URL="https://en.wikipedia.org/wiki/CD28";
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DR EMBL; J02988; AAA60581.1; -; mRNA.
DR EMBL; M37815; AAA51944.1; -; Genomic_DNA.
DR EMBL; M37812; AAA51944.1; JOINED; Genomic_DNA.
DR EMBL; M37813; AAA51944.1; JOINED; Genomic_DNA.
DR EMBL; M37814; AAA51944.1; JOINED; Genomic_DNA.
DR EMBL; M37815; AAA51945.1; -; Genomic_DNA.
DR EMBL; M37812; AAA51945.1; JOINED; Genomic_DNA.
DR EMBL; M37813; AAA51945.1; JOINED; Genomic_DNA.
DR EMBL; M37814; AAA51945.1; JOINED; Genomic_DNA.
DR EMBL; AJ295273; CAC29237.1; -; mRNA.
DR EMBL; AF222341; AAF33792.1; -; mRNA.
DR EMBL; AF222342; AAF33793.1; -; mRNA.
DR EMBL; AF222343; AAF33794.1; -; mRNA.
DR EMBL; AJ517504; CAD57003.1; -; mRNA.
DR EMBL; EF064755; ABK41938.1; -; Genomic_DNA.
DR EMBL; AK292986; BAF85675.1; -; mRNA.
DR EMBL; AK313313; BAG36118.1; -; mRNA.
DR EMBL; AC125238; AAY24123.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70348.1; -; Genomic_DNA.
DR EMBL; BC093698; AAH93698.1; -; mRNA.
DR EMBL; BC112085; AAI12086.1; -; mRNA.
DR EMBL; AF411057; AAL40931.1; -; Genomic_DNA.
DR CCDS; CCDS2361.1; -. [P10747-1]
DR CCDS; CCDS58749.1; -. [P10747-2]
DR PIR; A39983; RWHU28.
DR RefSeq; NP_001230006.1; NM_001243077.1. [P10747-4]
DR RefSeq; NP_001230007.1; NM_001243078.1. [P10747-2]
DR RefSeq; NP_006130.1; NM_006139.3. [P10747-1]
DR RefSeq; XP_011510496.1; XM_011512194.2. [P10747-7]
DR RefSeq; XP_011510499.1; XM_011512197.2. [P10747-3]
DR PDB; 1YJD; X-ray; 2.70 A; C=17-152.
DR PDB; 3WA4; X-ray; 1.35 A; B=189-196.
DR PDB; 5AUL; X-ray; 1.10 A; B=189-196.
DR PDB; 5GJH; X-ray; 1.20 A; B/D=189-196.
DR PDB; 5GJI; X-ray; 0.90 A; B=189-196.
DR PDB; 6O8D; X-ray; 3.55 A; C=19-136.
DR PDB; 7VU5; NMR; -; A/B=148-188.
DR PDBsum; 1YJD; -.
DR PDBsum; 3WA4; -.
DR PDBsum; 5AUL; -.
DR PDBsum; 5GJH; -.
DR PDBsum; 5GJI; -.
DR PDBsum; 6O8D; -.
DR PDBsum; 7VU5; -.
DR AlphaFoldDB; P10747; -.
DR SMR; P10747; -.
DR BioGRID; 107378; 26.
DR CORUM; P10747; -.
DR DIP; DIP-6043N; -.
DR ELM; P10747; -.
DR IntAct; P10747; 10.
DR MINT; P10747; -.
DR STRING; 9606.ENSP00000324890; -.
DR ChEMBL; CHEMBL5191; -.
DR GuidetoPHARMACOLOGY; 2863; -.
DR GlyGen; P10747; 5 sites.
DR iPTMnet; P10747; -.
DR PhosphoSitePlus; P10747; -.
DR BioMuta; CD28; -.
DR DMDM; 115973; -.
DR MassIVE; P10747; -.
DR MaxQB; P10747; -.
DR PaxDb; P10747; -.
DR PeptideAtlas; P10747; -.
DR PRIDE; P10747; -.
DR ProteomicsDB; 52645; -. [P10747-1]
DR ProteomicsDB; 52646; -. [P10747-2]
DR ProteomicsDB; 52647; -. [P10747-3]
DR ProteomicsDB; 52648; -. [P10747-4]
DR ProteomicsDB; 68570; -.
DR ABCD; P10747; 16 sequenced antibodies.
DR Antibodypedia; 19958; 2966 antibodies from 48 providers.
DR DNASU; 940; -.
DR Ensembl; ENST00000324106.9; ENSP00000324890.7; ENSG00000178562.18. [P10747-1]
DR Ensembl; ENST00000374481.7; ENSP00000363605.4; ENSG00000178562.18. [P10747-2]
DR Ensembl; ENST00000458610.6; ENSP00000393648.2; ENSG00000178562.18. [P10747-7]
DR GeneID; 940; -.
DR KEGG; hsa:940; -.
DR MANE-Select; ENST00000324106.9; ENSP00000324890.7; NM_006139.4; NP_006130.1.
DR UCSC; uc002vah.6; human. [P10747-1]
DR CTD; 940; -.
DR DisGeNET; 940; -.
DR GeneCards; CD28; -.
DR HGNC; HGNC:1653; CD28.
DR HPA; ENSG00000178562; Group enriched (lymphoid tissue, placenta).
DR MalaCards; CD28; -.
DR MIM; 186760; gene.
DR neXtProt; NX_P10747; -.
DR OpenTargets; ENSG00000178562; -.
DR Orphanet; 2584; Classic mycosis fungoides.
DR Orphanet; 3162; Sezary syndrome.
DR PharmGKB; PA26207; -.
DR VEuPathDB; HostDB:ENSG00000178562; -.
DR eggNOG; ENOG502SAVP; Eukaryota.
DR GeneTree; ENSGT00530000063873; -.
DR HOGENOM; CLU_154699_0_0_1; -.
DR InParanoid; P10747; -.
DR OMA; CNYTYNG; -.
DR OrthoDB; 1222373at2759; -.
DR PhylomeDB; P10747; -.
DR TreeFam; TF335679; -.
DR PathwayCommons; P10747; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-164939; Nef mediated downregulation of CD28 cell surface expression.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-389356; CD28 co-stimulation.
DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-HSA-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR SignaLink; P10747; -.
DR SIGNOR; P10747; -.
DR BioGRID-ORCS; 940; 14 hits in 1075 CRISPR screens.
DR ChiTaRS; CD28; human.
DR EvolutionaryTrace; P10747; -.
DR GeneWiki; CD28; -.
DR GenomeRNAi; 940; -.
DR Pharos; P10747; Tbio.
DR PRO; PR:P10747; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P10747; protein.
DR Bgee; ENSG00000178562; Expressed in lymph node and 98 other tissues.
DR Genevisible; P10747; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0001772; C:immunological synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0098636; C:protein complex involved in cell adhesion; IDA:MGI.
DR GO; GO:0015026; F:coreceptor activity; TAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; NAS:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0097190; P:apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0006959; P:humoral immune response; TAS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045060; P:negative thymic T cell selection; IEA:Ensembl.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0001819; P:positive regulation of cytokine production; TAS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0002863; P:positive regulation of inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:UniProtKB.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IDA:UniProtKB.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IDA:UniProtKB.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IEA:Ensembl.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045727; P:positive regulation of translation; NAS:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; NAS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; IEA:Ensembl.
DR GO; GO:0045066; P:regulatory T cell differentiation; IDA:BHF-UCL.
DR GO; GO:0042110; P:T cell activation; IGI:BHF-UCL.
DR GO; GO:0031295; P:T cell costimulation; IBA:GO_Central.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 1.
DR IDEAL; IID00509; -.
DR InterPro; IPR008093; CD28.
DR InterPro; IPR040216; CTLA4/CD28.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013106; Ig_V-set.
DR PANTHER; PTHR11494; PTHR11494; 1.
DR Pfam; PF15910; V-set_2; 1.
DR PRINTS; PR01717; CD28ANTIGEN.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT CHAIN 19..220
FT /note="T-cell-specific surface glycoprotein CD28"
FT /id="PRO_0000014652"
FT TOPO_DOM 19..152
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 180..220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..137
FT /note="Ig-like V-type"
FT REGION 198..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 191
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 209
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15144186"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15696168"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15696168"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT DISULFID 40..112
FT /evidence="ECO:0000269|PubMed:15696168"
FT DISULFID 66..86
FT /evidence="ECO:0000269|PubMed:15696168"
FT VAR_SEQ 1..17
FT /note="MLRLLLALNLFPSIQVT -> MPCGLSALIMCPKGMVAVVVAVDDGDSQALA
FT (in isoform 7)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_047701"
FT VAR_SEQ 19..137
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11877290"
FT /id="VSP_002494"
FT VAR_SEQ 40..137
FT /note="CKYSYNLFSREFRASLHKGLDSAVEVCVVYGNYSQQLQVYSKTGFNCDGKLG
FT NESVTFYLQNLYVNQTDIYFCKIEVMYPPPYLDNEKSNGTIIHVKG -> W (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:11877290"
FT /id="VSP_002496"
FT VAR_SEQ 40..124
FT /note="CKYSYNLFSREFRASLHKGLDSAVEVCVVYGNYSQQLQVYSKTGFNCDGKLG
FT NESVTFYLQNLYVNQTDIYFCKIEVMYPPPYLD -> Y (in isoform 3,
FT isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11877290,
FT ECO:0000303|PubMed:11916166"
FT /id="VSP_002495"
FT VAR_SEQ 138..139
FT /note="KH -> EE (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11916166"
FT /id="VSP_002497"
FT VAR_SEQ 140..220
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11916166"
FT /id="VSP_002498"
FT VAR_SEQ 152..207
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:11877290"
FT /id="VSP_002499"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 35..43
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 64..74
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 92..101
FT /evidence="ECO:0007829|PDB:1YJD"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 108..121
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1YJD"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:1YJD"
SQ SEQUENCE 220 AA; 25066 MW; 1D9B6552A5878D0F CRC64;
MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSC KYSYNLFSRE FRASLHKGLD
SAVEVCVVYG NYSQQLQVYS KTGFNCDGKL GNESVTFYLQ NLYVNQTDIY FCKIEVMYPP
PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS KPFWVLVVVG GVLACYSLLV TVAFIIFWVR
SKRSRLLHSD YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS
