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Protein

T-cell-specific surface glycoprotein CD28

Gene

CD28

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation (PubMed:8617933). Isoform 3 enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells (PubMed:15067037).2 Publications

GO - Molecular functioni

  • coreceptor activity Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • protease binding Source: BHF-UCL
  • protein kinase binding Source: Ensembl
  • SH3/SH2 adaptor activity Source: UniProtKB

GO - Biological processi

  • apoptotic signaling pathway Source: Ensembl
  • cell surface receptor signaling pathway Source: UniProtKB
  • cytokine biosynthetic process Source: UniProtKB
  • humoral immune response Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of gene expression Source: UniProtKB
  • negative thymic T cell selection Source: Ensembl
  • positive regulation of alpha-beta T cell proliferation Source: Ensembl
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of inflammatory response to antigenic stimulus Source: Ensembl
  • positive regulation of interleukin-10 production Source: UniProtKB
  • positive regulation of interleukin-2 biosynthetic process Source: UniProtKB
  • positive regulation of interleukin-4 production Source: UniProtKB
  • positive regulation of isotype switching to IgG isotypes Source: Ensembl
  • positive regulation of mitotic nuclear division Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
  • positive regulation of protein kinase B signaling Source: Reactome
  • positive regulation of T cell proliferation Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: Ensembl
  • positive regulation of translation Source: UniProtKB
  • positive regulation of viral genome replication Source: UniProtKB
  • regulation of defense response to virus by virus Source: Reactome
  • regulation of regulatory T cell differentiation Source: Ensembl
  • regulatory T cell differentiation Source: BHF-UCL
  • T cell activation Source: BHF-UCL
  • T cell costimulation Source: UniProtKB
  • T cell receptor signaling pathway Source: Ensembl

Enzyme and pathway databases

ReactomeiR-HSA-1257604 PIP3 activates AKT signaling
R-HSA-164939 Nef mediated downregulation of CD28 cell surface expression
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-389356 CD28 co-stimulation
R-HSA-389357 CD28 dependent PI3K/Akt signaling
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
SignaLinkiP10747
SIGNORiP10747

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell-specific surface glycoprotein CD28
Alternative name(s):
TP44
CD_antigen: CD28
Gene namesi
Name:CD28
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000178562.17
HGNCiHGNC:1653 CD28
MIMi186760 gene
neXtProtiNX_P10747

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 152ExtracellularSequence analysisAdd BLAST134
Transmembranei153 – 179HelicalSequence analysisAdd BLAST27
Topological domaini180 – 220CytoplasmicSequence analysisAdd BLAST41

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi940
MalaCardsiCD28
OpenTargetsiENSG00000178562
PharmGKBiPA26207

Chemistry databases

ChEMBLiCHEMBL5191
GuidetoPHARMACOLOGYi2863

Polymorphism and mutation databases

BioMutaiCD28
DMDMi115973

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Add BLAST18
ChainiPRO_000001465219 – 220T-cell-specific surface glycoprotein CD28Add BLAST202

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi37N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi40 ↔ 1121 Publication
Disulfide bondi66 ↔ 861 Publication
Glycosylationi71N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi92N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi105N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi129N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei189PhosphoserineCombined sources1
Modified residuei191PhosphotyrosineCombined sources1
Modified residuei209PhosphotyrosineCombined sources1

Post-translational modificationi

CD40LG induces tyrosine phosphorylation of isoform 3.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP10747
PaxDbiP10747
PeptideAtlasiP10747
PRIDEiP10747

PTM databases

iPTMnetiP10747
PhosphoSitePlusiP10747

Expressioni

Tissue specificityi

Expressed in T-cells and plasma cells, but not in less mature B-cells.

Gene expression databases

BgeeiENSG00000178562
CleanExiHS_CD28
GenevisibleiP10747 HS

Organism-specific databases

HPAiHPA070003

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with DUSP14. Binds to CD80/B7-1 and CD86/B7-2/B70. Interacts with GRB2. Isoform 3 interacts with CD40LG (PubMed:15067037).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • protease binding Source: BHF-UCL
  • protein kinase binding Source: Ensembl
  • SH3/SH2 adaptor activity Source: UniProtKB

Protein-protein interaction databases

BioGridi107378, 20 interactors
CORUMiP10747
DIPiDIP-6043N
ELMiP10747
IntActiP10747, 10 interactors
MINTiP10747
STRINGi9606.ENSP00000324890

Structurei

Secondary structure

1220
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 30Combined sources4
Beta strandi35 – 43Combined sources9
Beta strandi49 – 58Combined sources10
Beta strandi64 – 74Combined sources11
Beta strandi77 – 79Combined sources3
Beta strandi81 – 83Combined sources3
Beta strandi85 – 90Combined sources6
Beta strandi92 – 101Combined sources10
Helixi104 – 106Combined sources3
Beta strandi108 – 121Combined sources14
Beta strandi123 – 125Combined sources3
Beta strandi131 – 134Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YJDX-ray2.70C17-152[»]
3WA4X-ray1.35B189-196[»]
5AULX-ray1.10B189-196[»]
5GJHX-ray1.20B/D189-196[»]
5GJIX-ray0.90B189-196[»]
ProteinModelPortaliP10747
SMRiP10747
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10747

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 137Ig-like V-typeAdd BLAST110

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IXMM Eukaryota
ENOG410Z063 LUCA
GeneTreeiENSGT00530000063873
HOGENOMiHOG000276892
HOVERGENiHBG004094
InParanoidiP10747
KOiK06470
OMAiVNGNYSH
OrthoDBiEOG091G0IGY
PhylomeDBiP10747
TreeFamiTF335679

Family and domain databases

Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR008093 CD28
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF15910 V-set_2, 1 hit
PRINTSiPR01717 CD28ANTIGEN
SMARTiView protein in SMART
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit

Sequences (7)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P10747-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSC KYSYNLFSRE
60 70 80 90 100
FRASLHKGLD SAVEVCVVYG NYSQQLQVYS KTGFNCDGKL GNESVTFYLQ
110 120 130 140 150
NLYVNQTDIY FCKIEVMYPP PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS
160 170 180 190 200
KPFWVLVVVG GVLACYSLLV TVAFIIFWVR SKRSRLLHSD YMNMTPRRPG
210 220
PTRKHYQPYA PPRDFAAYRS
Length:220
Mass (Da):25,066
Last modified:July 1, 1989 - v1
Checksum:i1D9B6552A5878D0F
GO
Isoform 2 (identifier: P10747-2) [UniParc]FASTAAdd to basket
Also known as: CD28-S2

The sequence of this isoform differs from the canonical sequence as follows:
     19-137: Missing.

Show »
Length:101
Mass (Da):11,528
Checksum:iF9B205F1D1BBFDC9
GO
Isoform 3 (identifier: P10747-3) [UniParc]FASTAAdd to basket
Also known as: CD28i

The sequence of this isoform differs from the canonical sequence as follows:
     40-124: CKYSYNLFSR...EVMYPPPYLD → Y

Show »
Length:136
Mass (Da):15,369
Checksum:iC9AF33467706D2BE
GO
Isoform 4 (identifier: P10747-4) [UniParc]FASTAAdd to basket
Also known as: CD28-S1

The sequence of this isoform differs from the canonical sequence as follows:
     40-137: CKYSYNLFSR...SNGTIIHVKG → W

Show »
Length:123
Mass (Da):14,014
Checksum:i3DE54211F2642520
GO
Isoform 5 (identifier: P10747-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     40-124: CKYSYNLFSR...EVMYPPPYLD → Y
     138-139: KH → EE
     140-220: Missing.

Show »
Length:55
Mass (Da):6,099
Checksum:iA2F24E0CFBD16D90
GO
Isoform 6 (identifier: P10747-6) [UniParc]FASTAAdd to basket
Also known as: CD28-S3

The sequence of this isoform differs from the canonical sequence as follows:
     40-124: CKYSYNLFSR...EVMYPPPYLD → Y
     152-207: Missing.

Show »
Length:80
Mass (Da):8,823
Checksum:iC09D0EC41F748AFC
GO
Isoform 7 (identifier: P10747-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MLRLLLALNLFPSIQVT → MPCGLSALIMCPKGMVAVVVAVDDGDSQALA

Show »
Length:234
Mass (Da):26,186
Checksum:i02AD85397834E57E
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0477011 – 17MLRLL…SIQVT → MPCGLSALIMCPKGMVAVVV AVDDGDSQALA in isoform 7. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_00249419 – 137Missing in isoform 2. 1 PublicationAdd BLAST119
Alternative sequenceiVSP_00249640 – 137CKYSY…IHVKG → W in isoform 4. 1 PublicationAdd BLAST98
Alternative sequenceiVSP_00249540 – 124CKYSY…PPYLD → Y in isoform 3, isoform 5 and isoform 6. 2 PublicationsAdd BLAST85
Alternative sequenceiVSP_002497138 – 139KH → EE in isoform 5. 1 Publication2
Alternative sequenceiVSP_002498140 – 220Missing in isoform 5. 1 PublicationAdd BLAST81
Alternative sequenceiVSP_002499152 – 207Missing in isoform 6. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02988 mRNA Translation: AAA60581.1
M37815
, M37812, M37813, M37814 Genomic DNA Translation: AAA51944.1
M37815
, M37812, M37813, M37814 Genomic DNA Translation: AAA51945.1
AJ295273 mRNA Translation: CAC29237.1
AF222341 mRNA Translation: AAF33792.1
AF222342 mRNA Translation: AAF33793.1
AF222343 mRNA Translation: AAF33794.1
AJ517504 mRNA Translation: CAD57003.1
EF064755 Genomic DNA Translation: ABK41938.1
AK292986 mRNA Translation: BAF85675.1
AK313313 mRNA Translation: BAG36118.1
AC125238 Genomic DNA Translation: AAY24123.1
CH471063 Genomic DNA Translation: EAW70348.1
BC093698 mRNA Translation: AAH93698.1
BC112085 mRNA Translation: AAI12086.1
AF411057 Genomic DNA Translation: AAL40931.1
CCDSiCCDS2361.1 [P10747-1]
CCDS58749.1 [P10747-2]
PIRiA39983 RWHU28
RefSeqiNP_001230006.1, NM_001243077.1 [P10747-4]
NP_001230007.1, NM_001243078.1 [P10747-2]
NP_006130.1, NM_006139.3 [P10747-1]
XP_011510496.1, XM_011512194.2 [P10747-7]
XP_011510499.1, XM_011512197.2 [P10747-3]
UniGeneiHs.443123

Genome annotation databases

EnsembliENST00000324106; ENSP00000324890; ENSG00000178562 [P10747-1]
ENST00000374481; ENSP00000363605; ENSG00000178562 [P10747-2]
ENST00000458610; ENSP00000393648; ENSG00000178562 [P10747-7]
GeneIDi940
KEGGihsa:940
UCSCiuc002vah.6 human [P10747-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCD28_HUMAN
AccessioniPrimary (citable) accession number: P10747
Secondary accession number(s): A8KAC1
, Q13964, Q52M23, Q70WG0, Q8NI54, Q8NI55, Q8NI56, Q8WXJ2, Q9BYV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: March 28, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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