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Protein

T-cell-specific surface glycoprotein CD28

Gene

CD28

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • 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 gene expression Source: UniProtKB
  • negative thymic T cell selection Source: Ensembl
  • phosphatidylinositol-mediated signaling Source: Reactome
  • 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: Ensembl
  • positive regulation of T cell proliferation Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter 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 phosphatidylinositol 3-kinase signaling Source: Reactome
  • regulation of regulatory T cell differentiation Source: Ensembl
  • regulatory T cell differentiation Source: BHF-UCL
  • T cell costimulation Source: UniProtKB
  • T cell receptor signaling pathway Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000178562-MONOMER.
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

HGNCiHGNC:1653. CD28.

Subcellular locationi

Isoform 3 :

Topology

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

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytosol Source: Reactome
  • external side of plasma membrane Source: MGI
  • immunological synapse Source: Ensembl
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: MGI
  • protein complex involved in cell adhesion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi940.
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...)1 Publication1
Disulfide bondi40 ↔ 1121 Publication
Disulfide bondi66 ↔ 861 Publication
Glycosylationi71N-linked (GlcNAc...)1 Publication1
Glycosylationi92N-linked (GlcNAc...)Sequence analysis1
Glycosylationi105N-linked (GlcNAc...)1 Publication1
Glycosylationi129N-linked (GlcNAc...)1 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.

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

WithEntry#Exp.IntActNotes
PIK3R1P279868EBI-4314301,EBI-79464

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi107378. 10 interactors.
DIPiDIP-6043N.
IntActiP10747. 7 interactors.
MINTiMINT-4656075.
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[»]
ProteinModelPortaliP10747.
SMRiP10747.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10747.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

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.
InterProiIPR008093. CD28.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF15910. V-set_2. 1 hit.
[Graphical view]
PRINTSiPR01717. CD28ANTIGEN.
SMARTiSM00406. IGv. 1 hit.
[Graphical view]
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

Cross-referencesi

Web resourcesi

Wikipedia

CD28 entry

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.

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[»]
ProteinModelPortaliP10747.
SMRiP10747.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107378. 10 interactors.
DIPiDIP-6043N.
IntActiP10747. 7 interactors.
MINTiMINT-4656075.
STRINGi9606.ENSP00000324890.

Chemistry databases

ChEMBLiCHEMBL5191.
GuidetoPHARMACOLOGYi2863.

PTM databases

iPTMnetiP10747.
PhosphoSitePlusiP10747.

Polymorphism and mutation databases

BioMutaiCD28.
DMDMi115973.

Proteomic databases

MaxQBiP10747.
PaxDbiP10747.
PeptideAtlasiP10747.
PRIDEiP10747.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi940.
DisGeNETi940.
GeneCardsiCD28.
HGNCiHGNC:1653. CD28.
MIMi186760. gene.
neXtProtiNX_P10747.
OpenTargetsiENSG00000178562.
PharmGKBiPA26207.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000178562-MONOMER.
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.

Miscellaneous databases

ChiTaRSiCD28. human.
EvolutionaryTraceiP10747.
GeneWikiiCD28.
GenomeRNAii940.
PROiP10747.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178562.
CleanExiHS_CD28.
GenevisibleiP10747. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR008093. CD28.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF15910. V-set_2. 1 hit.
[Graphical view]
PRINTSiPR01717. CD28ANTIGEN.
SMARTiSM00406. IGv. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCD28_HUMAN
AccessioniPrimary (citable) accession number: P10747
Secondary accession number(s): A8KAC1
, Q13964, Q52M23, Q70WG0, Q8NI54, Q8NI55, Q8NI56, Q8WXJ2, Q9BYV0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 2, 2016
This is version 178 of the entry and version 1 of the sequence. [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

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.