T-cell-specific surface glycoprotein CD28 precursor

Names and origin

Protein names

Recommended name:
    T-cell-specific surface glycoprotein CD28
Alternative name(s):
    TP44
    CD_antigen=CD28

Gene names

Name:

CD28

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	220 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival.
Subunit structure	Homodimer; disulfide-linked. Interacts with DUSP14. Binds to CD80/B7-1 and CD86/B7-2/B70. Ref.14
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in T-cells and plasma cells, but not in less mature B-cells.
Sequence similarities	Contains 1 Ig-like V-type (immunoglobulin-like) domain.

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Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Signal Transmembrane
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell surface receptor linked signal transduction Traceable author statement. Source: UniProtKB cytokine biosynthetic process Traceable author statement. Source: UniProtKB humoral immune response Traceable author statement. Source: UniProtKB positive regulation of T cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of anti-apoptosis Traceable author statement. Source: UniProtKB positive regulation of interleukin-2 biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of mitosis Inferred from direct assay. Source: UniProtKB positive regulation of translation Non-traceable author statement. Source: UniProtKB positive regulation of viral genome replication Non-traceable author statement. Source: UniProtKB regulation of defense response to virus by virus Inferred from Experiment. Source: Reactome regulatory T cell differentiation Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome external side of plasma membrane Inferred from direct assay. Source: MGI integral to plasma membrane Traceable author statement. Source: UniProtKB
Molecular function	SH3/SH2 adaptor activity Inferred from direct assay. Source: UniProtKB coreceptor activity Traceable author statement. Source: UniProtKB identical protein binding Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

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Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P10747-1) 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.

Isoform 2 (identifier: P10747-2) Also known as: CD28-S2; The sequence of this isoform differs from the canonical sequence as follows: 19-137: Missing.

Isoform 3 (identifier: P10747-3) Also known as: CD28i; The sequence of this isoform differs from the canonical sequence as follows: 40-124: CKYSYNLFSR...EVMYPPPYLD → Y

Isoform 4 (identifier: P10747-4) Also known as: CD28-S1; The sequence of this isoform differs from the canonical sequence as follows: 40-137: CKYSYNLFSR...SNGTIIHVKG → W

Isoform 5 (identifier: P10747-5) The sequence of this isoform differs from the canonical sequence as follows: 40-124: CKYSYNLFSR...EVMYPPPYLD → Y 138-139: KH → EE 140-220: Missing.

Isoform 6 (identifier: P10747-6) 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.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Chain

19 – 220

202

T-cell-specific surface glycoprotein CD28

PRO_0000014652

Regions

Topological domain

19 – 152

134

Extracellular Potential

Transmembrane

153 – 179

27

Potential

Topological domain

180 – 220

41

Cytoplasmic Potential

Domain

28 – 137

110

Ig-like V-type

Amino acid modifications

Modified residue

189

1

Phosphoserine Ref.13

Modified residue

191

1

Phosphotyrosine Ref.13 Ref.11

Modified residue

209

1

Phosphotyrosine Ref.11 Ref.10

Modified residue

218

1

Phosphotyrosine Ref.13

Glycosylation

37

1

N-linked (GlcNAc...) Ref.14

Glycosylation

71

1

N-linked (GlcNAc...) Ref.12

Glycosylation

92

1

N-linked (GlcNAc...) Potential

Glycosylation

105

1

N-linked (GlcNAc...) Ref.14

Glycosylation

129

1

N-linked (GlcNAc...) Ref.12

Disulfide bond

Disulfide bond

Natural variations

Alternative sequence

19 – 137

119

Missing in isoform 2.

VSP_002494

Alternative sequence

40 – 137

98

CKYSY…IHVKG → W in isoform 4.

VSP_002496

Alternative sequence

40 – 124

85

CKYSY…PPYLD → Y in isoform 3, isoform 5 and isoform 6.

VSP_002495

Alternative sequence

138 – 139

2

KH → EE in isoform 5.

VSP_002497

Alternative sequence

140 – 220

81

Missing in isoform 5.

VSP_002498

Alternative sequence

152 – 207

56

Missing in isoform 6.

VSP_002499

Secondary structure

1

.

220

Helix Strand Turn

Details...

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 1D9B6552A5878D0F Show »	FASTA	220	25,066
10 20 30 40 50 60 MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSC KYSYNLFSRE FRASLHKGLD 70 80 90 100 110 120 SAVEVCVVYG NYSQQLQVYS KTGFNCDGKL GNESVTFYLQ NLYVNQTDIY FCKIEVMYPP 130 140 150 160 170 180 PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS KPFWVLVVVG GVLACYSLLV TVAFIIFWVR 190 200 210 220 SKRSRLLHSD YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS « Hide
Isoform 2 (CD28-S2). Checksum: F9B205F1D1BBFDC9 Show »	FASTA	101	11,528
10 20 30 40 50 60 MLRLLLALNL FPSIQVTGKH LCPSPLFPGP SKPFWVLVVV GGVLACYSLL VTVAFIIFWV 70 80 90 100 RSKRSRLLHS DYMNMTPRRP GPTRKHYQPY APPRDFAAYR S « Hide
Isoform 3 (CD28i). Checksum: C9AF33467706D2BE Show »	FASTA	136	15,369
10 20 30 40 50 60 MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSY NEKSNGTIIH VKGKHLCPSP 70 80 90 100 110 120 LFPGPSKPFW VLVVVGGVLA CYSLLVTVAF IIFWVRSKRS RLLHSDYMNM TPRRPGPTRK 130 HYQPYAPPRD FAAYRS « Hide
Isoform 4 (CD28-S1). Checksum: 3DE54211F2642520 Show »	FASTA	123	14,014
10 20 30 40 50 60 MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSW KHLCPSPLFP GPSKPFWVLV 70 80 90 100 110 120 VVGGVLACYS LLVTVAFIIF WVRSKRSRLL HSDYMNMTPR RPGPTRKHYQ PYAPPRDFAA YRS « Hide
Isoform 5. Checksum: A2F24E0CFBD16D90 Show »	FASTA	55	6,099
10 20 30 40 50 MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSY NEKSNGTIIH VKGEE « Hide
Isoform 6 (CD28-S3). Checksum: C09D0EC41F748AFC Show »	FASTA	80	8,823
10 20 30 40 50 60 MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSY NEKSNGTIIH VKGKHLCPSP 70 80 LFPGPSKPYA PPRDFAAYRS « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system." Aruffo A., Seed B. Proc. Natl. Acad. Sci. U.S.A. 84:8573-8577(1987) [PubMed: 2825196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The genomic organization of the CD28 gene. Implications for the regulation of CD28 mRNA expression and heterogeneity." Lee K.P., Taylor C., Petryniak B., Turka L.A., June C.H., Thompson C.B. J. Immunol. 145:344-352(1990) [PubMed: 2162892] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3), ALTERNATIVE SPLICING.
[3]	"A novel CD28 mRNA variant and simultaneous presence of various CD28 mRNA isoforms in human T lymphocytes." Deshpande M., Venuprasad K., Parab P.B., Saha B., Mitra D. Hum. Immunol. 63:20-23(2002) [PubMed: 11916166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[4]	"A novel costimulatory signaling in human T lymphocytes by a splice variant of CD28." Hanawa H., Ma Y., Mikolajczak S.A., Charles M.L., Yoshida T., Yoshida R., Strathdee C.A., Litchfield D.W., Ochi A. Blood 99:2138-2145(2002) [PubMed: 11877290] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 4 AND 6), CHARACTERIZATION (ISOFORM 3). Tissue: Peripheral blood T-cell.
[5]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Synovium and Trachea.
[7]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	"Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches." Ling V., Wu P.W., Finnerty H.F., Agostino M.J., Graham J.R., Chen S., Jussiff J.M., Fisk G.J., Miller C.P., Collins M. Genomics 78:155-168(2001) [PubMed: 11735222] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-178 (ISOFORM 1).
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-209, MASS SPECTROMETRY.
[11]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-191 AND TYR-209, MASS SPECTROMETRY. Tissue: T-cell.
[12]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-71 AND ASN-129, MASS SPECTROMETRY.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-189; TYR-191 AND TYR-218, MASS SPECTROMETRY. Tissue: T-cell.
[14]	"Crystal structure of a soluble CD28-Fab complex." Evans E.J., Esnouf R.M., Manso-Sancho R., Gilbert R.J., James J.R., Yu C., Fennelly J.A., Vowles C., Hanke T., Walse B., Hunig T., Sorensen P., Stuart D.I., Davis S.J. Nat. Immunol. 6:271-279(2005) [PubMed: 15696168] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 17-152 IN COMPLEX WITH THE FAB FRAGMENT OF A MITOGENIC ANTIBODY, DISULFIDE BONDS, GLYCOSYLATION AT ASN-37 AND ASN-105.
+	Additional computationally mapped references.

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Web resources

Wikipedia

CD28 entry

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02988 mRNA. Translation: AAA60581.1.
M37815

M37814 Genomic DNA. Translation: AAA51944.1.
M37815

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.
EF064755 Genomic DNA. Translation: ABK41938.1.
AK292986 mRNA. Translation: BAF85675.1.
AK313313 mRNA. Translation: BAG36118.1.
AC125238 Genomic DNA. Translation: AAY24123.1.
BC093698 mRNA. Translation: AAH93698.1.
BC112085 mRNA. Translation: AAI12086.1.
AF411057 Genomic DNA. Translation: AAL40931.1.

IPI

IPI00022339.
IPI00215639.
IPI00215640.
IPI00215641.
IPI00215643.
IPI00215645.

PIR

RWHU28. A39983.

RefSeq

NP_006130.1.

UniGene

Hs.591629

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YJD	X-ray	2.70	C	17-152	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6043N.

STRING

P10747.

PTM databases

PhosphoSite

P10747.

Proteomic databases

PRIDE

P10747.

Genome annotation databases

Ensembl

ENST00000324106; ENSP00000324890; ENSG00000178562; Homo sapiens. [Genome view]

GeneID

940.

KEGG

hsa:940.

UCSC

uc002vah.2. human.
uc002vai.2. human.
uc010ftx.1. human.

Organism-specific databases

CTD

940.

GeneCards

GC02P204279.

H-InvDB

HIX0029832.

HGNC

HGNC:1653. CD28.

MIM

186760. gene.

PharmGKB

PA26207.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16344.

HOVERGEN

P10747.

InParanoid

P10747.

PhylomeDB

P10747.

Enzyme and pathway databases

Pathway_Interaction_DB

il12_stat4pathway. IL12 signaling mediated by STAT4.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_6185. HIV Infection.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P10747.

Bgee

P10747.

CleanEx

HS_CD28.

Genevestigator

P10747.

GermOnline

ENSG00000178562. Homo sapiens.

Family and domain databases

InterPro

IPR008093. CD28.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 1 hit.

Pfam

PF07686. V-set. 1 hit.
[Graphical view]

PRINTS

PR01717. CD28ANTIGEN.

PROSITE

PS50835. IG_LIKE. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

3894.

SOURCE

Search...

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Entry information

Entry name

CD28_HUMAN

Accession

Primary (citable) accession number: P10747
Secondary accession number(s): A8KAC1

Q9BYV0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	February 9, 2010
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

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Relevant documents

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families