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Reviewed, UniProtKB/Swiss-Prot P01732 (CD8A_HUMAN)

Last modified July 22, 2008. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    T-cell surface glycoprotein CD8 alpha chain
Alternative name(s):
    T-lymphocyte differentiation antigen T8/Leu-2
    CD_antigen=CD8a
Gene names
Name: CD8A
Synonyms: MAL
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length235 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Identifies cytotoxic/suppressor T-cells that interact with MHC class I bearing targets. CD8 is thought to play a role in the process of T-cell mediated killing. CD8 alpha chains binds to class I MHC molecules alpha-3 domains.

Subunit structure

In general heterodimer of an alpha and a beta chain linked by two disulfide bonds. Can also form homodimers. Shown to be expressed as heterdimer on thymocytes and as homodimer on peripheral blood T-lymphocytes. Interacts with the MHC class I HLA-A/B2M dimer. Interacts with LCK in a zinc-dependent manner.

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein.

Isoform 2: Secreted.

Post-translational modification

All of the five most carboxyl-terminal cysteines form inter-chain disulfide bonds in dimers and higher multimers, while the four N-terminal cysteines do not By similarity.

Involvement in disease

Defects in CD8A are a cause of familial CD8 deficiency (CD8 deficiency) [MIM:608957]. Familial CD8 deficiency is a novel autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.

Sequence similarities

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P01732-1)

Also known as: membrane; mCD8alpha;

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: P01732-2)

Also known as: secreted; sCD8alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     172-209: VHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHR → G

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Signal peptide1 – 2121
Chain22 – 235214T-cell surface glycoprotein CD8 alpha chain

Regions

Topological domain22 – 182161Extracellular Potential
Transmembrane183 – 20321 Potential
Topological domain204 – 23532Cytoplasmic Potential
Domain22 – 135114Ig-like V-type

Amino acid modifications

Disulfide bond43 ↔ 115

Natural variations

Alternative sequence172 – 20938VHTRG…YCNHR → G in isoform 2.
Natural variant1111G → S in CD8 deficiency; prevents CD8 expression.

Experimental info

Mutagenesis1111G → R: Prevents CD8 expression

Secondary structure

1 ...................... 235
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (membrane) (mCD8alpha) [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: FCCA29BAA73726BB

FASTA23525,729
        10         20         30         40         50         60 
MALPVTALLL PLALLLHAAR PSQFRVSPLD RTWNLGETVE LKCQVLLSNP TSGCSWLFQP 

        70         80         90        100        110        120 
RGAAASPTFL LYLSQNKPKA AEGLDTQRFS GKRLGDTFVL TLSDFRRENE GYYFCSALSN 

       130        140        150        160        170        180 
SIMYFSHFVP VFLPAKPTTT PAPRPPTPAP TIASQPLSLR PEACRPAAGG AVHTRGLDFA 

       190        200        210        220        230 
CDIYIWAPLA GTCGVLLLSL VITLYCNHRN RRRVCKCPRP VVKSGDKPSL SARYV

« Hide

Isoform 2 (secreted) (sCD8alpha) [UniParc].

Checksum: BC89FA59F150598F
Show »

19821,585

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References

[1]"The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes."
Littman D.R., Thomas Y., Maddon P.J., Chess L., Axel R.
Cell 40:237-246(1985) [PubMed: 3871356] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Structure of Leu-2/T8 as deduced from the sequence of a cDNA clone."
Parnes J.R., Sizer K.C., Sukhatme V.P., Hunkapiller T.
Behring Inst. Mitt. 77:48-55(1985) [PubMed: 3936473] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[3]"The T cell differentiation antigen Leu-2/T8 is homologous to immunoglobulin and T cell receptor variable regions."
Sukhatme V.P., Sizer K.C., Vollmer A.C., Hunkapiller T., Parnes J.R.
Cell 40:591-597(1985) [PubMed: 3918796] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Structure and expression of the gene encoding CD8 alpha chain (Leu-2/T8)."
Nakayama K., Tokito S., Okumura K., Nakauchi H.
Immunogenetics 30:393-397(1989) [PubMed: 2509342] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Alternatively spliced mRNA encodes a secreted form of human CD8 alpha. Characterization of the human CD8 alpha gene."
Norment A.M., Lonberg N., Lacy E., Littman D.R.
J. Immunol. 142:3312-3319(1989) [PubMed: 2496167] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[6]"A secreted form of the human lymphocyte cell surface molecule CD8 arises from alternative splicing."
Giblin P., Ledbetter J.A., Kavathas P.
Proc. Natl. Acad. Sci. U.S.A. 86:998-1002(1989) [PubMed: 2536941] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 168-235 (ISOFORMS 1 AND 2).
[7]"The T8 antigen is a multimeric complex of two distinct subunits on human thymocytes but consists of homomultimeric forms on peripheral blood T lymphocytes."
Snow P.M., Terhorst C.
J. Biol. Chem. 258:14675-14681(1983) [PubMed: 6605969] [Abstract]
Cited for: SUBUNIT.
[8]"Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6-A resolution."
Leahy D.J., Axel R., Hendrickson W.A.
Cell 68:1145-1162(1992) [PubMed: 1547508] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 22-135.
[9]"Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2."
Gao G.F., Tormo J., Gerth U.C., Wyer J.R., McMichael A.J., Stuart D.I., Bell J.I., Jones E.Y., Jakobsen B.K.
Nature 387:630-634(1997) [PubMed: 9177355] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 22-141 IN COMPLEX WITH HLA-A/B2M DIMER.
[10]"A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8."
Kim P.W., Sun Z.Y., Blacklow S.C., Wagner G., Eck M.J.
Science 301:1725-1728(2003) [PubMed: 14500983] [Abstract]
Cited for: STRUCTURE BY NMR OF 209-227 IN COMPLEX WITH LCK.
[11]"Familial CD8 deficiency due to a mutation in the CD8 alpha gene."
de la Calle-Martin O., Hernandez M., Ordi J., Casamitjana N., Arostegui J.I., Caragol I., Ferrando M., Labrador M., Rodriguez-Sanchez J.L., Espanol T.
J. Clin. Invest. 108:117-123(2001) [PubMed: 11435463] [Abstract]
Cited for: VARIANT CD8 DEFICIENCY SER-111, MUTAGENESIS OF GLY-111.
+Additional computationally mapped references.

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Web resources

CD8Abase

CD8A mutation db

Wikipedia

CD8 entry

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Cross-references

Sequence databases

M26315, M26313, M26314 Genomic DNA. Translation: AAA79217.1.
M26315, M26313, M26314 Genomic DNA. Translation: AAA79218.1.
M12824 mRNA. Translation: AAA61133.1.
M12828 mRNA. Translation: AAB04637.1.
M27161 Genomic DNA. Translation: AAA59674.1.
PIRRWHUT8. A30604.
RefSeqNP_001759.3.
UniGeneHs.85258

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1AKJX-ray2.65D/E22-141[»]
1CD8X-ray2.60A22-135[»]
1Q69NMR-A209-227[»]
2HP4X-ray2.10A/B22-135[»]
ModBaseSearch...

Genome annotation databases

EnsemblENSG00000153563. Homo sapiens. [Contig view]
GeneID925.
KEGGhsa:925.

Organism-specific databases

H-InvDBHIX0002241.
HGNCHGNC:1706. CD8A.
HPACAB000012.
MIM186910. gene.
608957. phenotype.
PharmGKBPA26244.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP01732.
HOVERGENP01732.

Enzyme and pathway databases

ReactomeREACT_6900. Signaling in Immune System.

Gene expression databases

ArrayExpressP01732.
CleanExHS_CD8A.
HS_MAL.
GermOnlineENSG00000153563. Homo sapiens.

Family and domain databases

InterProIPR015468. CD8_alpha.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
IPR003596. Ig_V-set_sub.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 1 hit.
PANTHERPTHR10441. CD8_alpha. 1 hit.
PfamPF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00406. IGv. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
[Graphical view]
BLOCKSSearch...

Other Resources

LinkHubP01732.
SOURCESearch...
ProtoNetSearch...

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Entry information

Entry nameCD8A_HUMAN
AccessionPrimary (citable) accession number: P01732
Secondary accession number(s): Q13970
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 22, 2008
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

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

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents