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P01732 (CD8A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

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) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

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 heterodimer 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. Ref.9

Subcellular location

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

Isoform 2: Secreted.

Post-translational modification

All of the five most C-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

CD8 deficiency, familial (CD8 deficiency) [MIM:608957]: An immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

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

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainImmunoglobulin domain
Signal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Non-traceable author statement PubMed 9830036. Source: UniProtKB

T cell mediated immunity

Inferred from electronic annotation. Source: Ensembl

antigen processing and presentation

Non-traceable author statement Ref.5. Source: UniProtKB

cytotoxic T cell differentiation

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from electronic annotation. Source: Ensembl

immune response

Non-traceable author statement PubMed 11131152. Source: UniProtKB

positive regulation of calcium-mediated signaling

Inferred from electronic annotation. Source: Ensembl

regulation of immune response

Traceable author statement. Source: Reactome

transmembrane receptor protein tyrosine kinase signaling pathway

Non-traceable author statement PubMed 9830036. Source: UniProtKB

   Cellular_componentT cell receptor complex

Non-traceable author statement PubMed 11131152. Source: UniProtKB

external side of plasma membrane

Inferred from direct assay PubMed 17213291. Source: MGI

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Non-traceable author statement Ref.5. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionMHC class I protein binding

Non-traceable author statement PubMed 11131152. Source: UniProtKB

coreceptor activity

Non-traceable author statement PubMed 11131152. Source: UniProtKB

Complete GO annotation...

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Chain22 – 235214T-cell surface glycoprotein CD8 alpha chain
PRO_0000014638

Regions

Topological domain22 – 182161Extracellular Potential
Transmembrane183 – 20321Helical; 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.
VSP_012653
Natural variant1111G → S in CD8 deficiency; prevents CD8 expression. Ref.13
VAR_021020

Experimental info

Mutagenesis1111G → R: Prevents CD8 expression. Ref.13

Secondary structure

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

Details...

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 »

FASTA19821,585

References

« Hide 'large scale' 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[6]"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. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 168-235 (ISOFORMS 1 AND 2).
[9]"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] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[10]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 22-135.
[11]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 22-141 IN COMPLEX WITH HLA-A/B2M DIMER.
[12]"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] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 209-227 IN COMPLEX WITH LCK.
[13]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CD8 DEFICIENCY SER-111, MUTAGENESIS OF GLY-111.
+Additional computationally mapped references.

Web resources

CD8Abase

CD8A mutation db

Wikipedia

CD8 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AC064848 Genomic DNA. Translation: AAX88864.1.
CH471053 Genomic DNA. Translation: EAW99438.1.
CH471053 Genomic DNA. Translation: EAW99439.1.
CH471053 Genomic DNA. Translation: EAW99440.1.
PIRRWHUT8. A30604.
RefSeqNP_001139345.1. NM_001145873.1.
NP_001759.3. NM_001768.6.
NP_741969.1. NM_171827.3.
UniGeneHs.85258.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AKJX-ray2.65D/E22-141[»]
1CD8X-ray2.60A22-135[»]
1Q69NMR-A209-227[»]
2HP4X-ray2.10A/B22-135[»]
3QZWX-ray2.80G/H/I/J22-135[»]
ProteinModelPortalP01732.
SMRP01732. Positions 22-135.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107363. 14 interactions.
IntActP01732. 4 interactions.
STRING9606.ENSP00000283635.

PTM databases

PhosphoSiteP01732.

Polymorphism databases

DMDM116035.

Proteomic databases

PaxDbP01732.
PRIDEP01732.

Protocols and materials databases

DNASU925.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000283635; ENSP00000283635; ENSG00000153563. [P01732-1]
ENST00000352580; ENSP00000321631; ENSG00000153563. [P01732-2]
ENST00000409511; ENSP00000386559; ENSG00000153563. [P01732-1]
ENST00000456996; ENSP00000398868; ENSG00000153563. [P01732-2]
GeneID925.
KEGGhsa:925.
UCSCuc002srt.3. human. [P01732-1]
uc002sru.3. human. [P01732-2]

Organism-specific databases

CTD925.
GeneCardsGC02M086923.
HGNCHGNC:1706. CD8A.
HPACAB000012.
HPA037756.
MIM186910. gene.
608957. phenotype.
neXtProtNX_P01732.
Orphanet169085. Susceptibility to respiratory infections associated with CD8alpha chain mutation.
PharmGKBPA26244.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46810.
HOGENOMHOG000004794.
HOVERGENHBG008488.
InParanoidP01732.
KOK06458.
OrthoDBEOG7N37F3.
PhylomeDBP01732.
TreeFamTF336070.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP01732.
BgeeP01732.
CleanExHS_CD8A.
HS_MAL.
GenevestigatorP01732.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR015468. CD8_asu.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
IPR003596. Ig_V-set_subgr.
[Graphical view]
PANTHERPTHR10441. PTHR10441. 1 hit.
PfamPF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00406. IGv. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01732.
GeneWikiCD8A.
GenomeRNAi925.
NextBio3826.
PROP01732.
SOURCESearch...

Entry information

Entry nameCD8A_HUMAN
AccessionPrimary (citable) accession number: P01732
Secondary accession number(s): D6W5M8, Q13970, Q4ZG17
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 162 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

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

Human cell differentiation molecules

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