P01732 (CD8A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	235 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Familial CD8 deficiency (CD8 deficiency) [MIM:608957]: Novel autosomal recessive 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 process	Adaptive immunity Immunity
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell activation Non-traceable author statement PubMed 9830036. Source: UniProtKB T cell mediated immunity Inferred from electronic annotation. Source: Compara antigen processing and presentation Non-traceable author statement Ref.5. Source: UniProtKB cytotoxic T cell differentiation Inferred from electronic annotation. Source: Compara defense response to virus Inferred from electronic annotation. Source: Compara immune response Non-traceable author statement PubMed 11131152. Source: UniProtKB positive regulation of calcium-mediated signaling Inferred from electronic annotation. Source: Compara 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_component	T 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 to plasma membrane Non-traceable author statement Ref.5. Source: UniProtKB
Molecular_function	MHC 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 235

214

T-cell surface glycoprotein CD8 alpha chain

PRO_0000014638

Regions

Topological domain

22 – 182

161

Extracellular Potential

Transmembrane

183 – 203

21

Helical; Potential

Topological domain

204 – 235

32

Cytoplasmic Potential

Domain

22 – 135

114

Ig-like V-type

Amino acid modifications

Disulfide bond

43 ↔ 115

Natural variations

Alternative sequence

172 – 209

38

VHTRG…YCNHR → G in isoform 2.

VSP_012653

Natural variant

111

1

G → S in CD8 deficiency; prevents CD8 expression. Ref.13

VAR_021020

Experimental info

Mutagenesis

111

1

G → R: Prevents CD8 expression. Ref.13

Secondary structure

1

.

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.

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235

Helix Strand Turn

Details...

Beta strand

24 – 27

4

Beta strand

39 – 45

7

Beta strand

54 – 64

11

Beta strand

68 – 77

10

Turn

86 – 88

3

Beta strand

89 – 94

6

Beta strand

97 – 104

8

Helix

107 – 109

3

Beta strand

111 – 119

9

Beta strand

122 – 125

4

Beta strand

129 – 131

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (membrane) (mCD8alpha) [UniParc]. Last modified July 21, 1986. Version 1. Checksum: FCCA29BAA73726BB	FASTA	235	25,729
	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
	Isoform 2 (secreted) (sCD8alpha) [UniParc]. Checksum: BC89FA59F150598F	FASTA	198	21,585
	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 AGNRRRVCKC 190 PRPVVKSGDK PSLSARYV

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00016781.
IPI00941413.

PIR

RWHUT8. A30604.

RefSeq

NP_001139345.1. NM_001145873.1.
NP_001759.3. NM_001768.6.
NP_741969.1. NM_171827.3.

UniGene

Hs.85258.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AKJ	X-ray	2.65	D/E	22-141	[»]
1CD8	X-ray	2.60	A	22-135	[»]
1Q69	NMR	-	A	209-227	[»]
2HP4	X-ray	2.10	A/B	22-135	[»]
3QZW	X-ray	2.80	G/H/I/J	22-135	[»]

ProteinModelPortal

P01732.

ModBase

Search...

Protein-protein interaction databases

IntAct

P01732. 4 interactions.

STRING

9606.ENSP00000283635.

PTM databases

PhosphoSite

P01732.

Polymorphism databases

DMDM

116035.

Proteomic databases

PaxDb

P01732.

PRIDE

P01732.

Protocols and materials databases

DNASU

925.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000283635; ENSP00000283635; ENSG00000153563.
ENST00000352580; ENSP00000321631; ENSG00000153563.
ENST00000409511; ENSP00000386559; ENSG00000153563.
ENST00000456996; ENSP00000398868; ENSG00000153563.

GeneID

925.

KEGG

hsa:925.

UCSC

uc002srt.3. human.
uc002sru.3. human.

Organism-specific databases

CTD

925.

GeneCards

GC02M086923.

HGNC

HGNC:1706. CD8A.

HPA

CAB000012.

MIM

186910. gene.
608957. phenotype.

neXtProt

NX_P01732.

Orphanet

169085. Susceptibility to respiratory infections associated with CD8alpha chain mutation.

PharmGKB

PA26244.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46810.

HOGENOM

HOG000004794.

HOVERGEN

HBG008488.

InParanoid

P01732.

KO

K06458.

OrthoDB

EOG4JDH84.

PhylomeDB

P01732.

Enzyme and pathway databases

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
il12_2pathway. IL12-mediated signaling events.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P01732.

Bgee

P01732.

CleanEx

HS_CD8A.
HS_MAL.

Genevestigator

P01732.

GermOnline

ENSG00000153563. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR015468. CD8_asu.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
IPR003596. Ig_V-set_subgr.
[Graphical view]

PANTHER

PTHR10441. PTHR10441. 1 hit.

Pfam

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

SMART

SM00406. IGv. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P01732.

GenomeRNAi

925.

NextBio

3826.

SOURCE

Search...

Entry information

Entry name

CD8A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 153 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.