CD8A CD8 subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: CD8Aprovided by HGNC
Official Full Name: CD8 subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:1706
See related: Ensembl:ENSG00000153563 MIM:186910; AllianceGenome:HGNC:1706
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CD8; p32; Leu2; IMD116; CD8alpha
Summary: The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 antigen acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class I MHC molecules. The coreceptor functions as either a homodimer composed of two alpha chains or as a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. This gene encodes the CD8 alpha chain. Multiple transcript variants encoding different isoforms have been found for this gene. The major protein isoforms of this gene differ by the presence or absence of a transmembrane domain and thus differ in being a membrane-anchored or secreted protein. [provided by RefSeq, May 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for COVID-19 prognosis.
Expression: Biased expression in spleen (RPKM 38.0), lymph node (RPKM 12.5) and 8 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p11.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (86784605..86808396, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (86786504..86810303, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (87011728..87035519, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Joint effects of CD8A and ICOS in Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS).
Title: Joint effects of CD8A and ICOS in Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS).
Induced CD8alpha identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation.
Title: Induced CD8α identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation.
Striking a balance: the Goldilocks effect of CD8alpha expression on NK cells.
Title: Striking a balance: the Goldilocks effect of CD8α expression on NK cells.
Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked Parkinson's disease phenotypes in vivo and in cell models.
Title: Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked Parkinson's disease phenotypes in vivo and in cell models.
The Role of CD8A in the Immune Microenvironment of Breast Cancer.
Title: The Role of CD8A in the Immune Microenvironment of Breast Cancer.
Unraveling the potential of CD8, CD68, and VISTA as diagnostic and prognostic markers in patients with pancreatic ductal adenocarcinoma.
Title: Unraveling the potential of CD8, CD68, and VISTA as diagnostic and prognostic markers in patients with pancreatic ductal adenocarcinoma.
The relationship between high ratios of CD4/FOXP3 and CD8/CD163 and the improved survivability of metastatic triple-negative breast cancer patients: a multicenter cohort study.
Title: The relationship between high ratios of CD4/FOXP3 and CD8/CD163 and the improved survivability of metastatic triple-negative breast cancer patients: a multicenter cohort study.
Granulocyte transfusion during cord blood transplant for relapsed, refractory AML is associated with massive CD8[+] T-cell expansion, significant cytokine release syndrome and induction of disease remission.
Title: Granulocyte transfusion during cord blood transplant for relapsed, refractory AML is associated with massive CD8(+) T-cell expansion, significant cytokine release syndrome and induction of disease remission.
Shaping immunity for life: Layered development of CD8[+] T cells.
Title: Shaping immunity for life: Layered development of CD8(+) T cells.
Clonally expanded, thyrotoxic effector CD8[+] T cells driven by IL-21 contribute to checkpoint inhibitor thyroiditis.
Title: Clonally expanded, thyrotoxic effector CD8(+) T cells driven by IL-21 contribute to checkpoint inhibitor thyroiditis.

Submit: New GeneRIF Correction See all GeneRIFs (97)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Susceptibility to respiratory infections associated with CD8alpha chain mutation MedGen: C1837065 OMIM: 608957 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-infected cells are responsible for higher IL-10 secretion after activation, which serves as one of the reasons for suppressed CD8 responses to HIV-1 Pol and Env	PubMed
Envelope transmembrane glycoprotein gp41	env	HIV-1 gp41 cytoplasmic tail length determines interaction with CD8A; the presence of an amphipathic sequence in the HIV-1 Env cytoplasmic tail possibly modulates viral receptor specificity by inducing conformational changes in gp120	PubMed
Nef	nef	HIV-1 Nef co-localizes with CD8-CD3 zeta on the HEK293 cell surface	PubMed
	nef	beta-COP as a cellular cofactor is required for HIV-1 Nef-mediated HLA-A2, CD4, and CD8 downregulation	PubMed
	nef	HIV-inoculated and HIV-1 Nef-treated human peripheral blood lymphocytes downregulate cell surface CD8, and this down-modulation could inhibit anti-HIV cytotoxicity associated with cytotoxic T-cell function	PubMed
Pol	gag-pol	HIV-infected cells are responsible for higher IL-10 secretion after activation, which serves as one of the reasons for suppressed CD8 responses to HIV-1 Pol and Env	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:181237 (e-PCR)
- UniSTS:155205

D2S2642 (e-PCR)
- UniSTS:65124

SHGC-6997 (e-PCR)
- UniSTS:10470

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MHC class I protein binding	NAS Non-traceable Author Statement more info	PubMed
enables MHC class I protein complex binding	IDA Inferred from Direct Assay more info	PubMed
enables coreceptor activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in T cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in T cell activation	NAS Non-traceable Author Statement more info	PubMed
involved_in T cell mediated immunity	IBA Inferred from Biological aspect of Ancestor more info
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in adaptive immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in antigen processing and presentation	NAS Non-traceable Author Statement more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cytotoxic T cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of T cell receptor complex	NAS Non-traceable Author Statement more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in plasma membrane raft	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	IPI Inferred from Physical Interaction more info	PubMed
part_of receptor complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: T-cell surface glycoprotein CD8 alpha chain

Names: CD8 antigen, alpha polypeptide (p32); CD8a molecule; Leu2 T-lymphocyte antigen; OKT8 T-cell antigen; T cell co-receptor; T-cell antigen Leu2; T-lymphocyte differentiation antigen T8/Leu-2; T8 T-cell antigen

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011608.2 RefSeqGene

Range

5001..28792

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_44

mRNA and Protein(s)

NM_001145873.1 → NP_001139345.1 T-cell surface glycoprotein CD8 alpha chain isoform 1 precursor

See identical proteins and their annotated locations for NP_001139345.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) represents use of an alternate promoter and 5' UTR, compared to variant 1. Both variants 1 and 3 encode the longer, membrane associated isoform (1).

Source sequence(s)

AA668685, AK124156, BC025715, DA075688

Consensus CDS

CCDS1992.1

UniProtKB/Swiss-Prot

B4DT80, D6W5M8, P01732, Q13970, Q4ZG17

UniProtKB/TrEMBL

Q8TAW8, Q96QR6

Related

ENSP00000386559.2, ENST00000409511.6

Conserved Domains (1) summary

cd05720
Location:24 → 133

IgV_CD8_alpha; Immunoglobulin (Ig)-like variable (V) domain of Cluster of Differentiation (CD) 8 alpha chain
NM_001382698.1 → NP_001369627.1 T-cell surface glycoprotein CD8 alpha chain isoform 1 precursor

Status: REVIEWED

Source sequence(s)

AC064848, AC112696

Consensus CDS

CCDS1992.1

UniProtKB/Swiss-Prot

B4DT80, D6W5M8, P01732, Q13970, Q4ZG17

UniProtKB/TrEMBL

Q8TAW8, Q96QR6

Conserved Domains (1) summary

cd05720
Location:24 → 133

IgV_CD8_alpha; Immunoglobulin (Ig)-like variable (V) domain of Cluster of Differentiation (CD) 8 alpha chain
NM_001768.7 → NP_001759.3 T-cell surface glycoprotein CD8 alpha chain isoform 1 precursor

See identical proteins and their annotated locations for NP_001759.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer, membrane associated isoform (1). Both variants 1 and 3 encode the same isoform (1).

Source sequence(s)

AC064848, AK124156, BC025715

Consensus CDS

CCDS1992.1

UniProtKB/Swiss-Prot

B4DT80, D6W5M8, P01732, Q13970, Q4ZG17

UniProtKB/TrEMBL

Q8TAW8, Q96QR6

Related

ENSP00000283635.3, ENST00000283635.8

Conserved Domains (1) summary

cd05720
Location:24 → 133

IgV_CD8_alpha; Immunoglobulin (Ig)-like variable (V) domain of Cluster of Differentiation (CD) 8 alpha chain
NM_171827.4 → NP_741969.1 T-cell surface glycoprotein CD8 alpha chain isoform 2 precursor

See identical proteins and their annotated locations for NP_741969.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting protein (isoform 2) lacks an internal segment including the transmembrane domain compared to isoform 1, resulting in a secreted protein.

Source sequence(s)

AC064848

Consensus CDS

CCDS1993.1

UniProtKB/TrEMBL

Q8TAW8, Q96QR6

Related

ENSP00000321631.3, ENST00000352580.7

Conserved Domains (2) summary

cd05720
Location:31 → 133

Ig_CD8_alpha; Immunoglobulin (Ig) like domain of CD8 alpha chain

smart00410
Location:28 → 128

IG_like; Immunoglobulin like

RNA

NR_027353.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate 5' splice pattern, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC064848, AK300089, BC025715
NR_168478.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC064848, AC112696
NR_168479.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC064848, AC112696
NR_168480.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC064848, AC112696
NR_168481.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC064848, AC112696

Related

ENST00000699437.1