SLC7A11 solute carrier family 7 member 11 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC7A11provided by HGNC
Official Full Name: solute carrier family 7 member 11provided by HGNC
Primary source: HGNC:HGNC:11059
See related: Ensembl:ENSG00000151012 MIM:607933
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: xCT; CCBR1
Summary: This gene encodes a member of a heteromeric, sodium-independent, anionic amino acid transport system that is highly specific for cysteine and glutamate. In this system, designated Xc(-), the anionic form of cysteine is transported in exchange for glutamate. This protein has been identified as the predominant mediator of Kaposi sarcoma-associated herpesvirus fusion and entry permissiveness into cells. Also, increased expression of this gene in primary gliomas (compared to normal brain tissue) was associated with increased glutamate secretion via the XCT channels, resulting in neuronal cell death. [provided by RefSeq, Sep 2011]
Expression: Biased expression in brain (RPKM 12.7), thyroid (RPKM 4.9) and 8 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 4q28.3

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	4	NC_000004.12 (138164097..138242349, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (139085248..139163572, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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?

The results identify a coupling between SLC7A11-associated cystine metabolism and the pentose phosphate pathway, and uncover an accompanying metabolic vulnerability for therapeutic targeting in SLC7A11-high cancers.
Title: Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer.
Cystine and glutamate bind xCT with favorable binding energies.
Title: In silico characterization of residues essential for substrate binding of human cystine transporter, xCT.
The expression of SLC7A11, but not of the other genes, was significantly higher in melanoma patients than in healthy individuals.
Title: High SLC7A11 expression in normal skin of melanoma patients.
Identification of drugs for combination with xCT inhibitors that are able to overcome resistance to xCT-targeted therapy .
Title: Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy.
This study demonstrated that xCT knockdown in human breast cancer cells delays onset of cancer-induced bone pain.
Title: xCT knockdown in human breast cancer cells delays onset of cancer-induced bone pain.
CD44v overexpression is not involved in cancer stem cell properties but increases xCT expression, which leads to the acquisition of Cisplatin-resistance.
Title: CD44v-dependent upregulation of xCT is involved in the acquisition of cisplatin-resistance in human lung cancer A549 cells.
Smoking could induce the expression of xCT (SLC7A11) in oral cancer cells.
Title: xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression.
Studies indicate that SLC7A11 plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.
Title: Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer.
In a multivariate analysis, high xCT expression and WHO tumor grade but not IDH1 R132H mutation, were significantly associated with epileptic seizures at diagnosis.
Title: High expression of cystine-glutamate antiporter xCT (SLC7A11) is an independent biomarker for epileptic seizures at diagnosis in glioma.
Results showed that xCT-mediated glutamate release promotes glioma cell migration via N-methyl-d- aspartate- sensitive glutamate receptor signaling.
Title: Epidermal growth factor receptor promotes glioma progression by regulating xCT and GluN2B-containing N-methyl-d-aspartate-sensitive glutamate receptor signaling.

Submit: New GeneRIF Correction See all GeneRIFs (69)

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

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
Tat	tat	HIV-1 Tat upregulates the expression of solute carrier family 7, member 11 (SLC7A11) in human primary T cells	PubMed
	tat	HIV-1 Tat-induced glutamate release is mediated through p38 and p42/44 MAPK and through NADPH oxidase and the x(c)(-) cystine-glutamate antiporter (xCT)	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

SHGC-51593 (e-PCR)
- UniSTS:57862

D4S265 (e-PCR)
- UniSTS:16904

D4S3103 (e-PCR)
- UniSTS:22797

D8S2279 (e-PCR)
- UniSTS:473907

L18426 (e-PCR)
- UniSTS:34648

D15S1477 (e-PCR)
- UniSTS:474482

RH36905 (e-PCR)
- UniSTS:87932

RH121262 (e-PCR)
- UniSTS:138373

RH36112 (e-PCR)
- UniSTS:55259

Homology

Homologs of the SLC7A11 gene: The SLC7A11 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 304 organisms have orthologs with human gene SLC7A11
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
L-amino acid transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cystine:glutamate antiporter activity	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
L-glutamate import across plasma membrane	IEA Inferred from Electronic Annotation more info
adult behavior	IEA Inferred from Electronic Annotation more info
amino acid transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
amino acid transport	TAS Traceable Author Statement more info
cellular response to oxidative stress	IEA Inferred from Electronic Annotation more info
dipeptide import across plasma membrane	IEA Inferred from Electronic Annotation more info
glutamate homeostasis	IEA Inferred from Electronic Annotation more info
glutathione metabolic process	IEA Inferred from Electronic Annotation more info
glutathione transmembrane transport	IEA Inferred from Electronic Annotation more info
lens fiber cell differentiation	IEA Inferred from Electronic Annotation more info
leukocyte migration	TAS Traceable Author Statement more info
limb development	IEA Inferred from Electronic Annotation more info
lung alveolus development	IEA Inferred from Electronic Annotation more info
modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
negative regulation of oxidative stress-induced neuron death	IEA Inferred from Electronic Annotation more info
platelet aggregation	IEA Inferred from Electronic Annotation more info
regulation of AMPA glutamate receptor clustering	IEA Inferred from Electronic Annotation more info
regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
regulation of cysteine metabolic process	IEA Inferred from Electronic Annotation more info
regulation of glutamate metabolic process	IEA Inferred from Electronic Annotation more info
regulation of glutathione biosynthetic process	IEA Inferred from Electronic Annotation more info
regulation of melanin biosynthetic process	IEA Inferred from Electronic Annotation more info
regulation of neutrophil apoptotic process	IEA Inferred from Electronic Annotation more info
regulation of protein transport	IEA Inferred from Electronic Annotation more info
response to nicotine	IEA Inferred from Electronic Annotation more info
response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
response to redox state	IEA Inferred from Electronic Annotation more info
response to toxic substance	IDA Inferred from Direct Assay more info	PubMed
striatum development	IEA Inferred from Electronic Annotation more info
ventricular system development	IEA Inferred from Electronic Annotation more info
visual learning	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
apical part of cell	IEA Inferred from Electronic Annotation more info
astrocyte projection	IEA Inferred from Electronic Annotation more info
brush border membrane	IEA Inferred from Electronic Annotation more info
cell surface	IDA Inferred from Direct Assay more info	PubMed
cytoskeleton	IEA Inferred from Electronic Annotation more info
integral component of membrane	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info
rough endoplasmic reticulum	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: cystine/glutamate transporter

Names: amino acid transport system xc-; calcium channel blocker resistance protein CCBR1; solute carrier family 7 (anionic amino acid transporter light chain, xc- system), member 11; solute carrier family 7, (cationic amino acid transporter, y+ system) member 11

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.

mRNA and Protein(s)

NM_014331.4 → NP_055146.1 cystine/glutamate transporter

See identical proteins and their annotated locations for NP_055146.1

Status: VALIDATED

Source sequence(s)

AC093903, AC110804, AC116610

Consensus CDS

CCDS3742.1

UniProtKB/Swiss-Prot

Q9UPY5

Related

ENSP00000280612.5, ENST00000280612.9

Conserved Domains (1) summary

TIGR00911
Location:1 → 499

2A0308; L-type amino acid transporter

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p13 Primary Assembly

Range

138164097..138242349 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011531802.3 → XP_011530104.1 cystine/glutamate transporter isoform X1

Conserved Domains (1) summary

TIGR00911
Location:1 → 483

2A0308; L-type amino acid transporter