NR1I2

Protein identityUniProt · HPA

UniProt accession

O75469

Gene

NR1I2

Ensembl

ENSG00000144852

Chromosome

3

Canonical length

434 aa

Protein class

FDA approved drug targets, Nuclear receptors, Plasma proteins, Predicted intracellular proteins, Transcription factors, Transporters

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene product belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

434 residues, UniProt reviewed canonical sequence.

>O75469|NR1I2
     1  MEVRPKESWN HADFVHCEDT ESVPGKPSVN ADEEVGGPQI CRVCGDKATG YHFNVMTCEG
    61  CKGFFRRAMK RNARLRCPFR KGACEITRKT RRQCQACRLR KCLESGMKKE MIMSDEAVEE
   121  RRALIKRKKS ERTGTQPLGV QGLTEEQRMM IRELMDAQMK TFDTTFSHFK NFRLPGVLSS
   181  GCELPESLQA PSREEAAKWS QVRKDLCSLK VSLQLRGEDG SVWNYKPPAD SGGKEIFSLL
   241  PHMADMSTYM FKGIISFAKV ISYFRDLPIE DQISLLKGAA FELCQLRFNT VFNAETGTWE
   301  CGRLSYCLED TAGGFQQLLL EPMLKFHYML KKLQLHEEEY VLMQAISLFS PDRPGVLQHR
   361  VVDQLQEQFA ITLKSYIECN RPQPAHRFLF LKIMAMLTEL RSINAQHTQR LLRIQDIHPF
   421  ATPLMQELFG ITGS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NR1I2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

44 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.17

gnomAD pLI

0

gnomAD missense Z

-0.62

DepMap mean gene effect

0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell differentiation
• cellular response to molecule of bacterial origin
• gene expression
• intestinal epithelial structure maintenance
• intracellular receptor signaling pathway
• negative regulation of DNA-templated transcription
• negative regulation of transcription by RNA polymerase II
• positive regulation of DNA-templated transcription
• positive regulation of gene expression
• positive regulation of transcription by RNA polymerase II
• regulation of DNA-templated transcription
• signal transduction
• steroid metabolic process
• xenobiotic catabolic process
• xenobiotic metabolic process
• xenobiotic transport

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• nuclear receptor activity
• nuclear receptor binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• zinc ion binding

Cellular components

• chromatin
• intermediate filament cytoskeleton
• nuclear body
• nucleoplasm
• nucleus
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Nuclear hormone receptor, ligand-binding domain
• Zinc finger, nuclear hormone receptor-type
• Nuclear hormone receptor
• Zinc finger, NHR/GATA-type
• Nuclear hormone receptor-like domain superfamily
• Nuclear hormone receptor family NR1 subfamily
• Ligand-binding domain of nuclear hormone receptor
• Double treble clef zinc finger, C4 type

KeywordsUniProt

• Activator
• Cytoplasm
• DNA-binding
• Metal-binding
• Nucleus
• Phosphoprotein
• Receptor
• Transcription
• Transcription regulation
• Ubl conjugation
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of NR1I2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FBXO44
• NCOA1
• SIRT1