IREB2

Protein identityUniProt · HPA

UniProt accession

P48200

Gene

IREB2

Ensembl

ENSG00000136381

Chromosome

15

Canonical length

963 aa

Protein class

Disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Cell Junctions,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is an RNA-binding protein that acts to regulate iron levels in the cells by regulating the translation and stability of mRNAs that affect iron homeostasis under conditions when iron is depleted. When iron levels are low, this protein binds to iron-responsive elements (IRES), stem-loop structures located either in the 5' or 3' UTRs. Binding to the 5' UTR represses translation, while binding to the 3' UTR inhibits mRNA degradation. When iron is found in the cell, this protein is degraded in a F-box and leucine rich repeat protein 5-dependent manner. Variants in this gene have been associated with lung cancer and chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

963 residues, UniProt reviewed canonical sequence.

>P48200|IREB2
     1  MDAPKAGYAF EYLIETLNDS SHKKFFDVSK LGTKYDVLPY SIRVLLEAAV RNCDGFLMKK
    61  EDVMNILDWK TKQSNVEVPF FPARVLLQDF TGIPAMVDFA AMREAVKTLG GDPEKVHPAC
   121  PTDLTVDHSL QIDFSKCAIQ NAPNPGGGDL QKAGKLSPLK VQPKKLPCRG QTTCRGSCDS
   181  GELGRNSGTF SSQIENTPIL CPFHLQPVPE PETVLKNQEV EFGRNRERLQ FFKWSSRVFK
   241  NVAVIPPGTG MAHQINLEYL SRVVFEEKDL LFPDSVVGTD SHITMVNGLG ILGWGVGGIE
   301  TEAVMLGLPV SLTLPEVVGC ELTGSSNPFV TSIDVVLGIT KHLRQVGVAG KFVEFFGSGV
   361  SQLSIVDRTT IANMCPEYGA ILSFFPVDNV TLKHLEHTGF SKAKLESMET YLKAVKLFRN
   421  DQNSSGEPEY SQVIQINLNS IVPSVSGPKR PQDRVAVTDM KSDFQACLNE KVGFKGFQIA
   481  AEKQKDIVSI HYEGSEYKLS HGSVVIAAVI SCTNNCNPSV MLAAGLLAKK AVEAGLRVKP
   541  YIRTSLSPGS GMVTHYLSSS GVLPYLSKLG FEIVGYGCSI CVGNTAPLSD AVLNAVKQGD
   601  LVTCGILSGN KNFEGRLCDC VRANYLASPP LVVAYAIAGT VNIDFQTEPL GTDPTGKNIY
   661  LHDIWPSREE VHRVEEEHVI LSMFKALKDK IEMGNKRWNS LEAPDSVLFP WDLKSTYIRC
   721  PSFFDKLTKE PIALQAIENA HVLLYLGDSV TTDHISPAGS IARNSAAAKY LTNRGLTPRE
   781  FNSYGARRGN DAVMTRGTFA NIKLFNKFIG KPAPKTIHFP SGQTLDVFEA AELYQKEGIP
   841  LIILAGKKYG SGNSRDWAAK GPYLLGVKAV LAESYEKIHK DHLIGIGIAP LQFLPGENAD
   901  SLGLSGRETF SLTFPEELSP GITLNIQTST GKVFSVIASF EDDVEITLYK HGGLLNFVAR
   961  KFS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IREB2 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)

0.23

Highest tissue expression

28 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IREB2.

Disease | AllUniProt

Conditions IREB2 is implicated in, by any mechanism.

• Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia (NDCAMA) MIM:618451

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 300 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• NEURODEGENERATION, EARLY-ONSET, WITH CHOREOATHETOSIS AND MICROCYTIC ANEMIA
• Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia

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)

0.22

gnomAD pLI

1

gnomAD missense Z

2.03

DepMap mean gene effect

-0.3

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• erythrocyte homeostasis
• intestinal absorption
• intracellular iron ion homeostasis
• mRNA stabilization
• multicellular organismal-level iron ion homeostasis
• osteoclast differentiation
• post-embryonic development
• protoporphyrinogen IX biosynthetic process

Molecular functions

• 4 iron, 4 sulfur cluster binding
• aconitate hydratase activity
• iron-responsive element binding
• metal ion binding
• mRNA regulatory element binding translation repressor activity
• RNA binding

Cellular components

• cytoplasm
• cytosol

Protein domainsUniProt · Pfam · InterPro

• Aconitase A/isopropylmalate dehydratase small subunit, swivel domain
• Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
• Aconitase/Iron-responsive element-binding protein 2
• Aconitase/3-isopropylmalate dehydratase, swivel
• Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
• Aconitase family, 4Fe-4S cluster binding site
• Aconitase, iron-sulfur domain
• Aconitase A, swivel domain
• Aconitase family (aconitate hydratase)
• Aconitase C-terminal domain

KeywordsUniProt

• 4Fe-4S
• Cytoplasm
• Iron
• Iron-sulfur
• Metal-binding
• Neurodegeneration
• RNA-binding
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of IREB2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CIAO1
• CIAO2A
• TFRC