CRABP1

Last updated
CRABP1
Protein CRABP1 PDB 1cbi.png
Identifiers
Aliases CRABP1 , CRABP, CRABP-I, CRABPI, RBP5, cellular retinoic acid binding protein 1
External IDs OMIM: 180230 MGI: 88490 HomoloGene: 3222 GeneCards: CRABP1
Orthologs
SpeciesHumanMouse
Entrez

1381

12903

Ensembl

ENSG00000166426

ENSMUSG00000032291

UniProt

P29762

P62965

RefSeq (mRNA)

NM_004378

NM_001284507
NM_013496

RefSeq (protein)

NP_004369

NP_001271436
NP_038524

Location (UCSC) Chr 15: 78.34 – 78.35 Mb Chr 9: 54.76 – 54.77 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cellular retinoic acid-binding protein 1 is a protein that in humans is encoded by the CRABP1 gene. [5] [6]

Contents

CRABP1 is assumed to play an important role in retinoic acid-mediated differentiation and proliferation processes. It is structurally similar to the cellular retinol-binding proteins, but binds only retinoic acid. CRABP1 is constitutively expressed and is believed to have different functions in the cell than the related CRABP2. [6]

Function

Figure 1. An overview of retinoid transfer by CRABP. R = Retinoic acid, RAR = retinoic acid receptor, RXR = Retinoic X receptor, RRE = retinoid response element. CRABP binds to retinoic acid and transports it to the nucleus where binding with RAR or RXR homodimers or heterodimers further regulates RREs to regulate transcription events on DNA. Retinoid Transfer by CRABP1.png
Figure 1. An overview of retinoid transfer by CRABP. R = Retinoic acid, RAR = retinoic acid receptor, RXR = Retinoic X receptor, RRE = retinoid response element. CRABP binds to retinoic acid and transports it to the nucleus where binding with RAR or RXR homodimers or heterodimers further regulates RREs to regulate transcription events on DNA.
Figure 2. Retinoic acid (RA) is processed from vitamin A to bind to fatty acid binding protein (FABP5) along with CRABP to associate with the binding to DNA to mediate pathways. RA binds with CRABP to mediate further action with retinoic acid receptor (RAR) on DNA for pathway mediation as well. Cellular Effects of CRABP1.png
Figure 2. Retinoic acid (RA) is processed from vitamin A to bind to fatty acid binding protein (FABP5) along with CRABP to associate with the binding to DNA to mediate pathways. RA binds with CRABP to mediate further action with retinoic acid receptor (RAR) on DNA for pathway mediation as well.
Figure 3. Image of the domain locations for CRABP1. The nuclear localization signal (NLS) is at position 21-31 and the retinoic acid binding site (RBS) is at position 132-134. Domains of CRABP1.png
Figure 3. Image of the domain locations for CRABP1. The nuclear localization signal (NLS) is at position 21-31 and the retinoic acid binding site (RBS) is at position 132-134.

CRABP1 binds to retinoid acid and helps to transport it into the nucleus (Figure 1). Both CRABP1 and CRABP2 perform this activity. The retinoic acid molecule is then released and further bound to retinoic acid receptor (RAR) and the retinoid X receptor (RXR) as homodimers or heterodimers. This complex then further binds to retinoic acid response elements (RARE) on DNA that regulates transcription of retinoid acid dependent null genes. [10] The domains for the nuclear localization and the retinoic acid binding are shown in Figure 3.

CRABP1 has been found to be involved in multiple cancer proliferation pathways. CRABP1 activates the extracellular signal-regulated kinase, ERK1 and ERK2 kinases, which are involved in the cell cycle. CRABP1 activity can thus extend the cell cycle, e.g. in embryonic and neural stem cells. Knockout mice without CRABP1 showed increased neural stem cell proliferation and thus hippocampus neurogenesis. Furthermore, learning and memory were improved in knockout mice, as measured by the Morris water maze test and an object recognition task. [11]

CRABP1 is also involved in cancer cell apoptosis. trans-retinoic acid was considered a [null therapeutic target for cancer] as a ligand of CRABP1. [12] It was observed that CRABP1 regulated ERK1/2) which in turn activates the protein phosphatase 2A (PP2A) that induces apoptosis of cancer cells and lengthens the cell cycle of embryonic stem cells. PP2A activity promotes the stem cells renewal ability during the differentiation process. When CRABP1 was knocked down the apoptotic induction ability was also removed and allowed for cell proliferation. The re-expression of CRABP1 in CRABP1 null cells brought back the induced apoptotic activity. Thus CRABP1 may be used as a therapeutic target along with trans-retinoic acid for apoptotic activity within cancer cells. [12] Figure 2 illustrates both pathways of retinoic acid binding to CRABP for cell proliferation and apoptotic activity.

Related Research Articles

Retinoic acid Metabolite of vitamin A

Retinoic acid (used simplified here for all-trans-retinoic acid) is a metabolite of vitamin A1 (all-trans-retinol) that mediates the functions of vitamin A1 required for growth and development. All-trans-retinoic acid is required in chordate animals, which includes all higher animals from fish to humans. During early embryonic development, all-trans-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages.

c-Fos

In the fields of molecular biology and genetics, c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun, resulting in the formation of AP-1 complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.

Midkine

Midkine, also known as neurite growth-promoting factor 2 (NEGF2), is a protein that in humans is encoded by the MDK gene.

GJA1 Protein-coding gene in humans

Gap junction alpha-1 protein (GJA1), also known as connexin 43 (Cx43), is a protein that in humans is encoded by the GJA1 gene on chromosome 6. As a connexin, GJA1 is a component of gap junctions, which allow for gap junction intercellular communication (GJIC) between cells to regulate cell death, proliferation, and differentiation. As a result of its function, GJA1 is implicated in many biological processes, including muscle contraction, embryonic development, inflammation, and spermatogenesis, as well as diseases, including oculodentodigital dysplasia (ODDD), heart malformations, and cancers.

Retinoic acid receptor alpha

Retinoic acid receptor alpha (RAR-α), also known as NR1B1 is a nuclear receptor that in humans is encoded by the RARA gene.

Retinoid X receptor gamma

Retinoid X receptor gamma (RXR-gamma), also known as NR2B3 is a nuclear receptor that in humans is encoded by the RXRG gene.

Retinoid X receptor beta

Retinoid X receptor beta (RXR-beta), also known as NR2B2 is a nuclear receptor that in humans is encoded by the RXRB gene.

Retinoic acid receptor beta

Retinoic acid receptor beta (RAR-beta), also known as NR1B2 is a nuclear receptor that in humans is encoded by the RARB gene.

Retinoic acid receptor gamma

Retinoic acid receptor gamma (RAR-γ), also known as NR1B3 is a nuclear receptor encoded by the RARG gene.

NK2 homeobox 1

NK2 homeobox 1 (NKX2-1), also known as thyroid transcription factor 1 (TTF-1), is a protein which in humans is encoded by the NKX2-1 gene.

CRABP2

Cellular retinoic acid-binding protein 2 is a cytoplasmic binding protein that in humans is encoded by the CRABP2 gene.

RBP1

Retinol binding protein 1, cellular, also known as RBP1, is a protein that in humans is encoded by the RBP1 gene.

DLC1

Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.

CYP26A1

Cytochrome P450 26A1 is a protein that in humans is encoded by the CYP26A1 gene.

RARRES3

Retinoic acid receptor responder protein 3 is a protein that in humans is encoded by the RARRES3 gene.

ID4 Protein-coding gene in humans

ID4 is a protein coding gene. In humans, it encodes for the protein known as DNA-binding protein inhibitor ID-4. This protein is known to be involved in the regulation of many cellular processes during both prenatal development and tumorigenesis. This is inclusive of embryonic cellular growth, senescence, cellular differentiation, apoptosis, and as an oncogene in angiogenesis.

RBP2 Protein-coding gene in the species Homo sapiens

Retinol-binding protein 2 (RBP2) is a protein that in humans is encoded by the RBP2 gene.

HOXC10

Homeobox protein Hox-C10 is a protein that in humans is encoded by the HOXC10 gene.

RARRES1

Retinoic acid receptor responder protein 1 is a protein that in humans is encoded by the RARRES1 gene.

CYP26B1

Cytochrome P450 26B1 is a protein that in humans is encoded by the CYP26B1 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000166426 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032291 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Flagiello D, Apiou F, Gibaud A, Poupon MF, Dutrillaux B, Malfoy B (Jun 1997). "Assignment of the genes for cellular retinoic acid binding protein 1 (CRABP1) and 2 (CRABP2) to human chromosome band 15q24 and 1q21.3, respectively, by in situ hybridization". Cytogenetics and Cell Genetics. 76 (1–2): 17–8. doi:10.1159/000134502. PMID   9154115.
  6. 1 2 "Entrez Gene: CRABP1 cellular retinoic acid binding protein 1".
  7. ↑ Redrawn from Lee K (April 2017). "Retinol for all". The Regime.
  8. ↑ Redrawn from Michalik L, Wahli W (May 2007). "Guiding ligands to nuclear receptors". Cell. 129 (4): 649–51. doi: 10.1016/j.cell.2007.05.001 . PMID   17512397. S2CID   17253347.
  9. ↑ Adapted from Universal protein resource accession number P29762 for "RABP1_HUMAN" at UniProt.
  10. ↑ Liu RZ, Garcia E, Glubrecht DD, Poon HY, Mackey JR, Godbout R (July 2015). "CRABP1 is associated with a poor prognosis in breast cancer: adding to the complexity of breast cancer cell response to retinoic acid". Molecular Cancer. 14: 129. doi:10.1186/s12943-015-0380-7. PMC   4491424 . PMID   26142905.
  11. ↑ Lin YL, Persaud SD, Nhieu J, Wei LN (September 2017). "Cellular Retinoic Acid-Binding Protein 1 Modulates Stem Cell Proliferation to Affect Learning and Memory in Male Mice". Endocrinology. 158 (9): 3004–3014. doi:10.1210/en.2017-00353. PMC   5659671 . PMID   28911165.
  12. 1 2 Persaud SD, Park SW, Ishigami-Yuasa M, Koyano-Nakagawa N, Kagechika H, Wei LN (March 2016). "All trans-retinoic acid analogs promote cancer cell apoptosis through non-genomic Crabp1 mediating ERK1/2 phosphorylation". Scientific Reports. 6: 22396. Bibcode:2016NatSR...622396P. doi:10.1038/srep22396. PMC   4776112 . PMID   26935534.

Further reading

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