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CAMP responsive element modulator

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CREM
Identifiers
AliasesCREM, CREM-2, ICER, hCREM-2, cAMP responsive element modulator
External IDsOMIM: 123812; MGI: 88495; HomoloGene: 84591; GeneCards: CREM; OMA:CREM - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1390

12916

Ensembl

ENSG00000095794

ENSMUSG00000063889

UniProt

Q03060

P27699

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 10: 35.13 – 35.21 MbChr 18: 3.27 – 3.34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

cAMP-responsive element modulator is a protein that in humans is encoded by the CREM gene[5][6][7], and it belongs to the CAMP-Responsive Element Binding protein family. It has multiple isoforms, which act either as repressors or activators [8]. CREB family is important for in regulating transcription in response to various stresses, metabolic and developmental signals[9] . CREM transcription factors also play an important role in many physiological systems, such as cardiac function[10], circadian rhythms[11],locomotion and spermatogenesis[12].

Function

This gene encodes a bZIP transcription factor that binds to the cAMP responsive element found in many viral and cellular promoters. It is an important component of cAMP-mediated signal transduction during the spermatogenetic cycle, as well as other complex processes. Alternative promoter and translation initiation site usage allows this gene to exert spatial and temporal specificity to cAMP responsiveness. Multiple alternatively spliced transcript variants encoding several different isoforms have been found for this gene, with some of them functioning as activators and some as repressors of transcriptnhunion.[7]

Interactions

CAMP responsive element modulator has been shown to interact with FHL5.[13][14]

Disease relevance of CREM

Panic disorder

One study reported the DNA sequence variations in the gene for CREM in panic disorder patients. It showed a significant excess of the shorter eight-repeat allele and of genotypes containing the eight-repeat allele in panic disorder patients [15]. The observed associations were limited to panic disorder without agoraphobia, and they were more prominent in females. But, the independent Italian and Spanish samples in this study not supported their results. An anther study family-based study showed little evidence of any susceptibility locus for panic disorder either within the CREM gene or in a nearby region on chromosome 10p11[16]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000095794 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063889 – 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. ^ Meyer TE, Habener JF (Nov 1992). "Cyclic AMP response element binding protein CREB and modulator protein CREM are products of distinct genes". Nucleic Acids Research. 20 (22): 6106. doi:10.1093/nar/20.22.6106. PMC 334485. PMID 1461747.
  6. ^ Masquilier D, Foulkes NS, Mattei MG, Sassone-Corsi P (Nov 1993). "Human CREM gene: evolutionary conservation, chromosomal localization, and inducibility of the transcript". Cell Growth & Differentiation. 4 (11): 931–7. PMID 7916662.
  7. ^ a b "Entrez Gene: CREM cAMP responsive element modulator".
  8. ^ Foulkes, N. S.; Sassone-Corsi, P. (1992-02-07). "More is better: activators and repressors from the same gene". Cell. 68 (3): 411–414. ISSN 0092-8674.
  9. ^ Sassone-Corsi, P. (1995-01-01). "Transcription factors responsive to cAMP". Annual Review of Cell and Developmental Biology. 11: 355–377. doi:10.1146/annurev.cb.11.110195.002035. ISSN 1081-0706.
  10. ^ Isoda, Takayoshi; Paolocci, Nazareno; Haghighi, Kobra; Wang, Congrong; Wang, Yibin; Georgakopoulos, Dimitrios; Servillo, Giuseppe; Della Fazia, Maria Agnese; Kranias, Evangelia G. (2003-02-01). "Novel regulation of cardiac force-frequency relation by CREM (cAMP response element modulator)". FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 17 (2): 144–151. doi:10.1096/fj.01-0981com. ISSN 1530-6860.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  11. ^ Sassone-Corsi, P. (2000-06-01). "CREM: a master-switch regulating the balance between differentiation and apoptosis in male germ cells". Molecular Reproduction and Development. 56 (2 Suppl): 228–229. doi:10.1002/(SICI)1098-2795(200006)56:2+3.0.CO;2-B. ISSN 1040-452X.
  12. ^ Sassone-Corsi, P. (1998-08-01). "CREM: a master-switch governing male germ cells differentiation and apoptosis". Seminars in Cell & Developmental Biology. 9 (4): 475–482. doi:10.1006/scdb.1998.0200. ISSN 1084-9521.
  13. ^ Fimia GM, De Cesare D, Sassone-Corsi P (Nov 2000). "A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM". Molecular and Cellular Biology. 20 (22): 8613–22. doi:10.1128/MCB.20.22.8613-8622.2000. PMC 102166. PMID 11046156.
  14. ^ Fimia GM, De Cesare D, Sassone-Corsi P (Mar 1999). "CBP-independent activation of CREM and CREB by the LIM-only protein ACT". Nature. 398 (6723): 165–9. doi:10.1038/18237. PMID 10086359.
  15. ^ Domschke, K.; Kuhlenbäumer, G.; Schirmacher, A.; Lorenzi, C.; Armengol, L.; DiBella, D.; Gratacos, M.; Garritsen, H. S.; Nöthen, M. M. (2003-02-01). "Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics. 117B (1): 70–78. doi:10.1002/ajmg.b.10018. ISSN 1552-4841.
  16. ^ Hamilton, Steven P.; Slager, Susan L.; Mayo, David; Heiman, Gary A.; Klein, Donald F.; Hodge, Susan E.; Fyer, Abby J.; Weissman, Myrna M.; Knowles, James A. (2004-04-01). "Investigation of polymorphisms in the CREM gene in panic disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics. 126B (1): 111–115. doi:10.1002/ajmg.b.20121. ISSN 1552-4841.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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