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CREM Gene(Protein Coding)

CAMP Responsive Element Modulator

GCID:
GC10P035126
GIFtS:
50
Genes Participants
UDN Logo

Aliases for CREM Gene

Aliases for CREM Gene

  • CAMP Responsive Element Modulator 2 3 5
  • ICER 3 4
  • Inducible CAMP Early Repressor ICER 3
  • CAMP-Responsive Element Modulator 3
  • CAMP Response Element Modulator 3
  • Inducible CAMP Early Repressor 4
  • CREM 2alpha-B Protein 3
  • CREM 2beta-A Protein 3
  • HCREM-2 3
  • CREM-2 3

External Ids for CREM Gene

Previous GeneCards Identifiers for CREM Gene

  • GC10P035163
  • GC10P035566
  • GC10P035419
  • GC10P035455
  • GC10P035415

Summaries for CREM Gene

Entrez Gene Summary for CREM Gene

  • 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 transcription. [provided by RefSeq, Jul 2008]

GeneCards Summary for CREM Gene

CREM (CAMP Responsive Element Modulator) is a Protein Coding gene. Diseases associated with CREM include Female Stress Incontinence and Type 1 Diabetes Mellitus 10. Among its related pathways are Transcription_CREM signaling in testis and Aldosterone synthesis and secretion. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and core promoter sequence-specific DNA binding. An important paralog of this gene is CREB1.

UniProtKB/Swiss-Prot for CREM Gene

  • Transcriptional regulator that binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. Isoforms are either transcriptional activators or repressors. Plays a role in spermatogenesis and is involved in spermatid maturation (PubMed:10373550).

  • Isoform 6: May play a role in the regulation of the circadian clock: acts as a transcriptional repressor of the core circadian component PER1 by directly binding to cAMP response elements in its promoter.

Gene Wiki entry for CREM Gene

Additional gene information for CREM Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CREM Gene

Genomics for CREM Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for CREM Gene

Promoters and enhancers for CREM Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH10I035191 Promoter/Enhancer 2.5 EPDnew Ensembl ENCODE dbSUPER 569.4 +67.6 67567 6.1 HDGF PKNOX1 ARNT ZFP64 SIN3A FEZF1 ZNF2 IRF4 YY1 POLR2B CREM ENSG00000271335 CUL2 PARD3-AS1 RNU7-77P ENSG00000230534 GC10M035186 ENSG00000269952
GH10I035125 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 558.3 +1.2 1171 4.3 HDGF PKNOX1 SMAD1 ARNT ARID4B NEUROD1 SIN3A DMAP1 ZNF2 YY1 CREM CUL2 ENSG00000230534 RNU7-77P
GH10I035167 Promoter 0.7 EPDnew 562.1 +40.8 40754 0.1 CREB1 ATF7 ATF2 CREM GC10P035167 RNU7-77P GC10P035169 GC10M035186
GH10I035124 Enhancer 0.6 dbSUPER 550.8 -1.9 -1873 1.3 PKNOX1 L3MBTL2 CEBPB ZMYM3 CEBPG DPF2 ATF4 NFIC SMARCA4 HMBOX1 CUL2 CREM ENSG00000230534 MIR3611
GH10I035175 Promoter 0.5 EPDnew 562 +48.8 48788 0.1 CREM RNU7-77P ENSG00000230534 GC10P035167 GC10M035186
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around CREM on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CREM gene promoter:

Genomic Locations for CREM Gene

Genomic Locations for CREM Gene
chr10:35,126,791-35,212,958
(GRCh38/hg38)
Size:
86,168 bases
Orientation:
Plus strand
chr10:35,415,719-35,501,886
(GRCh37/hg19)

Genomic View for CREM Gene

Genes around CREM on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CREM Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CREM Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for CREM Gene

Proteins for CREM Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

neXtProt entry for CREM Gene

Protein Expression for CREM Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for CREM Gene

Other Protein References for CREM Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CREM Gene

Domains & Families for CREM Gene

Gene Families for CREM Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for CREM Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for CREM Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q03060

UniProtKB/Swiss-Prot:

CREM_HUMAN :
  • Belongs to the bZIP family.
Family:
  • Belongs to the bZIP family.
genes like me logo Genes that share domains with CREM: view

Function for CREM Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for CREM Gene

GENATLAS Biochemistry:
cAMP response element modulator,playing a key role within the hypopituitary-pituitary-gonadal axis,involved lin spermiogenesis,including a truncated isoform (early response repressor ICER=inducible cAMP early repressor) acting as repressor,regulated in a circadian manner in the pineal gland
UniProtKB/Swiss-Prot Function:
Transcriptional regulator that binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. Isoforms are either transcriptional activators or repressors. Plays a role in spermatogenesis and is involved in spermatid maturation (PubMed:10373550).
UniProtKB/Swiss-Prot Function:
Isoform 6: May play a role in the regulation of the circadian clock: acts as a transcriptional repressor of the core circadian component PER1 by directly binding to cAMP response elements in its promoter.

Phenotypes From GWAS Catalog for CREM Gene

Gene Ontology (GO) - Molecular Function for CREM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 16899810
GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding IC --
GO:0003677 DNA binding NAS 7916662
GO:0003700 DNA binding transcription factor activity IEA --
GO:0005515 protein binding IPI 21976679
genes like me logo Genes that share ontologies with CREM: view
genes like me logo Genes that share phenotypes with CREM: view

Animal Models for CREM Gene

MGI Knock Outs for CREM:

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CREM Gene

Localization for CREM Gene

Subcellular locations from UniProtKB/Swiss-Prot for CREM Gene

Nucleus.
Isoform 6: Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CREM gene
Compartment Confidence
nucleus 5
cytosol 3
extracellular 1
cytoskeleton 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleus (3)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CREM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus NAS,TAS 8206879
GO:0005667 transcription factor complex IEA --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with CREM: view

Pathways & Interactions for CREM Gene

genes like me logo Genes that share pathways with CREM: view

Gene Ontology (GO) - Biological Process for CREM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 12626549
GO:0006006 glucose metabolic process IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated NAS 7916662
GO:0006631 fatty acid metabolic process IEA --
genes like me logo Genes that share ontologies with CREM: view

No data available for SIGNOR curated interactions for CREM Gene

Drugs & Compounds for CREM Gene

Products:

  1. Drug

(6) Drugs for CREM Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0

(2) Additional Compounds for CREM Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CREM: view

Transcripts for CREM Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for CREM Gene

(71) REFSEQ mRNAs :
(23) Additional mRNA sequences :
(5) Selected AceView cDNA sequences:
(48) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for CREM Gene

CAMP responsive element modulator:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CREM Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f · 1g · 1h · 1i ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b · 10c · 10d · 10e ·
SP1: - - - - - - - - - - - - -
SP2: - - - -
SP3: - - - - - - - - - - - - - -
SP4: - - - - - - - - - - - - - - -
SP5: - - - - - - - - - -
SP6: - - - - - - - - - - - - - - - -
SP7: - - - - - - - - - -
SP8: - - - - - - - - -
SP9: - - - - - -
SP10: - - - -
SP11: - - - - - - - - - - -
SP12: -
SP13: - - - - - - - - - - - - - - - - -
SP14: - - - - - - -
SP15:
SP16:
SP17:
SP18:
SP19:
SP20:
SP21:
SP22:
SP23:
SP24:
SP25: -

ExUns: 10f ^ 11 ^ 12 ^ 13a · 13b · 13c ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b · 18c · 18d · 18e ^ 19a · 19b · 19c · 19d · 19e · 19f
SP1: - - - - - - -
SP2: - - - - - - - - - - - - -
SP3: -
SP4: - - - - - - - - - - - - - -
SP5:
SP6: - - - - - - - - -
SP7:
SP8:
SP9: - - - - - - - - - - - - -
SP10:
SP11:
SP12:
SP13: - - - - - - - - -
SP14:
SP15:
SP16: - - - - - -
SP17: - - - - -
SP18: - - - - - - - - - - -
SP19: - - - -
SP20: - - -
SP21: - - - - - - - -
SP22: - -
SP23: -
SP24: - - - - - -
SP25:

Relevant External Links for CREM Gene

GeneLoc Exon Structure for
CREM
ECgene alternative splicing isoforms for
CREM

Expression for CREM Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CREM Gene

mRNA expression in normal human tissues for CREM Gene
mRNA expression by GTEx for CREM GenemRNA expression by BioGPS for CREM Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CREM Gene

This gene is overexpressed in Testis (x5.1).

Protein differential expression in normal tissues from HIPED for CREM Gene

This gene is overexpressed in Testis (54.2) and Ovary (7.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CREM Gene



Protein tissue co-expression partners for CREM Gene

NURSA nuclear receptor signaling pathways regulating expression of CREM Gene:

CREM

SOURCE GeneReport for Unigene cluster for CREM Gene:

Hs.200250

mRNA Expression by UniProt/SwissProt for CREM Gene:

Q03060-CREM_HUMAN
Tissue specificity: Expressed in testes (round spermatids) (at protein level). Isoform 14 is the major activator form in testes.

Evidence on tissue expression from TISSUES for CREM Gene

  • Nervous system(4.7)
  • Adrenal gland(4.6)
  • Heart(4.4)
  • Blood(2.9)
  • Liver(2.2)
  • Intestine(2.1)
  • Muscle(2.1)
genes like me logo Genes that share expression patterns with CREM: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CREM Gene

Orthologs for CREM Gene

This gene was present in the common ancestor of animals.

Orthologs for CREM Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia CREM 33 34
  • 94.98 (n)
dog
(Canis familiaris)
 Mammalia CREM 33 34
  • 94.94 (n)
rat
(Rattus norvegicus)
 Mammalia Crem 33
  • 92.57 (n)
mouse
(Mus musculus)
 Mammalia Crem 33 16 34
  • 92.34 (n)
cow
(Bos Taurus)
 Mammalia CREM 33 34
  • 88.74 (n)
oppossum
(Monodelphis domestica)
 Mammalia CREM 34
  • 81 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia CREM 34
  • 49 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves CREM 33 34
  • 73.81 (n)
lizard
(Anolis carolinensis)
 Reptilia CREM 34
  • 67 (a)
 OneToOne
zebrafish
(Danio rerio)
 Actinopterygii crema 33 34
  • 67.26 (n)
cremb 34
  • 33 (a)
 ManyToMany
fruit fly
(Drosophila melanogaster)
 Insecta CrebB-17A 34
  • 22 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea crh-1 34
  • 20 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea CSA.714 34
  • 42 (a)
 OneToMany
sea squirt
(Ciona intestinalis)
 Ascidiacea Cin.3621 33
Species where no ortholog for CREM was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for CREM Gene

ENSEMBL:
Gene Tree for CREM (if available)
TreeFam:
Gene Tree for CREM (if available)

Paralogs for CREM Gene

Variants for CREM Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for CREM Gene

SNP ID Clin Chr 10 pos Variation AA Info Type
rs1000022950 -- 35,132,082(+) T/C genic_upstream_transcript_variant, intron_variant
rs1000069706 -- 35,126,713(+) C/T upstream_transcript_variant
rs1000074583 -- 35,181,201(+) C/A genic_downstream_transcript_variant, genic_upstream_transcript_variant, intron_variant
rs1000092954 -- 35,201,862(+) T/C genic_downstream_transcript_variant, intron_variant
rs1000121464 -- 35,134,145(+) C/A genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for CREM Gene

Variant ID Type Subtype PubMed ID
dgv706n100 CNV gain 25217958
dgv707n100 CNV gain 25217958
dgv96e201 CNV deletion 23290073
esv2659986 CNV deletion 23128226
esv2668859 CNV deletion 23128226
esv2735328 CNV deletion 23290073
esv2735362 CNV deletion 23290073
esv3546152 CNV deletion 23714750
esv3576372 CNV gain 25503493
esv3622893 CNV loss 21293372
esv3622894 CNV loss 21293372
nsv1039051 CNV gain 25217958
nsv475915 CNV novel sequence insertion 20440878
nsv550398 CNV gain 21841781
nsv820199 CNV loss 19587683

Variation tolerance for CREM Gene

Residual Variation Intolerance Score: 45.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.31; 76.60% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CREM Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CREM

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CREM Gene

Disorders for CREM Gene

MalaCards: The human disease database

(2) MalaCards diseases for CREM Gene - From: DISEASES

Disorder Aliases PubMed IDs
female stress incontinence
  • female urinary stress incontinence
type 1 diabetes mellitus 10
  • diabetes mellitus, insulin-dependent, 10
- elite association - COSMIC cancer census association via MalaCards
Search CREM in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CREM

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CREM: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CREM Gene

Publications for CREM Gene

  1. Human CREM gene: evolutionary conservation, chromosomal localization, and inducibility of the transcript. (PMID: 7916662) Masquilier D … Sassone-Corsi P (Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 1993) 2 3 4 22 58
  2. Novel leader exons of the cyclic adenosine 3',5'-monophosphate response element modulator (CREM) gene, transcribed from promoters P3 and P4, are highly testis-specific in primates. (PMID: 12397208) Gellersen B … Behr R (Molecular human reproduction 2002) 3 4 22 58
  3. Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis. (PMID: 10373550) Pati D … Plon SE (Molecular and cellular biology 1999) 3 4 22 58
  4. Novel isoforms of human cyclic AMP-responsive element modulator (hCREM) mRNA. (PMID: 8206879) Fujimoto T … Yoshida M (Journal of biochemistry 1994) 3 4 22 58
  5. Cyclic AMP response element binding protein CREB and modulator protein CREM are products of distinct genes. (PMID: 1461747) Meyer TE … Habener JF (Nucleic acids research 1992) 2 3 4 58

Products for CREM Gene