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 specif... See more...

Aliases for CREM Gene

Aliases for CREM Gene

  • CAMP Responsive Element Modulator 2 3 5
  • CAMP-Responsive Element Modulator 3 4
  • ICER 3 4
  • Inducible CAMP Early Repressor ICER 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 Male Infertility and Myasthenic Syndrome, Congenital, 9, Associated With Acetylcholine Receptor Deficiency. Among its related pathways are Circadian rythm related genes and BMAL1-CLOCK,NPAS2 activates circadian gene expression. 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 Summary 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 , Rfam classification and piRNA Summary for CREM Gene

Genomics for CREM Gene

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
GH10J035191 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 519.4 +67.6 67567 6.1 ZBTB40 EP300 CTCF ZSCAN5C TCF12 SP1 RBAK GTF2E2 ZNF639 ZNF354C CREM ENSG00000271335 CUL2 PARD3-AS1 RNU7-77P ENSG00000230534 RF00017-652 ENSG00000269952
GH10J035125 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 508.2 +1.2 1171 4.3 RXRA EP300 HNRNPK ZBTB40 ZNF217 CTCF SIN3A NRF1 TCF12 POLR2G CREM CUL2 ENSG00000230534 piR-57460-052 CCNY
GH10J035175 Promoter 0.3 EPDnew 512.1 +48.8 48788 0.1 CREM RNU7-77P ENSG00000230534 RF00017-652 NONHSAG005611.2
GH10J035335 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 15.2 +210.2 210210 5.6 HNRNPK ZBTB40 SIN3A POLR2G PHF8 ZFX ZIC2 POLR2A ZBTB10 ZBTB11 ENSG00000271335 CUL2 CCNY CREM ENSG00000230534 RNU7-77P piR-50738
GH10J035208 Enhancer 1.2 FANTOM5 Ensembl ENCODE dbSUPER 19.8 +84.3 84343 5.9 TEAD4 TCF7 NFYB FOXA2 CHD1 JUND TBP RAD21 RXRA ATF4 ENSG00000269952 CREM CUL2 RNU7-77P ENSG00000230534 CCNY FJ601684-039
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CREM on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CREM

Top Transcription factor binding sites by QIAGEN in the CREM gene promoter:
  • ATF-2

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)
Size:
86,168 bases
Orientation:
Plus strand

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 StructureGene Density

RefSeq DNA sequence for CREM Gene

Proteins for CREM Gene

  • Protein details for CREM Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q03060-CREM_HUMAN
    Recommended name:
    cAMP-responsive element modulator
    Protein Accession:
    Q03060
    Secondary Accessions:
    • A8K014
    • A8K3J7
    • A8K6A1
    • A8MPQ2
    • B4DXC1
    • C9J785
    • C9JZ10
    • E9PAR4
    • E9PHM1
    • O75519
    • Q14501
    • Q14503
    • Q14504
    • Q14505
    • Q14506
    • Q15731
    • Q16114
    • Q16116
    • Q5T9H7
    • Q5W1A6
    • Q5W1A7
    • Q5W1A8
    • Q5W1A9
    • Q5W1B0
    • Q5W1B2
    • Q7Z2Q6
    • Q8IVD4
    • Q96AG7
    • Q9NZ98
    • Q9NZ99
    • Q9NZB9

    Protein attributes for CREM Gene

    Size:
    345 amino acids
    Molecular mass:
    37006 Da
    Quaternary structure:
    • Binds DNA as a dimer. Interacts with FHL5 (By similarity). Interacts with CDC34 (PubMed:10373550). May interact with TSSK4 (By similarity).
    Miscellaneous:
    • [Isoform 1]: Produced by alternative promoter usage.
    • [Isoform 2]: Produced by alternative splicing of isoform 1. Activator.
    • [Isoform 3]: Produced by alternative splicing of isoform 1. Activator.
    • [Isoform 4]: Produced by alternative splicing of isoform 1.
    • [Isoform 5]: Produced by alternative promoter usage. Activator.
    • [Isoform 6]: Produced by alternative promoter usage. Repressor.
    • [Isoform 7]: Produced by alternative splicing of isoform 6. Repressor.
    • [Isoform 8]: Produced by alternative splicing of isoform 6. Repressor.
    • [Isoform 9]: Produced by alternative splicing of isoform 6. Repressor.
    • [Isoform 10]: Produced by alternative promoter usage. Activator.
    • [Isoform 11]: Produced by alternative splicing of isoform 10. Repressor.
    • [Isoform 12]: Produced by alternative splicing of isoform 5. Repressor.
    • [Isoform 13]: Produced by alternative splicing of isoform 1. Activator.
    • [Isoform 14]: Produced by alternative splicing of isoform 1. Activator.
    • [Isoform 15]: Produced by alternative splicing of isoform 1. Repressor.
    • [Isoform 16]: Produced by alternative splicing of isoform 1. Repressor.
    • [Isoform 17]: Produced by alternative splicing of isoform 1. Repressor.
    • [Isoform 18]: Produced by alternative splicing of isoform 1. Repressor.
    • [Isoform 19]: Produced by alternative splicing of isoform 10. Activator.
    • [Isoform 24]: Produced by alternative splicing.
    • [Isoform 25]: Produced by alternative splicing.
    • [Isoform 26]: Produced by alternative splicing.
    • [Isoform 27]: Produced by alternative splicing.
    • [Isoform 28]: Produced by alternative splicing.
    • [Isoform 29]: Produced by alternative splicing.
    SequenceCaution:
    • Sequence=AAB03751.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAF68266.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

neXtProt entry for CREM Gene

Post-translational modifications for CREM Gene

  • Isoform 9 is ubiquitinated by CDC34 and RAD6B in order to be degraded by the proteasome.
  • Stimulated by phosphorylation. Phosphorylated on Ser-116 by TSSK4 in vitro.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

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

Blocks:
  • bZIP transcription factor, bZIP_1
  • cAMP response element binding (CREB) protein signature
  • Coactivator CBP, pKID
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CREM Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ76503, highly similar to Homo sapiens cAMP responsive element modulator (CREM), transcript variant 8, mRNA (A8K014_HUMAN)
  • cDNA FLJ76412, highly similar to Homo sapiens cAMP responsive element modulator (CREM), transcript variant 10, mRNA (A8K6A1_HUMAN)
  • Inducible cAMP early repressor (CREM_HUMAN)
  • cAMP responsive element modulator (Q5T9H8_HUMAN)
  • cAMP responsive element modulator (Q5T9I5_HUMAN)

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

Molecular function for CREM Gene

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.
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

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:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IC --
GO:0003677 DNA binding NAS 7916662
GO:0003700 DNA-binding transcription factor activity IEA --
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:

Animal Model Products

CRISPR Products

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
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

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

Gene Ontology (GO) - Cellular Components for CREM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus NAS,TAS 8206879
GO:0005667 transcription factor complex IBA 21873635
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with CREM: view

Pathways & Interactions for CREM Gene

PathCards logo

SuperPathways for CREM Gene

SuperPathway Contained pathways
1 Activation of cAMP-Dependent PKA
.77
.77
.71
.56
2 BMAL1-CLOCK,NPAS2 activates circadian gene expression
3 cGMP-PKG signaling pathway
4 Dopamine-DARPP32 Feedback onto cAMP Pathway
-
5 DREAM Repression and Dynorphin Expression
.44
genes like me logo Genes that share pathways with CREM: view

Pathways by source for CREM Gene

1 GeneGo (Thomson Reuters) pathway for CREM Gene
  • Transcription_CREM signaling in testis
6 Qiagen pathways for CREM Gene
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • cAMP Pathway
  • Dopamine-DARPP32 Feedback onto cAMP Pathway
  • DREAM Repression and Dynorphin Expression

SIGNOR curated interactions for CREM Gene

Is activated by:

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:0006355 regulation of transcription, DNA-templated NAS 7916662
GO:0006631 fatty acid metabolic process IEA --
GO:0006687 glycosphingolipid metabolic process IEA --
genes like me logo Genes that share ontologies with CREM: view

Drugs & Compounds for CREM Gene

(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

mRNA/cDNA for CREM Gene

35 REFSEQ mRNAs :
48 NCBI additional mRNA sequence :
48 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

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

Expression for CREM Gene

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



Protein tissue co-expression partners for CREM Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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 31 30
  • 94.98 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CREM 31 30
  • 94.94 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Crem 30
  • 92.57 (n)
mouse
(Mus musculus)
Mammalia Crem 17 31 30
  • 92.34 (n)
cow
(Bos Taurus)
Mammalia CREM 31 30
  • 88.74 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CREM 31
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CREM 31
  • 49 (a)
OneToOne
chicken
(Gallus gallus)
Aves CREM 31 30
  • 73.81 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CREM 31
  • 67 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii crema 31 30
  • 67.26 (n)
ManyToMany
cremb 31
  • 33 (a)
ManyToMany
fruit fly
(Drosophila melanogaster)
Insecta CrebB-17A 31
  • 22 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea crh-1 31
  • 20 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.714 31
  • 42 (a)
OneToMany
Cin.3621 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.3621 30
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)
Aminode:
Evolutionary constrained regions (ECRs) for CREM: view image

Paralogs for CREM Gene

Paralogs for CREM Gene

(5) SIMAP similar genes for CREM Gene using alignment to 17 proteins:

  • CREM_HUMAN
  • C9IYM9_HUMAN
  • C9J2J0_HUMAN
  • C9J5A7_HUMAN
  • C9JK96_HUMAN
  • C9K092_HUMAN
  • E9PAR2_HUMAN
  • E9PB41_HUMAN
  • E9PBM5_HUMAN
  • F8WB03_HUMAN
  • F8WDF2_HUMAN
  • G5E998_HUMAN
  • H7C4X0_HUMAN
  • J3KQC0_HUMAN
  • J3KR46_HUMAN
  • Q9BYY5_HUMAN
  • R4GN75_HUMAN
genes like me logo Genes that share paralogs with CREM: view

Variants for CREM Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CREM Gene