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Protein

cAMP-responsive element modulator

Gene

Crem

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Isoform Delta is an activator. Plays a role in spermatogenesis and is involved in spermatid maturation. Binding of isoform Tau (activator) to CRE is increased by CREB3L4. The CREM isoform Tau-CREB3L4 heterodimer functions through CRE and may recruit HIRA to CRE to regulate histone exchange (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

  • cAMP-mediated signaling Source: RGD
  • circadian regulation of gene expression Source: Ensembl
  • fatty acid metabolic process Source: RGD
  • glucose metabolic process Source: RGD
  • glycosphingolipid metabolic process Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: Ensembl
  • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • regulation of circadian rhythm Source: RGD
  • regulation of transcription, DNA-templated Source: RGD
  • response to cAMP Source: Ensembl
  • retinoic acid receptor signaling pathway Source: RGD
  • spermatogenesis Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-responsive element modulator
Gene namesi
Name:Crem
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi2402. Crem.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 357357cAMP-responsive element modulatorPRO_0000076609Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei284 – 2841PhosphoserinePROSITE-ProRule annotationBy similarity
Modified residuei287 – 2871PhosphoserinePROSITE-ProRule annotationBy similarity
Modified residuei290 – 2901PhosphoserinePROSITE-ProRule annotationBy similarity

Post-translational modificationi

Stimulated by phosphorylation.By similarity
Ubiquitinated by CDC34 and RAD6B in order to be degraded by the proteasome.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ03061.

Expressioni

Tissue specificityi

Isoform Tau is expressed in testis germ cells. CREM-theta1- and CREM-theta2-containing isoforms are expressed in testis.2 Publications

Gene expression databases

ExpressionAtlasiQ03061. baseline and differential.
GenevisibleiQ03061. RN.

Interactioni

Subunit structurei

Binds DNA as a dimer (By similarity). Interacts with CDC34 (By similarity). Interacts with FHL5. Isoform delta forms a heterodimer with CREB3L4 (By similarity).By similarity

Protein-protein interaction databases

BioGridi247649. 3 interactions.
STRINGi10116.ENSRNOP00000062109.

Structurei

3D structure databases

ProteinModelPortaliQ03061.
SMRiQ03061. Positions 120-146, 301-355.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini101 – 16060KIDPROSITE-ProRule annotationAdd
BLAST
Domaini299 – 35759bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni300 – 32526Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni327 – 34822Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the bZIP family.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation
Contains 1 KID (kinase-inducible) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3584. Eukaryota.
ENOG410ZZJZ. LUCA.
GeneTreeiENSGT00390000008655.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiQ03061.
KOiK09052.
OMAiCLENRVH.
PhylomeDBiQ03061.

Family and domain databases

InterProiIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
[Graphical view]
PfamiPF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view]
PRINTSiPR00041. LEUZIPPRCREB.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 7 (identifier: Q03061-7) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSKCGRKKYM RTNVRQMTME TVESQQDRSV THSVAEHSSA HMQTGQISVP
60 70 80 90 100
TLAQVSVAGS GTGRGSPAVT LVQLPSGQTV QVQGVIQTPH PSVIQSPQIQ
110 120 130 140 150
TVQVATIAET DDSADSEVID SHKRREILSR RPSYRKILNE LSSDVPGIPK
160 170 180 190 200
IEEEKSEEEG TPPNIATMAV PTSIYQTSTG QYIAIAQGGT IQISNPGSDG
210 220 230 240 250
VQGLQALTMT NSGAPPPGAT IVQYAAQSAD GTQQFFVPGS QVVVQDEETD
260 270 280 290 300
LAPSHMAAAT GDMPTYQIRA PTTALPQGVV MAASPGSLHS PQQLAEEATR
310 320 330 340 350
KRELRLMKNR EAAKECRRRK KEYVKCLESR VAVLEVQNKK LIEELETLKD

ICSPKTD
Note: Produced by alternative splicing.
Length:357
Mass (Da):38,497
Last modified:September 22, 2009 - v2
Checksum:i5660B6802B3047B2
GO
Isoform Tau (identifier: Q03061-1) [UniParc]FASTAAdd to basket

Also known as: CREM-BCEFGgammaHIbeta

The sequence of this isoform differs from the canonical sequence as follows:
     314-357: KECRRRKKEY...LKDICSPKTD → RECRRKKKEY...LKDLYCHKAE

Note: Produced by alternative promoter usage. Activator.
Show »
Length:357
Mass (Da):38,554
Checksum:i0B37BA54D5CE2030
GO
Isoform Alpha (identifier: Q03061-2)

Sequence is not available
Length:
Mass (Da):
Isoform Beta (identifier: Q03061-3)

Sequence is not available
Length:
Mass (Da):
Isoform Gamma (identifier: Q03061-4)

Sequence is not available
Length:
Mass (Da):
Isoform 5 (identifier: Q03061-5) [UniParc]FASTAAdd to basket

Also known as: CREM-theta1CEFGgammaHIbeta

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: MSKCGRKKYM...GQISVPTLAQ → MWWHQHNLCFRHPVEEDYSSGDLDKK

Note: Produced by alternative promoter usage. Activator.
Show »
Length:329
Mass (Da):35,647
Checksum:i33373B755E3464B0
GO
Isoform 6 (identifier: Q03061-6) [UniParc]FASTAAdd to basket

Also known as: CREM-theta2CEFGgammaHIbeta

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: MSKCGRKKYMRTNVRQMTMETVESQQDRSVTHSVAEHSSAHMQTGQISVPTLAQ → M

Note: Produced by alternative promoter usage. Activator.
Show »
Length:304
Mass (Da):32,538
Checksum:i166073651D77B37D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti40 – 401A → L in CAA78857 (PubMed:1461747).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5454MSKCG…PTLAQ → MWWHQHNLCFRHPVEEDYSS GDLDKK in isoform 5. 1 PublicationVSP_026079Add
BLAST
Alternative sequencei1 – 5454MSKCG…PTLAQ → M in isoform 6. 1 PublicationVSP_026080Add
BLAST
Alternative sequencei314 – 35744KECRR…SPKTD → RECRRKKKEYVKCLENRVAV LESQNKTLIEELKALKDLYC HKAE in isoform Tau. 1 PublicationVSP_038017Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC078899 mRNA. Translation: AAH78899.1.
Z15158 mRNA. Translation: CAA78857.1.
PIRiS26686.
RefSeqiNP_001104330.1. NM_001110860.2.
NP_001258030.1. NM_001271101.1. [Q03061-7]
UniGeneiRn.10251.

Genome annotation databases

EnsembliENSRNOT00000068545; ENSRNOP00000062109; ENSRNOG00000014900. [Q03061-7]
GeneIDi25620.
KEGGirno:25620.
UCSCiRGD:2402. rat. [Q03061-7]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC078899 mRNA. Translation: AAH78899.1.
Z15158 mRNA. Translation: CAA78857.1.
PIRiS26686.
RefSeqiNP_001104330.1. NM_001110860.2.
NP_001258030.1. NM_001271101.1. [Q03061-7]
UniGeneiRn.10251.

3D structure databases

ProteinModelPortaliQ03061.
SMRiQ03061. Positions 120-146, 301-355.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247649. 3 interactions.
STRINGi10116.ENSRNOP00000062109.

Proteomic databases

PaxDbiQ03061.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000068545; ENSRNOP00000062109; ENSRNOG00000014900. [Q03061-7]
GeneIDi25620.
KEGGirno:25620.
UCSCiRGD:2402. rat. [Q03061-7]

Organism-specific databases

CTDi1390.
RGDi2402. Crem.

Phylogenomic databases

eggNOGiKOG3584. Eukaryota.
ENOG410ZZJZ. LUCA.
GeneTreeiENSGT00390000008655.
HOGENOMiHOG000007365.
HOVERGENiHBG011077.
InParanoidiQ03061.
KOiK09052.
OMAiCLENRVH.
PhylomeDBiQ03061.

Miscellaneous databases

PROiQ03061.

Gene expression databases

ExpressionAtlasiQ03061. baseline and differential.
GenevisibleiQ03061. RN.

Family and domain databases

InterProiIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
[Graphical view]
PfamiPF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view]
PRINTSiPR00041. LEUZIPPRCREB.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
    Strain: Brown Norway.
    Tissue: Testis.
  2. "Cyclic AMP response element binding protein CREB and modulator protein CREM are products of distinct genes."
    Meyer T.E., Habener J.F.
    Nucleic Acids Res. 20:6106-6106(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-357 (ISOFORM TAU).
    Tissue: Testis.
  3. "Novel cyclic adenosine 3',5'-monophosphate (cAMP) response element modulator theta isoforms expressed by two newly identified cAMP-responsive promoters active in the testis."
    Daniel P.B., Rohrbach L., Habener J.F.
    Endocrinology 141:3923-3930(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-68 (ISOFORM 5), NUCLEOTIDE SEQUENCE [MRNA] OF 1-62 (ISOFORM 6), TISSUE SPECIFICITY.
  4. "Differential regulation of cyclic adenosine 3',5'-monophosphate (cAMP) response element-binding protein and cAMP response element modulator messenger ribonucleic acid transcripts by follicle-stimulating hormone and androgen in the adult rat testis."
    West A.P., Sharpe R.M., Saunders P.T.
    Biol. Reprod. 50:869-881(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
  5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiCREM_RAT
AccessioniPrimary (citable) accession number: Q03061
Secondary accession number(s): Q6AYV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: September 22, 2009
Last modified: June 8, 2016
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.