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P27699 (CREM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-responsive element modulator
Gene names
Name:Crem
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length357 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Isoform 2, isoform 3 and isoform 4 are repressors, while isoform 1 is an activator. Plays a role in spermatogenesis and is involved in spermatid maturation. Binding of isoform 1 (activator) to CRE is increased by CREB3L4. The CREM isoform 1-CREB3L4heterodimer functions through CRE and may recruit HIRA to CRE to regulate histone exchange. Ref.6

Subunit structure

Binds DNA as a dimer By similarity. Interacts with CDC34 By similarity. Interacts with FHL5. Isoform 1 forms a heterodimer with CREB3L4. Ref.5 Ref.6

Subcellular location

Nucleus.

Developmental stage

In premeiotic germ cells, expressed at low amounts in the antagonist form. Subsequently, during spermatogenesis, isoform 1 (activator) is generated exclusively and in extremely high amounts.

Post-translational modification

Stimulated by phosphorylation By similarity.

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

Miscellaneous

CREM-null deficient mice display male infertility: while spermatogonia differentiate normally into round spermatids, all the elongating spermatids are eliminated by apoptosis during spermiogenesis.

Sequence similarities

Belongs to the bZIP family.

Contains 1 bZIP (basic-leucine zipper) domain.

Contains 1 KID (kinase-inducible) domain.

Sequence caution

The sequence AAA17495.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAA17496.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAA17497.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAV28551.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAV28552.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAV28553.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAV28554.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAV28555.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAV28556.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 10 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P27699-1)

Also known as: CREM-BCEFGgammaHIbeta; Tau;

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.
Isoform 2 (identifier: P27699-2)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     55-103: Missing.
     183-245: Missing.
     246-246: D → N
     314-357: KECRRRKKEY...LKDICSPKTD → RECRRKKKEY...LKDLYCHKAE
Isoform 3 (identifier: P27699-3)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     55-103: Missing.
     183-245: Missing.
     246-246: D → N
Isoform 4 (identifier: P27699-4)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     55-103: Missing.
     183-257: Missing.
     258-258: A → T
Isoform 5 (identifier: P27699-5)

Also known as: Tau Alpha Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     246-257: Missing.
     314-357: KECRRRKKEY...LKDICSPKTD → RECRRKKKEY...LKDLYCHKAE
Isoform 6 (identifier: P27699-6)

Also known as: Tau 2 Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     55-103: Missing.
     314-357: KECRRRKKEY...LKDICSPKTD → RECRRKKKEY...LKDLYCHKAE
Isoform 7 (identifier: P27699-7)

Also known as: Tau 1 Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     183-245: Missing.
     246-246: D → N
     314-357: KECRRRKKEY...LKDICSPKTD → RECRRKKKEY...LKDLYCHKAE
Isoform 8 (identifier: P27699-8)

Also known as: Tau 1 Alpha Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     183-257: Missing.
     258-258: A → T
     314-357: KECRRRKKEY...LKDICSPKTD → RECRRKKKEY...LKDLYCHKAE
Isoform 9 (identifier: P27699-9)

Also known as: Tau 1 Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     183-257: Missing.
     258-258: A → T
Isoform 10 (identifier: P27699-10)

Also known as: Alpha Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     55-103: Missing.
     183-257: Missing.
     258-258: A → T
     314-357: KECRRRKKEY...LKDICSPKTD → RECRRKKKEY...LKDLYCHKAE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 357357cAMP-responsive element modulator
PRO_0000076608

Regions

Domain101 – 16060KID
Domain299 – 35759bZIP
Region300 – 32526Basic motif By similarity
Region327 – 34822Leucine-zipper By similarity

Amino acid modifications

Modified residue2841Phosphoserine By similarity
Modified residue2871Phosphoserine By similarity
Modified residue2901Phosphoserine By similarity

Natural variations

Alternative sequence55 – 10349Missing in isoform 2, isoform 3, isoform 4, isoform 6 and isoform 10.
VSP_000602
Alternative sequence183 – 25775Missing in isoform 4, isoform 8, isoform 9 and isoform 10.
VSP_000605
Alternative sequence183 – 24563Missing in isoform 2, isoform 3 and isoform 7.
VSP_000603
Alternative sequence246 – 25712Missing in isoform 5.
VSP_038016
Alternative sequence2461D → N in isoform 2, isoform 3 and isoform 7.
VSP_000604
Alternative sequence2581A → T in isoform 4, isoform 8, isoform 9 and isoform 10.
VSP_000606
Alternative sequence314 – 35744KECRR…SPKTD → RECRRKKKEYVKCLENRVAV LENQNKTLIEELKALKDLYC HKAE in isoform 2, isoform 5, isoform 6, isoform 7, isoform 8 and isoform 10.
VSP_000607

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CREM-BCEFGgammaHIbeta) (Tau) [UniParc].

Last modified September 22, 2009. Version 2.
Checksum: 0B387B7247113088

FASTA35738,516
        10         20         30         40         50         60 
MSKCGRKKYM RTNVRQMTME TVESQQDRSV TRSVAEHSSA HMQTGQISVP TLAQVSVAGS 

        70         80         90        100        110        120 
GTGRGSPAVT LVQLPSGQTV QVQGVIQTPH PSVIQSPQIQ TVQVATIAET DDSADSEVID 

       130        140        150        160        170        180 
SHKRREILSR RPSYRKILNE LSSDVPGIPK IEEEKSEEEG TPPNIATMAV PTSIYQTSTG 

       190        200        210        220        230        240 
QYIAIAQGGT IQISNPGSDG VQGLQALTMT NSGAPPPGAT IVQYAAQSAD GTQQFFVPGS 

       250        260        270        280        290        300 
QVVVQDEETD LAPSHMAAAT GDMPTYQIRA PTTALPQGVV MAASPGSLHS PQQLAEEATR 

       310        320        330        340        350 
KRELRLMKNR EAAKECRRRK KEYVKCLESR VAVLEVQNKK LIEELETLKD ICSPKTD 

« Hide

Isoform 2 (Alpha) [UniParc].

Checksum: A508BB074EAEA8A6
Show »

FASTA24527,473
Isoform 3 (Beta) [UniParc].

Checksum: F85FB7D3B0451514
Show »

FASTA24527,389
Isoform 4 (Gamma) [UniParc].

Checksum: 9645439A10824456
Show »

FASTA23326,123
Isoform 5 (Tau Alpha Gamma) [UniParc].

Checksum: 508E5448D03B5F8D
Show »

FASTA34537,303
Isoform 6 (Tau 2 Alpha) [UniParc].

Checksum: 438CD86068BA7DAF
Show »

FASTA30833,698
Isoform 7 (Tau 1 Alpha) [UniParc].

Checksum: C637D53AC9A9BCF8
Show »

FASTA29432,376
Isoform 8 (Tau 1 Alpha Gamma) [UniParc].

Checksum: 46A1DA7CDA89F4B5
Show »

FASTA28231,109
Isoform 9 (Tau 1 Gamma) [UniParc].

Checksum: 1BF6D6A824624907
Show »

FASTA28231,025
Isoform 10 (Alpha Gamma) [UniParc].

Checksum: CB124F4EEE69F9E4
Show »

FASTA23326,207

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[2]"CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription."
Foulkes N.S., Borrelli E., Sassone-Corsi P.
Cell 64:739-749(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-357 (ISOFORMS 2; 3 AND 4).
[3]"Identification of novel cAMP responsive element modulator (CREM) isoforms expressed by osteoblasts."
Liu F., Huang Y.-F., Kream B.E.
Calcif. Tissue Int. 77:91-95(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-357 (ISOFORMS 5; 6; 7; 8; 9 AND 10).
Tissue: Osteoblast.
[4]"Developmental switch of CREM function during spermatogenesis: from antagonist to activator."
Foulkes N.S., Mellstroem B., Benusiglio E., Sassone-Corsi P.
Nature 355:80-84(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-357 (ISOFORM 1).
[5]"CBP-independent activation of CREM and CREB by the LIM-only protein ACT."
Fimia G.M., De Cesare D., Sassone-Corsi P.
Nature 398:165-169(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FHL5.
[6]"Transcription factors, cAMP-responsive element modulator (CREM) and Tisp40, act in concert in postmeiotic transcriptional regulation."
Nagamori I., Yomogida K., Adams P.D., Sassone-Corsi P., Nojima H.
J. Biol. Chem. 281:15073-15081(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CREB3L4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC117589 Genomic DNA. No translation available.
M60285 mRNA. Translation: AAA17495.1. Different initiation.
M60285 mRNA. Translation: AAA17496.1. Different initiation.
M60285 mRNA. Translation: AAA17497.1. Different initiation.
AY738715 mRNA. Translation: AAV28551.1. Different initiation.
AY738716 mRNA. Translation: AAV28552.1. Different initiation.
AY738717 mRNA. Translation: AAV28553.1. Different initiation.
AY738718 mRNA. Translation: AAV28554.1. Different initiation.
AY738719 mRNA. Translation: AAV28555.1. Different initiation.
AY738721 mRNA. Translation: AAV28556.1. Different initiation.
PIRA37944.
B37944.
C37944.
S20827.
RefSeqNP_001104320.1. NM_001110850.2.
NP_001104324.2. NM_001110854.1.
NP_001104325.2. NM_001110855.1.
NP_001104326.1. NM_001110856.2.
NP_001104327.1. NM_001110857.2.
NP_001104328.1. NM_001110858.2.
NP_001104329.1. NM_001110859.2.
NP_001258432.1. NM_001271503.1.
NP_001258433.1. NM_001271504.1.
NP_001258434.1. NM_001271505.1.
NP_001258435.1. NM_001271506.1.
NP_038526.2. NM_013498.3.
XP_006525618.1. XM_006525555.1.
XP_006525619.1. XM_006525556.1.
XP_006525624.1. XM_006525561.1.
XP_006525628.1. XM_006525565.1.
XP_006525630.1. XM_006525567.1.
XP_006525631.1. XM_006525568.1.
XP_006525636.1. XM_006525573.1.
XP_006525637.1. XM_006525574.1.
XP_006525638.1. XM_006525575.1.
XP_006525639.1. XM_006525576.1.
UniGeneMm.5244.

3D structure databases

ProteinModelPortalP27699.
SMRP27699. Positions 120-146, 301-355.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198877. 5 interactions.
IntActP27699. 1 interaction.

Proteomic databases

PRIDEP27699.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025069; ENSMUSP00000025069; ENSMUSG00000063889. [P27699-5]
ENSMUST00000082141; ENSMUSP00000080780; ENSMUSG00000063889. [P27699-6]
ENSMUST00000123672; ENSMUSP00000120557; ENSMUSG00000063889.
ENSMUST00000130599; ENSMUSP00000115471; ENSMUSG00000063889.
ENSMUST00000150235; ENSMUSP00000121233; ENSMUSG00000063889. [P27699-1]
ENSMUST00000154135; ENSMUSP00000122051; ENSMUSG00000063889. [P27699-2]
ENSMUST00000154470; ENSMUSP00000118128; ENSMUSG00000063889. [P27699-8]
ENSMUST00000165086; ENSMUSP00000127353; ENSMUSG00000063889. [P27699-7]
GeneID12916.
KEGGmmu:12916.
UCSCuc008dxn.2. mouse. [P27699-2]
uc008dxo.2. mouse. [P27699-7]
uc008dxp.2. mouse. [P27699-8]
uc008dxq.2. mouse. [P27699-9]
uc008dxr.2. mouse. [P27699-5]
uc008dxs.2. mouse. [P27699-6]
uc008dxt.2. mouse. [P27699-10]
uc012ayt.1. mouse. [P27699-1]
uc012ayu.1. mouse. [P27699-3]
uc012ayv.1. mouse. [P27699-4]

Organism-specific databases

CTD1390.
MGIMGI:88495. Crem.

Phylogenomic databases

eggNOGNOG300199.
GeneTreeENSGT00390000008655.
HOVERGENHBG011077.
InParanoidQ5XTP8.
KOK09052.
PhylomeDBP27699.
TreeFamTF106464.

Gene expression databases

ArrayExpressP27699.
BgeeP27699.
CleanExMM_CREM.
GenevestigatorP27699.

Family and domain databases

InterProIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view]
PRINTSPR00041. LEUZIPPRCREB.
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio282558.
PROP27699.
SOURCESearch...

Entry information

Entry nameCREM_MOUSE
AccessionPrimary (citable) accession number: P27699
Secondary accession number(s): P27698 expand/collapse secondary AC list , Q5XTP8, Q5XTP9, Q5XTQ0, Q5XTQ1, Q5XTQ2, Q5XTQ3
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: September 22, 2009
Last modified: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot