CREM_RAT
ID CREM_RAT Reviewed; 357 AA.
AC Q03061; Q6AYV1;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=cAMP-responsive element modulator;
GN Name=Crem;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC STRAIN=Brown Norway; TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-357 (ISOFORM TAU).
RC TISSUE=Testis;
RX PubMed=1461747; DOI=10.1093/nar/20.22.6106;
RA Meyer T.E., Habener J.F.;
RT "Cyclic AMP response element binding protein CREB and modulator protein
RT CREM are products of distinct genes.";
RL Nucleic Acids Res. 20:6106-6106(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-68 (ISOFORM 5), NUCLEOTIDE SEQUENCE [MRNA]
RP OF 1-62 (ISOFORM 6), AND TISSUE SPECIFICITY.
RX PubMed=11089521; DOI=10.1210/endo.141.11.7758;
RA Daniel P.B., Rohrbach L., Habener J.F.;
RT "Novel cyclic adenosine 3',5'-monophosphate (cAMP) response element
RT modulator theta isoforms expressed by two newly identified cAMP-responsive
RT promoters active in the testis.";
RL Endocrinology 141:3923-3930(2000).
RN [4]
RP TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING.
RX PubMed=7515286; DOI=10.1095/biolreprod50.4.869;
RA West A.P., Sharpe R.M., Saunders P.T.;
RT "Differential regulation of cyclic adenosine 3',5'-monophosphate (cAMP)
RT response element-binding protein and cAMP response element modulator
RT messenger ribonucleic acid transcripts by follicle-stimulating hormone and
RT androgen in the adult rat testis.";
RL Biol. Reprod. 50:869-881(1994).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Transcriptional regulator that binds the cAMP response
CC element (CRE), a sequence present in many viral and cellular promoters.
CC Isoforms are either transcriptional activators or repressors. Isoform
CC Delta is an activator. Plays a role in spermatogenesis and is involved
CC in spermatid maturation. Binding of isoform Tau (activator) to CRE is
CC increased by CREB3L4. The CREM isoform Tau-CREB3L4 heterodimer
CC functions through CRE and may recruit HIRA to CRE to regulate histone
CC exchange (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds DNA as a dimer. Interacts with CDC34. Interacts with
CC FHL5. Isoform delta forms a heterodimer with CREB3L4. May interact with
CC TSSK4. {ECO:0000250|UniProtKB:P27699, ECO:0000250|UniProtKB:Q03060}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=7;
CC Name=7;
CC IsoId=Q03061-7; Sequence=Displayed;
CC Name=Tau; Synonyms=CREM-BCEFGgammaHIbeta;
CC IsoId=Q03061-1; Sequence=VSP_038017;
CC Name=Alpha;
CC IsoId=Q03061-2; Sequence=Not described;
CC Name=Beta;
CC IsoId=Q03061-3; Sequence=Not described;
CC Name=Gamma;
CC IsoId=Q03061-4; Sequence=Not described;
CC Name=5; Synonyms=CREM-theta1CEFGgammaHIbeta;
CC IsoId=Q03061-5; Sequence=VSP_026079;
CC Name=6; Synonyms=CREM-theta2CEFGgammaHIbeta;
CC IsoId=Q03061-6; Sequence=VSP_026080;
CC -!- TISSUE SPECIFICITY: Isoform Tau is expressed in testis germ cells.
CC CREM-theta1- and CREM-theta2-containing isoforms are expressed in
CC testis. {ECO:0000269|PubMed:11089521, ECO:0000269|PubMed:7515286}.
CC -!- PTM: Stimulated by phosphorylation. Phosphorylated on Ser-116 by TSSK4
CC in vitro. {ECO:0000250|UniProtKB:P27699, ECO:0000250|UniProtKB:Q01147}.
CC -!- PTM: Ubiquitinated by CDC34 and RAD6B in order to be degraded by the
CC proteasome. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 7]: Produced by alternative splicing.
CC -!- MISCELLANEOUS: [Isoform Tau]: Produced by alternative promoter usage.
CC Activator. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative promoter usage.
CC Activator. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Produced by alternative promoter usage.
CC Activator. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
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DR EMBL; BC078899; AAH78899.1; -; mRNA.
DR EMBL; Z15158; CAA78857.1; -; mRNA.
DR PIR; S26686; S26686.
DR RefSeq; NP_001104330.1; NM_001110860.2.
DR RefSeq; NP_001258030.1; NM_001271101.1. [Q03061-7]
DR AlphaFoldDB; Q03061; -.
DR SMR; Q03061; -.
DR BioGRID; 247649; 3.
DR STRING; 10116.ENSRNOP00000062109; -.
DR PaxDb; Q03061; -.
DR Ensembl; ENSRNOT00000089536; ENSRNOP00000074062; ENSRNOG00000014900. [Q03061-5]
DR Ensembl; ENSRNOT00000111611; ENSRNOP00000083222; ENSRNOG00000014900. [Q03061-6]
DR GeneID; 25620; -.
DR KEGG; rno:25620; -.
DR UCSC; RGD:2402; rat. [Q03061-7]
DR CTD; 1390; -.
DR RGD; 2402; Crem.
DR VEuPathDB; HostDB:ENSRNOG00000014900; -.
DR eggNOG; KOG3584; Eukaryota.
DR GeneTree; ENSGT00940000156952; -.
DR InParanoid; Q03061; -.
DR OMA; MSKCSRK; -.
DR OrthoDB; 957343at2759; -.
DR PhylomeDB; Q03061; -.
DR PRO; PR:Q03061; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000014900; Expressed in testis and 19 other tissues.
DR ExpressionAtlas; Q03061; baseline and differential.
DR Genevisible; Q03061; RN.
DR GO; GO:1990589; C:ATF4-CREB1 transcription factor complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0019933; P:cAMP-mediated signaling; TAS:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; IEP:RGD.
DR GO; GO:0006006; P:glucose metabolic process; IEP:RGD.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; IEP:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0051591; P:response to cAMP; ISO:RGD.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR003102; Coactivator_CBP_pKID.
DR InterPro; IPR001630; Leuzip_CREB.
DR PANTHER; PTHR45879; PTHR45879; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR Pfam; PF02173; pKID; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
DR PROSITE; PS50953; KID; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative promoter usage; Alternative splicing; DNA-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..357
FT /note="cAMP-responsive element modulator"
FT /id="PRO_0000076609"
FT DOMAIN 101..160
FT /note="KID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00312"
FT DOMAIN 299..357
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 300..325
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 327..348
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27699"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03060"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03060,
FT ECO:0000255|PROSITE-ProRule:PRU00312"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03060,
FT ECO:0000255|PROSITE-ProRule:PRU00312"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03060,
FT ECO:0000255|PROSITE-ProRule:PRU00312"
FT VAR_SEQ 1..54
FT /note="MSKCGRKKYMRTNVRQMTMETVESQQDRSVTHSVAEHSSAHMQTGQISVPTL
FT AQ -> MWWHQHNLCFRHPVEEDYSSGDLDKK (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11089521"
FT /id="VSP_026079"
FT VAR_SEQ 1..54
FT /note="MSKCGRKKYMRTNVRQMTMETVESQQDRSVTHSVAEHSSAHMQTGQISVPTL
FT AQ -> M (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:11089521"
FT /id="VSP_026080"
FT VAR_SEQ 314..357
FT /note="KECRRRKKEYVKCLESRVAVLEVQNKKLIEELETLKDICSPKTD -> RECR
FT RKKKEYVKCLENRVAVLESQNKTLIEELKALKDLYCHKAE (in isoform Tau)"
FT /evidence="ECO:0000303|PubMed:1461747"
FT /id="VSP_038017"
FT CONFLICT 40
FT /note="A -> L (in Ref. 2; CAA78857)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 357 AA; 38497 MW; 5660B6802B3047B2 CRC64;
MSKCGRKKYM RTNVRQMTME TVESQQDRSV THSVAEHSSA HMQTGQISVP TLAQVSVAGS
GTGRGSPAVT LVQLPSGQTV QVQGVIQTPH PSVIQSPQIQ TVQVATIAET DDSADSEVID
SHKRREILSR RPSYRKILNE LSSDVPGIPK IEEEKSEEEG TPPNIATMAV PTSIYQTSTG
QYIAIAQGGT IQISNPGSDG VQGLQALTMT NSGAPPPGAT IVQYAAQSAD GTQQFFVPGS
QVVVQDEETD LAPSHMAAAT GDMPTYQIRA PTTALPQGVV MAASPGSLHS PQQLAEEATR
KRELRLMKNR EAAKECRRRK KEYVKCLESR VAVLEVQNKK LIEELETLKD ICSPKTD
