CR3L4_MOUSE
ID CR3L4_MOUSE Reviewed; 370 AA.
AC Q9D2A5; Q9DAE0;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Cyclic AMP-responsive element-binding protein 3-like protein 4;
DE Short=cAMP-responsive element-binding protein 3-like protein 4;
DE AltName: Full=Attaching to CRE-like 1;
DE Short=ATCE1;
DE Short=Acre1;
DE AltName: Full=Transcript induced in spermiogenesis protein 40;
DE Short=Tisp40;
DE AltName: Full=mJAL;
DE Contains:
DE RecName: Full=Processed cyclic AMP-responsive element-binding protein 3-like protein 4;
GN Name=Creb3l4; Synonyms=Atce1, Jal, Tisp40;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=11943763; DOI=10.1093/embo-reports/kvf073;
RA Fujii T., Tamura K., Masai K., Tanaka H., Nishimune Y., Nojima H.;
RT "Use of stepwise subtraction to comprehensively isolate mouse genes whose
RT transcription is up-regulated during spermiogenesis.";
RL EMBO Rep. 3:367-372(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND
RP DNA-BINDING.
RX PubMed=11956138; DOI=10.1210/endo.143.5.8822;
RA Stelzer G., Don J.;
RT "Atce1: a novel mouse cyclic adenosine 3',5'-monophosphate-responsive
RT element-binding protein-like gene exclusively expressed in postmeiotic
RT spermatids.";
RL Endocrinology 143:1578-1588(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEOLYTIC PROCESSING,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF LEU-283 AND
RP ARG-311.
RC TISSUE=Testis;
RX PubMed=15938716; DOI=10.1111/j.1365-2443.2005.00860.x;
RA Nagamori I., Yabuta N., Fujii T., Tanaka H., Yomogida K., Nishimune Y.,
RA Nojima H.;
RT "Tisp40, a spermatid specific bZip transcription factor, functions by
RT binding to the unfolded protein response element via the Rip pathway.";
RL Genes Cells 10:575-594(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Fujita K., Hatakeyama S., Ishikawa F.;
RT "Homo sapiens and Mus musculus JAL gene.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Guo J.H., Dai F.Y., Yu L.;
RT "Mouse Acre1 contains CRE binding domain.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Pituitary, Testis, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16107712; DOI=10.1128/mcb.25.17.7657-7664.2005;
RA Adham I.M., Eck T.J., Mierau K., Muller N., Sallam M.A., Paprotta I.,
RA Schubert S., Hoyer-Fender S., Engel W.;
RT "Reduction of spermatogenesis but not fertility in Creb3l4-deficient
RT mice.";
RL Mol. Cell. Biol. 25:7657-7664(2005).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16925989; DOI=10.1016/j.ydbio.2006.06.029;
RA Gil S., Yosef D., Golan N., Don J.;
RT "The enigma of ATCE1, an acrosome-associated transcription factor.";
RL Dev. Biol. 298:201-211(2006).
RN [10]
RP FUNCTION.
RX PubMed=16999736; DOI=10.1111/j.1365-2443.2006.01013.x;
RA Nagamori I., Yomogida K., Ikawa M., Okabe M., Yabuta N., Nojima H.;
RT "The testes-specific bZip type transcription factor Tisp40 plays a role in
RT ER stress responses and chromatin packaging during spermiogenesis.";
RL Genes Cells 11:1161-1171(2006).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=16728718; DOI=10.2164/jandrol.106.000596;
RA El-Alfy M., Azzi L., Lessard J., Lavergne E., Pelletier M., Labrie C.;
RT "Stage-specific expression of the Atce1/Tisp40alpha isoform of CREB3L4 in
RT mouse spermatids.";
RL J. Androl. 27:686-694(2006).
RN [12]
RP FUNCTION, AND INTERACTION WITH CREM.
RX PubMed=16595651; DOI=10.1074/jbc.m602051200;
RA Nagamori I., Yomogida K., Adams P.D., Sassone-Corsi P., Nojima H.;
RT "Transcription factors, cAMP-responsive element modulator (CREM) and
RT Tisp40, act in concert in postmeiotic transcriptional regulation.";
RL J. Biol. Chem. 281:15073-15081(2006).
CC -!- FUNCTION: Transcriptional activator that may play a role in the
CC unfolded protein response of the testis. Proposed to be involved in
CC spermiogenesis. May be involved in regulating the maturation of sperm
CC head nuclei. Alternatively proposed to be a paternally delivered
CC transcription factor that may function in early zygotic gene
CC activation. Increases the binding of CREM isoform Tau with CRE. The
CC CREM isoform Tau-CREB3L4 heterodimer functions through CRE but not
CC through UPRE and may recruit HIRA to CRE to regulate histone exchange.
CC {ECO:0000269|PubMed:16107712, ECO:0000269|PubMed:16595651,
CC ECO:0000269|PubMed:16925989, ECO:0000269|PubMed:16999736}.
CC -!- SUBUNIT: Binds DNA as a dimer (By similarity). Forms a heterodimer with
CC CREM isoform Tau. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16925989}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:16925989}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome inner membrane {ECO:0000269|PubMed:16925989}; Single-pass type
CC II membrane protein {ECO:0000269|PubMed:16925989}. Note=According to
CC PubMed:16925989 is not observed within nuclei of haploid spermatids at
CC any spermiogenic stage.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding
CC protein 3-like protein 4]: Nucleus. Note=Under ER stress the cleaved N-
CC terminal cytoplasmic domain translocates into the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=Tisp40beta;
CC IsoId=Q9D2A5-1; Sequence=Displayed;
CC Name=2; Synonyms=Tisp40alpha;
CC IsoId=Q9D2A5-2; Sequence=VSP_025639;
CC -!- TISSUE SPECIFICITY: Predominantly expressed at high levels in testis
CC with isoform 2 being the predominant isoform. Specifically expressed in
CC postmeiotic spermatids and accumulates in the mid/late stage (at
CC protein level). Ubiquitously expressed at low levels.
CC {ECO:0000269|PubMed:11956138, ECO:0000269|PubMed:15938716,
CC ECO:0000269|PubMed:16107712, ECO:0000269|PubMed:16728718,
CC ECO:0000269|PubMed:16925989}.
CC -!- DEVELOPMENTAL STAGE: Expression is very low in the prepubertal testis
CC (2-5-, 8- and 17-day-old) but becomes abruptly induced in the
CC postpubertal testis (29-day-old), after which expression increased
CC (35- and 60-day-old). {ECO:0000269|PubMed:15938716}.
CC -!- PTM: Controlled by regulated intramembrane proteolysis (RIP). Following
CC ER stress a fragment containing the cytoplasmic transcription factor
CC domain is released by proteolysis. The cleavage seems to be performed
CC sequentially by site-1 and site-2 proteases (PS1 and PS2). PS1 cleavage
CC may be suppressed by a determinant in the C-terminal region.
CC {ECO:0000269|PubMed:15938716}.
CC -!- MISCELLANEOUS: Creb3l4 null-deficient mice show a reduced
CC spermatogenesis but are fertile.
CC -!- MISCELLANEOUS: [Isoform 1]: Minor.
CC -!- MISCELLANEOUS: [Isoform 2]: Major. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
CC -!- CAUTION: According to PubMed:15938716 binds to the UPR element (UPRE)
CC but not to CRE or the NF-kappa-B site. Preferentially binds DNA with to
CC the consensus sequence 5'-T[GT]ACGT[GA][GT]-3' and has transcriptional
CC activation activity from UPRE. According to PubMed:11956138 and to
CC PubMed:16925989 binds to NF-kappa-B site and has transcriptional
CC activation activity from NF-kappa-B-containing regulatory elements.
CC {ECO:0000305}.
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DR EMBL; AB047647; BAB97209.1; -; mRNA.
DR EMBL; AF287260; AAK73568.1; -; mRNA.
DR EMBL; AB182651; BAD26707.1; -; mRNA.
DR EMBL; AB182652; BAD26708.1; -; mRNA.
DR EMBL; AB052779; BAC45036.1; -; mRNA.
DR EMBL; AY049978; AAL13158.1; -; mRNA.
DR EMBL; AK019928; BAB31922.1; -; mRNA.
DR EMBL; AK088919; BAC40653.1; -; mRNA.
DR EMBL; AK005918; BAB24315.1; -; mRNA.
DR EMBL; BC022605; AAH22605.1; -; mRNA.
DR CCDS; CCDS17524.1; -. [Q9D2A5-1]
DR RefSeq; NP_001294863.1; NM_001307934.1. [Q9D2A5-1]
DR RefSeq; NP_001294864.1; NM_001307935.1. [Q9D2A5-2]
DR RefSeq; NP_084356.1; NM_030080.3. [Q9D2A5-1]
DR RefSeq; XP_017175297.1; XM_017319808.1. [Q9D2A5-1]
DR AlphaFoldDB; Q9D2A5; -.
DR SMR; Q9D2A5; -.
DR BioGRID; 219303; 10.
DR STRING; 10090.ENSMUSP00000029547; -.
DR GlyGen; Q9D2A5; 2 sites.
DR iPTMnet; Q9D2A5; -.
DR PhosphoSitePlus; Q9D2A5; -.
DR PaxDb; Q9D2A5; -.
DR PRIDE; Q9D2A5; -.
DR ProteomicsDB; 285299; -. [Q9D2A5-1]
DR ProteomicsDB; 285300; -. [Q9D2A5-2]
DR Antibodypedia; 34142; 262 antibodies from 35 providers.
DR DNASU; 78284; -.
DR Ensembl; ENSMUST00000029547; ENSMUSP00000029547; ENSMUSG00000027938. [Q9D2A5-1]
DR Ensembl; ENSMUST00000107369; ENSMUSP00000102992; ENSMUSG00000027938. [Q9D2A5-1]
DR GeneID; 78284; -.
DR KEGG; mmu:78284; -.
DR UCSC; uc008qbp.1; mouse. [Q9D2A5-1]
DR CTD; 148327; -.
DR MGI; MGI:1916603; Creb3l4.
DR VEuPathDB; HostDB:ENSMUSG00000027938; -.
DR eggNOG; KOG0709; Eukaryota.
DR GeneTree; ENSGT00940000160806; -.
DR HOGENOM; CLU_047257_3_0_1; -.
DR InParanoid; Q9D2A5; -.
DR OMA; DSCIFSD; -.
DR OrthoDB; 644485at2759; -.
DR PhylomeDB; Q9D2A5; -.
DR TreeFam; TF316079; -.
DR BioGRID-ORCS; 78284; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Gata3; mouse.
DR PRO; PR:Q9D2A5; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9D2A5; protein.
DR Bgee; ENSMUSG00000027938; Expressed in spermatid and 105 other tissues.
DR Genevisible; Q9D2A5; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0002079; C:inner acrosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0035497; F:cAMP response element binding; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:InterPro.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR029807; CREB4.
DR PANTHER; PTHR45996:SF2; PTHR45996:SF2; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative promoter usage; Cytoplasmic vesicle;
KW Developmental protein; Differentiation; DNA-binding; Endoplasmic reticulum;
KW Glycoprotein; Membrane; Nucleus; Reference proteome; Signal-anchor;
KW Spermatogenesis; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Unfolded protein response.
FT CHAIN 1..370
FT /note="Cyclic AMP-responsive element-binding protein 3-like
FT protein 4"
FT /id="PRO_0000288081"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-responsive element-binding
FT protein 3-like protein 4"
FT /id="PRO_0000296221"
FT TOPO_DOM 1..271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..370
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 193..256
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..55
FT /note="Required for transcriptional activation"
FT REGION 61..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 195..234
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 235..256
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT SITE 314..315
FT /note="Cleavage; by PS1"
FT /evidence="ECO:0000250"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..55
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11943763,
FT ECO:0000303|PubMed:11956138, ECO:0000303|PubMed:15938716,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_025639"
FT MUTAGEN 283
FT /note="L->P: Lowers translocation to the nucleus."
FT /evidence="ECO:0000269|PubMed:15938716"
FT MUTAGEN 311
FT /note="R->A: Abolishes cleavage by SP1."
FT /evidence="ECO:0000269|PubMed:15938716"
SQ SEQUENCE 370 AA; 41025 MW; F64D7F2F14547B4F CRC64;
MELGCPELLE PPEDIFSTGS FLELGFNGPA SKVPVTRGLQ KSEPDDFLNL FIDPNMIHCS
ETSPGRDSGV SEDPGSPAQQ ASSSPALYEV VYDSGTLQGT QREAGPTFGL ISIQIDQWTP
ALMVPDACTV SGLPSDSHRH ILPRVSTRAP APPAAMPSCQ HHLFLTDEEK QLLAQEGITL
PSHLPLTKAE ERILKKIRRK IRNKQSAQDS RRRKKEYLDG LESRVAACSE QNQKLQRKVQ
ELERQNIFLM EQVRQLQKLT AQTSSRAAQT STCVLILLFS LALIILPSFS PFQGQSEARP
EDYQLHGVIS RNILTHENVT ENLESPVLKS KLEELPEAPT TNGSTKTHLK MRVKARPPGQ
IRGMVHTDEM
