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Protein

Cyclic AMP-responsive element-binding protein 3-like protein 4

Gene

Creb3l4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional activator that may play a role in the unfolded protein response of the testis. Proposed to be involved in spermiogenesis. May be involved in regulating the maturation of sperm head nuclei. Alternatively proposed to be a paternally delivered transcription factor that may function in early zygotic gene activation. Increases the binding of CREM isoform Tau with CRE. The CREM isoform Tau-CREB3L4 heterodimer functions through CRE but not through UPRE and may recruit HIRA to CRE to regulate histone exchange.4 Publications

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • endoplasmic reticulum unfolded protein response Source: InterPro
  • multicellular organism development Source: UniProtKB-KW
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • spermatogenesis Source: MGI
  • transcription from RNA polymerase II promoter Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Differentiation, Spermatogenesis, Transcription, Transcription regulation, Unfolded protein response

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic AMP-responsive element-binding protein 3-like protein 4
Short name:
cAMP-responsive element-binding protein 3-like protein 4
Alternative name(s):
Attaching to CRE-like 1
Short name:
ATCE1
Short name:
Acre1
Transcript induced in spermiogenesis protein 40
Short name:
Tisp40
mJAL
Cleaved into the following chain:
Gene namesi
Name:Creb3l4
Synonyms:Atce1, Jal, Tisp40
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1916603. Creb3l4.

Subcellular locationi

Processed cyclic AMP-responsive element-binding protein 3-like protein 4 :
  • Nucleus

  • Note: Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 271271CytoplasmicSequence analysisAdd
BLAST
Transmembranei272 – 29221Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini293 – 37078LumenalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi283 – 2831L → P: Lowers translocation to the nucleus. 1 Publication
Mutagenesisi311 – 3111R → A: Abolishes cleavage by SP1. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 370370Cyclic AMP-responsive element-binding protein 3-like protein 4PRO_0000288081Add
BLAST
Chaini1 – ?Processed cyclic AMP-responsive element-binding protein 3-like protein 4PRO_0000296221

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi318 – 3181N-linked (GlcNAc...)Sequence analysis
Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Controlled by regulated intramembrane proteolysis (RIP). Following ER stress a fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases (PS1 and PS2). PS1 cleavage may be suppressed by a determinant in the C-terminal region.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei314 – 3152Cleavage; by PS1By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9D2A5.
PRIDEiQ9D2A5.

PTM databases

iPTMnetiQ9D2A5.
PhosphoSiteiQ9D2A5.

Expressioni

Tissue specificityi

Predominantly expressed at high levels in testis with isoform 2 being the predominant isoform. Specifically expressed in postmeiotic spermatids and accumulates in the mid/late stage (at protein level). Ubiquitously expressed at low levels.5 Publications

Developmental stagei

Expression is very low in the prepubertal testis (2-5-, 8- and 17-day-old) but becomes abruptly induced in the postpubertal testis (29-day-old), after which expression increased (35- and 60-day-old).1 Publication

Gene expression databases

BgeeiQ9D2A5.
CleanExiMM_CREB3L4.
GenevisibleiQ9D2A5. MM.

Interactioni

Subunit structurei

Binds DNA as a dimer (By similarity). Forms a heterodimer with CREM isoform Tau.By similarity

Protein-protein interaction databases

BioGridi219303. 10 interactions.
STRINGi10090.ENSMUSP00000029547.

Structurei

3D structure databases

ProteinModelPortaliQ9D2A5.
SMRiQ9D2A5. Positions 199-244.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini193 – 25664bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 5555Required for transcriptional activationAdd
BLAST
Regioni195 – 23440Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni235 – 25622Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the bZIP family. ATF subfamily.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0709. Eukaryota.
ENOG410ZZQM. LUCA.
GeneTreeiENSGT00520000055538.
HOGENOMiHOG000059566.
HOVERGENiHBG058316.
InParanoidiQ9D2A5.
KOiK09048.
OMAiEDYQPHG.
OrthoDBiEOG7KM5SZ.
PhylomeDBiQ9D2A5.
TreeFamiTF316079.

Family and domain databases

InterProiIPR004827. bZIP.
IPR029807. CREB4.
[Graphical view]
PANTHERiPTHR22952:SF105. PTHR22952:SF105. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

Isoform 1 (identifier: Q9D2A5-1) [UniParc]FASTAAdd to basket

Also known as: Tisp40beta

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
MELGCPELLE PPEDIFSTGS FLELGFNGPA SKVPVTRGLQ KSEPDDFLNL
60 70 80 90 100
FIDPNMIHCS ETSPGRDSGV SEDPGSPAQQ ASSSPALYEV VYDSGTLQGT
110 120 130 140 150
QREAGPTFGL ISIQIDQWTP ALMVPDACTV SGLPSDSHRH ILPRVSTRAP
160 170 180 190 200
APPAAMPSCQ HHLFLTDEEK QLLAQEGITL PSHLPLTKAE ERILKKIRRK
210 220 230 240 250
IRNKQSAQDS RRRKKEYLDG LESRVAACSE QNQKLQRKVQ ELERQNIFLM
260 270 280 290 300
EQVRQLQKLT AQTSSRAAQT STCVLILLFS LALIILPSFS PFQGQSEARP
310 320 330 340 350
EDYQLHGVIS RNILTHENVT ENLESPVLKS KLEELPEAPT TNGSTKTHLK
360 370
MRVKARPPGQ IRGMVHTDEM
Note: Minor.
Length:370
Mass (Da):41,025
Last modified:June 1, 2001 - v1
Checksum:iF64D7F2F14547B4F
GO
Isoform 2 (identifier: Q9D2A5-2) [UniParc]FASTAAdd to basket

Also known as: Tisp40alpha

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.

Note: Major.
Show »
Length:315
Mass (Da):35,020
Checksum:iBCE2B0EBA240DD16
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5555Missing in isoform 2. 4 PublicationsVSP_025639Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB047647 mRNA. Translation: BAB97209.1.
AF287260 mRNA. Translation: AAK73568.1.
AB182651 mRNA. Translation: BAD26707.1.
AB182652 mRNA. Translation: BAD26708.1.
AB052779 mRNA. Translation: BAC45036.1.
AY049978 mRNA. Translation: AAL13158.1.
AK019928 mRNA. Translation: BAB31922.1.
AK088919 mRNA. Translation: BAC40653.1.
AK005918 mRNA. Translation: BAB24315.1.
BC022605 mRNA. Translation: AAH22605.1.
CCDSiCCDS17524.1. [Q9D2A5-1]
RefSeqiNP_001294863.1. NM_001307934.1. [Q9D2A5-1]
NP_001294864.1. NM_001307935.1. [Q9D2A5-2]
NP_084356.1. NM_030080.3. [Q9D2A5-1]
UniGeneiMm.299952.

Genome annotation databases

EnsembliENSMUST00000029547; ENSMUSP00000029547; ENSMUSG00000027938. [Q9D2A5-1]
ENSMUST00000107369; ENSMUSP00000102992; ENSMUSG00000027938. [Q9D2A5-1]
GeneIDi78284.
KEGGimmu:78284.
UCSCiuc008qbp.1. mouse. [Q9D2A5-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB047647 mRNA. Translation: BAB97209.1.
AF287260 mRNA. Translation: AAK73568.1.
AB182651 mRNA. Translation: BAD26707.1.
AB182652 mRNA. Translation: BAD26708.1.
AB052779 mRNA. Translation: BAC45036.1.
AY049978 mRNA. Translation: AAL13158.1.
AK019928 mRNA. Translation: BAB31922.1.
AK088919 mRNA. Translation: BAC40653.1.
AK005918 mRNA. Translation: BAB24315.1.
BC022605 mRNA. Translation: AAH22605.1.
CCDSiCCDS17524.1. [Q9D2A5-1]
RefSeqiNP_001294863.1. NM_001307934.1. [Q9D2A5-1]
NP_001294864.1. NM_001307935.1. [Q9D2A5-2]
NP_084356.1. NM_030080.3. [Q9D2A5-1]
UniGeneiMm.299952.

3D structure databases

ProteinModelPortaliQ9D2A5.
SMRiQ9D2A5. Positions 199-244.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219303. 10 interactions.
STRINGi10090.ENSMUSP00000029547.

PTM databases

iPTMnetiQ9D2A5.
PhosphoSiteiQ9D2A5.

Proteomic databases

PaxDbiQ9D2A5.
PRIDEiQ9D2A5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029547; ENSMUSP00000029547; ENSMUSG00000027938. [Q9D2A5-1]
ENSMUST00000107369; ENSMUSP00000102992; ENSMUSG00000027938. [Q9D2A5-1]
GeneIDi78284.
KEGGimmu:78284.
UCSCiuc008qbp.1. mouse. [Q9D2A5-1]

Organism-specific databases

CTDi148327.
MGIiMGI:1916603. Creb3l4.

Phylogenomic databases

eggNOGiKOG0709. Eukaryota.
ENOG410ZZQM. LUCA.
GeneTreeiENSGT00520000055538.
HOGENOMiHOG000059566.
HOVERGENiHBG058316.
InParanoidiQ9D2A5.
KOiK09048.
OMAiEDYQPHG.
OrthoDBiEOG7KM5SZ.
PhylomeDBiQ9D2A5.
TreeFamiTF316079.

Miscellaneous databases

NextBioi348617.
PROiQ9D2A5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9D2A5.
CleanExiMM_CREB3L4.
GenevisibleiQ9D2A5. MM.

Family and domain databases

InterProiIPR004827. bZIP.
IPR029807. CREB4.
[Graphical view]
PANTHERiPTHR22952:SF105. PTHR22952:SF105. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Use of stepwise subtraction to comprehensively isolate mouse genes whose transcription is up-regulated during spermiogenesis."
    Fujii T., Tamura K., Masai K., Tanaka H., Nishimune Y., Nojima H.
    EMBO Rep. 3:367-372(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Testis.
  2. "Atce1: a novel mouse cyclic adenosine 3',5'-monophosphate-responsive element-binding protein-like gene exclusively expressed in postmeiotic spermatids."
    Stelzer G., Don J.
    Endocrinology 143:1578-1588(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, DNA-BINDING.
  3. "Tisp40, a spermatid specific bZip transcription factor, functions by binding to the unfolded protein response element via the Rip pathway."
    Nagamori I., Yabuta N., Fujii T., Tanaka H., Yomogida K., Nishimune Y., Nojima H.
    Genes Cells 10:575-594(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF LEU-283 AND ARG-311.
    Tissue: Testis.
  4. "Homo sapiens and Mus musculus JAL gene."
    Fujita K., Hatakeyama S., Ishikawa F.
    Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  5. "Mouse Acre1 contains CRE binding domain."
    Guo J.H., Dai F.Y., Yu L.
    Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  6. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J and NOD.
    Tissue: Pituitary, Testis and Thymus.
  7. "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 1).
    Strain: FVB/N.
    Tissue: Salivary gland.
  8. Cited for: FUNCTION, TISSUE SPECIFICITY.
  9. "The enigma of ATCE1, an acrosome-associated transcription factor."
    Gil S., Yosef D., Golan N., Don J.
    Dev. Biol. 298:201-211(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  10. "The testes-specific bZip type transcription factor Tisp40 plays a role in ER stress responses and chromatin packaging during spermiogenesis."
    Nagamori I., Yomogida K., Ikawa M., Okabe M., Yabuta N., Nojima H.
    Genes Cells 11:1161-1171(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Stage-specific expression of the Atce1/Tisp40alpha isoform of CREB3L4 in mouse spermatids."
    El-Alfy M., Azzi L., Lessard J., Lavergne E., Pelletier M., Labrie C.
    J. Androl. 27:686-694(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  12. "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 CREM.

Entry informationi

Entry nameiCR3L4_MOUSE
AccessioniPrimary (citable) accession number: Q9D2A5
Secondary accession number(s): Q9DAE0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: June 1, 2001
Last modified: May 11, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Creb3l4 null-deficient mice show a reduced spermatogenesis but are fertile.

Caution

According to PubMed:15938716 binds to the UPR element (UPRE) but not to CRE or the NF-kappa-B site. Preferentially binds DNA with to the consensus sequence 5'-T[GT]ACGT[GA][GT]-3' and has transcriptional activation activity from UPRE. According to PubMed:11956138 and to PubMed:16925989 binds to NF-kappa-B site and has transcriptional activation activity from NF-kappa-B-containing regulatory elements.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.