Q6UUV9 (CRTC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
April 3, 2013.
Version 89.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: CREB-regulated transcription coactivator 1 Alternative name(s): Mucoepidermoid carcinoma translocated protein 1 Transducer of regulated cAMP response element-binding protein 1 Short name=TORC-1 Short name=Transducer of CREB protein 1 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 634 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). In the hippocampus, involved in late-phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. May be required for dendritic growth of developing cortical neurons By similarity. Ref.1 Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 |
| Subunit structure | Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1. 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction. Interaction, via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1. Binds HTLV1 Tax. Ref.10 |
| Subcellular location | Cytoplasm. Nucleus. Note: Cytoplasmic when phosphorylated by SIK or AMPK and when sequestered by 14-3-3 proteins By similarity. Translocated to the nucleus on Ser-151 dephosphorylation, instigated by a number of factors including calcium ion and cAMP levels. Ref.1 Ref.11 Ref.13 |
| Tissue specificity | Highly expressed in adult and fetal brain. Located to specific regions such as the prefrontal cortex and cerebellum. Very low expression in other tissues such as heart, spleen, lung, skeletal muscle, salivary gland, ovary and kidney. Ref.8 Ref.15 |
| Post-translational modification | Phosphorylation/dephosphorylation states of Ser-151 are required for regulating transduction of CREB activity. TORCs are inactive when phosphorylated, and active when dephosphorylated at this site. This primary site of phosphorylation is mediated by SIKs (SIK1 and SIK2), is regulated by cAMP and calcium levels and is dependent on the phosphorylation of SIKs by LKB1 By similarity. Ref.11 Ref.13 |
| Involvement in disease | A chromosomal aberration involving CRTC1 is found in mucoepidermoid carcinomas, benign Warthin tumors and clear cell hidradenomas. Translocation t(11;19)(q21;p13) with MAML2. The fusion protein consists of the N-terminus of CRTC1 joined to the C-terminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the C-terminus of CRTC1 has been detected in a small number of mucoepidermoid carcinomas. |
| Sequence similarities | Belongs to the TORC family. |
| Sequence caution | The sequence AAH17075.3 differs from that shown. Reason: Erroneous initiation. The sequence AAH23614.2 differs from that shown. Reason: Erroneous initiation. The sequence AAP12463.1 differs from that shown. Reason: Erroneous initiation. |
Ontologies
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 Ref.1 (identifier: Q6UUV9-1) 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: Q6UUV9-2) The sequence of this isoform differs from the canonical sequence as follows: 81-81: Q → QPSGFLGEALAAAPVSL | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 Ref.2 (identifier: Q6UUV9-3) The sequence of this isoform differs from the canonical sequence as follows: 475-503: Missing. 580-634: SLAGVGDVSF...TEDTFRMDRL → HRGHLPDGPP...CSVPRQRPSL |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 634 | 634 | CREB-regulated transcription coactivator 1 | PRO_0000096354 | |||||
Regions | |||||||||
| Motif | 242 – 258 | 17 | Nuclear export signal By similarity | ||||||
| Compositional bias | 299 – 366 | 68 | Ser-rich | ||||||
Sites | |||||||||
| Site | 42 – 43 | 2 | Breakpoint for translocation to form the MECT1-MAML2 and MAML2-MECT1 fusion proteins Ref.2 Ref.8 | ||||||
| Site | 575 | 1 | Required for ubiquitination and degradation By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 151 | 1 | Phosphoserine; by SIK1 and SIK2 Ref.13 | ||||||
| Modified residue | 161 | 1 | Phosphothreonine Ref.18 | ||||||
Natural variations | |||||||||
| Alternative sequence | 81 | 1 | Q → QPSGFLGEALAAAPVSL in isoform 2. | VSP_051749 | |||||
| Alternative sequence | 475 – 503 | 29 | Missing in isoform 3. | VSP_051750 | |||||
| Alternative sequence | 580 – 634 | 55 | SLAGV…RMDRL → HRGHLPDGPPVSGHAGTLPL SRPDGASPARGRPCSVPRQR PSL in isoform 3. | VSP_051751 | |||||
| Natural variant | 286 | 1 | T → A. Corresponds to variant rs3746266 [ dbSNP | Ensembl ]. | VAR_053934 | |||||
| Natural variant | 311 | 1 | V → I. Ref.7 Corresponds to variant rs36070283 [ dbSNP | Ensembl ]. | VAR_053935 | |||||
| Natural variant | 328 | 1 | T → A. Ref.7 Corresponds to variant rs3746266 [ dbSNP | Ensembl ]. | VAR_053936 | |||||
Experimental info | |||||||||
| Sequence conflict | 84 | 1 | F → S in BAB14822. Ref.4 | ||||||
| Sequence conflict | 384 | 1 | P → S in BAB14822. Ref.4 | ||||||
| Sequence conflict | 556 | 1 | S → G in BAB14822. Ref.4 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells." Iourgenko V., Zhang W., Mickanin C., Daly I., Jiang C., Hexham J.M., Orth A.P., Miraglia L., Meltzer J., Garza D., Chirn G.-W., McWhinnie E., Cohen D., Skelton J., Terry R., Yu Y., Bodian D., Buxton F.P. Labow M.A.Proc. Natl. Acad. Sci. U.S.A. 100:12147-12152(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CREB1. |
| [2] | "t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway." Tonon G., Modi S., Wu L., Kubo A., Coxon A.B., Komiya T., O'Neil K., Stover K., El-Naggar A., Griffin J.D., Kirsch I.R., Kaye F.J. Nat. Genet. 33:208-213(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), CHROMOSOMAL TRANSLOCATION WITH MAML2. |
| [3] | Erratum Tonon G., Modi S., Wu L., Kubo A., Coxon A.B., Komiya T., O'Neil K., Stover K., El-Naggar A., Griffin J.D., Kirsch I.R., Kaye F.J. Nat. Genet. 33:408-408(2003) |
| [4] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Embryo. |
| [5] | "The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. Lucas S.M.Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [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), VARIANTS ILE-311 AND ALA-328. Tissue: Brain, Colon and Eye. |
| [8] | "Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors." Enlund F., Behboudi A., Andren Y., Oberg C., Lendahl U., Mark J., Stenman G. Exp. Cell Res. 292:21-28(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-104 (ISOFORMS 1/3), TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION WITH MAML2. Tissue: Carcinoma. |
| [9] | "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 17-634 (ISOFORM 2). Tissue: Brain. |
| [10] | "TORCs: transducers of regulated CREB activity." Conkright M.D., Canettieri G., Screaton R., Guzman E., Miraglia L., Hogenesch J.B., Montminy M. Mol. Cell 12:413-423(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH CREB1 AND TAF4. |
| [11] | "Activation of cAMP response element-mediated gene expression by regulated nuclear transport of TORC proteins." Bittinger M.A., McWhinnie E., Meltzer J., Iourgenko V., Latario B., Liu X., Chen C.H., Song C., Garza D., Labow M. Curr. Biol. 14:2156-2161(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION. |
| [12] | "Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)-associated TORC1-MAML2 gene fusion." Behboudi A., Winnes M., Gorunova L., van den Oord J.J., Mertens F., Enlund F., Stenman G. Genes Chromosomes Cancer 43:202-205(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION. |
| [13] | "Silencing the constitutive active transcription factor CREB by the LKB1-SIK signaling cascade." Katoh Y., Takemori H., Lin X.-Z., Tamura M., Muraoka M., Satoh T., Tsuchiya Y., Min L., Doi J., Miyauchi A., Witters L.A., Nakamura H., Okamoto M. FEBS J. 273:2730-2748(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-151, SUBCELLULAR LOCATION. |
| [14] | "TORC1 and TORC2 coactivators are required for tax activation of the human T-cell leukemia virus type 1 long terminal repeats." Siu Y.-T., Chin K.-T., Siu K.-L., Yee Wai Choy E., Jeang K.-T., Jin D.-Y. J. Virol. 80:7052-7059(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HTLV-1 TAX, FUNCTION. |
| [15] | "Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha transcription and mitochondrial biogenesis in muscle cells." Wu Z., Huang X., Feng Y., Handschin C., Feng Y., Gullicksen P.S., Bare O., Labow M., Spiegelman B., Stevenson S.C. Proc. Natl. Acad. Sci. U.S.A. 103:14379-14384(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY. |
| [16] | "Dephosphorylation of TORC initiates expression of the StAR gene." Takemori H., Kanematsu M., Kajimura J., Hatano O., Katoh Y., Lin X.-Z., Min L., Yamazaki T., Doi J., Okamoto M. Mol. Cell. Endocrinol. 265:196-204(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [17] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney. |
| [18] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [19] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AY360171 mRNA. Translation: AAQ98856.1. AY040323 mRNA. Translation: AAK93832.1. AY040324 mRNA. Translation: AAK93833.1. Different termination. AK024089 mRNA. Translation: BAB14822.1. AC003107 Genomic DNA. No translation available. AC004476 Genomic DNA. No translation available. AC006123 Genomic DNA. Translation: AAC97072.1. CH471106 Genomic DNA. Translation: EAW84730.1. BC017075 mRNA. Translation: AAH17075.3. Different initiation. BC023614 mRNA. Translation: AAH23614.2. Different initiation. BC028050 mRNA. Translation: AAH28050.1. AB014516 mRNA. Translation: BAA31591.1. AY186997 mRNA. Translation: AAP12462.1. Different termination. AY186998 mRNA. Translation: AAP12463.1. Different initiation. |
| IPI | IPI00303383. IPI00412329. IPI00783099. |
| PIR | T00388. |
| RefSeq | NP_001091952.1. NM_001098482.1. NP_056136.2. NM_015321.2. |
| UniGene | Hs.371096. Hs.428214. |
3D structure databases | |
| ProteinModelPortal | Q6UUV9. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q6UUV9. 3 interactions. |
PTM databases | |
| PhosphoSite | Q6UUV9. |
Polymorphism databases | |
| DMDM | 68565585. |
Proteomic databases | |
| PaxDb | Q6UUV9. |
| PRIDE | Q6UUV9. |
Protocols and materials databases | |
| DNASU | 23373. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000321949; ENSP00000323332; ENSG00000105662. ENST00000338797; ENSP00000345001; ENSG00000105662. |
| GeneID | 23373. |
| KEGG | hsa:23373. |
| UCSC | uc002nkb.4. human. uc010ebv.3. human. |
Organism-specific databases | |
| CTD | 23373. |
| GeneCards | GC19P018794. |
| HGNC | HGNC:16062. CRTC1. |
| HPA | HPA022035. |
| MIM | 607536. gene. |
| neXtProt | NX_Q6UUV9. |
| PharmGKB | PA30730. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG85958. |
| HOVERGEN | HBG058314. |
| KO | K15309. |
| OMA | MAARQAN. |
Gene expression databases | |
| Bgee | Q6UUV9. |
| Genevestigator | Q6UUV9. |
| GermOnline | ENSG00000105662. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR024786. TORC. IPR024785. TORC_C. IPR024784. TORC_M. IPR024783. TORC_N. [Graphical view] |
| PANTHER | PTHR13589. PTHR13589. 1 hit. |
| Pfam | PF12886. TORC_C. 1 hit. PF12885. TORC_M. 1 hit. PF12884. TORC_N. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| ChiTaRS | CRTC1. human. |
| GenomeRNAi | 23373. |
| NextBio | 45456. |
| SOURCE | Search... |
Entry information
| Entry name | CRTC1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q6UUV9 Secondary accession number(s): A6NMG5 Q9H801 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 19 Human chromosome 19: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
