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Q6UUV7 (CRTC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 75. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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:
CREB-regulated transcription coactivator 3
Alternative name(s):
Transducer of regulated cAMP response element-binding protein 3
Short name=TORC-3
Short name=Transducer of CREB protein 3
Gene names
Name:CRTC3
Synonyms:TORC3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length619 AA.
Sequence statusComplete.
Protein existenceEvidence 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 PPARGC1A 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). Ref.1 Ref.7 Ref.8 Ref.11 Ref.13 Ref.14 Ref.15

Subunit structure

Binding, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1 enhances recruitment of TAF4 to the promoter. 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction By similarity. Interaction with HTLV-1 TAX enhances its transcriptional activity. Interacts, via the N-terminal with the ankyrin repeats of BCL3, to form a complex with CREB1 on CRE and TxRE responsive elements and represses HTLV-1 LTR-mediated transcription. Ref.1 Ref.8 Ref.12 Ref.14

Subcellular location

Nucleus. Cytoplasm. Note: Appears to be mainly nuclear. Ref.1 Ref.7 Ref.9 Ref.11

Tissue specificity

Predominantly expressed in B and T lymphocytes. Highest levels in lung. Also expressed in brain, colon, heart, kidney, ovary, and prostate. Weak expression in liver, pancreas, muscle, small intestine, spleen and stomach. Ref.6 Ref.13

Sequence similarities

Belongs to the TORC family.

Sequence caution

The sequence BAC03424.1 differs from that shown. Reason: Frameshift at position 82.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6UUV7-1)

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 3 (identifier: Q6UUV7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     551-551: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 619619CREB-regulated transcription coactivator 3
PRO_0000318531

Regions

Region1 – 103103Required for interaction with HTLV-1 TAX
Compositional bias180 – 1834Poly-Gly
Compositional bias444 – 4518Poly-Pro

Amino acid modifications

Modified residue41Phosphoserine Ref.17
Modified residue621Phosphoserine Ref.20
Modified residue1621Phosphoserine; by SIK2 By similarity
Modified residue3291Phosphoserine Ref.19
Modified residue3701Phosphoserine Ref.19
Modified residue3911Phosphoserine Ref.18 Ref.20
Modified residue4431Phosphoserine Ref.16 Ref.18 Ref.19

Natural variations

Alternative sequence5511Missing in isoform 3.
VSP_031220
Natural variant721S → N. Ref.1 Ref.2
Corresponds to variant rs8033595 [ dbSNP | Ensembl ].
VAR_038758
Natural variant3461L → S. Ref.5
VAR_038759

Experimental info

Mutagenesis2821Y → F: Translocates to the cytoplasm. Represses basal TORC3 activity towards CREB. Ref.7
Sequence conflict5451P → S in BAB15160. Ref.4
Sequence conflict6161A → T in BAC03424. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 5, 2008. Version 2.
Checksum: A274B96DD1C2678E

FASTA61966,959
        10         20         30         40         50         60 
MAASPGSGSA NPRKFSEKIA LHTQRQAEET RAFEQLMTDL TLSRVQFQKL QQLRLTQYHG 

        70         80         90        100        110        120 
GSLPNVSQLR SSASEFQPSF HQADNVRGTR HHGLVERPSR NRFHPLHRRS GDKPGRQFDG 

       130        140        150        160        170        180 
SAFGANYSSQ PLDESWPRQQ PPWKDEKHPG FRLTSALNRT NSDSALHTSA LSTKPQDPYG 

       190        200        210        220        230        240 
GGGQSAWPAP YMGFCDGENN GHGEVASFPG PLKEENLLNV PKPLPKQLWE TKEIQSLSGR 

       250        260        270        280        290        300 
PRSCDVGGGN AFPHNGQNLG LSPFLGTLNT GGSLPDLTNL HYSTPLPASL DTTDHHFGSM 

       310        320        330        340        350        360 
SVGNSVNNIP AAMTHLGIRS SSGLQSSRSN PSIQATLNKT VLSSSLNNHP QTSVPNASAL 

       370        380        390        400        410        420 
HPSLRLFSLS NPSLSTTNLS GPSRRRQPPV SPLTLSPGPE AHQGFSRQLS STSPLAPYPT 

       430        440        450        460        470        480 
SQMVSSDRSQ LSFLPTEAQA QVSPPPPYPA PQELTQPLLQ QPRAPEAPAQ QPQAASSLPQ 

       490        500        510        520        530        540 
SDFQLLPAQG SSLTNFFPDV GFDQQSMRPG PAFPQQVPLV QQGSRELQDS FHLRPSPYSN 

       550        560        570        580        590        600 
CGSLPNTILP EDSSTSLFKD LNSALAGLPE VSLNVDTPFP LEEELQIEPL SLDGLNMLSD 

       610 
SSMGLLDPSV EETFRADRL 

« Hide

Isoform 3 [UniParc].

Checksum: 9825C1290FBD27C4
Show »

FASTA61866,830

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. expand/collapse author list , Zhu J., Song C., Labow M.A.
Proc. Natl. Acad. Sci. U.S.A. 100:12147-12152(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CREB1, VARIANT ASN-72.
[2]"Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones."
Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N., Ohara O.
DNA Res. 10:49-57(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT ASN-72.
Tissue: Spleen.
[3]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 217-619 (ISOFORM 1).
Tissue: Hepatoma.
[5]"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] OF 292-619 (ISOFORM 1), VARIANT SER-346.
Tissue: Brain.
[6]"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: TISSUE SPECIFICITY.
[7]"The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector."
Screaton R.A., Conkright M.D., Katoh Y., Best J.L., Canettieri G., Jeffries S., Guzman E., Niessen S., Yates J.R. III, Takemori H., Okamoto M., Montminy M.
Cell 119:61-74(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF TYR-282.
[8]"Enhanced activation of tax-dependent transcription of human T-cell leukemia virus type I (HTLV-I) long terminal repeat by TORC3."
Koga H., Ohshima T., Shimotohno K.
J. Biol. Chem. 279:52978-52983(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HTLV-1 TAX, FUNCTION.
[9]"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.
[10]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"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, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[12]"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.
[13]"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.
[14]"BCL3 acts as a negative regulator of transcription from the human T-cell leukemia virus type 1 long terminal repeat through interactions with TORC3."
Hishiki T., Ohshima T., Ego T., Shimotohno K.
J. Biol. Chem. 282:28335-28343(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BCL3 IN BCL3/TORC3/CREB1 COMPLEX, FUNCTION.
[15]"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.
[16]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-443, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[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 SER-391 AND SER-443, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329; SER-370 AND SER-443, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[20]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-391, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY360173 mRNA. Translation: AAQ98858.1.
AK090443 mRNA. Translation: BAC03424.1. Frameshift.
AC021422 Genomic DNA. No translation available.
AC103739 Genomic DNA. No translation available.
AK025521 mRNA. Translation: BAB15160.1.
BC074730 mRNA. Translation: AAH74730.2.
BC074731 mRNA. Translation: AAH74731.3.
CCDSCCDS32331.1. [Q6UUV7-1]
CCDS45348.1. [Q6UUV7-3]
RefSeqNP_001036039.1. NM_001042574.2. [Q6UUV7-3]
NP_073606.3. NM_022769.4. [Q6UUV7-1]
UniGeneHs.567572.

3D structure databases

ProteinModelPortalQ6UUV7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122294. 4 interactions.
DIPDIP-59211N.
IntActQ6UUV7. 3 interactions.
STRING9606.ENSP00000268184.

PTM databases

PhosphoSiteQ6UUV7.

Polymorphism databases

DMDM167009130.

Proteomic databases

MaxQBQ6UUV7.
PaxDbQ6UUV7.
PRIDEQ6UUV7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268184; ENSP00000268184; ENSG00000140577. [Q6UUV7-1]
ENST00000420329; ENSP00000416573; ENSG00000140577. [Q6UUV7-3]
GeneID64784.
KEGGhsa:64784.
UCSCuc002bpo.4. human. [Q6UUV7-3]
uc002bpp.4. human. [Q6UUV7-1]

Organism-specific databases

CTD64784.
GeneCardsGC15P091073.
HGNCHGNC:26148. CRTC3.
HPAHPA043735.
MIM608986. gene.
neXtProtNX_Q6UUV7.
PharmGKBPA142672074.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG74259.
HOGENOMHOG000111980.
HOVERGENHBG058314.
InParanoidQ6UUV7.
KOK16334.
OMAYMGFCDG.
OrthoDBEOG7MKW5P.
PhylomeDBQ6UUV7.
TreeFamTF321571.

Gene expression databases

ArrayExpressQ6UUV7.
BgeeQ6UUV7.
CleanExHS_CRTC3.
GenevestigatorQ6UUV7.

Family and domain databases

InterProIPR024786. TORC.
IPR024785. TORC_C.
IPR024784. TORC_M.
IPR024783. TORC_N.
[Graphical view]
PANTHERPTHR13589. PTHR13589. 1 hit.
PfamPF12886. TORC_C. 1 hit.
PF12885. TORC_M. 1 hit.
PF12884. TORC_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCRTC3. human.
GeneWikiCRTC3.
GenomeRNAi64784.
NextBio66826.
PROQ6UUV7.
SOURCESearch...

Entry information

Entry nameCRTC3_HUMAN
AccessionPrimary (citable) accession number: Q6UUV7
Secondary accession number(s): Q6DK61 expand/collapse secondary AC list , Q6DK62, Q8NF38, Q9H6U2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: July 9, 2014
This is version 75 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM