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Protein

CREB-regulated transcription coactivator 1

Gene

CRTC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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). In concert with SIK1, regulates the light-induced entrainment of the circadian clock. In response to light stimulus, coactivates the CREB-mediated transcription of PER1 which plays an important role in the photic entrainment of the circadian clock.By similarity1 Publication
(Microbial infection) Plays a role of coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei575Required for ubiquitination and degradationBy similarity1

GO - Molecular functioni

  • cAMP response element binding protein binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionActivator
Biological processBiological rhythms, Host-virus interaction, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-400253 Circadian Clock
SIGNORiQ6UUV9

Names & Taxonomyi

Protein namesi
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 namesi
Name:CRTC1Imported
Synonyms:KIAA0616Imported, MECT1Imported, TORC1Imported, WAMTP11 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105662.15
HGNCiHGNC:16062 CRTC1
MIMi607536 gene
neXtProtiNX_Q6UUV9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei42 – 43Breakpoint for translocation to form the MECT1-MAML2 and MAML2-MECT1 fusion proteins2 Publications2

Organism-specific databases

DisGeNETi23373
OpenTargetsiENSG00000105662
PharmGKBiPA30730

Polymorphism and mutation databases

BioMutaiCRTC1
DMDMi68565585

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000963541 – 634CREB-regulated transcription coactivator 1Add BLAST634

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei64PhosphoserineBy similarity1
Modified residuei113PhosphoserineCombined sources1
Modified residuei149PhosphothreonineBy similarity1
Modified residuei151Phosphoserine; by SIK1 and SIK21 Publication1
Modified residuei161PhosphothreonineCombined sources1

Post-translational modificationi

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).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6UUV9
MaxQBiQ6UUV9
PaxDbiQ6UUV9
PeptideAtlasiQ6UUV9
PRIDEiQ6UUV9
ProteomicsDBi67426
67427 [Q6UUV9-2]
67428 [Q6UUV9-3]

PTM databases

iPTMnetiQ6UUV9
PhosphoSitePlusiQ6UUV9

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000105662 Expressed in 184 organ(s), highest expression level in dorsal plus ventral thalamus
ExpressionAtlasiQ6UUV9 baseline and differential
GenevisibleiQ6UUV9 HS

Organism-specific databases

HPAiHPA022035

Interactioni

Subunit structurei

Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1 (PubMed:14536081). 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction (PubMed:14536081). Interaction, via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1 (PubMed:14536081). Binds HTLV1 Tax. Interacts with 14-3-3 proteins (By similarity).By similarity1 Publication
(Microbial infection) Interacts with HTLV1 Tax.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CREB1P162203EBI-1644259,EBI-711855

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116952, 11 interactors
IntActiQ6UUV9, 5 interactors
STRINGi9606.ENSP00000345001

Structurei

3D structure databases

ProteinModelPortaliQ6UUV9
SMRiQ6UUV9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi242 – 258Nuclear export signalBy similarityAdd BLAST17

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi299 – 366Ser-richAdd BLAST68

Sequence similaritiesi

Belongs to the TORC family.Curated

Phylogenomic databases

eggNOGiENOG410IGNT Eukaryota
ENOG410XPDQ LUCA
GeneTreeiENSGT00390000010652
HOVERGENiHBG058314
InParanoidiQ6UUV9
KOiK15309
OMAiCSTLNYS
OrthoDBiEOG091G03YN
PhylomeDBiQ6UUV9
TreeFamiTF321571

Family and domain databases

InterProiView protein in InterPro
IPR024786 TORC
IPR024785 TORC_C
IPR024784 TORC_M
IPR024783 TORC_N
PANTHERiPTHR13589 PTHR13589, 1 hit
PfamiView protein in Pfam
PF12886 TORC_C, 1 hit
PF12885 TORC_M, 1 hit
PF12884 TORC_N, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 11 Publication (identifier: Q6UUV9-1) [UniParc]FASTAAdd to basket

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
MATSNNPRKF SEKIALHNQK QAEETAAFEE VMKDLSLTRA ARLQLQKSQY
60 70 80 90 100
LQLGPSRGQY YGGSLPNVNQ IGSGTMDLPF QTPFQSSGLD TSRTTRHHGL
110 120 130 140 150
VDRVYRERGR LGSPHRRPLS VDKHGRQADS CPYGTMYLSP PADTSWRRTN
160 170 180 190 200
SDSALHQSTM TPTQPESFSS GSQDVHQKRV LLLTVPGMEE TTSEADKNLS
210 220 230 240 250
KQAWDTKKTG SRPKSCEVPG INIFPSADQE NTTALIPATH NTGGSLPDLT
260 270 280 290 300
NIHFPSPLPT PLDPEEPTFP ALSSSSSTGN LAANLTHLGI GGAGQGMSTP
310 320 330 340 350
GSSPQHRPAG VSPLSLSTEA RRQQASPTLS PLSPITQAVA MDALSLEQQL
360 370 380 390 400
PYAFFTQAGS QQPPPQPQPP PPPPPASQQP PPPPPPQAPV RLPPGGPLLP
410 420 430 440 450
SASLTRGPQP PPLAVTVPSS LPQSPPENPG QPSMGIDIAS APALQQYRTS
460 470 480 490 500
AGSPANQSPT SPVSNQGFSP GSSPQHTSTL GSVFGDAYYE QQMAARQANA
510 520 530 540 550
LSHQLEQFNM MENAISSSSL YSPGSTLNYS QAAMMGLTGS HGSLPDSQQL
560 570 580 590 600
GYASHSGIPN IILTVTGESP PSLSKELTSS LAGVGDVSFD SDSQFPLDEL
610 620 630
KIDPLTLDGL HMLNDPDMVL ADPATEDTFR MDRL
Length:634
Mass (Da):67,300
Last modified:July 5, 2005 - v2
Checksum:iECDC427FF9D6920B
GO
Isoform 2Curated (identifier: Q6UUV9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     81-81: Q → QPSGFLGEALAAAPVSL

Note: No experimental confirmation available.
Show »
Length:650
Mass (Da):68,782
Checksum:i0458940C57945F4A
GO
Isoform 31 Publication (identifier: Q6UUV9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     475-503: Missing.
     580-634: SLAGVGDVSF...TEDTFRMDRL → HRGHLPDGPP...CSVPRQRPSL

Show »
Length:593
Mass (Da):62,530
Checksum:iB7D8709B0C731D29
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0QX46M0QX46_HUMAN
CREB-regulated transcription coacti...
CRTC1
593Annotation score:
M0QXN6M0QXN6_HUMAN
CREB-regulated transcription coacti...
CRTC1
392Annotation score:

Sequence cautioni

The sequence AAH17075 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH23614 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAP12463 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti84F → S in BAB14822 (PubMed:14702039).Curated1
Sequence conflicti384P → S in BAB14822 (PubMed:14702039).Curated1
Sequence conflicti556S → G in BAB14822 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053934286T → A. Corresponds to variant dbSNP:rs3746266Ensembl.1
Natural variantiVAR_053935311V → I1 PublicationCorresponds to variant dbSNP:rs36070283Ensembl.1
Natural variantiVAR_053936328T → A1 PublicationCorresponds to variant dbSNP:rs3746266Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05174981Q → QPSGFLGEALAAAPVSL in isoform 2. 2 Publications1
Alternative sequenceiVSP_051750475 – 503Missing in isoform 3. 3 PublicationsAdd BLAST29
Alternative sequenceiVSP_051751580 – 634SLAGV…RMDRL → HRGHLPDGPPVSGHAGTLPL SRPDGASPARGRPCSVPRQR PSL in isoform 3. 3 PublicationsAdd BLAST55

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32963.1 [Q6UUV9-1]
CCDS42525.1 [Q6UUV9-2]
PIRiT00388
RefSeqiNP_001091952.1, NM_001098482.1 [Q6UUV9-2]
NP_056136.2, NM_015321.2 [Q6UUV9-1]
UniGeneiHs.371096

Genome annotation databases

EnsembliENST00000321949; ENSP00000323332; ENSG00000105662 [Q6UUV9-1]
ENST00000338797; ENSP00000345001; ENSG00000105662 [Q6UUV9-2]
GeneIDi23373
KEGGihsa:23373
UCSCiuc002nkb.5 human [Q6UUV9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32963.1 [Q6UUV9-1]
CCDS42525.1 [Q6UUV9-2]
PIRiT00388
RefSeqiNP_001091952.1, NM_001098482.1 [Q6UUV9-2]
NP_056136.2, NM_015321.2 [Q6UUV9-1]
UniGeneiHs.371096

3D structure databases

ProteinModelPortaliQ6UUV9
SMRiQ6UUV9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116952, 11 interactors
IntActiQ6UUV9, 5 interactors
STRINGi9606.ENSP00000345001

PTM databases

iPTMnetiQ6UUV9
PhosphoSitePlusiQ6UUV9

Polymorphism and mutation databases

BioMutaiCRTC1
DMDMi68565585

Proteomic databases

EPDiQ6UUV9
MaxQBiQ6UUV9
PaxDbiQ6UUV9
PeptideAtlasiQ6UUV9
PRIDEiQ6UUV9
ProteomicsDBi67426
67427 [Q6UUV9-2]
67428 [Q6UUV9-3]

Protocols and materials databases

DNASUi23373
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321949; ENSP00000323332; ENSG00000105662 [Q6UUV9-1]
ENST00000338797; ENSP00000345001; ENSG00000105662 [Q6UUV9-2]
GeneIDi23373
KEGGihsa:23373
UCSCiuc002nkb.5 human [Q6UUV9-1]

Organism-specific databases

CTDi23373
DisGeNETi23373
EuPathDBiHostDB:ENSG00000105662.15
GeneCardsiCRTC1
HGNCiHGNC:16062 CRTC1
HPAiHPA022035
MIMi607536 gene
neXtProtiNX_Q6UUV9
OpenTargetsiENSG00000105662
PharmGKBiPA30730
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGNT Eukaryota
ENOG410XPDQ LUCA
GeneTreeiENSGT00390000010652
HOVERGENiHBG058314
InParanoidiQ6UUV9
KOiK15309
OMAiCSTLNYS
OrthoDBiEOG091G03YN
PhylomeDBiQ6UUV9
TreeFamiTF321571

Enzyme and pathway databases

ReactomeiR-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-400253 Circadian Clock
SIGNORiQ6UUV9

Miscellaneous databases

ChiTaRSiCRTC1 human
GeneWikiiCRTC1
GenomeRNAii23373
PROiPR:Q6UUV9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105662 Expressed in 184 organ(s), highest expression level in dorsal plus ventral thalamus
ExpressionAtlasiQ6UUV9 baseline and differential
GenevisibleiQ6UUV9 HS

Family and domain databases

InterProiView protein in InterPro
IPR024786 TORC
IPR024785 TORC_C
IPR024784 TORC_M
IPR024783 TORC_N
PANTHERiPTHR13589 PTHR13589, 1 hit
PfamiView protein in Pfam
PF12886 TORC_C, 1 hit
PF12885 TORC_M, 1 hit
PF12884 TORC_N, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCRTC1_HUMAN
AccessioniPrimary (citable) accession number: Q6UUV9
Secondary accession number(s): A6NMG5
, O75114, Q6Y3A3, Q7LDZ2, Q8IUL3, Q8IZ34, Q8IZL1, Q8N6W3, Q96AI8, Q9H801
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: November 7, 2018
This is version 136 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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