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Protein

CREB-regulated transcription coactivator 1

Gene

CRTC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. 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). 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

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

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Biological rhythms, Host-virus interaction, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-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

HGNCiHGNC:16062. CRTC1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • dendrite Source: Ensembl
  • neuronal cell body Source: Ensembl
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
  • synapse Source: Ensembl
Complete GO annotation...

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 residuei113PhosphoserineCombined sources1
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.

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.
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. '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.1 Publication

Binary interactionsi

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

GO - Molecular functioni

  • cAMP response element binding protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116952. 8 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.
OMAiIPQSPPG.
OrthoDBiEOG091G03YN.
PhylomeDBiQ6UUV9.
TreeFamiTF321571.

Family and domain databases

InterProiIPR024786. TORC.
IPR024785. TORC_C.
IPR024784. TORC_M.
IPR024783. TORC_N.
[Graphical view]
PANTHERiPTHR13589. PTHR13589. 1 hit.
PfamiPF12886. TORC_C. 1 hit.
PF12885. TORC_M. 1 hit.
PF12884. TORC_N. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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.Curated
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

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 rs3746266dbSNPEnsembl.1
Natural variantiVAR_053935311V → I.1 PublicationCorresponds to variant rs36070283dbSNPEnsembl.1
Natural variantiVAR_053936328T → A.1 PublicationCorresponds to variant rs3746266dbSNPEnsembl.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

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. 8 interactors.
IntActiQ6UUV9. 5 interactors.
STRINGi9606.ENSP00000345001.

PTM databases

iPTMnetiQ6UUV9.
PhosphoSitePlusiQ6UUV9.

Polymorphism and mutation databases

BioMutaiCRTC1.
DMDMi68565585.

Proteomic databases

EPDiQ6UUV9.
MaxQBiQ6UUV9.
PaxDbiQ6UUV9.
PeptideAtlasiQ6UUV9.
PRIDEiQ6UUV9.

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.
GeneCardsiCRTC1.
HGNCiHGNC:16062. CRTC1.
HPAiHPA022035.
MIMi607536. gene.
neXtProtiNX_Q6UUV9.
OpenTargetsiENSG00000105662.
PharmGKBiPA30730.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGNT. Eukaryota.
ENOG410XPDQ. LUCA.
GeneTreeiENSGT00390000010652.
HOVERGENiHBG058314.
InParanoidiQ6UUV9.
KOiK15309.
OMAiIPQSPPG.
OrthoDBiEOG091G03YN.
PhylomeDBiQ6UUV9.
TreeFamiTF321571.

Enzyme and pathway databases

ReactomeiR-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-400253. Circadian Clock.
SIGNORiQ6UUV9.

Miscellaneous databases

ChiTaRSiCRTC1. human.
GeneWikiiCRTC1.
GenomeRNAii23373.
PROiQ6UUV9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105662.
ExpressionAtlasiQ6UUV9. baseline and differential.
GenevisibleiQ6UUV9. HS.

Family and domain databases

InterProiIPR024786. TORC.
IPR024785. TORC_C.
IPR024784. TORC_M.
IPR024783. TORC_N.
[Graphical view]
PANTHERiPTHR13589. PTHR13589. 1 hit.
PfamiPF12886. TORC_C. 1 hit.
PF12885. TORC_M. 1 hit.
PF12884. TORC_N. 1 hit.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: November 30, 2016
This is version 122 of the entry and version 2 of the sequence. [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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  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. 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.