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CCNT1 cyclin T1 [ Homo sapiens (human) ]

Gene ID: 904, updated on 26-May-2016
Official Symbol
CCNT1provided by HGNC
Official Full Name
cyclin T1provided by HGNC
Primary source
HGNC:HGNC:1599
See related
Ensembl:ENSG00000129315 HPRD:03938; MIM:143055; Vega:OTTHUMG00000170393
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CCNT; CYCT1; HIVE1
Summary
This gene encodes a member of the highly conserved cyclin C subfamily. The encoded protein tightly associates with cyclin-dependent kinase 9, and is a major subunit of positive transcription elongation factor b (p-TEFb). In humans, there are multiple forms of positive transcription elongation factor b, which may include one of several different cyclins along with cyclin-dependent kinase 9. The complex containing the encoded cyclin and cyclin-dependent kinase 9 acts as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and is both necessary and sufficient for full activation of viral transcription. This cyclin and its kinase partner are also involved in triggering transcript elongation through phosphorylation of the carboxy-terminal domain of the largest RNA polymerase II subunit. Overexpression of this gene is implicated in tumor growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]
Orthologs
Location:
12q13.11
Exon count:
9
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 12 NC_000012.12 (48688458..48716998, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (49082241..49110781, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene KAT8 regulatory NSL complex subunit 2 Neighboring gene small nucleolar RNA, H/ACA box 2A Neighboring gene small nucleolar RNA, H/ACA box 2B Neighboring gene long intergenic non-protein coding RNA 935 Neighboring gene adenylate cyclase 6 Neighboring gene microRNA 4701

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.
NHGRI GWA Catalog

Replication interactions

Interaction Pubs
Knockdown of cyclin T1 (CCNT1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed
Knockdown of cyclin T1 (CCNT1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag CCNT1 isoform b inhibits HIV-1 RT activity in the media and HIV-1 Gag protein expression in the cell lysate in a dose-dependent manner PubMed
gag Expression of CycT1 increases Gag production 20-50 fold in rat T cells. Expression of both CRM1 and CycT1 factors synergistically enhances Gag production to levels approximately 10-40% of those detected in human cells PubMed
Tat tat Cyclin T1 mutant N60A fails to bind to HIV-1 Tat and impairs the effect on Tat-mediated transactivation, but H183A mutant exhibits Tat-binding activity and partially disrupts Tat-mediated transactivation PubMed
tat PKR-mediated Tat phosphorylation inhibits Tat nuclear localization, and disrupts Tat binding to HIV-1 TAR RNA and interaction with cyclin T1 in HeLa cells PubMed
tat A La-related protein, LARP7, is associated with P-TEFb, HEXIM1/2, MEPCE, and 7SK RNA in a large stable complex form. Knockdown of LARP7 decreases the steady-state level of 7SK, but increases free P-TEFb and enhances Tat-mediated transcription PubMed
tat Amino acids Q46, Q50 and F176 of human CycT1 protein are involved in its binding to HIV-1 Tat. A triple-mutant containing Q46A, Q50A and F176A mutations in CycT1 completely abolishes the transcriptional activity PubMed
tat HIV-1 Tat recruits P-TEFb to the HIV-1 Transcription Activation Response (TAR) RNA during Tat-mediated transactivation of the HIV-1 LTR promoter PubMed
tat P-TEFb interacts with HIV-1 Tat as part of both the HIV-1 transcription preinitiation and elongation complexes PubMed
tat Cyclin T1 (CCNT1) is identified to interact with HIV-1 Tat mutant Nullbasic in HeLa cells by LC MS/MS PubMed
tat A homogeneous assay in AlphaLISA indicates that the affinity between HIV-1 Tat and pTEFb is determined to be approximately 20pM, and only 7% of purified Tat is found to be active in forming tertiary complex with pTEFb PubMed
tat Cyclin T1 V107E mutant that exhibits no binding to CDK9 or HEXIM1 has weak interaction with HIV-1 Tat, and inhibits Tat-mediated transactivation in human cells PubMed
tat Cyclin T1 N60K mutant that binds weakly with CDK9, but not with HEXIM1 and AFF4, has weak interaction with HIV-1 Tat and inhibits Tat-mediated transactivation in human cells PubMed
tat Cyclin T1 Y175E and Y175S mutants exhibit no binding to HEXIM1 and HIV-1 Tat, leading to impair Tat-dependent transactivation of HIV LTR PubMed
tat CDK9-CycT1-AFF1 is stimulated by HIV-1 Tat and transferred as a single complex unit to BRD4 upon stress-induced disruption of AFF1-containing 7SK snRNP (HEMX1, MEPCE, LARP7, 7SK RNA, CDK9, CycT1, and AFF1) PubMed
tat AFF1 enhances the affinity of HIV-1 Tat for CycT1, which competitively dissociates HEXIM1 and is responsible for AFF1's promotion of Tat's extraction of CDK9/CycT1 from 7SK snRNP PubMed
tat Brd4 inhibits HIV-1 Tat-human super elongation complex (components AFF4, ELL2, CycT1, and CDK9) by competing with HIV-1 Tat for binding to P-TEFb on HIV-1 promoter PubMed
tat TAR binds Tat and P-TEFb as it emerges on the nascent transcript, competitively displacing the inhibitory 7SK snRNP (HEXIM1 and LARP7) and activating the P-TEFb kinase PubMed
tat HIV-1 Tat displaces HEXIM1 from Cyclin T1 in the context of the native 7SK snRNP by interacting with the Cyclin T1-binding domain (amino acid 255-359) of HEXIM1 PubMed
tat The interaction of HIV-1 Tat with HIV-1 Transcription Activation Response (TAR) RNA is enhanced by the interaction of Tat with P-TEFb, and TAR RNA also enhances the interaction between Tat and cyclin T1 PubMed
tat During HIV-1 Tat mediated transactivation of the HIV-1 LTR promoter, Tat stimulates the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II by P-TEFb, leading to transcription elongation PubMed
tat ZASC1, a cellular transcription factor, interacts with HIV-1 Tat and cellular proteins CDK9/Cyclin T1 (P-TEFb) in a TAR-independent manner, suggesting that the Tat/P-TEFb complex in the transcriptional elongation site is promoted by ZASC1 PubMed
tat Binding of isolated AFF1(1-308) CBS to CDK9/CycT1 prevents HIV-1 Tat from activating HIV transcription and assembling complete SECs (AFF1, AFF4, ELL2, and ENL). The AFF1(1-308) M60A/L61A mutant shows no suppression of Tat transactivation PubMed
tat The crystal structure provides a structural basis for the modulation of TAR RNA binding by acetylation of Lys28 in Tat and for involvement of Asn257 in Cyclin T1 PubMed
tat The crystal structure demonstrates that Met55Thr substitution in AFF4 forms a hydrogen bond with Glu246 of Cyclin T1, which is not as favorable for HIV-1 Tat docking PubMed
tat The Tat-AFF4-P-TEFb complex containing HIV-1 Tat (residues 1-48), human Cyclin T1 (residues 1-266), human Cdk9 (residues 7-332), and human AFF4 (residues 27-69) is determined by the crystal structure analysis PubMed
tat HIV-1 Tat recruits PPM1G phosphatase protein to dephosphorylate the T loop of CDK9 and release P-TEFb from the 7SK snRNP complex PubMed
tat The interaction of Tip110 with HIV-1 Tat and the RNAPII C-terminal domain leads to the recruitment of increased CDK9/CycT1 to the transcription complex PubMed
tat HIV-1 Tat forms at least two distinct P-TEFb-containing complexes. Tatcom1 is composed of P-TEFb, AF9, ENL, ELL, AFF1, AFF4, and PAF1, presenting strong CTD-kinase activity, while Tatcom2 consists of 7SK, LARP7, and MEPCE with two molecules of Tat/P-TEFb PubMed
tat The N-terminus (amino acids 1-48, including activation domain) of HIV-1 Tat binds to P-TEFb through a direct interaction with the N-terminus (amino acids 1-290) of cyclin T1 during Tat-mediated transactivation of the HIV-1 LTR promoter PubMed
tat A small molecule compound C3 inhibits HIV-1 replication by suppressing HIV-1 Tat-mediated HIV-1 LTR-driven gene expression and phosphorylation of RNAPII through inhibition of Tat binding to CycT1 PubMed
tat Small molecule ligands disrupt the CDK9/Cyclin T1/Tat complex and dissociate CDK9 away from the HIV-1 transcription complex PubMed
tat Phosphorylation of CDK9 at position Ser175 regulates the competition between HIV-1 Tat and BRD4 for P-TEFb binding PubMed
tat Yeast two-hybrid assay shows that CCNT1 isoform b loss the ability of binding to HIV-1 Tat PubMed
tat JQ1, a small molecule inhibitor of Brd4, increases CDK9 T-loop phosphorylation in a Tat-dependent manner and partially dissociates P-TEFb from 7SK snRNP in Jurkat cells PubMed
tat CCNT1 that lacks exon 7 inhibits HIV-1 replication through the attenuation of HIV-1 Tat/long terminal repeat (LTR)-driven transcription PubMed
tat HIV-1 Tat mutations at positions Y26 and K28 show the most defect in the Tat:TAR:P-TEFb complex formation, but Tat:P-TEFb assembly is not abolished PubMed
tat HIV-1 Tat mutations at positions P3, P6, W11, K12, T20, T23, V36, I39, T40, and Y47 show decreased Tat activity and P-TEFb assembly/Cdk9 activation, with three residues P3, P6, and W11 possibly involved in Cdk9 interactions PubMed
tat Coexpression of RNA-binding domain deficient Tat (T-RS) and two fusion proteins CycT1N-Rev and Cdk9-Rev synergistically stimulates transcription when P-TEFb is tethered to RNA through Rev, and thus T-RS is no longer an inhibitor PubMed
tat An RNA-binding domain deficient Tat excludes wild-type Tat from the promoter by preferentially assembling with P-TEFb through the Tat activation domain, but can not facilitate transfer of P-TEFb to TAR, thus blocking transition to elongation PubMed
tat The P-TEFb binding region (amino acids 1209-1362) of BRD4 is required for HIV-1 Tat-mediated release of P-TEFb from the 7SK snRNP PubMed
tat HIV-1 Tat-mediated release of P-TEFb from the 7SK sn RNP results in a conformational change in 7SK RNA and release of HEXIM1 from the complex PubMed
tat P-TEFb is required for HIV-1 Tat-mediated transcriptional activation PubMed
tat HIV-1 Tat stimulates the phosphorylation of SPT5 by P-TEFb during transactivation of the HIV-1 LTR promoter PubMed
tat Expression of human cyclin T1 in transgenic mice is sufficient to support HIV-1 Tat-mediated transactivation in primary mouse CD4 T lymphocytes and monocytes/macrophages and increases in vitro and in vivo HIV-1 production PubMed
tat HIV-1 Q35L mutant fails to efficiently bind either CDK9 or CycT1 resulting in the defective gene expression. However, the I39Q mutation rescues the Q35L mutant's loss of function PubMed
tat Mutant CycT1-U7, which contains four substitutions and one deletion in the N-terminal cyclin box (67HRFYM71 to IIWE), binds HIV-1 Tat to inhibit HIV transcription. The CycT1-U7 protein fails to interact with Cdk9 or HEXIM1 PubMed
tat SKIP is required for Tat transactivation in vivo and stimulates HIV-1 transcription elongation by associating with CycT1:CDK9 (P-TEFb) and Tat:P-TEFb complexes both in nuclear extracts and in recombinant Tat:P-TEFb:TAR RNA complexes in vitro PubMed
tat HIV-1 Tat and P-TEFb undergo constant association and dissociation cycles with TAR and the elongating polymerase in living cells PubMed
tat Mutant CycT1-U7 shows a potent dominant negative effect on Tat-dependent HIV transcription by specifically targeting Tat into the proteasome degradation pathway PubMed
tat HIV-1 Tat Lys-28 is required for CycT1-dependent RNA binding. Asn 250, but not Asn-257, in the TRM region of CycT1 is important for unacetylated Tat binding PubMed
tat Tat-SF1 is a required cofactor for HIV-1 Tat activity that complexes with P-TEFb and Tat, and stimulates Tat-mediated activation of the HIV-1 LTR promoter PubMed
tat Hsp70 and Hsp90/Cdc37 stabilize CDK9 as well as the assembly of an active P-TEFb complex which is stimulated by HIV-1 Tat during HIV-1 transcriptional activation PubMed
tat HIV-1 Tat competes with CIITA for the binding to P-TEFb, leading to the downregulation of MHC class II gene expression PubMed
tat MAQ1 and 7SK RNA interact with P-TEFb and compete with the binding of HIV-1 Tat to cyclin T1, suggesting the TAR RNA/Tat lentivirus system evolved to subvert the cellular 7SK RNA/MAQ1 system PubMed
tat The p160 nuclear receptor co-activator GRIP1 binds to the N-terminal region of HIV-1 Tat, bridging HIV-1 LTR promoter-bound factors to the Tat-P-TEFb complex and enhancing the transactivating activity of Tat PubMed
tat The human I-mfa domain-containing protein (HIC) interacts with both P-TEFb and HIV-1 Tat, and modulates Tat transactivation of the HIV-1 LTR promoter PubMed
tat Cyclin T1 is capable of recruiting CDK9 and HIV-1 Tat to splicing factor-rich nuclear speckle regions, suggesting nuclear speckles are a site of P-TEFb and Tat function PubMed
tat The up and downregulation of expression of CDK9 and cyclin T1 or sequestration of cyclin T1 in infected cells may regulate HIV-1 latency by up or downregulating HIV-1 Tat transcriptional activation PubMed
tat Amino acids 260-263 of cyclin T1 are critical for HIV-1 Tat-mediated transcriptional activation, and mediate the species specificity of cyclin T1 and P-TEFb binding to Tat PubMed
tat P-TEFb regulates HIV-1 Tat-mediated activation of transcription through two built-in auto inhibitory mechanisms, autophosphorylation of CDK9 and cyclin T1 binding to the transcription elongation factor Tat-SF1 PubMed
tat Mutant CycT1 protein containing triple T-to-A mutations in the N-terminal region (amino acids T143, T149, and T155) associates with CDK9 and HIV-1 Tat as a kinase-negative complex and blocks HIV transactivation PubMed
tat Undetectable CycT1 protein and un-phosphorylation of CDK9 in undifferentiated monocytes result in the lack of Tat transactivation of the LTR promoter in early viral life cycle PubMed
tat The growth factor granulin and the promyelocytic leukemia (PML) protein regulate HIV-1 Tat-mediated transcriptional activation by competing with the Tat interaction with cyclin T1/P-TEFb PubMed
tat HIV-1 Tat-mediated stimulation of RNA polymerase II C-terminal domain phosphorylation by P-TEFb leads to stimulation of co-transcriptional capping of HIV-1 mRNA PubMed
tat Acetylation of HIV-1 Tat by cellular histone acetyltransferases regulates the binding of Tat to P-TEFb PubMed
tat Interaction of P-TEFb with histone H1 results in its phosphorylation at position Ser-183 in a Tat-dependent manner, which is necessary for transcription from the HIV-1 LTR PubMed
tat PARP1 negatively regulates HIV-1 transcription by directly competing with Tat-P-TEFb complex for binding to TAR RNA PubMed
tat PRMT6-mediated arginine methylation of HIV-1 Tat negatively affects Tat-TAR-cyclin T1 ternary complex formation and diminishes cyclin T1-dependent Tat transcriptional activation PubMed
tat Cyclin T1-P-TEFb is important for prostratin stimulation of HIV-1 virus expression in the presence of functional Tat PubMed
tat IL-10 inhibits HIV-1 gene expression in an HIV-1 Tat-dependent manner by downregulating cyclin T1 expression through the induction of proteasome-mediated proteolysis in human macrophages PubMed
tat HIV-1 Tat interaction with cyclin T1 is required for the repression of mannose receptor (MR) and bone morphogenetic protein receptor-2 (BMPR2) promoters PubMed
tat P-TEFb, Puralpha and HIV-1 Tat cooperate to activate the TNFalpha promoter PubMed
Vpr vpr HIV-1 Vpr binds to cyclin T1 (amino acids 300-479) in a ternary complex of HIV-1 Tat, Vpr, Cyclin T1, and CDK9, and enhances Tat transactivation of the viral LTR promoter PubMed
reverse transcriptase gag-pol CCNT1 isoform b inhibits HIV-1 RT activity in the media and HIV-1 Gag protein expression in the cell lysate in a dose-dependent manner PubMed

Go to the HIV-1, Human Interaction Database

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ11223, DKFZp313A1331, DKFZp313N0919, DKFZp313O1211

Gene Ontology Provided by GOA

Function Evidence Code Pubs
7SK snRNA binding IDA
Inferred from Direct Assay
more info
PubMed 
DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase binding IPI
Inferred from Physical Interaction
more info
PubMed 
chromatin binding IEA
Inferred from Electronic Annotation
more info
 
cyclin-dependent protein serine/threonine kinase regulator activity IBA
Inferred from Biological aspect of Ancestor
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
 
transcription regulatory region DNA binding IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cyclin/CDK positive transcription elongation factor complex IDA
Inferred from Direct Assay
more info
PubMed 
NOT nucleolus IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
cyclin-T1
Names
CDK9-associated C-type protein
cyclin C-related protein
human immunodeficiency virus type 1 (HIV-1) expression (elevated) 1

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001240.3NP_001231.2  cyclin-T1 isoform a

    See identical proteins and their annotated locations for NP_001231.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (a, also known as FL and CycT1a) represents the longer transcript and encodes the longer isoform (a).
    Source sequence(s)
    AC079951, AF045161, BX098766
    Consensus CDS
    CCDS8766.1
    UniProtKB/Swiss-Prot
    O60563
    Related
    ENSP00000261900, OTTHUMP00000243665, ENST00000261900, OTTHUMT00000408853
    Conserved Domains (2) summary
    COG5333
    Location:32217
    CCL1; Cdk activating kinase (CAK)/RNA polymerase II transcription initiation/nucleotide excision repair factor TFIIH/TFIIK, cyclin H subunit [Cell division and chromosome partitioning / Transcription / DNA replication, recombination, and repair]
    cd00043
    Location:38109
    CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB and Retinoblastoma (RB).The cyclins consist of 8 classes of cell cycle regulators that regulate cyclin dependent kinases (CDKs). TFIIB ...
  2. NM_001277842.1NP_001264771.1  cyclin-T1 isoform b

    See identical proteins and their annotated locations for NP_001264771.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (b, also known as dE7 and CycT1b) lacks an exon in the coding region, which results in a frameshift and an early stop codon, compared to variant a. The encoded isoform (b) has a shorter and distinct C-terminus, compared to isoform a. While this variant may be considered a candidate for nonsense-mediated decay, experimental evidence suggests that it is protein coding (PMID: 23569210 and PMID: 22692005).
    Source sequence(s)
    AC079951, AK290990, EF688064, HY016640
    Consensus CDS
    CCDS61109.1
    UniProtKB/Swiss-Prot
    O60563
    UniProtKB/TrEMBL
    A8K4M5
    Related
    ENSP00000481035, ENST00000618666
    Conserved Domains (1) summary
    cd00043
    Location:38109
    CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB and Retinoblastoma (RB).The cyclins consist of 8 classes of cell cycle regulators that regulate cyclin dependent kinases (CDKs). TFIIB ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p2 Primary Assembly

    Range
    48688458..48716998 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018923.2 Alternate CHM1_1.1

    Range
    49048056..49076621 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)