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O60563 (CCNT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-T1

Short name=CycT1
Short name=Cyclin-T
Gene names
Name:CCNT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length726 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes. Ref.12 Ref.13

Subunit structure

Cyclin-T1 is the predominant cyclin that associates with CDK9 to form a heterodimer called P-TEFb. P-TEFb forms a complex with AFF4/AF5Q31. Interacts with the transactivation region of HIV-1, HIV-2 and SIV Tat. Component of a complex which is at least composed of HTATSF1/Tat-SF1, P-TEFb complex, RNA pol II, SUPT5H, and NCL/nucleolin. Component of the 7SK snRNP complex at least composed of P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, BCDIN3, SART3 proteins and 7SK and U6 snRNAs. Interacts with BRD4, probably to target chromatin binding. Interacts with MDFIC. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14

Subcellular location

Nucleus Ref.10.

Tissue specificity

Ubiquitously expressed.

Miscellaneous

Interaction between Tat and cyclin-T1 requires zinc.

Sequence similarities

Belongs to the cyclin family. Cyclin C subfamily.

Ontologies

Keywords
   Biological processCell cycle
Cell division
Host-virus interaction
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DomainCoiled coil
   Molecular functionCyclin
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

gene expression

Traceable author statement. Source: Reactome

positive regulation of transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

positive regulation of viral transcription

Traceable author statement. Source: Reactome

protein phosphorylation

Inferred from physical interaction Ref.12. Source: MGI

regulation of cyclin-dependent protein serine/threonine kinase activity

Traceable author statement Ref.2. Source: ProtInc

transcription elongation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Traceable author statement. Source: Reactome

transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.10. Source: UniProtKB

positive transcription elongation factor complex b

Inferred from direct assay PubMed 15905409. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay Ref.12. Source: MGI

chromatin binding

Inferred from electronic annotation. Source: Ensembl

snRNA binding

Inferred from electronic annotation. Source: Ensembl

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AFF4Q9UHB75EBI-2479671,EBI-395282
CDK9P5075013EBI-2479671,EBI-1383449
tatP046085EBI-2479671,EBI-6164389From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 726726Cyclin-T1
PRO_0000080491

Regions

Coiled coil384 – 42542 Potential
Motif253 – 27018Nuclear localization signal, and interaction with Tat-TAR RNA Potential
Compositional bias506 – 53025His-rich
Compositional bias548 – 62982Ser-rich
Compositional bias708 – 72518Pro-rich

Sites

Site2611Essential for interacting with HIV-1 Tat

Amino acid modifications

Modified residue1171Phosphoserine Ref.16
Modified residue3401Phosphoserine Ref.16
Modified residue3901N6-acetyllysine Ref.17
Modified residue4951Phosphoserine Ref.15
Modified residue4991Phosphoserine Ref.18
Modified residue5771Phosphoserine Ref.15

Natural variations

Natural variant3621H → R.
Corresponds to variant rs17123261 [ dbSNP | Ensembl ].
VAR_053054
Natural variant5411R → C. Ref.20
VAR_069400

Experimental info

Mutagenesis2611C → Y: Loss of HIV-1 Tat transactivation. Ref.5
Sequence conflict771Q → R in AAC39664. Ref.2

Secondary structure

.......................................... 726
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O60563 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 4637EFB2DDEDFE13

FASTA72680,685
        10         20         30         40         50         60 
MEGERKNNNK RWYFTREQLE NSPSRRFGVD PDKELSYRQQ AANLLQDMGQ RLNVSQLTIN 

        70         80         90        100        110        120 
TAIVYMHRFY MIQSFTQFPG NSVAPAALFL AAKVEEQPKK LEHVIKVAHT CLHPQESLPD 

       130        140        150        160        170        180 
TRSEAYLQQV QDLVILESII LQTLGFELTI DHPHTHVVKC TQLVRASKDL AQTSYFMATN 

       190        200        210        220        230        240 
SLHLTTFSLQ YTPPVVACVC IHLACKWSNW EIPVSTDGKH WWEYVDATVT LELLDELTHE 

       250        260        270        280        290        300 
FLQILEKTPN RLKRIWNWRA CEAAKKTKAD DRGTDEKTSE QTILNMISQS SSDTTIAGLM 

       310        320        330        340        350        360 
SMSTSTTSAV PSLPVSEESS SNLTSVEMLP GKRWLSSQPS FKLEPTQGHR TSENLALTGV 

       370        380        390        400        410        420 
DHSLPQDGSN AFISQKQNSK SVPSAKVSLK EYRAKHAEEL AAQKRQLENM EANVKSQYAY 

       430        440        450        460        470        480 
AAQNLLSHHD SHSSVILKMP IEGSENPERP FLEKADKTAL KMRIPVAGGD KAASSKPEEI 

       490        500        510        520        530        540 
KMRIKVHAAA DKHNSVEDSV TKSREHKEKH KTHPSNHHHH HNHHSHKHSH SQLPVGTGNK 

       550        560        570        580        590        600 
RPGDPKHSSQ TSNLAHKTYS LSSSFSSSSS TRKRGPSEET GGAVFDHPAK IAKSTKSSSL 

       610        620        630        640        650        660 
NFSFPSLPTM GQMPGHSSDT SGLSFSQPSC KTRVPHSKLD KGPTGANGHN TTQTIDYQDT 

       670        680        690        700        710        720 
VNMLHSLLSA QGVQPTQPTA FEFVRPYSDY LNPRSGGISS RSGNTDKPRP PPLPSEPPPP 


LPPLPK 

« Hide

References

« Hide 'large scale' references
[1]"A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA."
Wei P., Garber M.E., Fang S.-M., Fischer W.H., Jones K.A.
Cell 92:451-462(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, INTERACTION WITH HIV-1 TAT.
Tissue: T-cell lymphoma.
[2]"Identification of multiple cyclin subunits of human P-TEFb."
Peng J.-M., Zhu Y., Milton J.T., Price D.H.
Genes Dev. 12:755-762(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Mammary cancer.
[3]"A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription."
Parada C.A., Roeder R.G.
EMBO J. 18:3688-3701(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH HTATSF1; CDK9; RNA POL II; SUPT5H AND NCL.
[4]"Cyclin T1 domains involved in complex formation with Tat and TAR RNA are critical for tat-activation."
Ivanov D., Kwak Y.T., Nee E., Guo J., Garcia-Martinez L.F., Gaynor R.B.
J. Mol. Biol. 288:41-56(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 TAT.
[5]"Role of the human and murine cyclin T proteins in regulating HIV-1 Tat-activation."
Kwak Y.T., Ivanov D., Guo J., Nee E., Gaynor R.B.
J. Mol. Biol. 288:57-69(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-261, INTERACTION WITH HIV-1 TAT.
[6]"The interaction between HIV-1 Tat and human cyclin T1 requires zinc and a critical cysteine residue that is not conserved in the murine CycT1 protein."
Garber M.E., Wei P., KewalRamani V.N., Mayall T.P., Herrmann C.H., Rice A.P., Littman D.R., Jones K.A.
Genes Dev. 12:3512-3527(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 TAT, ROLE OF CYS-261.
[7]"Analysis of the effect of natural sequence variation in Tat and in cyclin T on the formation and RNA binding properties of Tat-cyclin T complexes."
Bieniasz P.D., Grdina T.A., Bogerd H.P., Cullen B.R.
J. Virol. 73:5777-5786(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 TAT; HIV-2 TAT AND SIV TAT.
[8]"Relief of two built-In autoinhibitory mechanisms in P-TEFb is required for assembly of a multicomponent transcription elongation complex at the human immunodeficiency virus type 1 promoter."
Fong Y.W., Zhou Q.
Mol. Cell. Biol. 20:5897-5907(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HTATSF1.
[9]"MCEF, the newest member of the AF4 family of transcription factors involved in leukemia, is a positive transcription elongation factor-b-associated protein."
Estable M.C., Naghavi M.H., Kato H., Xiao H., Qin J., Vahlne A., Roeder R.G.
J. Biomed. Sci. 9:234-245(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AFF4.
[10]"The human I-mfa domain-containing protein, HIC, interacts with cyclin T1 and modulates P-TEFb-dependent transcription."
Young T.M., Wang Q., Pe'ery T., Mathews M.B.
Mol. Cell. Biol. 23:6373-6384(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MDFIC, SUBCELLULAR LOCATION.
[11]"Evidence for conformational flexibility in the Tat-TAR recognition motif of cyclin T1."
Das C., Edgcomb S.P., Peteranderl R., Chen L., Frankel A.D.
Virology 318:306-317(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[12]"The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription."
Jang M.K., Mochizuki K., Zhou M., Jeong H.S., Brady J.N., Ozato K.
Mol. Cell 19:523-534(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BRD4.
[13]"Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4."
Yang Z., Yik J.H., Chen R., He N., Jang M.K., Ozato K., Zhou Q.
Mol. Cell 19:535-545(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BRD4.
[14]"Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme."
Jeronimo C., Forget D., Bouchard A., Li Q., Chua G., Poitras C., Therien C., Bergeron D., Bourassa S., Greenblatt J., Chabot B., Poirier G.G., Hughes T.R., Blanchette M., Price D.H., Coulombe B.
Mol. Cell 27:262-274(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE 7SK SNRNP COMPLEX.
[15]"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-495 AND SER-577, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117 AND SER-340, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-390, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"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-499, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Diagnostic exome sequencing in persons with severe intellectual disability."
de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., Veltman J.A., Vissers L.E.
N. Engl. J. Med. 367:1921-1929(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CYS-541.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF045161 mRNA. Translation: AAC39638.1.
AF048730 mRNA. Translation: AAC39664.1.
RefSeqNP_001231.2. NM_001240.3.
UniGeneHs.92308.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2PK2X-ray2.67A/B/C/D1-281[»]
3BLHX-ray2.48B2-259[»]
3BLQX-ray2.90B2-259[»]
3BLRX-ray2.80B2-259[»]
3LQ5X-ray3.00B2-259[»]
3MI9X-ray2.10B1-266[»]
3MIAX-ray3.00B1-266[»]
3MY1X-ray2.80B2-259[»]
3TN8X-ray2.95B2-259[»]
3TNHX-ray3.20B1-259[»]
3TNIX-ray3.23B1-259[»]
4BCFX-ray3.01B2-259[»]
4BCGX-ray3.08B2-259[»]
4BCHX-ray2.96B2-259[»]
4BCIX-ray3.10B2-259[»]
4BCJX-ray3.16B2-259[»]
4EC8X-ray3.60B2-259[»]
4EC9X-ray3.21B2-259[»]
4IMYX-ray2.94B/D/F1-264[»]
ProteinModelPortalO60563.
SMRO60563. Positions 7-252.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107343. 60 interactions.
DIPDIP-29891N.
IntActO60563. 21 interactions.
MINTMINT-142682.
STRING9606.ENSP00000261900.

Chemistry

BindingDBO60563.
ChEMBLCHEMBL2111389.

PTM databases

PhosphoSiteO60563.

Proteomic databases

PaxDbO60563.
PeptideAtlasO60563.
PRIDEO60563.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261900; ENSP00000261900; ENSG00000129315.
GeneID904.
KEGGhsa:904.
UCSCuc001rsd.4. human.

Organism-specific databases

CTD904.
GeneCardsGC12M049087.
HGNCHGNC:1599. CCNT1.
HPACAB009016.
HPA004892.
MIM143055. gene.
neXtProtNX_O60563.
PharmGKBPA26163.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5333.
HOGENOMHOG000013208.
HOVERGENHBG050843.
InParanoidO60563.
KOK15188.
OMAFELTIDH.
OrthoDBEOG7VQJCR.
PhylomeDBO60563.
TreeFamTF101014.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_1788. Transcription.
REACT_1892. Elongation arrest and recovery.
REACT_71. Gene Expression.
SignaLinkO60563.

Gene expression databases

ArrayExpressO60563.
BgeeO60563.
CleanExHS_CCNT1.
GenevestigatorO60563.

Family and domain databases

Gene3D1.10.472.10. 1 hit.
InterProIPR028863. CCNT1.
IPR013763. Cyclin-like.
IPR015429. Cyclin_C/H/T/L.
IPR006671. Cyclin_N.
[Graphical view]
PANTHERPTHR10026. PTHR10026. 1 hit.
PTHR10026:SF42. PTHR10026:SF42. 1 hit.
PfamPF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMSSF47954. SSF47954. 2 hits.
ProtoNetSearch...

Other

EvolutionaryTraceO60563.
GeneWikiCyclin_T1.
GenomeRNAi904.
NextBio3732.
PROO60563.
SOURCESearch...

Entry information

Entry nameCCNT1_HUMAN
AccessionPrimary (citable) accession number: O60563
Secondary accession number(s): O60581
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 1, 1998
Last modified: April 16, 2014
This is version 142 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 12

Human chromosome 12: entries, gene names and cross-references to MIM