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P53999 (TCP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 131. 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:
Activated RNA polymerase II transcriptional coactivator p15
Alternative name(s):
Positive cofactor 4
Short name=PC4
SUB1 homolog
p14
Gene names
Name:SUB1
Synonyms:PC4, RPO2TC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length127 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

General coactivator that functions cooperatively with TAFs and mediates functional interactions between upstream activators and the general transcriptional machinery. May be involved in stabilizing the multiprotein transcription complex. Binds single-stranded DNA. Also binds, in vitro, non-specifically to double-stranded DNA (ds DNA). Ref.1 Ref.2 Ref.5 Ref.6 Ref.8 Ref.16 Ref.17

Subunit structure

Homodimer. Interacts with CSTF2. Ref.7 Ref.16 Ref.18

Subcellular location

Nucleus.

Post-translational modification

Activity is controlled by protein kinases that target the regulatory region. Phosphorylation inactivates both ds DNA-binding and cofactor function, but does not affect binding to ssDNA. Seems to be phosphorylated in vivo by CK2 in at least 7 sites in the N-terminal Ser-rich region. Ref.4 Ref.6 Ref.8

Sequence similarities

Belongs to the transcriptional coactivator PC4 family.

Mass spectrometry

Molecular mass is 14266±4 Da from positions 2 - 127. Determined by MALDI. Ref.4

Molecular mass is 14263 Da from positions 2 - 127. Determined by ESI. Ref.8

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CSTF2P33240-13EBI-998260,EBI-711374

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2
Chain2 – 127126Activated RNA polymerase II transcriptional coactivator p15
PRO_0000215944

Regions

Region2 – 5049Regulatory
Region77 – 10125Interaction with ssDNA
Compositional bias4 – 1916Ser-rich
Compositional bias23 – 5331Lys-rich
Compositional bias50 – 589Ser-rich

Sites

Site50 – 512Cleavage

Amino acid modifications

Modified residue111Phosphoserine Ref.8
Modified residue131Phosphoserine Ref.8
Modified residue151Phosphoserine Ref.8
Modified residue171Phosphoserine Ref.8 Ref.9
Modified residue191Phosphoserine Ref.8 Ref.9
Modified residue351N6-acetyllysine Ref.11
Modified residue531N6-acetyllysine By similarity
Modified residue681N6-acetyllysine Ref.11
Modified residue1181Phosphoserine Ref.10 Ref.12 Ref.14

Natural variations

Natural variant111S → G. Ref.3
Corresponds to variant rs17850527 [ dbSNP | Ensembl ].
VAR_032870

Experimental info

Mutagenesis681K → G: Reduced ssDNA binding. Ref.17
Mutagenesis751R → G: Reduced ssDNA binding. Ref.17
Mutagenesis77 – 804FKGK → AGG: Loss of ssDNA binding. Ref.17
Mutagenesis861R → G: Loss of ssDNA binding. Ref.17
Mutagenesis1011K → G: Loss of ssDNA binding. Ref.17

Secondary structure

............. 127
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P53999 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 0DAE0CAAAD5E4E15

FASTA12714,395
        10         20         30         40         50         60 
MPKSKELVSS SSSGSDSDSE VDKKLKRKKQ VAPEKPVKKQ KTGETSRALS SSKQSSSSRD 

        70         80         90        100        110        120 
DNMFQIGKMR YVSVRDFKGK VLIDIREYWM DPEGEMKPGR KGISLNPEQW SQLKEQISDI 


DDAVRKL 

« Hide

References

« Hide 'large scale' references
[1]"A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators."
Kretzschmar M., Kaiser K., Lottspeich F., Meisterernst M.
Cell 78:525-534(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION.
[2]"Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes."
Ge H., Roeder R.G.
Cell 78:513-523(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-11 AND 81-97, FUNCTION.
[3]"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], VARIANT GLY-11.
Tissue: Bone marrow, Cervix, Lung and Prostate.
[4]"Phosphorylation negatively regulates the function of coactivator PC4."
Ge H., Zhao Y., Chait B.T., Roeder R.G.
Proc. Natl. Acad. Sci. U.S.A. 91:12691-12695(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, MASS SPECTROMETRY.
[5]"The coactivator p15 (PC4) initiates transcriptional activation during TFIIA-TFIID-promoter complex formation."
Kaiser K., Stelzer G., Meisterernst M.
EMBO J. 14:3520-3527(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING.
[6]"A dynamic model for PC4 coactivator function in RNA polymerase II transcription."
Malik S., Guermah M., Roeder R.G.
Proc. Natl. Acad. Sci. U.S.A. 95:2192-2197(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION BY CK2.
[7]"Evolutionarily conserved interaction between CstF-64 and PC4 links transcription, polyadenylation, and termination."
Calvo O., Manley J.L.
Mol. Cell 7:1013-1023(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CSTF2.
[8]"Gradual phosphorylation regulates PC4 coactivator function."
Jonker H.R.A., Wechselberger R.W., Pinkse M., Kaptein R., Folkers G.E.
FEBS J. 273:1430-1444(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: MASS SPECTROMETRY, FUNCTION, DNA-BINDING, PHOSPHORYLATION AT SER-11; SER-13; SER-15; SER-17 AND SER-19.
[9]"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-17 AND SER-19, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"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-118, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[11]"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-35 AND LYS-68, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"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-118, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"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].
[14]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-118, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"C-terminal domain of transcription cofactor PC4 reveals dimeric ssDNA binding site."
Brandsen J., Werten S., van der Vliet P.C., Meisterernst M., Kroon J., Gros P.
Nat. Struct. Biol. 4:900-903(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 63-127, FUNCTION, SUBUNIT.
[17]"The intrinsically unstructured domain of PC4 modulates the activity of the structured core through inter- and intramolecular interactions."
Jonker H.R.A., Wechselberger R.W., Boelens R., Kaptein R., Folkers G.E.
Biochemistry 45:5067-5081(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, FUNCTION, MUTAGENESIS OF LYS-68; ARG-75; 77-PHE--LYS-80; ARG-86 AND LYS-101.
[18]"A global transcription cofactor bound to juxtaposed strands of unwound DNA."
Werten S., Moras D.
Nat. Struct. Biol. 13:181-182(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 63-127 IN COMPLEX WITH SINGLE-STRANDED DNA, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X79805 mRNA. Translation: CAA56200.1.
U12979 mRNA. Translation: AAA20980.1.
BC009610 mRNA. Translation: AAH09610.1.
BC010537 mRNA. Translation: AAH10537.1.
BC018189 mRNA. Translation: AAH18189.1.
BC022339 mRNA. Translation: AAH22339.1.
PIRA54670.
RefSeqNP_006704.3. NM_006713.3.
XP_005248289.1. XM_005248232.1.
UniGeneHs.229641.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PCFX-ray1.74A/B/C/D/E/F/G/H63-127[»]
2C62X-ray1.74A/B63-127[»]
2PHENMR-A/B63-127[»]
ProteinModelPortalP53999.
SMRP53999. Positions 63-127.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116127. 41 interactions.
DIPDIP-29044N.
IntActP53999. 7 interactions.
MINTMINT-138673.
STRING9606.ENSP00000265073.

PTM databases

PhosphoSiteP53999.

Polymorphism databases

DMDM1709514.

Proteomic databases

PaxDbP53999.
PeptideAtlasP53999.
PRIDEP53999.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265073; ENSP00000265073; ENSG00000113387.
ENST00000502897; ENSP00000427100; ENSG00000113387.
ENST00000506237; ENSP00000422078; ENSG00000113387.
ENST00000512913; ENSP00000422806; ENSG00000113387.
ENST00000515355; ENSP00000426850; ENSG00000113387.
GeneID10923.
KEGGhsa:10923.
UCSCuc003jhs.2. human.

Organism-specific databases

CTD10923.
GeneCardsGC05P032622.
HGNCHGNC:19985. SUB1.
HPACAB015351.
HPA001311.
MIM600503. gene.
neXtProtNX_P53999.
PharmGKBPA142670858.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG299238.
HOVERGENHBG028243.
InParanoidP53999.
OMAREYWMNQ.
OrthoDBEOG76MKBV.
PhylomeDBP53999.
TreeFamTF313859.

Gene expression databases

ArrayExpressP53999.
BgeeP53999.
CleanExHS_SUB1.
GenevestigatorP53999.

Family and domain databases

Gene3D2.30.31.10. 1 hit.
InterProIPR003173. PC4.
IPR009044. ssDNA-bd_transcriptional_reg.
[Graphical view]
PfamPF02229. PC4. 1 hit.
[Graphical view]
SUPFAMSSF54447. SSF54447. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSUB1. human.
EvolutionaryTraceP53999.
GeneWikiSUB1.
GenomeRNAi10923.
NextBio41499.
PROP53999.
SOURCESearch...

Entry information

Entry nameTCP4_HUMAN
AccessionPrimary (citable) accession number: P53999
Secondary accession number(s): Q96L29
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 131 of the entry and version 3 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 5

Human chromosome 5: entries, gene names and cross-references to MIM