P53999 (TCP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	127 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.15 Ref.16
Subunit structure	Homodimer. Interacts with CSTF2. Ref.7 Ref.15 Ref.17
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

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.2. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleolus Inferred from direct assay. Source: HPA transcription factor complex Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	single-stranded DNA binding Inferred from direct assay Ref.2. Source: UniProtKB transcription coactivator activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CSTF2	P33240-1	3	EBI-998260,EBI-711374

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.2

Chain

2 – 127

126

Activated RNA polymerase II transcriptional coactivator p15

PRO_0000215944

Regions

Region

2 – 50

49

Regulatory

Region

77 – 101

25

Interaction with ssDNA

Compositional bias

4 – 19

16

Ser-rich

Compositional bias

23 – 53

31

Lys-rich

Compositional bias

50 – 58

9

Ser-rich

Sites

Site

50 – 51

2

Cleavage

Amino acid modifications

Modified residue

9

1

Phosphoserine By similarity

Modified residue

10

1

Phosphoserine By similarity

Modified residue

11

1

Phosphoserine Ref.8

Modified residue

12

1

Phosphoserine By similarity

Modified residue

13

1

Phosphoserine Ref.8

Modified residue

15

1

Phosphoserine Ref.8

Modified residue

17

1

Phosphoserine Ref.8 Ref.9

Modified residue

19

1

Phosphoserine Ref.8 Ref.9

Modified residue

35

1

N6-acetyllysine Ref.11

Modified residue

68

1

N6-acetyllysine Ref.11

Modified residue

118

1

Phosphoserine Ref.10 Ref.12 Ref.14

Natural variations

Natural variant

11

1

S → G. Ref.3
Corresponds to variant rs17850527 [ dbSNP | Ensembl ].

VAR_032870

Experimental info

Mutagenesis

68

1

K → G: Reduced ssDNA binding. Ref.16

Mutagenesis

75

1

R → G: Reduced ssDNA binding. Ref.16

Mutagenesis

77 – 80

4

FKGK → AGG: Loss of ssDNA binding. Ref.16

Mutagenesis

86

1

R → G: Loss of ssDNA binding. Ref.16

Mutagenesis

101

1

K → G: Loss of ssDNA binding. Ref.16

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

127

Helix Strand Turn

Details...

Beta strand

63 – 67

5

Beta strand

70 – 77

8

Beta strand

80 – 90

11

Beta strand

92 – 94

3

Beta strand

96 – 105

10

Helix

107 – 126

20

Sequences

	Sequence		Length	Mass (Da)
	P53999 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 0DAE0CAAAD5E4E15	FASTA	127	14,395
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[15]	"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.
[16]	"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.
[17]	"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.

IPI

IPI00221222.

PIR

A54670.

RefSeq

NP_006704.3. NM_006713.3.

UniGene

Hs.229641.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PCF	X-ray	1.74	A/B/C/D/E/F/G/H	63-127	[»]
2C62	X-ray	1.74	A/B	63-127	[»]
2PHE	NMR	-	A/B	63-127	[»]

ProteinModelPortal

P53999.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29044N.

IntAct

P53999. 6 interactions.

MINT

MINT-138673.

STRING

9606.ENSP00000265073.

PTM databases

PhosphoSite

P53999.

Polymorphism databases

DMDM

1709514.

Proteomic databases

PaxDb

P53999.

PeptideAtlas

P53999.

PRIDE

P53999.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265073; ENSP00000265073; ENSG00000113387.
ENST00000502897; ENSP00000427100; ENSG00000113387.
ENST00000506237; ENSP00000422078; ENSG00000113387.
ENST00000512913; ENSP00000422806; ENSG00000113387.
ENST00000515355; ENSP00000426850; ENSG00000113387.

GeneID

10923.

KEGG

hsa:10923.

UCSC

uc003jhs.2. human.

Organism-specific databases

CTD

10923.

GeneCards

GC05P032622.

HGNC

HGNC:19985. SUB1.

HPA

CAB015351.
HPA001311.

MIM

600503. gene.

neXtProt

NX_P53999.

PharmGKB

PA142670858.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG299238.

HOVERGEN

HBG028243.

InParanoid

P53999.

OMA

QWNQLKD.

OrthoDB

EOG4NS3D2.

PhylomeDB

P53999.

Gene expression databases

ArrayExpress

P53999.

Bgee

P53999.

CleanEx

HS_SUB1.

Genevestigator

P53999.

GermOnline

ENSG00000113387. Homo sapiens.

Family and domain databases

Gene3D

2.30.31.10. 1 hit.

InterPro

IPR003173. PC4.
IPR009044. ssDNA-bd_transcriptional_reg.
[Graphical view]

Pfam

PF02229. PC4. 1 hit.
[Graphical view]

SUPFAM

SSF54447. ssDNA_bind_regul. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

SUB1. human.

EvolutionaryTrace

P53999.

GenomeRNAi

10923.

NextBio

41499.

SOURCE

Search...

Entry information

Entry name

TCP4_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 125 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.