Q01664 (TFAP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor AP-4

Alternative name(s):
Activating enhancer-binding protein 4
Class C basic helix-loop-helix protein 41
Short name=bHLHc41

Gene names

Name:	TFAP4
Synonyms:	BHLHC41

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	338 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor that activates both viral and cellular genes by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Homodimer.
Subcellular location	Nucleus.
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Inferred from direct assay PubMed 18818310. Source: UniProtKB cellular response to dexamethasone stimulus Inferred from electronic annotation. Source: Ensembl negative regulation by host of viral transcription Inferred from direct assay PubMed 14645924PubMed 16540471. Source: UniProtKB negative regulation of DNA binding Inferred from direct assay PubMed 16540471Ref.1. Source: UniProtKB negative regulation of apoptotic process Inferred from electronic annotation. Source: Ensembl negative regulation of cell cycle arrest Inferred from mutant phenotype PubMed 18818310. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype PubMed 18818310. Source: UniProtKB negative regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from direct assay PubMed 18818310. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 16924111PubMed 19505873PubMed 9931457. Source: UniProtKB positive regulation by host of viral transcription Inferred from direct assay PubMed 2833704. Source: UniProtKB positive regulation of apoptotic process Inferred from direct assay PubMed 18818310. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 12663744. Source: UniProtKB protein complex assembly Inferred from direct assay PubMed 19505873. Source: UniProtKB
Cellular_component	transcriptional repressor complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	E-box binding Inferred from direct assay PubMed 11171123PubMed 12663744PubMed 18818310PubMed 19505873Ref.1. Source: UniProtKB RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 2833704. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 338	338	Transcription factor AP-4		PRO_0000127458
Regions
	Domain	48 – 99	52	bHLH
	Region	100 – 120	21	Leucine-zipper 1
	Region	151 – 179	29	Leucine-zipper 2
	Compositional bias	193 – 222	30	Gln-rich
	Compositional bias	225 – 244	20	Pro-rich
Amino acid modifications
	Modified residue	123	1	Phosphoserine Ref.9
	Modified residue	124	1	Phosphoserine Ref.6 Ref.8 Ref.9
	Modified residue	139	1	Phosphoserine Ref.5 Ref.8 Ref.9
	Modified residue	282	1	Phosphothreonine Ref.9
Natural variations
	Natural variant	218	1	Q → H. Ref.2 Corresponds to variant rs251732 [ dbSNP | Ensembl ].		VAR_059346

Sequences

	Sequence		Length	Mass (Da)
	Q01664 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 540C008658596B83	FASTA	338	38,726
	10 20 30 40 50 60 MEYFMVPTQK VPSLQHFRKT EKEVIGGLCS LANIPLTPET QRDQERRIRR EIANSNERRR 70 80 90 100 110 120 MQSINAGFQS LKTLIPHTDG EKLSKAAILQ QTAEYIFSLE QEKTRLLQQN TQLKRFIQEL 130 140 150 160 170 180 SGSSPKRRRA EDKDEGIGSP DIWEDEKAED LRREMIELRQ QLDKERSVRM MLEEQVRSLE 190 200 210 220 230 240 AHMYPEKLKV IAQQVQLQQQ QEQVRLLHQE KLEREQQQLR TQLLPPPAPT HHPTVIVPAP 250 260 270 280 290 300 PPPPSHHINV VTMGPSSVIN SVSTSRQNLD TIVQAIQHIE GTQEKQELEE EQRRAVIVKP 310 320 330 VRSCPEAPTS DTASDSEASD SDAMDQSREE PSGDGELP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Role of flanking E box motifs in human immunodeficiency virus type 1 TATA element function." Ou S.H., Garcia-Martinez L.F., Paulssen E.J., Gaynor R.B. J. Virol. 68:7188-7199(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT HIS-218.
[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]. Tissue: Brain.
[4]	"Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity." Hu Y.-F., Luescher B., Admon A., Mermod N., Tjian R. Genes Dev. 4:1741-1752(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-338, PARTIAL PROTEIN SEQUENCE.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"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-124, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"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-124 AND SER-139, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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-123; SER-124; SER-139 AND THR-282, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S73885 mRNA. Translation: AAB32235.1. AC004653 Genomic DNA. Translation: AAC17116.1. BC010576 mRNA. Translation: AAH10576.1. X57435 mRNA. Translation: CAA40683.1.
IPI	IPI00009005.
PIR	I56893.
RefSeq	NP_003214.1. NM_003223.2.
UniGene	Hs.513305.
3D structure databases
ProteinModelPortal	Q01664.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q01664. 1 interaction.
STRING	9606.ENSP00000204517.
PTM databases
PhosphoSite	Q01664.
Polymorphism databases
DMDM	1729833.
Proteomic databases
PaxDb	Q01664.
PRIDE	Q01664.
Protocols and materials databases
DNASU	7023.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000204517; ENSP00000204517; ENSG00000090447.
GeneID	7023.
KEGG	hsa:7023.
UCSC	uc010uxg.2. human.
Organism-specific databases
CTD	7023.
GeneCards	GC16M004307.
HGNC	HGNC:11745. TFAP4.
HPA	HPA001912.
MIM	600743. gene.
neXtProt	NX_Q01664.
PharmGKB	PA36462.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG270566.
HOGENOM	HOG000294087.
HOVERGEN	HBG061473.
InParanoid	Q01664.
KO	K09108.
OMA	PTHHATV.
OrthoDB	EOG7BP83C.
PhylomeDB	Q01664.
Gene expression databases
ArrayExpress	Q01664.
Bgee	Q01664.
CleanEx	HS_TFAP4.
Genevestigator	Q01664.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. [Graphical view]
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. SSF47459. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GeneWiki	TFAP4.
GenomeRNAi	7023.
NextBio	27439.
PRO	Q01664.
SOURCE	Search...

Entry information

Entry name

TFAP4_HUMAN

Accession

Primary (citable) accession number: Q01664
Secondary accession number(s): O60409

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1996
Last modified:	November 13, 2013
This is version 132 of the entry and version 2 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.