Q6NXT2 (H3C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone H3.3C

Gene names

Name:

H3F3C

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	135 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	Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Subunit structure	The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.
Subcellular location	Nucleus. Chromosome.
Post-translational modification	Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me) By similarity. Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription By similarity. Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters By similarity. Methylation at Lys-5 (H3K4me) is linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) requires preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin By similarity. Phosphorylated at Thr-4 (H3T3ph) by GSG2/haspin during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MLTK isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-41 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin By similarity. Ref.4
Sequence similarities	Belongs to the histone H3 family.

Ontologies

Keywords
Cellular component	Chromosome Nucleosome core Nucleus
Ligand	DNA-binding
PTM	Acetylation Citrullination Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	nucleosome assembly Inferred from electronic annotation. Source: InterPro
Cellular component	nucleosome Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: HPA
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 135	134	Histone H3.3C		PRO_0000253960
Amino acid modifications
	Modified residue	3	1	Asymmetric dimethylarginine; by PRMT6 By similarity
	Modified residue	4	1	Phosphothreonine; by GSG2 By similarity
	Modified residue	5	1	N6-methylated lysine By similarity
	Modified residue	7	1	Phosphothreonine; by PKC By similarity
	Modified residue	9	1	Citrulline; alternate By similarity
	Modified residue	9	1	Symmetric dimethylarginine; by PRMT5; alternate By similarity
	Modified residue	10	1	N6-acetyllysine; alternate By similarity
	Modified residue	10	1	N6-methylated lysine; alternate By similarity
	Modified residue	11	1	Phosphoserine; by AURKB, AURKC, RPS6KA3, RPS6KA4 and RPS6KA5 By similarity
	Modified residue	12	1	Phosphothreonine; by PKC By similarity
	Modified residue	15	1	N6-acetyllysine Ref.3
	Modified residue	18	1	Asymmetric dimethylarginine; by CARM1; alternate By similarity
	Modified residue	18	1	Citrulline; alternate By similarity
	Modified residue	19	1	N6-acetyllysine; alternate By similarity
	Modified residue	19	1	N6-methylated lysine; alternate By similarity
	Modified residue	24	1	N6-acetyllysine Ref.3
	Modified residue	28	1	N6-acetyllysine; alternate By similarity
	Modified residue	28	1	N6-methylated lysine; alternate By similarity
	Modified residue	29	1	Phosphoserine; by AURKB, AURKC and RPS6KA5 By similarity
	Modified residue	32	1	Phosphoserine By similarity
	Modified residue	41	1	Phosphotyrosine By similarity
	Modified residue	56	1	N6-acetyllysine Ref.3
	Modified residue	57	1	Phosphoserine Ref.4
	Modified residue	80	1	Phosphothreonine Ref.4
	Modified residue	122	1	N6-acetyllysine Ref.3
	Modified residue	122	1	N6-methylated lysine By similarity
Experimental info
	Sequence conflict	88	1	A → V in AAH66906. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q6NXT2 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: F2941F8A9BC61BB5	FASTA	135	15,214
	10 20 30 40 50 60 MARTKQTARK STGGKAPRKQ LATKAARKST PSTCGVKPHR YRPGTVALRE IRRYQKSTEL 70 80 90 100 110 120 LIRKLPFQRL VREIAQDFNT DLRFQSAAVG ALQEASEAYL VGLLEDTNLC AIHAKRVTIM 130 PKDIQLARRI RGERA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[3]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-10; LYS-15; LYS-19; LYS-24; LYS-56 AND LYS-122, MASS SPECTROMETRY.
[4]	"Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers." Vermeulen M., Eberl H.C., Matarese F., Marks H., Denissov S., Butter F., Lee K.K., Olsen J.V., Hyman A.A., Stunnenberg H.G., Mann M. Cell 142:967-980(2010) [PubMed: 20850016] [Abstract] Cited for: PHOSPHORYLATION AT SER-57 AND THR-80.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AC023050 Genomic DNA. No translation available.
BC066906 mRNA. Translation: AAH66906.1.

IPI

IPI00419884.

RefSeq

NP_001013721.2. NM_001013699.2.

UniGene

Hs.448697.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3KV4	X-ray	2.19	B	2-25	[»]

ProteinModelPortal

Q6NXT2.

SMR

Q6NXT2. Positions 2-135.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q6NXT2. 1 interaction.

STRING

Q6NXT2.

Polymorphism databases

DMDM

116248097.

Proteomic databases

PRIDE

Q6NXT2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340398; ENSP00000339835; ENSG00000188375.

GeneID

440093.

KEGG

hsa:440093.

NMPDR

fig|9606.3.peg.7374.

UCSC

uc001rkr.1. human.

Organism-specific databases

CTD

440093.

GeneCards

GC12M031944.

HGNC

HGNC:33164. H3F3C.

neXtProt

NX_Q6NXT2.

PharmGKB

PA165512903.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04423.

GeneTree

ENSGT00560000076889.

HOGENOM

HBG715487.

HOVERGEN

HBG001172.

InParanoid

Q6NXT2.

OMA

HRIRGEC.

PhylomeDB

Q6NXT2.

Gene expression databases

Genevestigator

Q6NXT2.

GermOnline

ENSG00000188375. Homo sapiens.

Family and domain databases

InterPro

IPR009072. Histone-fold.
IPR007125. Histone_core_D.
IPR000164. Histone_H3.
[Graphical view]

Gene3D

G3DSA:1.10.20.10. Histone-fold. 1 hit.

KO

K11253.

PANTHER

PTHR11426. Histone_H3. 1 hit.

Pfam

PF00125. Histone. 1 hit.
[Graphical view]

PRINTS

PR00622. HISTONEH3.

SMART

SM00428. H3. 1 hit.
[Graphical view]

SUPFAM

SSF47113. Histone-fold. 1 hit.

PROSITE

PS00322. HISTONE_H3_1. 1 hit.
PS00959. HISTONE_H3_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

108939.

Entry information

Entry name

H3C_HUMAN

Accession

Primary (citable) accession number: Q6NXT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 72 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.