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Protein

Histone H3.3C

Gene

H3F3C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Hominid-specific H3.5/H3F3C preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes.1 Publication

GO - Molecular functioni

  • nucleosomal DNA binding Source: UniProtKB

GO - Biological processi

  • nucleosome assembly Source: GO_Central
  • positive regulation of cell growth Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Histone H3.3C
Alternative name(s):
Histone H3.5
Gene namesi
Name:H3F3C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:33164. H3F3C.

Subcellular locationi

GO - Cellular componenti

  • nuclear euchromatin Source: UniProtKB
  • nucleosome Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleosome core, Nucleus

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000188375.
PharmGKBiPA165512903.

Polymorphism and mutation databases

BioMutaiH3F3C.
DMDMi116248097.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002539602 – 135Histone H3.3CAdd BLAST134

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3Asymmetric dimethylarginine; by PRMT6; alternateBy similarity1
Modified residuei3Citrulline; alternateBy similarity1
Modified residuei4Phosphothreonine; by GSG2By similarity1
Modified residuei5Allysine; alternateBy similarity1
Modified residuei5N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei5N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei5N6-acetyllysine; alternateBy similarity1
Modified residuei5N6-methyllysine; alternateBy similarity1
Modified residuei7Phosphothreonine; by PKCBy similarity1
Modified residuei9Citrulline; alternateBy similarity1
Modified residuei9Symmetric dimethylarginine; by PRMT5; alternateBy similarity1
Modified residuei10N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei10N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei10N6-acetyllysine; alternateBy similarity1
Modified residuei10N6-methyllysine; alternateBy similarity1
Modified residuei11Phosphoserine; by AURKB, AURKC, RPS6KA3, RPS6KA4 and RPS6KA5By similarity1
Modified residuei12Phosphothreonine; by PKCBy similarity1
Modified residuei15N6-acetyllysineBy similarity1
Modified residuei18Asymmetric dimethylarginine; by CARM1; alternateBy similarity1
Modified residuei18Citrulline; alternateBy similarity1
Modified residuei19N6-acetyllysine; alternateBy similarity1
Modified residuei19N6-methyllysine; alternateBy similarity1
Modified residuei24N6-acetyllysine; alternateBy similarity1
Modified residuei24N6-methyllysine; alternateBy similarity1
Modified residuei27CitrullineBy similarity1
Modified residuei28N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei28N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei28N6-acetyllysine; alternateBy similarity1
Modified residuei28N6-methyllysine; alternateBy similarity1
Modified residuei29Phosphoserine; by AURKB, AURKC and RPS6KA5By similarity1
Modified residuei32PhosphoserineBy similarity1
Modified residuei37N6-methyllysineBy similarity1
Modified residuei41PhosphotyrosineBy similarity1
Modified residuei56N6,N6,N6-trimethyllysine; alternateBy similarity1
Modified residuei56N6-acetyllysine; alternateBy similarity1
Modified residuei56N6-methyllysine; by EHMT2; alternateBy similarity1
Modified residuei57Phosphoserine1 Publication1
Modified residuei64N6-methyllysineBy similarity1
Modified residuei80Phosphothreonine1 Publication1
Modified residuei86PhosphoserineBy similarity1
Modified residuei107PhosphothreonineBy similarity1
Modified residuei115N6-acetyllysineBy similarity1
Modified residuei122N6-acetyllysine; alternateBy similarity1
Modified residuei122N6-methyllysine; alternateBy similarity1

Post-translational modificationi

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). Acetylation at Lys-122 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability (By similarity).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).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. Monomethylation at Lys-56 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication (By similarity).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).By similarity
Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).By similarity

Keywords - PTMi

Acetylation, Citrullination, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ6NXT2.
MaxQBiQ6NXT2.
PaxDbiQ6NXT2.
PeptideAtlasiQ6NXT2.
PRIDEiQ6NXT2.
TopDownProteomicsiQ6NXT2.

PTM databases

iPTMnetiQ6NXT2.
PhosphoSitePlusiQ6NXT2.
SwissPalmiQ6NXT2.

Expressioni

Tissue specificityi

Specifically expressed in the seminiferous tubules of testis.1 Publication

Gene expression databases

BgeeiENSG00000188375.
GenevisibleiQ6NXT2. HS.

Organism-specific databases

HPAiHPA042570.

Interactioni

Subunit structurei

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.

Binary interactionsi

WithEntry#Exp.IntActNotes
NASPP49321-25EBI-2868501,EBI-7038920

Protein-protein interaction databases

BioGridi136289. 24 interactors.
IntActiQ6NXT2. 15 interactors.
MINTiMINT-8417671.
STRINGi9606.ENSP00000339835.

Structurei

Secondary structure

1135
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 12Combined sources8
Helixi45 – 56Combined sources12
Helixi64 – 78Combined sources15
Helixi86 – 113Combined sources28
Beta strandi117 – 119Combined sources3
Helixi121 – 130Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KV4X-ray2.19B2-25[»]
4Z5TX-ray2.80A/E1-135[»]
5BWOX-ray2.38B6-14[»]
5F6KX-ray2.41M2-10[»]
5I3LX-ray1.85C2-21[»]
ProteinModelPortaliQ6NXT2.
SMRiQ6NXT2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ6NXT2.

Family & Domainsi

Sequence similaritiesi

Belongs to the histone H3 family.Curated

Phylogenomic databases

eggNOGiKOG1745. Eukaryota.
COG2036. LUCA.
GeneTreeiENSGT00760000118967.
HOGENOMiHOG000155290.
HOVERGENiHBG001172.
InParanoidiQ6NXT2.
KOiK11253.
OMAiTPSTCGV.
OrthoDBiEOG091G0XGD.
PhylomeDBiQ6NXT2.
TreeFamiTF314241.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR009072. Histone-fold.
IPR007125. Histone_H2A/H2B/H3.
IPR000164. Histone_H3/CENP-A.
[Graphical view]
PANTHERiPTHR11426. PTHR11426. 1 hit.
PfamiPF00125. Histone. 1 hit.
[Graphical view]
PRINTSiPR00622. HISTONEH3.
SMARTiSM00428. H3. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS00322. HISTONE_H3_1. 1 hit.
PS00959. HISTONE_H3_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q6NXT2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARTKQTARK STGGKAPRKQ LATKAARKST PSTCGVKPHR YRPGTVALRE
60 70 80 90 100
IRRYQKSTEL LIRKLPFQRL VREIAQDFNT DLRFQSAAVG ALQEASEAYL
110 120 130
VGLLEDTNLC AIHAKRVTIM PKDIQLARRI RGERA
Length:135
Mass (Da):15,214
Last modified:January 23, 2007 - v3
Checksum:iF2941F8A9BC61BB5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88A → V in ADW85800 (PubMed:21274551).Curated1
Sequence conflicti88A → V in AAH66906 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06816439H → R.Corresponds to variant rs3759295dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
HQ873957 mRNA. Translation: ADW85800.1.
AC023050 Genomic DNA. No translation available.
BC066906 mRNA. Translation: AAH66906.1.
CCDSiCCDS31769.1.
RefSeqiNP_001013721.2. NM_001013699.2.
UniGeneiHs.448697.

Genome annotation databases

EnsembliENST00000340398; ENSP00000339835; ENSG00000188375.
GeneIDi440093.
KEGGihsa:440093.
UCSCiuc001rkr.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
HQ873957 mRNA. Translation: ADW85800.1.
AC023050 Genomic DNA. No translation available.
BC066906 mRNA. Translation: AAH66906.1.
CCDSiCCDS31769.1.
RefSeqiNP_001013721.2. NM_001013699.2.
UniGeneiHs.448697.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KV4X-ray2.19B2-25[»]
4Z5TX-ray2.80A/E1-135[»]
5BWOX-ray2.38B6-14[»]
5F6KX-ray2.41M2-10[»]
5I3LX-ray1.85C2-21[»]
ProteinModelPortaliQ6NXT2.
SMRiQ6NXT2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi136289. 24 interactors.
IntActiQ6NXT2. 15 interactors.
MINTiMINT-8417671.
STRINGi9606.ENSP00000339835.

PTM databases

iPTMnetiQ6NXT2.
PhosphoSitePlusiQ6NXT2.
SwissPalmiQ6NXT2.

Polymorphism and mutation databases

BioMutaiH3F3C.
DMDMi116248097.

Proteomic databases

EPDiQ6NXT2.
MaxQBiQ6NXT2.
PaxDbiQ6NXT2.
PeptideAtlasiQ6NXT2.
PRIDEiQ6NXT2.
TopDownProteomicsiQ6NXT2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340398; ENSP00000339835; ENSG00000188375.
GeneIDi440093.
KEGGihsa:440093.
UCSCiuc001rkr.3. human.

Organism-specific databases

CTDi440093.
GeneCardsiH3F3C.
HGNCiHGNC:33164. H3F3C.
HPAiHPA042570.
MIMi616134. gene.
neXtProtiNX_Q6NXT2.
OpenTargetsiENSG00000188375.
PharmGKBiPA165512903.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1745. Eukaryota.
COG2036. LUCA.
GeneTreeiENSGT00760000118967.
HOGENOMiHOG000155290.
HOVERGENiHBG001172.
InParanoidiQ6NXT2.
KOiK11253.
OMAiTPSTCGV.
OrthoDBiEOG091G0XGD.
PhylomeDBiQ6NXT2.
TreeFamiTF314241.

Miscellaneous databases

EvolutionaryTraceiQ6NXT2.
GenomeRNAii440093.
PROiQ6NXT2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188375.
GenevisibleiQ6NXT2. HS.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR009072. Histone-fold.
IPR007125. Histone_H2A/H2B/H3.
IPR000164. Histone_H3/CENP-A.
[Graphical view]
PANTHERiPTHR11426. PTHR11426. 1 hit.
PfamiPF00125. Histone. 1 hit.
[Graphical view]
PRINTSiPR00622. HISTONEH3.
SMARTiSM00428. H3. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS00322. HISTONE_H3_1. 1 hit.
PS00959. HISTONE_H3_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiH3C_HUMAN
AccessioniPrimary (citable) accession number: Q6NXT2
Secondary accession number(s): E9P281
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 119 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.