ID   H3C_HUMAN               Reviewed;         135 AA.
AC   Q6NXT2; E9P281;
DT   17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   11-NOV-2015, entry version 108.
DE   RecName: Full=Histone H3.3C;
DE   AltName: Full=Histone H3.5;
GN   Name=H3F3C;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Seminiferous tubule;
RX   PubMed=21274551; DOI=10.1007/s00412-011-0310-4;
RA   Schenk R., Jenke A., Zilbauer M., Wirth S., Postberg J.;
RT   "H3.5 is a novel hominid-specific histone H3 variant that is
RT   specifically expressed in the seminiferous tubules of human testes.";
RL   Chromosoma 120:275-285(2011).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA   Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA   Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA   Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA   Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA   Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA   Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA   Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA   Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA   Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA   Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA   Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA   Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA   Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA   Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA   Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA   Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA   Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA   Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA   Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA   Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA   Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA   Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA   Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA   Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA   Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA   Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA   Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA   Kucherlapati R., Weinstock G., Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PHOSPHORYLATION AT SER-57 AND THR-80.
RX   PubMed=20850016; DOI=10.1016/j.cell.2010.08.020;
RA   Vermeulen M., Eberl H.C., Matarese F., Marks H., Denissov S.,
RA   Butter F., Lee K.K., Olsen J.V., Hyman A.A., Stunnenberg H.G.,
RA   Mann M.;
RT   "Quantitative interaction proteomics and genome-wide profiling of
RT   epigenetic histone marks and their readers.";
RL   Cell 142:967-980(2010).
CC   -!- FUNCTION: Core component of nucleosome. Nucleosomes wrap and
CC       compact DNA into chromatin, limiting DNA accessibility to the
CC       cellular machineries which require DNA as a template. Histones
CC       thereby play a central role in transcription regulation, DNA
CC       repair, DNA replication and chromosomal stability. DNA
CC       accessibility is regulated via a complex set of post-translational
CC       modifications of histones, also called histone code, and
CC       nucleosome remodeling. Hominid-specific H3.5/H3F3C preferentially
CC       colocalizes with euchromatin, and it is associated with actively
CC       transcribed genes. {ECO:0000269|PubMed:21274551}.
CC   -!- SUBUNIT: The nucleosome is a histone octamer containing two
CC       molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4
CC       heterotetramer and two H2A-H2B heterodimers. The octamer wraps
CC       approximately 147 bp of DNA.
CC   -!- INTERACTION:
CC       P49321-2:NASP; NbExp=3; IntAct=EBI-2868501, EBI-7038920;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC   -!- TISSUE SPECIFICITY: Specifically expressed in the seminiferous
CC       tubules of testis. {ECO:0000269|PubMed:21274551}.
CC   -!- PTM: Acetylation is generally linked to gene activation.
CC       Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9
CC       (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac)
CC       favors methylation at Arg-18 (H3R17me). Acetylation at Lys-122
CC       (H3K122ac) by EP300/p300 plays a central role in chromatin
CC       structure: localizes at the surface of the histone octamer and
CC       stimulates transcription, possibly by promoting nucleosome
CC       instability (By similarity). {ECO:0000250}.
CC   -!- PTM: Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by
CC       PADI4 impairs methylation and represses transcription.
CC       {ECO:0000250}.
CC   -!- PTM: Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is
CC       linked to gene activation. Symmetric dimethylation at Arg-9
CC       (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric
CC       dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene
CC       repression and is mutually exclusive with H3 Lys-5 methylation
CC       (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes
CC       regardless of their transcription state and is enriched on
CC       inactive promoters, while it is absent on active promoters (By
CC       similarity). {ECO:0000250}.
CC   -!- PTM: Methylation at Lys-5 (H3K4me) is linked to gene activation.
CC       Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation
CC       of H3 and H4. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me)
CC       are linked to gene repression. Methylation at Lys-10 (H3K9me) is a
CC       specific target for HP1 proteins (CBX1, CBX3 and CBX5) and
CC       prevents subsequent phosphorylation at Ser-11 (H3S10ph) and
CC       acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) requires
CC       preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at
CC       Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X
CC       chromosome chromatin. Monomethylation at Lys-56 (H3K56me1) by
CC       EHMT2/G9A in G1 phase promotes interaction with PCNA and is
CC       required for DNA replication (By similarity). {ECO:0000250}.
CC   -!- PTM: Phosphorylated at Thr-4 (H3T3ph) by GSG2/haspin during
CC       prophase and dephosphorylated during anaphase. Phosphorylation at
CC       Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation
CC       and cell-cycle progression during mitosis and meiosis. In addition
CC       phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is
CC       important during interphase because it enables the transcription
CC       of genes following external stimulation, like mitogens, stress,
CC       growth factors or UV irradiation and result in the activation of
CC       genes, such as c-fos and c-jun. Phosphorylation at Ser-11
CC       (H3S10ph), which is linked to gene activation, prevents
CC       methylation at Lys-10 (H3K9me) but facilitates acetylation of H3
CC       and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the
CC       dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from
CC       heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an
CC       essential regulatory mechanism for neoplastic cell transformation.
CC       Phosphorylated at Ser-29 (H3S28ph) by MLTK isoform 1, RPS6KA5 or
CC       AURKB during mitosis or upon ultraviolet B irradiation.
CC       Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for
CC       epigenetic transcriptional activation that prevents demethylation
CC       of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically
CC       phosphorylated at Thr-12 (H3T11ph) from prophase to early
CC       anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph)
CC       by PKN1 is a specific tag for epigenetic transcriptional
CC       activation that promotes demethylation of Lys-10 (H3K9me) by
CC       KDM4C/JMJD2C. Phosphorylation at Tyr-41 (H3Y41ph) by JAK2 promotes
CC       exclusion of CBX5 (HP1 alpha) from chromatin (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: Lysine deamination at Lys-5 (H3K4all) to form allysine is
CC       mediated by LOXL2. Allysine formation by LOXL2 only takes place on
CC       H3K4me3 and results in gene repression (By similarity).
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the histone H3 family. {ECO:0000305}.
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DR   EMBL; HQ873957; ADW85800.1; -; mRNA.
DR   EMBL; AC023050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC066906; AAH66906.1; -; mRNA.
DR   CCDS; CCDS31769.1; -.
DR   RefSeq; NP_001013721.2; NM_001013699.2.
DR   UniGene; Hs.448697; -.
DR   PDB; 3KV4; X-ray; 2.19 A; B=2-25.
DR   PDBsum; 3KV4; -.
DR   ProteinModelPortal; Q6NXT2; -.
DR   SMR; Q6NXT2; 2-135.
DR   BioGrid; 136289; 13.
DR   IntAct; Q6NXT2; 14.
DR   MINT; MINT-8417671; -.
DR   STRING; 9606.ENSP00000339835; -.
DR   BioMuta; H3F3C; -.
DR   DMDM; 116248097; -.
DR   PaxDb; Q6NXT2; -.
DR   PRIDE; Q6NXT2; -.
DR   Ensembl; ENST00000340398; ENSP00000339835; ENSG00000188375.
DR   GeneID; 440093; -.
DR   KEGG; hsa:440093; -.
DR   UCSC; uc001rkr.3; human.
DR   CTD; 440093; -.
DR   GeneCards; H3F3C; -.
DR   HGNC; HGNC:33164; H3F3C.
DR   HPA; HPA042570; -.
DR   MIM; 616134; gene.
DR   neXtProt; NX_Q6NXT2; -.
DR   PharmGKB; PA165512903; -.
DR   eggNOG; KOG1745; Eukaryota.
DR   eggNOG; COG2036; LUCA.
DR   GeneTree; ENSGT00810000125408; -.
DR   HOGENOM; HOG000155290; -.
DR   HOVERGEN; HBG001172; -.
DR   InParanoid; Q6NXT2; -.
DR   KO; K11253; -.
DR   OMA; TPSTCGV; -.
DR   OrthoDB; EOG7HB5C2; -.
DR   PhylomeDB; Q6NXT2; -.
DR   TreeFam; TF314241; -.
DR   EvolutionaryTrace; Q6NXT2; -.
DR   GenomeRNAi; 440093; -.
DR   NextBio; 108939; -.
DR   PRO; PR:Q6NXT2; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; Q6NXT2; -.
DR   Genevisible; Q6NXT2; HS.
DR   GO; GO:0005719; C:nuclear euchromatin; IDA:UniProtKB.
DR   GO; GO:0000786; C:nucleosome; IEA:UniProtKB-KW.
DR   GO; GO:0031492; F:nucleosomal DNA binding; IDA:UniProtKB.
DR   GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR   Gene3D; 1.10.20.10; -; 1.
DR   InterPro; IPR009072; Histone-fold.
DR   InterPro; IPR007125; Histone_H2A/H2B/H3.
DR   InterPro; IPR000164; Histone_H3/CENP-A.
DR   PANTHER; PTHR11426; PTHR11426; 1.
DR   Pfam; PF00125; Histone; 1.
DR   PRINTS; PR00622; HISTONEH3.
DR   SMART; SM00428; H3; 1.
DR   SUPFAM; SSF47113; SSF47113; 1.
DR   PROSITE; PS00322; HISTONE_H3_1; 1.
DR   PROSITE; PS00959; HISTONE_H3_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Chromosome; Citrullination;
KW   Complete proteome; DNA-binding; Methylation; Nucleosome core; Nucleus;
KW   Phosphoprotein; Polymorphism; Reference proteome.
FT   INIT_MET      1      1       Removed. {ECO:0000250|UniProtKB:P68432}.
FT   CHAIN         2    135       Histone H3.3C.
FT                                /FTId=PRO_0000253960.
FT   MOD_RES       3      3       Asymmetric dimethylarginine; by PRMT6;
FT                                alternate. {ECO:0000250}.
FT   MOD_RES       3      3       Citrulline; alternate. {ECO:0000250}.
FT   MOD_RES       4      4       Phosphothreonine; by GSG2. {ECO:0000250}.
FT   MOD_RES       5      5       Allysine; alternate. {ECO:0000250}.
FT   MOD_RES       5      5       N6,N6,N6-trimethyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES       5      5       N6,N6-dimethyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES       5      5       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES       5      5       N6-methyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES       7      7       Phosphothreonine; by PKC. {ECO:0000250}.
FT   MOD_RES       9      9       Citrulline; alternate. {ECO:0000250}.
FT   MOD_RES       9      9       Symmetric dimethylarginine; by PRMT5;
FT                                alternate. {ECO:0000250}.
FT   MOD_RES      10     10       N6,N6,N6-trimethyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68432}.
FT   MOD_RES      10     10       N6,N6-dimethyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68432}.
FT   MOD_RES      10     10       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      10     10       N6-methyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68432}.
FT   MOD_RES      11     11       Phosphoserine; by AURKB, AURKC, RPS6KA3,
FT                                RPS6KA4 and RPS6KA5. {ECO:0000250}.
FT   MOD_RES      12     12       Phosphothreonine; by PKC. {ECO:0000250}.
FT   MOD_RES      15     15       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P68432}.
FT   MOD_RES      18     18       Asymmetric dimethylarginine; by CARM1;
FT                                alternate. {ECO:0000250}.
FT   MOD_RES      18     18       Citrulline; alternate. {ECO:0000250}.
FT   MOD_RES      19     19       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      19     19       N6-methyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      24     24       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68432}.
FT   MOD_RES      24     24       N6-methyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      27     27       Citrulline. {ECO:0000250}.
FT   MOD_RES      28     28       N6,N6,N6-trimethyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68432}.
FT   MOD_RES      28     28       N6,N6-dimethyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68432}.
FT   MOD_RES      28     28       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      28     28       N6-methyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68432}.
FT   MOD_RES      29     29       Phosphoserine; by AURKB, AURKC and
FT                                RPS6KA5. {ECO:0000250}.
FT   MOD_RES      32     32       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P84243}.
FT   MOD_RES      37     37       N6-methyllysine.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      41     41       Phosphotyrosine.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      56     56       N6,N6,N6-trimethyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      56     56       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      56     56       N6-methyllysine; by EHMT2; alternate.
FT                                {ECO:0000250}.
FT   MOD_RES      57     57       Phosphoserine.
FT                                {ECO:0000269|PubMed:20850016}.
FT   MOD_RES      64     64       N6-methyllysine.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES      80     80       Phosphothreonine.
FT                                {ECO:0000269|PubMed:20850016}.
FT   MOD_RES      86     86       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P84243}.
FT   MOD_RES     107    107       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q71DI3}.
FT   MOD_RES     115    115       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES     122    122       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   MOD_RES     122    122       N6-methyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P68431}.
FT   VARIANT      39     39       H -> R (in dbSNP:rs3759295).
FT                                /FTId=VAR_068164.
FT   CONFLICT     88     88       A -> V (in Ref. 1; ADW85800 and 3;
FT                                AAH66906). {ECO:0000305}.
SQ   SEQUENCE   135 AA;  15214 MW;  F2941F8A9BC61BB5 CRC64;
     MARTKQTARK STGGKAPRKQ LATKAARKST PSTCGVKPHR YRPGTVALRE IRRYQKSTEL
     LIRKLPFQRL VREIAQDFNT DLRFQSAAVG ALQEASEAYL VGLLEDTNLC AIHAKRVTIM
     PKDIQLARRI RGERA
//