Reviewed, UniProtKB/Swiss-Prot Q13111 (CAF1A_HUMAN)

Names and origin

Protein names

Recommended name:
    Chromatin assembly factor 1 subunit A
      Short name=CAF-1 subunit A
Alternative name(s):
    Chromatin assembly factor I p150 subunit
    CAF-I 150 kDa subunit
    CAF-Ip150

Gene names

Name:	CHAF1A
Synonyms:	CAF, CAF1P150

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	938 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Core component of the CAF-1 complex, a complex thought to mediate chromatin assembly in DNA replication and DNA repair. Assembles histone octamers onto replicating DNA in vitro. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer. CHAF1A binds to histones H3 and H4. It may play a role in heterochromatin maintenance in proliferating cells by bringing newly synthesized cbx proteins to heterochromatic DNA replication foci By similarity. The CCR4-NOT complex functions as general transcription regulation complex.
Subunit structure	Part of the CAF-1 complex that contains RBBP4, CHAF1B and CHAF1A. CHAF1A binds directly to CHAF1B. Only minor amounts of RBBP4 are complexed with CHAF1A and CHAF1B in G1 phase. Part of the CCR4-NOT core complex that contains CHAF1A, CHAF1B, CNOT1, CNOT2, CNOT3, CNOT4, CNOT6 and CNOT8. CHAF1A binds directly to PCNA and to CBX1. Binds MBD1. Interacts directly with CBX5 via the PxVxL motif. During DNA replication, it forms a S phase-specific complex that facilitates DNA methylation and histone H3 'Lys-9' methylation during replication-coupled chromatin assembly and is at least composed of the CHAF1A, MBD1 and SETDB1.
Subcellular location	Nucleus. Note= DNA replication foci.
Developmental stage	Active complex is found in G1, S and G2 phases.
Domain	Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Sequence caution	The sequence AAH52620.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence starting in position 408.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair DNA replication Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Chaperone
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW DNA replication Inferred from electronic annotation. Source: UniProtKB-KW DNA replication-dependent nucleosome assembly Ref.1 Traceable author statement. Source: ProtInc cell cycle Inferred from electronic annotation. Source: UniProtKB-KW protein complex assembly Ref.1 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	chromatin assembly complex Ref.1 Traceable author statement. Source: ProtInc
Molecular function	chromatin binding Ref.1 Traceable author statement. Source: ProtInc unfolded protein binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASF1B	Q9NVP2	1	EBI-1020839,EBI-1055650
FYN	P06241	1	EBI-1020839,EBI-515315
NCK1	P16333	1	EBI-1020839,EBI-389883
PCNA	P12004	1	EBI-1020839,EBI-358311
PIK3R1	P27986	1	EBI-1020839,EBI-79464
PLCG1	P19174	1	EBI-1020839,EBI-79387
ZNF408	Q9H9D4	1	EBI-1020839,EBI-347633

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Notes: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q13111-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q13111-2)

The sequence of this isoform differs from the canonical sequence as follows:
     692-731: CFLETLPAQE...LPLLHGNVNG → HWVHPESRGD...CVKSTLSCFT
     732-938: Missing.

Isoform 3 (identifier: Q13111-3)

The sequence of this isoform differs from the canonical sequence as follows:
     754-926: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 938	938	Chromatin assembly factor 1 subunit A		PRO_0000089276
Regions
	Region	1 – 296	296	Binds to CBX1 chromo shadow domain
	Region	1 – 31	31	Binds to PCNA
	Region	642 – 938	297	Binds to p60
	Motif	215 – 228	14	PxVxL motif
	Compositional bias	305 – 435	131	Arg/Glu/Lys-rich
	Compositional bias	584 – 590	7	Poly-Glu
	Compositional bias	601 – 605	5	Poly-Asp
	Compositional bias	887 – 893	7	Poly-Glu
Amino acid modifications
	Modified residue	47	1	Phosphoserine
	Modified residue	123	1	Phosphoserine
	Modified residue	181	1	Phosphoserine
	Modified residue	185	1	Phosphoserine
	Modified residue	188	1	Phosphoserine
	Modified residue	206	1	Phosphoserine
	Modified residue	237	1	Phosphoserine
	Modified residue	241	1	Phosphothreonine
	Modified residue	704	1	Phosphothreonine
	Modified residue	754	1	Phosphoserine
	Modified residue	855	1	Phosphoserine
	Modified residue	933	1	Phosphoserine
Natural variations
	Alternative sequence	692 – 731	40	CFLET…GNVNG → HWVHPESRGDVCRTLRVSSP QSRYLNRLNSCVKSTLSCFT in isoform 2.		VSP_004149
	Alternative sequence	732 – 938	207	Missing in isoform 2.		VSP_004150
	Alternative sequence	754 – 926	173	Missing in isoform 3.		VSP_004151
Experimental info
	Sequence conflict	757	1	T → S in AAF04291. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: DBD01B9F1A0E28B7	FASTA	938	105,223
	10 20 30 40 50 60 MDCKDRPAFP VKKLIQARLP FKRLNLVPKG KADDMSDDQG TSVQSKSPDL EASLDTLENN 70 80 90 100 110 120 CHVGSDIDFR PKLVNGKGPL DNFLRNRIET SIGQSTVIID LTEDSNEQPD SLVDHNKLNS 130 140 150 160 170 180 EASPSREAIN GQREDTGDQQ GLLKAIQNDK LAFPGETLSD IPCKTEEEGV GCGGAGRRGD 190 200 210 220 230 240 SQECSPRSCP ELTSGPRMCP RKEQDSWSEA GGILFKGKVP MVVLQDILAV RPPQIKSLPA 250 260 270 280 290 300 TPQGKNMTPE SEVLESFPEE DSVLSHSSLS SPSSTSSPEG PPAPPKQHSS TSPFPTSTPL 310 320 330 340 350 360 RRITKKFVKG STEKNKLRLQ RDQERLGKQL KLRAEREEKE KLKEEAKRAK EEAKKKKEEE 370 380 390 400 410 420 KELKEKERRE KREKDEKEKA EKQRLKEERR KERQEALEAK LEEKRKKEEE KRLREEEKRI 430 440 450 460 470 480 KAEKAEITRF FQKPKTPQAP KTLAGSCGKF APFEIKEHMV LAPRRRTAFH PDLCSQLDQL 490 500 510 520 530 540 LQQQSGEFSF LKDLKGRQPL RSGPTHVSTR NADIFNSDVV IVERGKGDGV PERRKFGRMK 550 560 570 580 590 600 LLQFCENHRP AYWGTWNKKT ALIRARDPWA QDTKLLDYEV DSDEEWEEEE PGESLSHSEG 610 620 630 640 650 660 DDDDDMGEDE DEDDGFFVPH GYLSEDEGVT EECADPENHK VRQKLKAKEW DEFLAKGKRF 670 680 690 700 710 720 RVLQPVKIGC VWAADRDCAG DDLKVLQQFA ACFLETLPAQ EEQTPKASKR ERRDEQILAQ 730 740 750 760 770 780 LLPLLHGNVN GSKVIIREFQ EHCRRGLLSN HTGSPRTPST TYLHTPTPSE DAAIPSKSRL 790 800 810 820 830 840 KRLISENSVY EKRPDFRMCW YVHPQVLQSF QQEHLPVPCQ WSYVTSVPSA PKEDSGSVPS 850 860 870 880 890 900 TGPSQGTPIS LKRKSAGSMC ITQFMKKRRH DGQIGAEDMD GFQADTEEEE EEEGDCMIVD 910 920 930 VPDAVEVQAP CGAASGAGGG VGVDTGKATL TASPLGAS
	Isoform 2 [UniParc]. Checksum: F7572877A06B9A70		731	82,956
	10 20 30 40 50 60 MDCKDRPAFP VKKLIQARLP FKRLNLVPKG KADDMSDDQG TSVQSKSPDL EASLDTLENN 70 80 90 100 110 120 CHVGSDIDFR PKLVNGKGPL DNFLRNRIET SIGQSTVIID LTEDSNEQPD SLVDHNKLNS 130 140 150 160 170 180 EASPSREAIN GQREDTGDQQ GLLKAIQNDK LAFPGETLSD IPCKTEEEGV GCGGAGRRGD 190 200 210 220 230 240 SQECSPRSCP ELTSGPRMCP RKEQDSWSEA GGILFKGKVP MVVLQDILAV RPPQIKSLPA 250 260 270 280 290 300 TPQGKNMTPE SEVLESFPEE DSVLSHSSLS SPSSTSSPEG PPAPPKQHSS TSPFPTSTPL 310 320 330 340 350 360 RRITKKFVKG STEKNKLRLQ RDQERLGKQL KLRAEREEKE KLKEEAKRAK EEAKKKKEEE 370 380 390 400 410 420 KELKEKERRE KREKDEKEKA EKQRLKEERR KERQEALEAK LEEKRKKEEE KRLREEEKRI 430 440 450 460 470 480 KAEKAEITRF FQKPKTPQAP KTLAGSCGKF APFEIKEHMV LAPRRRTAFH PDLCSQLDQL 490 500 510 520 530 540 LQQQSGEFSF LKDLKGRQPL RSGPTHVSTR NADIFNSDVV IVERGKGDGV PERRKFGRMK 550 560 570 580 590 600 LLQFCENHRP AYWGTWNKKT ALIRARDPWA QDTKLLDYEV DSDEEWEEEE PGESLSHSEG 610 620 630 640 650 660 DDDDDMGEDE DEDDGFFVPH GYLSEDEGVT EECADPENHK VRQKLKAKEW DEFLAKGKRF 670 680 690 700 710 720 RVLQPVKIGC VWAADRDCAG DDLKVLQQFA AHWVHPESRG DVCRTLRVSS PQSRYLNRLN 730 SCVKSTLSCF T
	Isoform 3 [UniParc]. Checksum: 8E56019C48629C6C		765	86,540
	10 20 30 40 50 60 MDCKDRPAFP VKKLIQARLP FKRLNLVPKG KADDMSDDQG TSVQSKSPDL EASLDTLENN 70 80 90 100 110 120 CHVGSDIDFR PKLVNGKGPL DNFLRNRIET SIGQSTVIID LTEDSNEQPD SLVDHNKLNS 130 140 150 160 170 180 EASPSREAIN GQREDTGDQQ GLLKAIQNDK LAFPGETLSD IPCKTEEEGV GCGGAGRRGD 190 200 210 220 230 240 SQECSPRSCP ELTSGPRMCP RKEQDSWSEA GGILFKGKVP MVVLQDILAV RPPQIKSLPA 250 260 270 280 290 300 TPQGKNMTPE SEVLESFPEE DSVLSHSSLS SPSSTSSPEG PPAPPKQHSS TSPFPTSTPL 310 320 330 340 350 360 RRITKKFVKG STEKNKLRLQ RDQERLGKQL KLRAEREEKE KLKEEAKRAK EEAKKKKEEE 370 380 390 400 410 420 KELKEKERRE KREKDEKEKA EKQRLKEERR KERQEALEAK LEEKRKKEEE KRLREEEKRI 430 440 450 460 470 480 KAEKAEITRF FQKPKTPQAP KTLAGSCGKF APFEIKEHMV LAPRRRTAFH PDLCSQLDQL 490 500 510 520 530 540 LQQQSGEFSF LKDLKGRQPL RSGPTHVSTR NADIFNSDVV IVERGKGDGV PERRKFGRMK 550 560 570 580 590 600 LLQFCENHRP AYWGTWNKKT ALIRARDPWA QDTKLLDYEV DSDEEWEEEE PGESLSHSEG 610 620 630 640 650 660 DDDDDMGEDE DEDDGFFVPH GYLSEDEGVT EECADPENHK VRQKLKAKEW DEFLAKGKRF 670 680 690 700 710 720 RVLQPVKIGC VWAADRDCAG DDLKVLQQFA ACFLETLPAQ EEQTPKASKR ERRDEQILAQ 730 740 750 760 LLPLLHGNVN GSKVIIREFQ EHCRRGLLSN HTGKATLTAS PLGAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication." Kaufman P.D., Kobayashi R., Kessler N., Stillman B. Cell 81:1105-1114(1995) [PubMed: 7600578] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Cervix adenocarcinoma.
[2]	"Genomic sequence and expression analyses of human chromatin assembly factor 1 p150 gene." Dong H., Lin W., Zhang C.-K., Xiong H., Fu G., Jin W.-R., Chen R., Chen Z., Qi Z.-T., Huang G.M. Gene 264:187-196(2001) [PubMed: 11250073] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-407. Tissue: Ovary.
[4]	"Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin." Shibahara K., Stillman B. Cell 96:575-585(1999) [PubMed: 10052459] [Abstract] Cited for: INTERACTION WITH PCNA, SUBCELLULAR LOCATION.
[5]	"A CAF-1-PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage." Moggs J.G., Grandi P., Quivy J.P., Jonsson Z.O., Hubscher U., Becker P.B., Almouzni G. Mol. Cell. Biol. 20:1206-1218(2000) [PubMed: 10648606] [Abstract] Cited for: INTERACTION WITH PCNA.
[6]	"CAF-1 and the inheritance of chromatin states: at the crossroads of DNA replication and repair." Ridgway P., Almouzni G. J. Cell Sci. 113:2647-2658(2000) [PubMed: 10893180] [Abstract] Cited for: REVIEW.
[7]	"BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms." Morel A.-P., Sentis S., Bianchin C., Le Romancer M., Jonard L., Rostan M.-C., Rimokh R., Corbo L. J. Cell Sci. 116:2929-2936(2003) [PubMed: 12771185] [Abstract] Cited for: INTERACTION WITH THE CCR4-NOT COMPLEX.
[8]	"The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1." Reese B.E., Bachman K.E., Baylin S.B., Rountree M.R. Mol. Cell. Biol. 23:3226-3236(2003) [PubMed: 12697822] [Abstract] Cited for: INTERACTION WITH MBD1.
[9]	"Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly." Sarraf S.A., Stancheva I. Mol. Cell 15:595-605(2004) [PubMed: 15327775] [Abstract] Cited for: FUNCTION, INTERACTION WITH MBD1 AND SETDB1.
[10]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123 AND SER-188, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain." Lechner M.S., Schultz D.C., Negorev D., Maul G.G., Rauscher F.J. III Biochem. Biophys. Res. Commun. 331:929-937(2005) [PubMed: 15882967] [Abstract] Cited for: INTERACTION WITH CBX5.
[12]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47; SER-123 AND SER-754, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237; THR-241 AND SER-933, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181; SER-185 AND SER-188, MASS SPECTROMETRY.
[15]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-188, MASS SPECTROMETRY.
[16]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206; THR-704; SER-754; SER-855 AND SER-933, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U20979 mRNA. Translation: AAA76736.1. AF190465 Genomic DNA. Translation: AAF04291.1. BC052620 mRNA. Translation: AAH52620.1. Sequence problems.
PIR	A56731.
RefSeq	NP_005474.2.
UniGene	Hs.79018
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13111.
PTM databases
PhosphoSite	Q13111.
Genome annotation databases
Ensembl	ENSG00000167670. Homo sapiens. [Contig view]
GeneID	10036.
KEGG	hsa:10036.
Organism-specific databases
H-InvDB	HIX0040076.
HGNC	HGNC:1910. CHAF1A.
HPA	CAB015186.
MIM	601246. gene.
PharmGKB	PA26446.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q13111.
Gene expression databases
ArrayExpress	Q13111.
CleanEx	HS_CHAF1A.
GermOnline	ENSG00000167670. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other Resources
NextBio	37903.
SOURCE	Search...

Entry information

Entry name

CAF1A_HUMAN

Accession

Primary (citable) accession number: Q13111
Secondary accession number(s): Q7Z7K3, Q9UJY8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)