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Q16630 (CPSF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cleavage and polyadenylation specificity factor subunit 6
Alternative name(s):
Cleavage and polyadenylation specificity factor 68 kDa subunit
Short name=CFIm68
Short name=CPSF 68 kDa subunit
Pre-mRNA cleavage factor Im 68 kDa subunit
Protein HPBRII-4/7
Gene names
Name:CPSF6
Synonyms:CFIM68
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length551 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of the cleavage factor Im complex (CFIm) that plays a key role in pre-mRNA 3'-processing. Involved in association with NUDT21/CPSF5 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. CPSF6 binds to cleavage and polyadenylation RNA substrates and promotes RNA looping. Ref.1 Ref.7 Ref.8 Ref.14 Ref.16

Subunit structure

Component of the cleavage factor Im (CFIm) complex, composed at least of NUDT21/CPSF5 and CPSF6 or CPSF7. Within the cleavage factor Im complex, the NUDT21/CPSF5 homodimer is at the core of a heterotetramer, and is clasped by two additional subunits (CPSF6 or CPSF7). Interacts with NUDT21/CPSF5, SFRS3, SFRS7, SNRNP70 and TRA2B/SFRS10. Ref.1 Ref.7 Ref.9 Ref.10 Ref.14 Ref.16

Subcellular location

Nucleus. Note: In punctate subnuclear structures localized adjacent to nuclear speckles, called paraspeckles. Ref.1 Ref.9 Ref.14

Sequence similarities

Belongs to the RRM CPSF6/7 family.

Contains 1 RRM (RNA recognition motif) domain.

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16630-1)

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: Q16630-2)

The sequence of this isoform differs from the canonical sequence as follows:
     231-231: P → PGNLIKHLVKGTRPLFLETRIPWHMGHSIEEIPIFGLK
Isoform 3 (identifier: Q16630-3)

The sequence of this isoform differs from the canonical sequence as follows:
     188-260: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 551551Cleavage and polyadenylation specificity factor subunit 6
PRO_0000081521

Regions

Domain81 – 16181RRM
Region81 – 16181Necessary for interaction with NUDT21/CPSF5
Region510 – 55142Sufficient for nuclear targeting
Compositional bias208 – 398191Pro-rich
Compositional bias490 – 55162Arg-rich

Amino acid modifications

Modified residue4041Phosphothreonine Ref.11
Modified residue4071Phosphothreonine Ref.13

Natural variations

Alternative sequence188 – 26073Missing in isoform 3.
VSP_017191
Alternative sequence2311P → PGNLIKHLVKGTRPLFLETR IPWHMGHSIEEIPIFGLK in isoform 2.
VSP_017192

Experimental info

Mutagenesis841Y → A: Reduces affinity for UGUA RNA by 40%; when associated with A-128. Ref.16
Mutagenesis861G → V: Abolishes interaction with NUDT21/CPSF5; when associated with V-87. Ref.9
Mutagenesis871N → V: Abolishes interaction with NUDT21/CPSF5; when associated with V-86. Ref.9
Mutagenesis90 – 912WW → AA: Reduces affinity for UGUA RNA by 70%. Strongly reduced affinity for UGUA RNA; when associated with A-94.
Mutagenesis941D → A: Strongly reduced affinity for UGUA RNA; when associated with 90-A-A-91. Ref.16
Mutagenesis1111E → A: Reduces affinity for UGUA RNA by 85%. Ref.16
Mutagenesis1261F → A: Increases affinity for UGUA RNA by 40%. Ref.16
Mutagenesis1281L → A: Reduces affinity for UGUA RNA by 40%; when associated with A-84. Ref.16
Sequence conflict91D → N in CAA47751. Ref.2
Sequence conflict91D → N in CAA47752. Ref.2

Secondary structure

..................... 551
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 7, 2006. Version 2.
Checksum: 721A5DA1B456AA79

FASTA55159,210
        10         20         30         40         50         60 
MADGVDHIDI YADVGEEFNQ EAEYGGHDQI DLYDDVISPS ANNGDAPEDR DYMDTLPPTV 

        70         80         90        100        110        120 
GDDVGKGAAP NVVYTYTGKR IALYIGNLTW WTTDEDLTEA VHSLGVNDIL EIKFFENRAN 

       130        140        150        160        170        180 
GQSKGFALVG VGSEASSKKL MDLLPKRELH GQNPVVTPCN KQFLSQFEMQ SRKTTQSGQM 

       190        200        210        220        230        240 
SGEGKAGPPG GSSRAAFPQG GRGRGRFPGA VPGGDRFPGP AGPGGPPPPF PAGQTPPRPP 

       250        260        270        280        290        300 
LGPPGPPGPP GPPPPGQVLP PPLAGPPNRG DRPPPPVLFP GQPFGQPPLG PLPPGPPPPV 

       310        320        330        340        350        360 
PGYGPPPGPP PPQQGPPPPP GPFPPRPPGP LGPPLTLAPP PHLPGPPPGA PPPAPHVNPA 

       370        380        390        400        410        420 
FFPPPTNSGM PTSDSRGPPP TDPYGRPPPY DRGDYGPPGR EMDTARTPLS EAEFEEIMNR 

       430        440        450        460        470        480 
NRAISSSAIS RAVSDASAGD YGSAIETLVT AISLIKQSKV SADDRCKVLI SSLQDCLHGI 

       490        500        510        520        530        540 
ESKSYGSGSR RERSRERDHS RSREKSRRHK SRSRDRHDDY YRERSRERER HRDRDRDRDR 

       550 
ERDREREYRH R 

« Hide

Isoform 2 [UniParc].

Checksum: 1F2B7051251A7E52
Show »

FASTA58863,471
Isoform 3 [UniParc].

Checksum: 464F41AA4386F880
Show »

FASTA47852,326

References

« Hide 'large scale' references
[1]"Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits."
Rueegsegger U., Blank D., Keller W.
Mol. Cell 1:243-253(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 125-138 AND 162-168, FUNCTION, IDENTIFICATION IN THE CLEAVAGE FACTOR IM COMPLEX, SUBCELLULAR LOCATION.
Tissue: Leukemia.
[2]Fleischhauer K.L.
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
Tissue: Leukemia.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Spleen.
[4]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Heart.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORMS 2 AND 3).
Tissue: Kidney.
[7]"Purification and characterization of human cleavage factor Im involved in the 3' end processing of messenger RNA precursors."
Rueegsegger U., Beyer K., Keller W.
J. Biol. Chem. 271:6107-6113(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX.
[8]"A mechanism for the regulation of pre-mRNA 3' processing by human cleavage factor Im."
Brown K.M., Gilmartin G.M.
Mol. Cell 12:1467-1476(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization."
Dettwiler S., Aringhieri C., Cardinale S., Keller W., Barabino S.M.
J. Biol. Chem. 279:35788-35797(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, INTERACTION WITH NUDT21/CPSF5; SFRS3; SFRS7 AND TRA2B, RNA-BINDING, MUTAGENESIS OF GLY-86 AND ASN-87, SUBCELLULAR LOCATION.
[10]"Association of polyadenylation cleavage factor I with U1 snRNP."
Awasthi S., Alwine J.C.
RNA 9:1400-1409(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A CLEAVAGE FACTOR IM COMPLEX, INTERACTION WITH NUDT21/CPSF5 AND SNRNP70.
[11]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-404, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-407, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[14]"Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation."
Kim S., Yamamoto J., Chen Y., Aida M., Wada T., Handa H., Yamaguchi Y.
Genes Cells 15:1003-1013(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex provides an insight into poly(A) site recognition and RNA looping."
Yang Q., Coseno M., Gilmartin G.M., Doublie S.
Structure 19:368-377(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 13-235 IN COMPLEX WITH NUDT21/CPSF5 AND RNA, FUNCTION, SUBUNIT, MUTAGENESIS OF TYR-84; 90-TRP-TRP-91; ASP-94; GLU-111; PHE-126 AND LEU-128.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X67336 Genomic DNA. Translation: CAA47751.1.
X67337 mRNA. Translation: CAA47752.1.
AK223568 mRNA. Translation: BAD97288.1.
AK292024 mRNA. Translation: BAF84713.1.
CH471054 Genomic DNA. Translation: EAW97215.1.
BC000714 mRNA. Translation: AAH00714.1.
BC005000 mRNA. Translation: AAH05000.1.
CCDSCCDS8988.1. [Q16630-1]
PIRS57447.
RefSeqNP_008938.2. NM_007007.2. [Q16630-1]
XP_005268646.1. XM_005268589.1. [Q16630-2]
UniGeneHs.369606.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3P5TX-ray2.70L/M/N/O/P/Q80-161[»]
3P6YX-ray2.90C/D/G/H/K/L/O/P80-161[»]
3Q2SX-ray2.90C/D13-235[»]
3Q2TX-ray3.06C/D13-235[»]
4B4NX-ray1.81B276-290[»]
ProteinModelPortalQ16630.
SMRQ16630. Positions 80-158.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116238. 61 interactions.
DIPDIP-34501N.
IntActQ16630. 28 interactions.
MINTMINT-1153789.
STRING9606.ENSP00000391774.

PTM databases

PhosphoSiteQ16630.

Polymorphism databases

DMDM88909266.

Proteomic databases

MaxQBQ16630.
PaxDbQ16630.
PeptideAtlasQ16630.
PRIDEQ16630.

Protocols and materials databases

DNASU11052.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000266679; ENSP00000266679; ENSG00000111605. [Q16630-2]
ENST00000435070; ENSP00000391774; ENSG00000111605. [Q16630-1]
GeneID11052.
KEGGhsa:11052.
UCSCuc001sut.4. human. [Q16630-1]
uc001suu.4. human. [Q16630-2]

Organism-specific databases

CTD11052.
GeneCardsGC12P069633.
HGNCHGNC:13871. CPSF6.
HPAHPA039973.
MIM604979. gene.
neXtProtNX_Q16630.
PharmGKBPA26846.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG313287.
HOGENOMHOG000111137.
KOK14398.
OMASAPNVVY.
OrthoDBEOG74TX09.
PhylomeDBQ16630.
TreeFamTF316430.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.

Gene expression databases

ArrayExpressQ16630.
BgeeQ16630.
CleanExHS_CPSF6.
GenevestigatorQ16630.

Family and domain databases

Gene3D3.30.70.330. 1 hit.
InterProIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
SMARTSM00360. RRM. 1 hit.
[Graphical view]
PROSITEPS50102. RRM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCPSF6.
GenomeRNAi11052.
NextBio41995.
PROQ16630.
SOURCESearch...

Entry information

Entry nameCPSF6_HUMAN
AccessionPrimary (citable) accession number: Q16630
Secondary accession number(s): A8K7K9 expand/collapse secondary AC list , Q53ES1, Q9BSJ7, Q9BW18
Entry history
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: February 7, 2006
Last modified: July 9, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM