Reviewed, UniProtKB/Swiss-Prot P33240 (CSTF2_HUMAN)

Names and origin

Protein names

Recommended name:
    Cleavage stimulation factor 64 kDa subunit
      Short name=CSTF 64 kDa subunit
      Short name=CstF-64
Alternative name(s):
    CF-1 64 kDa subunit

Gene names

Name:

CSTF2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	577 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. This subunit is directly involved in the binding to pre-mRNAs By similarity.
Subunit structure	The CSTF complex is composed of CSTF1 (50 kDa subunit), CSTF2 (64 kDa subunit) and CSTF3 (77 kDa subunit). CSTF2 directly interacts with CSTF3, SYMPK and RPO2TC1. Interacts with HSF1 in heat-stressed cells. Interacts with FIP1L1. Ref.7 Ref.8 Ref.9 Ref.10
Subcellular location	Nucleus.
Induction	Up-regulated during the G0 to S phase transition. Ref.6
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.1 Ref.11 Ref.12
Sequence similarities	Contains 1 RRM (RNA recognition motif) domain.
Sequence caution	The sequence CAI42681.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	mRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	RNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	mRNA cleavage Ref.1 Traceable author statement. Source: ProtInc mRNA polyadenylation Ref.1 Traceable author statement. Source: ProtInc nuclear mRNA splicing, via spliceosome Inferred from Experiment. Source: Reactome
Cellular component	nucleus Ref.1 Inferred from direct assay. Source: HPA
Molecular function	RNA binding Ref.1 Traceable author statement. Source: ProtInc nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Ref.8 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BARD1	Q99728	1	EBI-711360,EBI-473181
SUB1	P53999	1	EBI-711360,EBI-998260
SUB1	P53999	1	EBI-711374,EBI-998260

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P33240-1)

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: P33240-2)

The sequence of this isoform differs from the canonical sequence as follows:
     235-251: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 577

577

Cleavage stimulation factor 64 kDa subunit

PRO_0000081531

Regions

Domain

16 – 94

79

RRM

Repeat

410 – 414

5

1; approximate

Repeat

415 – 419

5

2

Repeat

420 – 424

5

3

Repeat

425 – 429

5

4; approximate

Repeat

430 – 434

5

5; approximate

Repeat

435 – 439

5

6

Repeat

440 – 444

5

7

Repeat

445 – 449

5

8

Repeat

450 – 454

5

9

Repeat

455 – 459

5

10; approximate

Repeat

460 – 464

5

11

Repeat

465 – 469

5

12; approximate

Region

108 – 248

141

Interactions with CSTF3 and SYMPK

Region

410 – 469

60

12 X 5 AA tandem repeats of M-E-A-R-[AG]

Region

514 – 577

64

Interaction with RPO2TC1

Compositional bias

198 – 409

212

Gly/Pro-rich

Compositional bias

470 – 526

57

Gly/Pro-rich

Amino acid modifications

Modified residue

154

1

Phosphoserine Ref.12

Modified residue

518

1

Phosphoserine Ref.11

Modified residue

524

1

Phosphoserine Ref.11 Ref.12

Natural variations

Alternative sequence

235 – 251

17

Missing in isoform 2.

VSP_014841

Secondary structure

1

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577

Helix Strand Turn

Details...

Helix

12 – 15

4

Beta strand

18 – 22

5

Helix

29 – 37

9

Beta strand

43 – 50

8

Turn

51 – 54

4

Beta strand

55 – 63

9

Helix

67 – 76

10

Beta strand

77 – 81

5

Beta strand

83 – 85

3

Beta strand

87 – 91

5

Helix

97 – 104

8

Helix

532 – 535

4

Helix

537 – 545

9

Helix

549 – 553

5

Helix

557 – 560

4

Helix

562 – 571

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: B76595E9BF8FABBD	FASTA	577	60,959
	10 20 30 40 50 60 MAGLTVRDPA VDRSLRSVFV GNIPYEATEE QLKDIFSEVG PVVSFRLVYD RETGKPKGYG 70 80 90 100 110 120 FCEYQDQETA LSAMRNLNGR EFSGRALRVD NAASEKNKEE LKSLGTGAPV IESPYGETIS 130 140 150 160 170 180 PEDAPESISK AVASLPPEQM FELMKQMKLC VQNSPQEARN MLLQNPQLAY ALLQAQVVMR 190 200 210 220 230 240 IVDPEIALKI LHRQTNIPTL IAGNPQPVHG AGPGSGSNVS MNQQNPQAPQ AQSLGGMHVN 250 260 270 280 290 300 GAPPLMQASM QGGVPAPGQM PAAVTGPGPG SLAPGGGMQA QVGMPGSGPV SMERGQVPMQ 310 320 330 340 350 360 DPRAAMQRGS LPANVPTPRG LLGDAPNDPR GGTLLSVTGE VEPRGYLGPP HQGPPMHHVP 370 380 390 400 410 420 GHESRGPPPH ELRGGPLPEP RPLMAEPRGP MLDQRGPPLD GRGGRDPRGI DARGMEARAM 430 440 450 460 470 480 EARGLDARGL EARAMEARAM EARAMEARAM EARAMEVRGM EARGMDTRGP VPGPRGPIPS 490 500 510 520 530 540 GMQGPSPINM GAVVPQGSRQ VPVMQGTGMQ GASIQGGSQP GGFSPGQNQV TPQDHEKAAL 550 560 570 IMQVLQLTAD QIAMLPPEQR QSILILKEQI QKSTGAP
	Isoform 2. Checksum: D76823A0FF6363B8	FASTA	560	59,251
	10 20 30 40 50 60 MAGLTVRDPA VDRSLRSVFV GNIPYEATEE QLKDIFSEVG PVVSFRLVYD RETGKPKGYG 70 80 90 100 110 120 FCEYQDQETA LSAMRNLNGR EFSGRALRVD NAASEKNKEE LKSLGTGAPV IESPYGETIS 130 140 150 160 170 180 PEDAPESISK AVASLPPEQM FELMKQMKLC VQNSPQEARN MLLQNPQLAY ALLQAQVVMR 190 200 210 220 230 240 IVDPEIALKI LHRQTNIPTL IAGNPQPVHG AGPGSGSNVS MNQQNPQAPQ AQSLGGVPAP 250 260 270 280 290 300 GQMPAAVTGP GPGSLAPGGG MQAQVGMPGS GPVSMERGQV PMQDPRAAMQ RGSLPANVPT 310 320 330 340 350 360 PRGLLGDAPN DPRGGTLLSV TGEVEPRGYL GPPHQGPPMH HVPGHESRGP PPHELRGGPL 370 380 390 400 410 420 PEPRPLMAEP RGPMLDQRGP PLDGRGGRDP RGIDARGMEA RAMEARGLDA RGLEARAMEA 430 440 450 460 470 480 RAMEARAMEA RAMEARAMEV RGMEARGMDT RGPVPGPRGP IPSGMQGPSP INMGAVVPQG 490 500 510 520 530 540 SRQVPVMQGT GMQGASIQGG SQPGGFSPGQ NQVTPQDHEK AALIMQVLQL TADQIAMLPP 550 560 EQRQSILILK EQIQKSTGAP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human 64-kDa polyadenylylation factor contains a ribonucleoprotein-type RNA binding domain and unusual auxiliary motifs." Takagaki Y., Macdonald C.C., Shenk T., Manley J.L. Proc. Natl. Acad. Sci. U.S.A. 89:1403-1407(1992) [PubMed: 1741396] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION, RNA-BINDING.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORMS 1 AND 2). Tissue: Kidney and Ovary.
[5]	"RNA recognition by the human polyadenylation factor CstF." Takagaki Y., Manley J.L. Mol. Cell. Biol. 17:3907-3914(1997) [PubMed: 9199325] [Abstract] Cited for: RNA-BINDING, FUNCTION.
[6]	"Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition." Martincic K., Campbell R., Edwalds-Gilbert G., Souan L., Lotze M.T., Milcarek C. Proc. Natl. Acad. Sci. U.S.A. 95:11095-11100(1998) [PubMed: 9736695] [Abstract] Cited for: INDUCTION.
[7]	"Complex protein interactions within the human polyadenylation machinery identify a novel component." Takagaki Y., Manley J.L. Mol. Cell. Biol. 20:1515-1525(2000) [PubMed: 10669729] [Abstract] Cited for: INTERACTION WITH CSTF3 AND SYMPK.
[8]	"Evolutionarily conserved interaction between CstF-64 and PC4 links transcription, polyadenylation, and termination." Calvo O., Manley J.L. Mol. Cell 7:1013-1023(2001) [PubMed: 11389848] [Abstract] Cited for: INTERACTION WITH RPO2TC1.
[9]	"Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase." Kaufmann I., Martin G., Friedlein A., Langen H., Keller W. EMBO J. 23:616-626(2004) [PubMed: 14749727] [Abstract] Cited for: INTERACTION WITH FIP1L1.
[10]	"HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with symplekin." Xing H., Mayhew C.N., Cullen K.E., Park-Sarge O.-K., Sarge K.D. J. Biol. Chem. 279:10551-10555(2004) [PubMed: 14707147] [Abstract] Cited for: INTERACTION WITH HSF1.
[11]	"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-518 AND SER-524, MASS SPECTROMETRY.
[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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154 AND SER-524, MASS SPECTROMETRY.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Recognition of GU-rich polyadenylation regulatory elements by human CstF-64 protein." Perez Canadillas J.M., Varani G. EMBO J. 22:2821-2830(2003) [PubMed: 12773396] [Abstract] Cited for: STRUCTURE BY NMR OF 8-111.
[15]	"The C-terminal domains of vertebrate CstF-64 and its yeast orthologue Rna15 form a new structure critical for mRNA 3'-end processing." Qu X., Perez-Canadillas J.M., Agrawal S., De Baecke J., Cheng H., Varani G., Moore C. J. Biol. Chem. 282:2101-2115(2007) [PubMed: 17116658] [Abstract] Cited for: STRUCTURE BY NMR OF 531-577.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M85085 mRNA. Translation: AAA35724.1.
BT009778 mRNA. Translation: AAP88780.1.
Z83819, Z95327 Genomic DNA. Translation: CAB06072.2.
Z95327, Z83819 Genomic DNA. Translation: CAI42680.1.
Z95327 Genomic DNA. Translation: CAI42681.1. Sequence problems.
BC017712 mRNA. Translation: AAH17712.1.
BC033135 mRNA. Translation: AAH33135.1.

IPI

IPI00013256.
IPI00607841.

PIR

A40220.

RefSeq

NP_001316.1.

UniGene

Hs.132370

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P1T	NMR	-	A	8-111	[»]
2J8P	NMR	-	A	531-577	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P33240. 16 interactions.

PTM databases

PhosphoSite

P33240.

Proteomic databases

PRIDE

P33240.

Genome annotation databases

Ensembl

ENSG00000101811. Homo sapiens. [Contig view]

GeneID

1478.

KEGG

hsa:1478.

UCSC

uc004egh.1. human.
uc004egi.1. human.

Organism-specific databases

GeneCards

GC0XP099881.

H-InvDB

HIX0016919.

HGNC

HGNC:2484. CSTF2.

HPA

CAB004680.
HPA000427.

MIM

600368. gene.

PharmGKB

PA26986.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P33240.

OMA

P33240. HVPGHES.

Enzyme and pathway databases

Reactome

REACT_125. Processing of Capped Intron-Containing Pre-mRNA.
REACT_1788. Transcription.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P33240.

Bgee

P33240.

CleanEx

HS_CSTF2.

GermOnline

ENSG00000101811. Homo sapiens.

Family and domain databases

InterPro

IPR012677. a_b_plait_nuc_bd.
IPR000504. RRM_RNP1.
[Graphical view]

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 1 hit.

Pfam

PF00076. RRM_1. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 1 hit.
[Graphical view]

PROSITE

PS50102. RRM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

6073.

SOURCE

Search...

Entry information

Entry name

CSTF2_HUMAN

Accession

Primary (citable) accession number: P33240
Secondary accession number(s): Q5H951, Q6LA74, Q8N502

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	July 7, 2009
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)