O95639 (CPSF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cleavage and polyadenylation specificity factor subunit 4

Alternative name(s):
Cleavage and polyadenylation specificity factor 30 kDa subunit
Short name=CPSF 30 kDa subunit
NS1 effector domain-binding protein 1
Short name=Neb-1
No arches homolog

Gene names

Name:	CPSF4
Synonyms:	CPSF30, NAR, NEB1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	269 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U). Ref.7 Ref.9
Subunit structure	Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Interacts with FIP1L1. Association with influenza A virus NS1 blocks processing of pre-mRNAs, thereby preventing nuclear export of host cell mRNAs. Ref.8 Ref.9 Ref.12
Subcellular location	Nucleus.
Sequence similarities	Belongs to the CPSF4/YTH1 family. Contains 5 C3H1-type zinc fingers. Contains 1 CCHC-type zinc finger.

Ontologies

Keywords
Biological process	Host-virus interaction mRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding RNA-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW modification by virus of host mRNA processing Traceable author statement. Source: Reactome viral infectious cycle Traceable author statement. Source: Reactome
Cellular_component	mRNA cleavage and polyadenylation specificity factor complex Inferred from direct assay Ref.12. Source: UniProtKB mitochondrion Inferred from direct assay. Source: HPA
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O95639-1)

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: O95639-2)

The sequence of this isoform differs from the canonical sequence as follows:
     191-215: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O95639-3)

The sequence of this isoform differs from the canonical sequence as follows:
     191-216: Missing.

Note: May be due to a competing acceptor splice site. No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 269

269

Cleavage and polyadenylation specificity factor subunit 4

PRO_0000074402

Regions

Zinc finger

35 – 61

27

C3H1-type 1

Zinc finger

62 – 89

28

C3H1-type 2

Zinc finger

90 – 117

28

C3H1-type 3

Zinc finger

118 – 142

25

C3H1-type 4

Zinc finger

143 – 169

27

C3H1-type 5

Zinc finger

243 – 260

18

CCHC-type

Amino acid modifications

Modified residue

202

1

Phosphoserine Ref.10 Ref.11

Modified residue

212

1

Phosphoserine Ref.10 Ref.11 Ref.14

Natural variations

Alternative sequence

191 – 216

26

Missing in isoform 3.

VSP_008602

Alternative sequence

191 – 215

25

Missing in isoform 2.

VSP_008601

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

269

Helix Strand Turn

Details...

Helix

69 – 72

4

Helix

79 – 81

3

Beta strand

82 – 85

4

Turn

90 – 92

3

Helix

97 – 102

6

Beta strand

111 – 113

3

Beta strand

122 – 125

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 49444E3EB840464A	FASTA	269	30,255
	10 20 30 40 50 60 MQEIIASVDH IKFDLEIAVE QQLGAQPLPF PGMDKSGAAV CEFFLKAACG KGGMCPFRHI 70 80 90 100 110 120 SGEKTVVCKH WLRGLCKKGD QCEFLHEYDM TKMPECYFYS KFGECSNKEC PFLHIDPESK 130 140 150 160 170 180 IKDCPWYDRG FCKHGPLCRH RHTRRVICVN YLVGFCPEGP SCKFMHPRFE LPMGTTEQPP 190 200 210 220 230 240 LPQQTQPPAK QSNNPPLQRS SSLIQLTSQN SSPNQQRTPQ VIGVMQSQNS SAGNRGPRPL 250 260 EQVTCYKCGE KGHYANRCTK GHLAFLSGQ
	Isoform 2 [UniParc]. Checksum: 0DF72BE36CF97106	FASTA	244	27,547
	10 20 30 40 50 60 MQEIIASVDH IKFDLEIAVE QQLGAQPLPF PGMDKSGAAV CEFFLKAACG KGGMCPFRHI 70 80 90 100 110 120 SGEKTVVCKH WLRGLCKKGD QCEFLHEYDM TKMPECYFYS KFGECSNKEC PFLHIDPESK 130 140 150 160 170 180 IKDCPWYDRG FCKHGPLCRH RHTRRVICVN YLVGFCPEGP SCKFMHPRFE LPMGTTEQPP 190 200 210 220 230 240 LPQQTQPPAK QRTPQVIGVM QSQNSSAGNR GPRPLEQVTC YKCGEKGHYA NRCTKGHLAF LSGQ
	Isoform 3 [UniParc]. Checksum: 3535FE5A0D525C8F	FASTA	243	27,419
	10 20 30 40 50 60 MQEIIASVDH IKFDLEIAVE QQLGAQPLPF PGMDKSGAAV CEFFLKAACG KGGMCPFRHI 70 80 90 100 110 120 SGEKTVVCKH WLRGLCKKGD QCEFLHEYDM TKMPECYFYS KFGECSNKEC PFLHIDPESK 130 140 150 160 170 180 IKDCPWYDRG FCKHGPLCRH RHTRRVICVN YLVGFCPEGP SCKFMHPRFE LPMGTTEQPP 190 200 210 220 230 240 LPQQTQPPAK RTPQVIGVMQ SQNSSAGNRG PRPLEQVTCY KCGEKGHYAN RCTKGHLAFL SGQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Assignment of the human homolog of the zebrafish essential gene no arches to 7q22.1." Kawakami K., Gaiano N., Grosshans D., Scherer S., Tsui L.-C., Hopkins N. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	SeattleSNPs variation discovery resource Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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. , 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 (SEP-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: Eye and PNS.
[7]	"The 30-kD subunit of mammalian cleavage and polyadenylation specificity factor and its yeast homolog are RNA-binding zinc finger proteins." Barabino S.M.L., Huebner W., Jenny A., Minvielle-Sebastia L., Keller W. Genes Dev. 11:1703-1716(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs." Nemeroff M.E., Barabino S.M.L., Li Y., Keller W., Krug R.M. Mol. Cell 1:991-1000(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INFLUENZA A VIRUS NS1 PROTEIN.
[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] [Europe PMC] [Abstract] Cited for: FUNCTION IN PRE-MRNA 3'-END PROCESSING, IDENTIFICATION IN THE CPSF COMPLEX, INTERACTION WITH FIP1L1.
[10]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-202 AND SER-212, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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 SER-202 AND SER-212, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA." Laishram R.S., Anderson R.A. EMBO J. 29:4132-4145(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE CPSF COMPLEX.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212, MASS SPECTROMETRY.
[15]	"Solution structure of CCCH-type zinc-finger domain 2 in cleavage and polyadenylation specificity factor." RIKEN structural genomics initiative (RSGI) Submitted (JUN-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 61-126.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U79569 mRNA. Translation: AAD00321.1.
CR542161 mRNA. Translation: CAG46958.1.
EF191081 Genomic DNA. Translation: ABN05292.1.
CH236956 Genomic DNA. Translation: EAL23878.1.
CH471091 Genomic DNA. Translation: EAW76667.1.
CH471091 Genomic DNA. Translation: EAW76668.1.
BC003101 mRNA. Translation: AAH03101.1.
BC050738 mRNA. Translation: AAH50738.1.

IPI

IPI00009137.
IPI00029707.
IPI00375469.

RefSeq

NP_001075028.1. NM_001081559.1.
NP_006684.1. NM_006693.2.

UniGene

Hs.489287.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D9N	NMR	-	A	61-126	[»]
2RHK	X-ray	1.95	C/D	61-121	[»]

ProteinModelPortal

O95639.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48675N.

IntAct

O95639. 3 interactions.

MINT

MINT-1429837.

STRING

9606.ENSP00000292476.

PTM databases

PhosphoSite

O95639.

Proteomic databases

PaxDb

O95639.

PRIDE

O95639.

Protocols and materials databases

DNASU

10898.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000292476; ENSP00000292476; ENSG00000160917.
ENST00000436336; ENSP00000395311; ENSG00000160917.

GeneID

10898.

KEGG

hsa:10898.

UCSC

uc003uqi.3. human.
uc003uqj.3. human.
uc003uqk.3. human.

Organism-specific databases

CTD

10898.

GeneCards

GC07P099036.

HGNC

HGNC:2327. CPSF4.

HPA

HPA049094.

MIM

603052. gene.

neXtProt

NX_O95639.

PharmGKB

PA26844.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5084.

HOGENOM

HOG000212457.

HOVERGEN

HBG051108.

InParanoid

O95639.

KO

K14404.

OMA

PLDQVTC.

OrthoDB

EOG4KH2VQ.

PhylomeDB

O95639.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

O95639.

Bgee

O95639.

CleanEx

HS_CPSF4.

Genevestigator

O95639.

GermOnline

ENSG00000160917. Homo sapiens.

Family and domain databases

Gene3D

4.10.60.10. 1 hit.

InterPro

IPR000571. Znf_CCCH.
IPR001878. Znf_CCHC.
[Graphical view]

Pfam

PF00642. zf-CCCH. 2 hits.
PF00098. zf-CCHC. 1 hit.
[Graphical view]

SMART

SM00343. ZnF_C2HC. 1 hit.
SM00356. ZnF_C3H1. 5 hits.
[Graphical view]

SUPFAM

SSF57756. SSF57756. 1 hit.

PROSITE

PS50103. ZF_C3H1. 5 hits.
PS50158. ZF_CCHC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O95639.

GenomeRNAi

10898.

NextBio

41385.

SOURCE

Search...

Entry information

Entry name

CPSF4_HUMAN

Accession

Primary (citable) accession number: O95639
Secondary accession number(s): D6W5S8 , Q6FGE6, Q86TF8, Q9BTW6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2003
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.