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Q9H611 (PIF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ATP-dependent DNA helicase PIF1

EC=3.6.4.12
Alternative name(s):
DNA repair and recombination helicase PIF1
PIF1/RRM3 DNA helicase-like protein
Gene names
Name:PIF1
Synonyms:C15orf20
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length641 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability. Efficiently unwinds G-quadruplex (G4) DNA structures and forked RNA-DNA hybrids. Resolves G4 structures, preventing replication pausing and double-strand breaks (DSBs) at G4 motifs. Involved in the maintenance of telomeric DNA. Inhibits telomere elongation, de novo telomere formation and telomere addition to DSBs via catalytic inhibition of telomerase. Reduces the processivity of telomerase by displacing active telomerase from DNA ends. Releases telomerase by unwinding the short telomerase RNA/telomeric DNA hybrid that is the intermediate in the telomerase reaction. Possesses an intrinsic strand annealing activity. Ref.1 Ref.2 Ref.7 Ref.8 Ref.10 Ref.11 Ref.14

Catalytic activity

ATP + H2O = ADP + phosphate. Ref.8

Cofactor

Magnesium. Ref.1

Subunit structure

Monomer. Interacts with telomerase. Ref.2 Ref.7

Subcellular location

Nucleus Ref.1 Ref.7 Ref.8 Ref.15.

Isoform 4: Mitochondrion Ref.1 Ref.7 Ref.8 Ref.15.

Tissue specificity

Weak ubiquitous expression.

Induction

Tightly cell cycle regulated and expressed in late S/G2 phase. Ref.7

Domain

The PIF1 N-terminal (PINT) domain enhances the interaction with ssDNA through intrinsic binding activity, it also harbors DNA strand-annealing activity. Ref.2

Sequence similarities

Belongs to the helicase family. PIF1 subfamily.

Biophysicochemical properties

Kinetic parameters:

KM=0.17 mM for ATP Ref.2

Ontologies

Keywords
   Biological processDNA damage
DNA recombination
DNA repair
   Cellular componentMitochondrion
Nucleus
   Coding sequence diversityAlternative initiation
Alternative splicing
Polymorphism
   LigandATP-binding
DNA-binding
Nucleotide-binding
   Molecular functionHelicase
Hydrolase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from direct assay Ref.1. Source: GOC

DNA duplex unwinding

Inferred from direct assay Ref.1. Source: GOC

DNA recombination

Inferred from electronic annotation. Source: UniProtKB-HAMAP

DNA repair

Inferred from electronic annotation. Source: UniProtKB-HAMAP

mitochondrial genome maintenance

Inferred from electronic annotation. Source: UniProtKB-HAMAP

negative regulation of telomerase activity

Inferred from direct assay Ref.1. Source: HGNC

negative regulation of telomere maintenance via telomerase

Inferred from electronic annotation. Source: UniProtKB-HAMAP

regulation of telomere maintenance

Inferred from direct assay Ref.1. Source: HGNC

telomere maintenance

Inferred from electronic annotation. Source: InterPro

   Cellular_componentmitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear chromosome, telomeric region

Inferred from direct assay Ref.1. Source: HGNC

   Molecular_functionATP binding

Inferred from direct assay Ref.1. Source: HGNC

ATP-dependent 5'-3' DNA helicase activity

Inferred from direct assay Ref.1. Source: HGNC

ATP-dependent 5'-3' DNA/RNA helicase activity

Inferred from direct assay Ref.1. Source: BHF-UCL

G-quadruplex DNA binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

magnesium ion binding

Inferred from direct assay Ref.1. Source: HGNC

single-stranded DNA-dependent ATP-dependent DNA helicase activity

Inferred from direct assay Ref.1. Source: HGNC

telomerase inhibitor activity

Inferred from electronic annotation. Source: UniProtKB-HAMAP

telomeric DNA binding

Inferred from direct assay Ref.1. Source: HGNC

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform 1 (identifier: Q9H611-1)

Also known as: Isoform alpha;

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: Q9H611-2)

The sequence of this isoform differs from the canonical sequence as follows:
     232-266: TGKSYLLKRILGSLPPTGTVATASTGVAACHIGGT → SGGREEVGGQWWGGIEEQGDLSNFAPVQEQGSHIC
     267-641: Missing.
Isoform 3 (identifier: Q9H611-3)

Also known as: Isoform beta;

The sequence of this isoform differs from the canonical sequence as follows:
     623-641: ESPDDDEAASDQENMDPIL → AAEGRGNEDR...FQGINSVWGH
Isoform 4 (identifier: Q9H611-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: Missing.
Note: Produced by alternative initiation of isoform 1.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 641641ATP-dependent DNA helicase PIF1 HAMAP-Rule MF_03176
PRO_0000089980

Regions

Nucleotide binding228 – 2358ATP Potential
DNA binding577 – 59620 Potential
Region1 – 180180PINT HAMAP-Rule MF_03176
Region167 – 641475Hydrolyzes ATP in the presence of both magnesium and single-stranded DNA; weak activity in the presence of RNA or double-stranded DNA; No unwinding activity HAMAP-Rule MF_03176

Amino acid modifications

Modified residue271Phosphoserine Ref.12
Modified residue1511Phosphoserine Ref.9 Ref.12 Ref.13

Natural variations

Alternative sequence1 – 5353Missing in isoform 4.
VSP_047457
Alternative sequence232 – 26635TGKSY…HIGGT → SGGREEVGGQWWGGIEEQGD LSNFAPVQEQGSHIC in isoform 2.
VSP_026715
Alternative sequence267 – 641375Missing in isoform 2.
VSP_026716
Alternative sequence623 – 64119ESPDD…MDPIL → AAEGRGNEDRCSGSSIRALG GDWWGLRLGAASKQRTELRC VSTARPSLAQPRTNTLQSLT KEHKLQNVHPYFKLLFQGIN SVWGH in isoform 3.
VSP_026717
Natural variant6401I → N.
Corresponds to variant rs17802279 [ dbSNP | Ensembl ].
VAR_033206

Experimental info

Mutagenesis2341K → A: Loss of ATPase activity. Lower activity for single-stranded DNA. Ref.1

Sequences

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

Last modified July 10, 2007. Version 2.
Checksum: D755470008BA3CA8

FASTA64169,799
        10         20         30         40         50         60 
MLSGIEAAAG EYEDSELRCR VAVEELSPGG QPRRRQALRT AELSLGRNER RELMLRLQAP 

        70         80         90        100        110        120 
GPAGRPRCFP LRAARLFTRF AEAGRSTLRL PAHDTPGAGA VQLLLSDCPP DRLRRFLRTL 

       130        140        150        160        170        180 
RLKLAAAPGP GPASARAQLL GPRPRDFVTI SPVQPEERRL RAATRVPDTT LVKRPVEPQA 

       190        200        210        220        230        240 
GAEPSTEAPR WPLPVKRLSL PSTKPQLSEE QAAVLRAVLK GQSIFFTGSA GTGKSYLLKR 

       250        260        270        280        290        300 
ILGSLPPTGT VATASTGVAA CHIGGTTLHA FAGIGSGQAP LAQCVALAQR PGVRQGWLNC 

       310        320        330        340        350        360 
QRLVIDEISM VEADLFDKLE AVARAVRQQN KPFGGIQLII CGDFLQLPPV TKGSQPPRFC 

       370        380        390        400        410        420 
FQSKSWKRCV PVTLELTKVW RQADQTFISL LQAVRLGRCS DEVTRQLQAT ASHKVGRDGI 

       430        440        450        460        470        480 
VATRLCTHQD DVALTNERRL QELPGKVHRF EAMDSNPELA STLDAQCPVS QLLQLKLGAQ 

       490        500        510        520        530        540 
VMLVKNLSVS RGLVNGARGV VVGFEAEGRG LPQVRFLCGV TEVIHADRWT VQATGGQLLS 

       550        560        570        580        590        600 
RQQLPLQLAW AMSIHKSQGM TLDCVEISLG RVFASGQAYV ALSRARSLQG LRVLDFDPMA 

       610        620        630        640 
VRCDPRVLHF YATLRRGRSL SLESPDDDEA ASDQENMDPI L 

« Hide

Isoform 2 [UniParc].

Checksum: 0A291FB7E1339D56
Show »

FASTA26628,907
Isoform 3 (Isoform beta) [UniParc].

Checksum: DA015E47D50F8541
Show »

FASTA70777,125
Isoform 4 [UniParc].

Checksum: 706C693424557525
Show »

FASTA58863,889

References

« Hide 'large scale' references
[1]"The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity."
Zhang D.-H., Zhou B., Huang Y., Xu L.-X., Zhou J.-Q.
Nucleic Acids Res. 34:1393-1404(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, REGION, MUTAGENESIS OF LYS-234, SUBCELLULAR LOCATION, COFACTOR.
[2]"Biochemical analysis of human PIF1 helicase and functions of its N-terminal domain."
Gu Y., Masuda Y., Kamiya K.
Nucleic Acids Res. 36:6295-6308(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, PINT DOMAIN.
[3]Snow B.E., Erdmann N., Harrington L.
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Human PIF1 DNA helicase."
Futami K., Furuichi Y., Shimamoto A.
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
[5]"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 2).
Tissue: Small intestine.
[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].
Tissue: Brain and Testis.
[7]"Human PIF helicase is cell cycle regulated and associates with telomerase."
Mateyak M.K., Zakian V.A.
Cell Cycle 5:2796-2804(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TELOMERASE, INDUCTION.
[8]"Mitochondrial and nuclear localization of human Pif1 helicase."
Futami K., Shimamoto A., Furuichi Y.
Biol. Pharm. Bull. 30:1685-1692(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
[9]"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-151, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Human Pif1 helicase unwinds synthetic DNA structures resembling stalled DNA replication forks."
George T., Wen Q., Griffiths R., Ganesh A., Meuth M., Sanders C.M.
Nucleic Acids Res. 37:6491-6502(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING.
[11]"Human Pif1 helicase is a G-quadruplex DNA-binding protein with G-quadruplex DNA-unwinding activity."
Sanders C.M.
Biochem. J. 430:119-128(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN G4-UNWINDING.
[12]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND SER-151, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"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-151, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Pif1 family helicases suppress genome instability at G-quadruplex motifs."
Paeschke K., Bochman M.L., Garcia P.D., Cejka P., Friedman K.L., Kowalczykowski S.C., Zakian V.A.
Nature 497:458-462(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN G4-UNWINDING AND TELOMERE LENGTH REGULATION.
[15]"Alternative translation initiation augments the human mitochondrial proteome."
Kazak L., Reyes A., Duncan A.L., Rorbach J., Wood S.R., Brea-Calvo G., Gammage P.A., Robinson A.J., Minczuk M., Holt I.J.
Nucleic Acids Res. 41:2354-2369(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE INITIATION (ISOFORM 4), SUBCELLULAR LOCATION (ISOFORM 4).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ437529 mRNA. Translation: ABD92708.1.
EU084033 mRNA. Translation: ABW71293.1.
AY498716 mRNA. Translation: AAS77398.1.
AB185926 mRNA. Translation: BAE47454.1.
AB185927 mRNA. Translation: BAE47455.1.
AK026345 mRNA. Translation: BAB15456.1.
BC137503 mRNA. Translation: AAI37504.1.
BC137504 mRNA. Translation: AAI37505.1.
CCDSCCDS10195.2. [Q9H611-1]
CCDS66797.1. [Q9H611-3]
RefSeqNP_001273425.1. NM_001286496.1. [Q9H611-1]
NP_001273426.1. NM_001286497.1. [Q9H611-3]
NP_001273428.1. NM_001286499.1. [Q9H611-4]
NP_079325.2. NM_025049.3. [Q9H611-1]
UniGeneHs.112160.

3D structure databases

ProteinModelPortalQ9H611.
SMRQ9H611. Positions 222-247.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000268043.

PTM databases

PhosphoSiteQ9H611.

Polymorphism databases

DMDM152031656.

Proteomic databases

PaxDbQ9H611.
PRIDEQ9H611.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268043; ENSP00000268043; ENSG00000140451. [Q9H611-1]
ENST00000333425; ENSP00000328174; ENSG00000140451. [Q9H611-3]
ENST00000559239; ENSP00000452792; ENSG00000140451. [Q9H611-1]
GeneID80119.
KEGGhsa:80119.
UCSCuc002ans.2. human. [Q9H611-1]
uc002anu.3. human. [Q9H611-2]

Organism-specific databases

CTD80119.
GeneCardsGC15M065107.
H-InvDBHIX0017918.
HGNCHGNC:26220. PIF1.
HPACAB018701.
MIM610953. gene.
neXtProtNX_Q9H611.
PharmGKBPA162399475.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0507.
HOGENOMHOG000132960.
HOVERGENHBG106706.
KOK15255.
OMAAMDSNPE.
OrthoDBEOG7RZ5PJ.
PhylomeDBQ9H611.
TreeFamTF319207.

Gene expression databases

ArrayExpressQ9H611.
BgeeQ9H611.
CleanExHS_PIF1.
GenevestigatorQ9H611.

Family and domain databases

Gene3D3.40.50.300. 3 hits.
HAMAPMF_03176. PIF1.
InterProIPR003840. DNA_helicase.
IPR010285. DNA_helicase_pif1_like.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF02689. Herpes_Helicase. 1 hit.
PF05970. PIF1. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 3 hits.
ProtoNetSearch...

Other

GenomeRNAi80119.
NextBio70350.
PROQ9H611.
SOURCESearch...

Entry information

Entry namePIF1_HUMAN
AccessionPrimary (citable) accession number: Q9H611
Secondary accession number(s): B2RPL7 expand/collapse secondary AC list , Q1W5B6, Q330H5, Q33E24
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: July 10, 2007
Last modified: July 9, 2014
This is version 88 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM