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Protein

PCNA-associated factor

Gene

KIAA0101

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

PCNA-binding protein that acts as a regulator of DNA repair during DNA replication. Following DNA damage, the interaction with PCNA is disrupted, facilitating the interaction between monoubiquitinated PCNA and the translesion DNA synthesis DNA polymerase eta (POLH) at stalled replisomes, facilitating the bypass of replication-fork-blocking lesions. Also acts as a regulator of centrosome number.2 Publications

GO - Molecular functioni

  • chromatin binding Source: UniProtKB

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • centrosome organization Source: UniProtKB
  • DNA replication Source: UniProtKB
  • regulation of cell cycle Source: UniProtKB
  • response to UV Source: UniProtKB
  • translesion synthesis Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166803-MONOMER.
ReactomeiR-HSA-5656169. Termination of translesion DNA synthesis.
SIGNORiQ15004.

Names & Taxonomyi

Protein namesi
Recommended name:
PCNA-associated factor
Alternative name(s):
Hepatitis C virus NS5A-transactivated protein 9
Short name:
HCV NS5A-transactivated protein 9
Overexpressed in anaplastic thyroid carcinoma 1
Short name:
OEATC-1
PCNA-associated factor of 15 kDa
Short name:
PAF15
Short name:
p15PAF
Gene namesi
Name:KIAA0101
Synonyms:NS5ATP9, PAF
ORF Names:L5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:28961. KIAA0101.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi15K → R: Loss of monoubiquitination; when associated with R-24. 1 Publication1
Mutagenesisi24K → R: Loss of monoubiquitination; when associated with R-15. 1 Publication1
Mutagenesisi65I → A: Loss of binding to PCNA. 1 Publication1
Mutagenesisi68 – 69FF → AA: Loss of binding to PCNA. 1 Publication2
Mutagenesisi68F → A: Loss of binding to PCNA. 1 Publication1
Mutagenesisi78K → A: Stabilizes the protein in G1 by preventing association with the APC/C complex and degradation by the proteasome. 1 Publication1
Mutagenesisi93 – 97KAKRK → AAAAA: Inhibits chain initiation by APC/C. 1 Publication5
Mutagenesisi93 – 97KAKRK → RARRR: No effect on chain initiation by APC/C. 1 Publication5

Organism-specific databases

DisGeNETi9768.
OpenTargetsiENSG00000166803.
ENSG00000259316.
PharmGKBiPA134974023.

Chemistry databases

ChEMBLiCHEMBL5574.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000966841 – 111PCNA-associated factorAdd BLAST111

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki15Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei24N6-acetyllysine; alternateBy similarity1
Cross-linki24Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Modified residuei31Phosphoserine1 Publication1
Modified residuei72Phosphoserine1 Publication1

Post-translational modificationi

Monoubiquitinated at Lys-15 and Lys-24 during normal S phase, promoting its association with PCNA. Also diubiquitinated at these 2 sites. Following DNA damage, monoubiquitin chains at Lys-15 and Lys-24 are probably extended, leading to disrupt the interaction with PCNA. Polyubiquitinated by the APC/C complex at the mitotic exit, leading to its degradation by the proteasome.3 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15004.
MaxQBiQ15004.
PaxDbiQ15004.
PeptideAtlasiQ15004.
PRIDEiQ15004.

PTM databases

iPTMnetiQ15004.
PhosphoSitePlusiQ15004.

Expressioni

Tissue specificityi

Expressed predominantly in liver, pancreas and placenta. Not detected in heart or brain. Highly expressed in a number of tumors, especially esophageal tumors, in anaplastic thyroid carcinomas, adrenocortical carcinomas, and in non-small-cell lung cancer lines.3 Publications

Developmental stagei

Present only during S and G2 phases of the cell cycle. Peaks at the G2/M phase of the cell cycle and drops rapidly at mitotic exit in an APC/C-dependent manner (at protein level).

Inductioni

By UV irradiation. By ATF3 in response to UV-stress.2 Publications

Gene expression databases

BgeeiENSG00000166803.
CleanExiHS_KIAA0101.
ExpressionAtlasiQ15004. baseline and differential.
GenevisibleiQ15004. HS.

Organism-specific databases

HPAiHPA055444.

Interactioni

Subunit structurei

Interacts (when monoubiquitinated at Lys-15 and Lys-24) with PCNA. Interacts with isoform 2/p33ING1b of ING1. Interacts with BRCA1.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PCNAP120043EBI-10971436,EBI-358311

Protein-protein interaction databases

BioGridi115114. 29 interactors.
IntActiQ15004. 2 interactors.
STRINGi9606.ENSP00000300035.

Structurei

Secondary structure

1111
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi65 – 67Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4D2GX-ray2.65D/E52-69[»]
ProteinModelPortaliQ15004.
SMRiQ15004.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi23 – 34D-boxAdd BLAST12
Motifi62 – 72PIP-boxAdd BLAST11
Motifi78 – 80KEN box3
Motifi85 – 97Initiation motifAdd BLAST13

Domaini

The PIP-box mediates the interaction with PCNA (PubMed:21628590, PubMed:23000965).2 Publications
The KEN box is required for the association with the APC/C complex.1 Publication
The D-box (destruction box) mediates the interaction with APC/C proteins, and acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.By similarity
The initiation motif is required for efficient chain initiation by the APC/C complex E2 ligase UBE2C. It determines the rate of substrate's degradation without affecting its affinity for the APC/C, a mechanism used by the APC/C to control the timing of substrate proteolysis during the cell cycle (PubMed:21700221).1 Publication

Phylogenomic databases

eggNOGiENOG410J101. Eukaryota.
ENOG410Y3KP. LUCA.
GeneTreeiENSGT00510000048252.
HOGENOMiHOG000013069.
HOVERGENiHBG052567.
InParanoidiQ15004.
OMAiVENKYAG.
PhylomeDBiQ15004.
TreeFamiTF333199.

Family and domain databases

InterProiIPR031444. PCNA-AF.
[Graphical view]
PfamiPF15715. PAF. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15004-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVRTKADSVP GTYRKVVAAR APRKVLGSST SATNSTSVSS RKAENKYAGG
60 70 80 90 100
NPVCVRPTPK WQKGIGEFFR LSPKDSEKEN QIPEEAGSSG LGKAKRKACP
110
LQPDHTNDEK E
Length:111
Mass (Da):11,986
Last modified:November 1, 1996 - v1
Checksum:iFEF2C4E398B70E40
GO
Isoform 2 (identifier: Q15004-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     43-111: AENKYAGGNP...QPDHTNDEKE → EHVLCNLITQMMKKNRTFSFIFE

Note: No experimental confirmation available.
Show »
Length:65
Mass (Da):7,221
Checksum:iEC33192CECBF8430
GO

Sequence cautioni

The sequence BAA03491 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05126279E → K.Corresponds to variant rs11554313dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04565943 – 111AENKY…NDEKE → EHVLCNLITQMMKKNRTFSF IFE in isoform 2. 1 PublicationAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF529370 mRNA. Translation: AAQ09604.1.
AY598324 mRNA. Translation: AAT06735.1.
JN245882 Genomic DNA. Translation: AEW89488.1.
JN245883 Genomic DNA. Translation: AEW89489.1.
JN245884 Genomic DNA. Translation: AEW89490.1.
JN245885 Genomic DNA. Translation: AEW89491.1.
JN245886 Genomic DNA. Translation: AEW89492.1.
JN245889 Genomic DNA. Translation: AEW89495.1.
JN245890 Genomic DNA. Translation: AEW89496.1.
JN245892 Genomic DNA. Translation: AEW89498.1.
JN245893 Genomic DNA. Translation: AEW89499.1.
JN245894 Genomic DNA. Translation: AEW89500.1.
JN245895 Genomic DNA. Translation: AEW89501.1.
JN245896 Genomic DNA. Translation: AEW89502.1.
JN245897 Genomic DNA. Translation: AEW89503.1.
JN245898 Genomic DNA. Translation: AEW89504.1.
JN245899 Genomic DNA. Translation: AEW89505.1.
JN245900 Genomic DNA. Translation: AEW89506.1.
JN245901 Genomic DNA. Translation: AEW89507.1.
JN245902 Genomic DNA. Translation: AEW89508.1.
JN245903 Genomic DNA. Translation: AEW89509.1.
JN245904 Genomic DNA. Translation: AEW89510.1.
JN245906 Genomic DNA. Translation: AEW89512.1.
JN245907 Genomic DNA. Translation: AEW89513.1.
JN245908 Genomic DNA. Translation: AEW89514.1.
JN245910 Genomic DNA. Translation: AEW89516.1.
JN245911 Genomic DNA. Translation: AEW89517.1.
JN245912 Genomic DNA. Translation: AEW89518.1.
JN245936 Genomic DNA. Translation: AEW89560.1.
JN245937 Genomic DNA. Translation: AEW89561.1.
JN245938 Genomic DNA. Translation: AEW89562.1.
JN245939 Genomic DNA. Translation: AEW89563.1.
JN245940 Genomic DNA. Translation: AEW89564.1.
JN245941 Genomic DNA. Translation: AEW89565.1.
JN245942 Genomic DNA. Translation: AEW89566.1.
JN245943 Genomic DNA. Translation: AEW89567.1.
JN245944 Genomic DNA. Translation: AEW89568.1.
JN245945 Genomic DNA. Translation: AEW89569.1.
JN245887 Genomic DNA. Translation: AEW89493.1.
JN245888 Genomic DNA. Translation: AEW89494.1.
JN245891 Genomic DNA. Translation: AEW89497.1.
JN245905 Genomic DNA. Translation: AEW89511.1.
JN245909 Genomic DNA. Translation: AEW89515.1.
JN245913 Genomic DNA. Translation: AEW89519.1.
JN245914 Genomic DNA. Translation: AEW89520.1.
JN245915 Genomic DNA. Translation: AEW89521.1.
JN245916 Genomic DNA. Translation: AEW89522.1.
JN245917 Genomic DNA. Translation: AEW89523.1.
D14657 mRNA. Translation: BAA03491.2. Different initiation.
AK290748 mRNA. Translation: BAF83437.1.
AC087632 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77679.1.
BC005832 mRNA. Translation: AAH05832.1.
BC007101 mRNA. Translation: AAH07101.1.
BC016782 mRNA. Translation: AAH16782.1.
BU170434 mRNA. No translation available.
CCDSiCCDS10193.1. [Q15004-1]
CCDS32269.1. [Q15004-2]
RefSeqiNP_001025160.1. NM_001029989.2. [Q15004-2]
NP_055551.1. NM_014736.5. [Q15004-1]
UniGeneiHs.81892.

Genome annotation databases

EnsembliENST00000300035; ENSP00000300035; ENSG00000166803. [Q15004-1]
ENST00000380258; ENSP00000369608; ENSG00000166803. [Q15004-2]
GeneIDi9768.
KEGGihsa:9768.
UCSCiuc002ank.5. human. [Q15004-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF529370 mRNA. Translation: AAQ09604.1.
AY598324 mRNA. Translation: AAT06735.1.
JN245882 Genomic DNA. Translation: AEW89488.1.
JN245883 Genomic DNA. Translation: AEW89489.1.
JN245884 Genomic DNA. Translation: AEW89490.1.
JN245885 Genomic DNA. Translation: AEW89491.1.
JN245886 Genomic DNA. Translation: AEW89492.1.
JN245889 Genomic DNA. Translation: AEW89495.1.
JN245890 Genomic DNA. Translation: AEW89496.1.
JN245892 Genomic DNA. Translation: AEW89498.1.
JN245893 Genomic DNA. Translation: AEW89499.1.
JN245894 Genomic DNA. Translation: AEW89500.1.
JN245895 Genomic DNA. Translation: AEW89501.1.
JN245896 Genomic DNA. Translation: AEW89502.1.
JN245897 Genomic DNA. Translation: AEW89503.1.
JN245898 Genomic DNA. Translation: AEW89504.1.
JN245899 Genomic DNA. Translation: AEW89505.1.
JN245900 Genomic DNA. Translation: AEW89506.1.
JN245901 Genomic DNA. Translation: AEW89507.1.
JN245902 Genomic DNA. Translation: AEW89508.1.
JN245903 Genomic DNA. Translation: AEW89509.1.
JN245904 Genomic DNA. Translation: AEW89510.1.
JN245906 Genomic DNA. Translation: AEW89512.1.
JN245907 Genomic DNA. Translation: AEW89513.1.
JN245908 Genomic DNA. Translation: AEW89514.1.
JN245910 Genomic DNA. Translation: AEW89516.1.
JN245911 Genomic DNA. Translation: AEW89517.1.
JN245912 Genomic DNA. Translation: AEW89518.1.
JN245936 Genomic DNA. Translation: AEW89560.1.
JN245937 Genomic DNA. Translation: AEW89561.1.
JN245938 Genomic DNA. Translation: AEW89562.1.
JN245939 Genomic DNA. Translation: AEW89563.1.
JN245940 Genomic DNA. Translation: AEW89564.1.
JN245941 Genomic DNA. Translation: AEW89565.1.
JN245942 Genomic DNA. Translation: AEW89566.1.
JN245943 Genomic DNA. Translation: AEW89567.1.
JN245944 Genomic DNA. Translation: AEW89568.1.
JN245945 Genomic DNA. Translation: AEW89569.1.
JN245887 Genomic DNA. Translation: AEW89493.1.
JN245888 Genomic DNA. Translation: AEW89494.1.
JN245891 Genomic DNA. Translation: AEW89497.1.
JN245905 Genomic DNA. Translation: AEW89511.1.
JN245909 Genomic DNA. Translation: AEW89515.1.
JN245913 Genomic DNA. Translation: AEW89519.1.
JN245914 Genomic DNA. Translation: AEW89520.1.
JN245915 Genomic DNA. Translation: AEW89521.1.
JN245916 Genomic DNA. Translation: AEW89522.1.
JN245917 Genomic DNA. Translation: AEW89523.1.
D14657 mRNA. Translation: BAA03491.2. Different initiation.
AK290748 mRNA. Translation: BAF83437.1.
AC087632 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77679.1.
BC005832 mRNA. Translation: AAH05832.1.
BC007101 mRNA. Translation: AAH07101.1.
BC016782 mRNA. Translation: AAH16782.1.
BU170434 mRNA. No translation available.
CCDSiCCDS10193.1. [Q15004-1]
CCDS32269.1. [Q15004-2]
RefSeqiNP_001025160.1. NM_001029989.2. [Q15004-2]
NP_055551.1. NM_014736.5. [Q15004-1]
UniGeneiHs.81892.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4D2GX-ray2.65D/E52-69[»]
ProteinModelPortaliQ15004.
SMRiQ15004.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115114. 29 interactors.
IntActiQ15004. 2 interactors.
STRINGi9606.ENSP00000300035.

Chemistry databases

ChEMBLiCHEMBL5574.

PTM databases

iPTMnetiQ15004.
PhosphoSitePlusiQ15004.

Proteomic databases

EPDiQ15004.
MaxQBiQ15004.
PaxDbiQ15004.
PeptideAtlasiQ15004.
PRIDEiQ15004.

Protocols and materials databases

DNASUi9768.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300035; ENSP00000300035; ENSG00000166803. [Q15004-1]
ENST00000380258; ENSP00000369608; ENSG00000166803. [Q15004-2]
GeneIDi9768.
KEGGihsa:9768.
UCSCiuc002ank.5. human. [Q15004-1]

Organism-specific databases

CTDi9768.
DisGeNETi9768.
GeneCardsiKIAA0101.
HGNCiHGNC:28961. KIAA0101.
HPAiHPA055444.
MIMi610696. gene.
neXtProtiNX_Q15004.
OpenTargetsiENSG00000166803.
ENSG00000259316.
PharmGKBiPA134974023.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J101. Eukaryota.
ENOG410Y3KP. LUCA.
GeneTreeiENSGT00510000048252.
HOGENOMiHOG000013069.
HOVERGENiHBG052567.
InParanoidiQ15004.
OMAiVENKYAG.
PhylomeDBiQ15004.
TreeFamiTF333199.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166803-MONOMER.
ReactomeiR-HSA-5656169. Termination of translesion DNA synthesis.
SIGNORiQ15004.

Miscellaneous databases

GeneWikiiKIAA0101.
GenomeRNAii9768.
PROiQ15004.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166803.
CleanExiHS_KIAA0101.
ExpressionAtlasiQ15004. baseline and differential.
GenevisibleiQ15004. HS.

Family and domain databases

InterProiIPR031444. PCNA-AF.
[Graphical view]
PfamiPF15715. PAF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPAF15_HUMAN
AccessioniPrimary (citable) accession number: Q15004
Secondary accession number(s): A6NNU5
, A8K3Y3, G9G694, G9G696
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

Overexpression in adrenocortical neoplasms (ACC), may promote growth and invasion in adrenal cancer.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.