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Protein

PCNA-associated factor

Gene

PCLAF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

GO - Molecular functioni

  • chromatin binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processDNA damage, DNA repair

Enzyme and pathway databases

ReactomeiR-HSA-5656169 Termination of translesion DNA synthesis
SIGNORiQ15004

Names & Taxonomyi

Protein namesi
Recommended name:
PCNA-associated factorCurated
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
PCNA-clamp-associated factorImported
Gene namesi
Name:PCLAFImported
Synonyms:KIAA0101, NS5ATP9, PAF
ORF Names:L5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000166803.10
HGNCiHGNC:28961 PCLAF
MIMi610696 gene
neXtProtiNX_Q15004

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
Modified residuei8PhosphoserineCombined sources1
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 residuei28PhosphoserineCombined sources1
Modified residuei31Phosphoserine1 Publication1
Modified residuei72PhosphoserineCombined sources1 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
ProteomicsDBi60355

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 Expressed in 217 organ(s), highest expression level in bone marrow
CleanExiHS_KIAA0101
ExpressionAtlasiQ15004 baseline and differential
GenevisibleiQ15004 HS

Organism-specific databases

HPAiHPA047929

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, 32 interactors
CORUMiQ15004
IntActiQ15004, 3 interactors
STRINGi9606.ENSP00000300035

Structurei

Secondary structure

1111
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiDHRDDEN
PhylomeDBiQ15004
TreeFamiTF333199

Family and domain databases

InterProiView protein in InterPro
IPR031444 PCNA-AF
PANTHERiPTHR15679 PTHR15679, 1 hit
PfamiView protein in Pfam
PF15715 PAF, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YMA4H0YMA4_HUMAN
HCG2039386, isoform CRA_b
PCLAF hCG_2039386
115Annotation score:
H0YKX3H0YKX3_HUMAN
PCNA-associated factor
PCLAF
84Annotation score:

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 dbSNP:rs11554313Ensembl.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

Similar proteinsi

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[»]
6EHTX-ray3.20D/E52-71[»]
6GWSX-ray2.90D/E/F41-72[»]
ProteinModelPortaliQ15004
SMRiQ15004
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115114, 32 interactors
CORUMiQ15004
IntActiQ15004, 3 interactors
STRINGi9606.ENSP00000300035

Chemistry databases

ChEMBLiCHEMBL5574

PTM databases

iPTMnetiQ15004
PhosphoSitePlusiQ15004

Proteomic databases

EPDiQ15004
MaxQBiQ15004
PaxDbiQ15004
PeptideAtlasiQ15004
PRIDEiQ15004
ProteomicsDBi60355

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
EuPathDBiHostDB:ENSG00000166803.10
GeneCardsiPCLAF
HGNCiHGNC:28961 PCLAF
HPAiHPA047929
MIMi610696 gene
neXtProtiNX_Q15004
OpenTargetsiENSG00000166803
ENSG00000259316
PharmGKBiPA134974023
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J101 Eukaryota
ENOG410Y3KP LUCA
GeneTreeiENSGT00510000048252
HOGENOMiHOG000013069
HOVERGENiHBG052567
InParanoidiQ15004
OMAiDHRDDEN
PhylomeDBiQ15004
TreeFamiTF333199

Enzyme and pathway databases

ReactomeiR-HSA-5656169 Termination of translesion DNA synthesis
SIGNORiQ15004

Miscellaneous databases

ChiTaRSiKIAA0101 human
GeneWikiiKIAA0101
GenomeRNAii9768
PROiPR:Q15004
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166803 Expressed in 217 organ(s), highest expression level in bone marrow
CleanExiHS_KIAA0101
ExpressionAtlasiQ15004 baseline and differential
GenevisibleiQ15004 HS

Family and domain databases

InterProiView protein in InterPro
IPR031444 PCNA-AF
PANTHERiPTHR15679 PTHR15679, 1 hit
PfamiView protein in Pfam
PF15715 PAF, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPAF15_HUMAN
AccessioniPrimary (citable) accession number: Q15004
Secondary accession number(s): A6NNU5
, A8K3Y3, G9G694, G9G696
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: October 10, 2018
This is version 152 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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