ID:PAF15_HUMAN DESCRIPTION: RecName: Full=PCNA-associated factor; AltName: Full=Hepatitis C virus NS5A-transactivated protein 9; Short=HCV NS5A-transactivated protein 9; AltName: Full=Overexpressed in anaplastic thyroid carcinoma 1; Short=OEATC-1; AltName: Full=PCNA-associated factor of 15 kDa; Short=PAF15; Short=p15PAF; FUNCTION: 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. SUBUNIT: Interacts (when monoubiquitinated at Lys-15 and Lys-24) with PCNA. Interacts with isoform 2/p33ING1b of ING1. Interacts with BRCA1. SUBCELLULAR LOCATION: Nucleus. Cytoplasm, perinuclear region. Note=Following DNA damage, localizes to DNA damage sites. Colocalizes with centrosomes in perinuclear region. TISSUE SPECIFICITY: 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. DEVELOPMENTAL STAGE: 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). INDUCTION: By UV irradiation. By ATF3 in response to UV-stress. DOMAIN: The PIP-box mediates the interaction with PCNA (PubMed:21628590, PubMed:23000965). DOMAIN: The KEN box is required for the association with the APC/C complex (PubMed:21628590). DOMAIN: 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). DOMAIN: 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). PTM: 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. MISCELLANEOUS: Overexpression in adrenocortical neoplasms (ACC), may promote growth and invasion in adrenal cancer (PubMed:22096502). SEQUENCE CAUTION: Sequence=BAA03491.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15004
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK301858 - Homo sapiens cDNA FLJ58702 complete cds, highly similar to Casein kinase I isoform gamma-1 (EC 2.7.11.1). BC005832 - Homo sapiens KIAA0101, mRNA (cDNA clone MGC:2250 IMAGE:2988995), complete cds. BC016782 - Homo sapiens KIAA0101, mRNA (cDNA clone MGC:23764 IMAGE:4109322), complete cds. BC007101 - Homo sapiens KIAA0101, mRNA (cDNA clone MGC:14744 IMAGE:4281110), complete cds. D14657 - Homo sapiens KIAA0101 mRNA. JD048923 - Sequence 29947 from Patent EP1572962. AK290748 - Homo sapiens cDNA FLJ76548 complete cds. JD348726 - Sequence 329750 from Patent EP1572962. JD235194 - Sequence 216218 from Patent EP1572962. JD562713 - Sequence 543737 from Patent EP1572962. AF529370 - Homo sapiens NS5ATP9 (NS5ATP9) mRNA, complete cds. AY598324 - Homo sapiens L5 mRNA, complete cds. CU675545 - Synthetic construct Homo sapiens gateway clone IMAGE:100018494 5' read KIAA0101 mRNA. HQ447907 - Synthetic construct Homo sapiens clone IMAGE:100071263; CCSB004523_01 KIAA0101 (KIAA0101) gene, encodes complete protein. KJ892844 - Synthetic construct Homo sapiens clone ccsbBroadEn_02238 KIAA0101 gene, encodes complete protein. AB463081 - Synthetic construct DNA, clone: pF1KA0101, Homo sapiens KIAA0101 gene, without stop codon, in Flexi system. JD525852 - Sequence 506876 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q15004 (Reactome details) participates in the following event(s):
R-HSA-5656169 Termination of translesion DNA synthesis R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template R-HSA-73893 DNA Damage Bypass R-HSA-73894 DNA Repair