STRINGSTRING
Xpa Xpa Chek2 Chek2 Fancm Fancm Tp53 Tp53 Fancd2 Fancd2 Fancb Fancb Exo1 Exo1 Ogg1 Ogg1 Fancg Fancg Pms2 Pms2 Smug1 Smug1 Pnkp Pnkp Ercc6 Ercc6 Tdg Tdg Rad50 Rad50 Xrcc6 Xrcc6 Polq Polq Rnf8 Rnf8 Bard1 Bard1 Neil1 Neil1 Mdc1 Mdc1 Aptx Aptx Aplf Aplf Fanci Fanci Ccnh Ccnh Prkdc Prkdc Fancf Fancf Fancl Fancl Pcna Pcna Mpg Mpg Fen1 Fen1 Parg Parg Xrcc1 Xrcc1 Inpp4b Inpp4b Nhej1 Nhej1 Mutyh Mutyh Ercc1 Ercc1 Poll Poll Fancc Fancc Fanca Fanca Msh6 Msh6 Xrcc5 Xrcc5 Paxx Paxx Lig1 Lig1 Lig4 Lig4 Rbbp8 Rbbp8 Nthl1 Nthl1 Neil3 Neil3 Neil2 Neil2 Ercc8 Ercc8 Wee1 Wee1 Rad52 Rad52 Fance Fance Myc Myc Tdp1 Tdp1 Parp1 Parp1 Rnf168 Rnf168 Brca2 Brca2 Slc25a16 Slc25a16
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
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colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
Edges:
Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding to each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
Your Input:
XpaXeroderma pigmentosum, complementation group A (Predicted), isoform CRA_a. (241 aa)
Chek2CHK2 checkpoint homolog (S. pombe), isoform CRA_a. (545 aa)
FancmFA complementation group M. (2017 aa)
Tp53Cellular tumor antigen p53; Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its intera [...] (391 aa)
Fancd2Fanconi anemia group D2 protein homolog; Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (By similarity). Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-ce [...] (1453 aa)
FancbFA complementation group B. (853 aa)
Exo1Exonuclease 1. (836 aa)
Ogg1DNA-(apurinic or apyrimidinic site) lyase; DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N- methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-lyase activity that nicks DNA 3' to the lesion. (345 aa)
FancgFA complementation group G. (623 aa)
Pms2PMS1 homolog 2, mismatch repair system component. (853 aa)
Smug1Single-strand selective monofunctional uracil-DNA glycosylase; Recognizes base lesions in the genome and initiates base excision DNA repair. Acts as a monofunctional DNA glycosylase specific for uracil (U) residues in DNA with a preference for single-stranded DNA substrates. The activity is greater toward mismatches (U/G) compared to matches (U/A). Excises uracil (U), 5-formyluracil (fU) and uracil derivatives bearing an oxidized group at C5 [5-hydroxyuracil (hoU) and 5-hydroxymethyluracil (hmU)] in ssDNA and dsDNA, but not analogous cytosine derivatives (5-hydroxycytosine and 5- formy [...] (278 aa)
PnkpPolynucleotide kinase 3'-phosphatase. (548 aa)
Ercc6ERCC excision repair 6, chromatin-remodeling factor. (1474 aa)
TdgThymine-DNA glycosylase. (410 aa)
Rad50DNA repair protein RAD50; Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease [...] (1312 aa)
Xrcc6X-ray repair cross-complementing 6. (609 aa)
PolqPolymerase (DNA directed), theta (Predicted), isoform CRA_a. (2547 aa)
Rnf8E3 ubiquitin-protein ligase RNF8; E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53 [...] (487 aa)
Bard1BRCA1-associated RING domain protein 1; E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II [...] (768 aa)
Neil1Nei endonuclease VIII-like 1 (E. coli). (387 aa)
Mdc1Mediator of DNA damage checkpoint protein 1; Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be ac [...] (1279 aa)
AptxAprataxin; DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP- NH(2)) and diadenosine tetraphosphate (AppppA), b [...] (329 aa)
AplfAprataxin and PNKP-like factor. (510 aa)
FanciFA complementation group I. (1333 aa)
CcnhCyclin-H; Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout t [...] (323 aa)
PrkdcProtein kinase, DNA-activated, catalytic subunit; Belongs to the PI3/PI4-kinase family. (4126 aa)
FancfFA complementation group F. (338 aa)
FanclFA complementation group L. (375 aa)
PcnaProliferating cell nuclear antigen; Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'- phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA rep [...] (261 aa)
MpgDNA-3-methyladenine glycosylase; Hydrolysis of the deoxyribose N-glycosidic bond to excise 3- methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions. (329 aa)
Fen1Flap endonuclease 1; Structure-specific nuclease with 5'-flap endonuclease and 5'- 3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site- terminated flap. Acts as [...] (380 aa)
PargPoly(ADP-ribose) glycohydrolase; Poly(ADP-ribose) glycohydrolase that degrades poly(ADP- ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP- ribose). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers. It is however unable to cleave the ester bond between the terminal ADP- ribose and ADP-ribosylated residues, leaving proteins that are mono- ADP-ribosylated. Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG. Required to prevent detrimental [...] (972 aa)
Xrcc1DNA repair protein XRCC1; Involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes. Probably during DNA repair, negatively regulates ADP-ribose levels by modulating ADP- ribosyltransferase PARP1 activity. (631 aa)
Inpp4bType II inositol 3,4-bisphosphate 4-phosphatase; Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4-bisphosphate. Plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles (By similarity). The lipid phosphatase activity is critical for tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (By similarity). (942 aa)
Nhej1Non-homologous end-joining factor 1; DNA repair protein involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. May serve as a bridge between XRCC4 and the other NHEJ factors located at DNA ends, or may participate in reconfiguration of the end bound NHEJ factors to allow XRCC4 access to the DNA termini. It may act in concert with XRCC6/XRCC5 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are noncomplementary or partially complementary. Binds DNA in a length- dependent mann [...] (304 aa)
MutyhAdenine DNA glycosylase; Involved in oxidative DNA damage repair. Initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. Possesses both adenine and 2-OH-A DNA glycosylase activities. (516 aa)
Ercc1ERCC excision repair 1, endonuclease non-catalytic subunit. (298 aa)
PollDNA polymerase lambda; DNA polymerase that functions in several pathways of DNA repair. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Also contributes to DNA double-strand break repair by non-homologous end joining and homologous recombination. Has both template-dependent and template- independent (terminal transferase) DNA polymerase activities. Has also a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity. (573 aa)
FanccFanconi anemia group C protein homolog; DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. Upon IFNG induction, may facilitate STAT1 activation by recruiting STAT1 to IFNGR1 (By similarity). (557 aa)
FancaFanconi anemia, complementation group A (Predicted). (1190 aa)
Msh6DNA mismatch repair protein; Component of the post-replicative DNA mismatch repair system (MMR). (1362 aa)
Xrcc5X-ray repair cross-complementing protein 5; Single-stranded DNA-dependent ATP-dependent helicase. Belongs to the ku80 family. (732 aa)
PaxxPAXX, non-homologous end joining factor. (205 aa)
Lig1DNA ligase 1; DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair. (913 aa)
Lig4DNA ligase. (911 aa)
Rbbp8DNA endonuclease RBBP8; Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phas [...] (893 aa)
Nthl1Endonuclease III-like protein 1; Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines. (300 aa)
Neil3Nei-like DNA glycosylase 3. (606 aa)
Neil2Nei like 2 (E. coli) (Predicted). (330 aa)
Ercc8ERCC excision repair 8, CSA ubiquitin ligase complex subunit. (397 aa)
Wee1Wee1-like protein kinase; Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15'. Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur. Its activity increases during S and G2 phases and decreases at M phase wh [...] (646 aa)
Rad52RAD52 homolog, DNA repair protein. (426 aa)
FanceFA complementation group E. (547 aa)
MycMyc proto-oncogene protein; Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (By similarity). Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). (439 aa)
Tdp1Tyrosyl-DNA phosphodiesterase 1; DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead- end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the [...] (625 aa)
Parp1Poly [ADP-ribose] polymerase 1; Poly-ADP-ribosyltransferase that mediates poly-ADP- ribosylation of proteins and plays a key role in DNA repair. Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate residues and further ADP- ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF an [...] (1014 aa)
Rnf168E3 ubiquitin-protein ligase RNF168; E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recrui [...] (566 aa)
Brca2Breast cancer type 2 susceptibility protein homolog; Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51- ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint acti [...] (3343 aa)
Slc25a16DNA replication ATP-dependent helicase/nuclease DNA2; Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double-strand break (DSB) repair: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavag [...] (1215 aa)
Your Current Organism:
Rattus norvegicus
NCBI taxonomy Id: 10116
Other names: Buffalo rat, Norway rat, R. norvegicus, Rattus PC12 clone IS, Rattus sp. strain Wistar, Sprague-Dawley rat, Wistar rats, brown rat, laboratory rat, rat, rats, zitter rats
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