Reactome | UniProt:Q12888 TP53BP1

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UniProt:Q12888 TP53BP1 Show undefined attributes

chain	chain:1-1972
checksum	13E2CC8A265F9D2A
comment	FUNCTION Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112).SUBUNIT Homoligomer (PubMed:16294047, PubMed:23345425, PubMed:23760478). Interacts with p53/TP53 (via the central domain) (PubMed:11877378, PubMed:12110597). Interacts with DCLRE1C (PubMed:15574327). Interacts with histone H2AX and this requires phosphorylation of H2AX on 'Ser-139' (PubMed:12607005). Interacts with histone H4 that has been dimethylated at 'Lys-20' (H4K20me2) (PubMed:17190600). Has low affinity for histone H4 containing monomethylated 'Lys-20' (H4K20me1) (PubMed:17190600). Does not bind histone H4 containing unmethylated or trimethylated 'Lys-20' (H4K20me3) (PubMed:17190600). Has low affinity for histone H3 that has been dimethylated on 'Lys-79' (PubMed:15525939). Has very low affinity for histone H3 that has been monomethylated on 'Lys-79' (in vitro) (PubMed:15525939). Does not bind unmethylated histone H3 (PubMed:15525939). Interacts with histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) (PubMed:23760478). Interacts with PWWP3A/EXPAND1 (PubMed:20347427). Interacts with CHEK2; modulates CHEK2 phosphorylation at 'Thr-68' in response to infrared (PubMed:12364621). Interacts with MSL1; this interaction may be required for MSL1 DNA repair activity, but not for histone acetyltransferase activity (PubMed:19650074). Interacts (when phosphorylated by ATM) with RIF1 (PubMed:23333306, PubMed:23727112, PubMed:28241136). Interacts (via the Tudor-like domain) with NUDT16L1/TIRR; interaction masks the Tudor-like domain and prevents recruitment to chromatin (PubMed:28241136). Interacts with PAXIP1 (PubMed:23727112). Interacts with SHLD2 (PubMed:29789392). Interacts (when phosphorylated) with TOPBP1 (PubMed:31135337). Interacts with GFI1; promoting methylation by PRMT1 (PubMed:29651020). Interacts with (phosphorylated) DYNLL1; specifically binds DYNLL1 phosphorylated at 'Ser-88' and promotes its recruitment to double strand breaks (DSBs) (PubMed:37696958).SUBUNIT (Microbial infection) Interacts (via C-terminus) with Epstein-Barr virus lytic switch protein BZLF1 (via C-terminus); this interaction is involved in the activation of the viral lytic cycle.INTERACTION Localizes to the nucleus in absence of DNA damage (PubMed:28241136). Following DNA damage, recruited to sites of DNA damage, such as double strand breaks (DSBs): recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23333306, PubMed:23760478, PubMed:24703952, PubMed:28241136, PubMed:31135337, PubMed:37696958). Associated with kinetochores during mitosis (By similarity).ALTERNATIVE PRODUCTS The Tudor-like region mediates binding to histone H4 dimethylated at 'Lys-20' (H4K20me2) (PubMed:17190600). Interaction with NUDT16L1/TIRR masks the Tudor-like domain and prevents recruitment to chromatin (PubMed:28241136).DOMAIN The UDR (ubiquitin-dependent recruitment) motif specifically recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15ub) (PubMed:23760478, PubMed:24703952). Phosphorylation of the UDR blocks interaction with H2AK15ub (PubMed:24703952).PTM Asymmetrically dimethylated on Arg residues by PRMT1. Methylation is required for DNA binding.PTM Phosphorylated at basal level in the absence of DNA damage (PubMed:11042216, PubMed:11331310). Phosphorylated by ATM in response to DNA damage: phosphorylation at different sites promotes interaction with different set of proteins: phosphorylation at the N-terminus by ATM (residues from 6-178) promotes interaction with PAXIP1 and non-homologous end joining (NHEJ) of dysfunctional telomeres (PubMed:23727112). Phosphorylation by ATM at residues that are located more C-terminus (residues 300-650) leads to promote interaction with RIF1 (PubMed:23333306, PubMed:23727112, PubMed:28241136). Interaction with RIF1 leads to disrupt interaction with NUDT16L1/TIRR (PubMed:28241136). Phosphorylation at Thr-1609 and Ser-1618 in the UDR motif blocks interaction with H2AK15ub (PubMed:24703952). Dephosphorylated by PPP4C (PubMed:24703952). Hyperphosphorylation during mitosis correlates with its exclusion from chromatin and DNA lesions. Hyperphosphorylated in an ATR-dependent manner in response to DNA damage induced by UV irradiation (PubMed:17553757, PubMed:21144835). Dephosphorylated by PPP5C (PubMed:19176521). Phosphorylation at Ser-366 and Thr-670 promotes interaction with TOPBP1 (PubMed:31135337). Phosphorylated by VRK1 (PubMed:31527692).PTM Monoubiquitinated at Lys-1685 by MSL2 in response to DNA damage, leading to its stabilization.DISEASE A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein.SEQUENCE CAUTION Extended N-terminus.
crossReference	[DatabaseIdentifier:11445880] ENSEMBL:ENSG00000067369 [DatabaseIdentifier:12815998] ZINC target:Q12888 [DatabaseIdentifier:12812624] ZINC - Substances:TP53B_HUMAN [DatabaseIdentifier:12808136] ZINC - Predictions - Purchasable:TP53B_HUMAN [DatabaseIdentifier:12312096] RefSeq:NP_001135452.1 [DatabaseIdentifier:12312094] RefSeq:XP_054234711.1 [DatabaseIdentifier:12312098] RefSeq:XP_047288951.1 [DatabaseIdentifier:12312093] RefSeq:XP_054234710.1 [DatabaseIdentifier:12312097] RefSeq:NP_001135451.1 [DatabaseIdentifier:12312095] RefSeq:NP_005648.1 [DatabaseIdentifier:12312099] RefSeq:XP_047288950.1 [DatabaseIdentifier:12282342] Pharos - Targets:Q12888 [DatabaseIdentifier:12240072] PRO:Q12888 [DatabaseIdentifier:12144512] PDB:2MWP [DatabaseIdentifier:12144749] PDB:1GZH [DatabaseIdentifier:12157808] PDB:5Z78 [DatabaseIdentifier:12157805] PDB:2IG0 [DatabaseIdentifier:12157800] PDB:8F0W [DatabaseIdentifier:12157804] PDB:8T2D [DatabaseIdentifier:12157794] PDB:5J26 [DatabaseIdentifier:12157798] PDB:8HKW [DatabaseIdentifier:12155447] PDB:5ZCJ [DatabaseIdentifier:12157806] PDB:3LH0 [DatabaseIdentifier:12157801] PDB:4RG2 [DatabaseIdentifier:12144513] PDB:2MWO [DatabaseIdentifier:12157796] PDB:8U4U [DatabaseIdentifier:12157802] PDB:8EOM [DatabaseIdentifier:12157807] PDB:6UPT [DatabaseIdentifier:12157803] PDB:8SWJ [DatabaseIdentifier:12157799] PDB:6VA5 [DatabaseIdentifier:12157795] PDB:6RML [DatabaseIdentifier:12144609] PDB:1KZY [DatabaseIdentifier:12157797] PDB:6RMM [DatabaseIdentifier:12157775] PDB:6MXZ [DatabaseIdentifier:12157787] PDB:1XNI [DatabaseIdentifier:12157788] PDB:8SVJ [DatabaseIdentifier:12157783] PDB:6CO2 [DatabaseIdentifier:12155448] PDB:6CO1 [DatabaseIdentifier:12157793] PDB:6VIP [DatabaseIdentifier:12157784] PDB:5KGF [DatabaseIdentifier:12157781] PDB:3LGL [DatabaseIdentifier:12157776] PDB:7LIN [DatabaseIdentifier:12157791] PDB:8SVH [DatabaseIdentifier:12144482] PDB:4X34 [DatabaseIdentifier:12157782] PDB:7YQK [DatabaseIdentifier:12157780] PDB:2LVM [DatabaseIdentifier:12157790] PDB:6MY0 [DatabaseIdentifier:12157779] PDB:2G3R [DatabaseIdentifier:12144616] PDB:5ECG [DatabaseIdentifier:12157792] PDB:4CRI [DatabaseIdentifier:12147112] PDB:6IUA [DatabaseIdentifier:12157777] PDB:6MXY [DatabaseIdentifier:12157785] PDB:6MXX [DatabaseIdentifier:12157789] PDB:8SVG [DatabaseIdentifier:12157778] PDB:7LIO [DatabaseIdentifier:12147114] PDB:6IU7 [DatabaseIdentifier:12157774] PDB:3LGF [DatabaseIdentifier:12157786] PDB:8SVI [DatabaseIdentifier:12122018] OpenTargets:ENSG00000067369 [DatabaseIdentifier:11837523] HPA:ENSG00000067369-TP53BP1 [DatabaseIdentifier:11799903] GlyGen:Q12888 [DatabaseIdentifier:11784426] GeneCards:TP53BP1 [DatabaseIdentifier:11655673] ENSEMBL:ENST00000450115 [DatabaseIdentifier:11655674] ENSEMBL:ENST00000382044 [DatabaseIdentifier:11655675] ENSEMBL:ENST00000263801 [DatabaseIdentifier:11532974] ENSEMBL:ENSP00000371475 [DatabaseIdentifier:11532976] ENSEMBL:ENSP00000263801 [DatabaseIdentifier:11532975] ENSEMBL:ENSP00000393497
databaseName	UniProt
dbId	61176
description	recommendedName: fullName evidence="43"TP53-binding protein 1 shortName evidence="41"53BP1 shortName evidence="41"p53-binding protein 1 shortName: p53BP1
displayName	UniProt:Q12888 TP53BP1
geneName	TP53BP1
identifier	Q12888
isSequenceChanged	false
keyword	3D-structure Activator Alternative splicing Centromere Chromosomal rearrangement Chromosome DNA damage DNA repair DNA-binding Host-virus interaction Isopeptide bond Kinetochore Methylation Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Transcription Transcription regulation Ubl conjugation
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	TP53BP1
physicalEntity	[EntityWithAccessionedSequence:R-HSA-61175] TP53BP1 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5683418] p-S25,S1778-TP53BP1 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2997591] monoSUMO1-K-TP53BP1 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000067369] ENSEMBL:ENSG00000067369 TP53BP1 [ReferenceDNASequence:12722609] UCSC:Q12888 TP53BP1 [ReferenceDNASequence:12107670] OMIM:605230 TP53BP1 [ReferenceDNASequence:12025428] NCBI Gene:7158 TP53BP1 [ReferenceDNASequence:11941335] Monarch:7158 TP53BP1 [ReferenceDNASequence:11855203] KEGG:hsa:7158 TP53BP1 [ReferenceDNASequence:11816051] HGNC:11999 TP53BP1 [ReferenceDNASequence:11434147] dbSNP Gene:7158 TP53BP1 [ReferenceDNASequence:11408354] CTD Gene:7158 TP53BP1 [ReferenceDNASequence:11397458] COSMIC - genes:TP53BP1 TP53BP1 [ReferenceDNASequence:11311546] BioGPS Gene:7158 TP53BP1
referenceTranscript	[ReferenceRNASequence:12494168] RefSeq:XM_054378736.1 TP53BP1 [ReferenceRNASequence:12494165] RefSeq:NM_001141980.3 TP53BP1 [ReferenceRNASequence:12494163] RefSeq:NM_001141979.3 TP53BP1 [ReferenceRNASequence:12494162] RefSeq:XM_047432995.1 TP53BP1 [ReferenceRNASequence:12494164] RefSeq:XM_047432994.1 TP53BP1 [ReferenceRNASequence:12494167] RefSeq:XM_054378735.1 TP53BP1 [ReferenceRNASequence:12494166] RefSeq:NM_005657.4 TP53BP1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	TP53B_HUMAN F8VY86 Q2M1Z7 Q4LE46 Q5FWZ3 Q7Z3U4
sequenceLength	1972
species	[Species:48887] Homo sapiens
stId	uniprot:Q12888
url	http://purl.uniprot.org/uniprot/Q12888

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-61175] TP53BP1 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-5683418] p-S25,S1778-TP53BP1 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-2997591] monoSUMO1-K-TP53BP1 [nucleoplasm]
(referenceSequence)	[ModifiedResidue:5683414] O-phospho-L-serine at 25 [ModifiedResidue:5683419] O-phospho-L-serine at 1778 [GroupModifiedResidue:2997731] sumoylated lysine (monoSUMO1 [nucleoplasm]) at unknown position
(interactor)	[UndirectedInteraction:11300335] UniProt:Q12888 <-> UniProt:Q96SB8 (IntAct) [UndirectedInteraction:11300333] UniProt:Q12888 <-> UniProt:Q96RU2 (IntAct) [UndirectedInteraction:11300331] UniProt:Q12888 <-> UniProt:Q71F56 (IntAct) [UndirectedInteraction:11300329] UniProt:Q12888 <-> UniProt:Q86V20-2 (IntAct) [UndirectedInteraction:11300325] UniProt:Q12888 <-> UniProt:O43257 (IntAct) [UndirectedInteraction:11300323] UniProt:Q12888 <-> UniProt:P62807 (IntAct) [UndirectedInteraction:11300321] UniProt:Q12888 <-> UniProt:Q7Z699 (IntAct) [UndirectedInteraction:11300319] UniProt:Q12888 <-> UniProt:P23763-3 (IntAct) [UndirectedInteraction:11300317] UniProt:Q12888 <-> UniProt:P50570-2 (IntAct) [UndirectedInteraction:11300315] UniProt:Q12888 <-> UniProt:Q5SWW7 (IntAct) [UndirectedInteraction:11300313] UniProt:Q12888 <-> UniProt:A0A6Q8PF08 (IntAct) [UndirectedInteraction:11300311] UniProt:Q12888 <-> IntAct:EBI-25857482 (IntAct) [UndirectedInteraction:11300309] UniProt:Q12888 <-> UniProt:P62826 (IntAct) [UndirectedInteraction:11300307] UniProt:Q12888 <-> UniProt:Q13393 (IntAct) [UndirectedInteraction:11300305] UniProt:Q12888 <-> UniProt:Q02930-3 (IntAct) [UndirectedInteraction:11300303] UniProt:Q12888 <-> UniProt:P61086 (IntAct) [UndirectedInteraction:11300301] UniProt:Q12888 <-> UniProt:P46379-2 (IntAct) [UndirectedInteraction:11300299] UniProt:Q12888 <-> UniProt:Q5T6F2 (IntAct) [UndirectedInteraction:11300297] UniProt:Q12888 <-> UniProt:O14645 (IntAct) [UndirectedInteraction:11300295] UniProt:Q12888 <-> IntAct:EBI-25847655 (IntAct) [UndirectedInteraction:11300293] UniProt:Q12888 <-> UniProt:O75400-2 (IntAct) [UndirectedInteraction:11300291] UniProt:Q12888 <-> UniProt:P13637 (IntAct) [UndirectedInteraction:11300289] UniProt:Q12888 <-> UniProt:P41182 (IntAct) [UndirectedInteraction:11300287] UniProt:Q12888 <-> UniProt:Q49AR9 (IntAct) [UndirectedInteraction:11132169] UniProt:O14964 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11133833] UniProt:P08670 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11142697] UniProt:Q9UBL3 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11149579] UniProt:P13569 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11162681] UniProt:P62805 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11167393] UniProt:P55212 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11183859] UniProt:P63165 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11186615] UniProt:Q14686 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11189041] UniProt:P55072 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11194995] UniProt:Q6NZQ4 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11200117] UniProt:P04637 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11208253] UniProt:P01106 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11233403] UniProt:Q8NAV1 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11254077] UniProt:Q9UMN6 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11265599] UniProt:Q13315 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11267869] UniProt:P16284 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11274413] UniProt:P16104 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11282273] UniProt:Q14676 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11285915] UniProt:P53350 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11287887] UniProt:Q8TDS5 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11289495] UniProt:P38398 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11294491] UniProt:Q6ZW49 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11296311] UniProt:P10809 <-> UniProt:Q12888 (IntAct) [UndirectedInteraction:11300251] UniProt:Q12888 <-> UniProt:P63167 (IntAct) [UndirectedInteraction:11300253] UniProt:Q12888 <-> UniProt:Q08AM6 (IntAct) [UndirectedInteraction:11300255] UniProt:Q12888 <-> UniProt:P0C0S8 (IntAct) [UndirectedInteraction:11300257] UniProt:Q12888 <-> UniProt:P68431 (IntAct) [UndirectedInteraction:11300259] UniProt:Q12888 <-> UniProt:Q96FJ2 (IntAct) [UndirectedInteraction:11300261] UniProt:Q12888 <-> UniProt:Q99986 (IntAct) [UndirectedInteraction:11300263] UniProt:Q12888 <-> UniProt:O75190-2 (IntAct) [UndirectedInteraction:11300265] UniProt:Q12888 <-> UniProt:O14901 (IntAct) [UndirectedInteraction:11300267] UniProt:Q12888 <-> UniProt:P50222 (IntAct) [UndirectedInteraction:11300269] UniProt:Q12888 <-> UniProt:P78337 (IntAct) [UndirectedInteraction:11300271] UniProt:Q12888 <-> UniProt:G5E9A7 (IntAct) [UndirectedInteraction:11300275] UniProt:Q12888 <-> UniProt:P04275-2 (IntAct) [UndirectedInteraction:11300277] UniProt:Q12888 <-> UniProt:Q96HB5 (IntAct) [UndirectedInteraction:11300279] UniProt:Q12888 <-> UniProt:P13473-2 (IntAct) [UndirectedInteraction:11300281] UniProt:Q12888 <-> UniProt:O43711 (IntAct) [UndirectedInteraction:11300283] UniProt:Q12888 <-> UniProt:Q96G42 (IntAct) [UndirectedInteraction:11300285] UniProt:Q12888 <-> UniProt:P78424 (IntAct)

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