RBBP8 RB binding protein 8, endonuclease [Homo sapiens (human)] - Gene

Summary

Official Symbol: RBBP8provided by HGNC
Official Full Name: RB binding protein 8, endonucleaseprovided by HGNC
Primary source: HGNC:HGNC:9891
See related: Ensembl:ENSG00000101773 MIM:604124
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RIM; COM1; CTIP; JWDS; SAE2; SCKL2
Summary: The protein encoded by this gene is a ubiquitously expressed nuclear protein. It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. This protein complexes with transcriptional co-repressor CTBP. It is also associated with BRCA1 and is thought to modulate the functions of BRCA1 in transcriptional regulation, DNA repair, and/or cell cycle checkpoint control. It is suggested that this gene may itself be a tumor suppressor acting in the same pathway as BRCA1. Three transcript variants encoding two different isoforms have been found for this gene. More transcript variants exist, but their full-length natures have not been determined. [provided by RefSeq, Jul 2008]
Expression: Broad expression in testis (RPKM 11.3), kidney (RPKM 6.6) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 18q11.2

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	18	NC_000018.10 (22914121..23026486)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (20513295..20606451)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CtIP is required for faithful replication through telomeres via its roles at stalled replication tracts.
Title: CtIP is essential for telomere replication.
The N-terminus of CTCF is able to bind to only MRE11 and its C-terminus is incapable of binding to MRE11 and CtIP, thereby resulting in compromised CtIP recruitment, DSB resection and HR. Overall, this suggests an important function of CTCF in DNA end resection through the recruitment of CtIP at DSBs.
Title: CTCF cooperates with CtIP to drive homologous recombination repair of double-strand breaks.
HGF/c-Met regulates expression of SAE2 and cirRNA CCDC66 to increase epithelial-to-mesenchymal transition and drug resistance of lung adenocarcinoma cells.
Title: The role of HGF-MET pathway and CCDC66 cirRNA expression in EGFR resistance and epithelial-to-mesenchymal transition of lung adenocarcinoma cells.
We propose that BRCA1-CTIP and MRE11 prepare nascent DNA ends, blocked from synthesis by CTNAs, for further repair.
Title: CtIP-BRCA1 complex and MRE11 maintain replication forks in the presence of chain terminating nucleoside analogs.
Data sufgest that polo like kinase 1 (PLK1) may target retinoblastoma binding protein 8 (RBBP8; CtIP) to promote error-prone microhomology-mediated end joining (MMEJ) and inactivate the G2/M checkpoint.
Title: PLK1 targets CtIP to promote microhomology-mediated end joining.
Bioinformatics predicted the putative binding site of miR18a5p in the 3' untranslated region of CtIP/RBBP8. Study using nasopharyngeal carcinoma cell line further confirmed that miR18a5p could directly bind with RBBP8 and inhibit RBBP8 expression.
Title: lncRNA CASC2/miR‑18a‑5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8.
Data demonstrate that RBBP8 is almost exclusively methylated in 45% primary bladder cancer, suggesting the development of methylation in a distinct molecular context. A close association between RBBP8 methylation and its gene expression in primary tumors as well as after demethylation treatment in vitro indicate that RBBP8 methylation could be responsible for its gene inactivation.
Title: Promoter methylation of DNA damage repair (DDR) genes in human tumor entities: <i>RBBP8</i>/<i>CtIP</i> is almost exclusively methylated in bladder cancer.
Study identifies the KLHL15 as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway.
Title: Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection.
ATM-dependent phosphorylation of CtIP and the epistatic and coordinated actions of MRE11 and CtIP nuclease activities are required to limit the stable loading of Ku on single-ended DNA double-strand breaks.
Title: Coordinated nuclease activities counteract Ku at single-ended DNA double-strand breaks.
53BP1/RIF1 has a role in limiting BRCA1/CtIP-mediated end resection to control double strand break repair pathway choice
Title: Impaired 53BP1/RIF1 DSB mediated end-protection stimulates CtIP-dependent end resection and switches the repair to PARP1-dependent end joining in G1.

Submit: New GeneRIF Correction See all GeneRIFs (69)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Microcephaly with mental retardation and digital anomalies MedGen: C0796063 OMIM: 251255 GeneReviews: Not available	Compare labs
Seckel syndrome 2 MedGen: C1847572 OMIM: 606744 GeneReviews: Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of intracranial aneurysm identifies three new risk loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Many sequence variants affecting diversity of adult human height. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-57607 (e-PCR)
- UniSTS:72504

D18S78 (e-PCR), detects polymorphism
- UniSTS:147771

D18S866 (e-PCR), detects polymorphism
- UniSTS:60557

SHGC-58091 (e-PCR)
- UniSTS:59073

D7S663 (e-PCR), detects polymorphism
- UniSTS:21462

RH70701 (e-PCR)
- UniSTS:35320

Homology

Homologs of the RBBP8 gene: The RBBP8 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and frog.
Orthologs from Annotation Pipeline: 299 organisms have orthologs with human gene RBBP8
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
RNA polymerase II repressing transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
Y-form DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
damaged DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
damaged DNA binding	IDA Inferred from Direct Assay more info	PubMed
double-strand/single-strand DNA junction binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
double-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
flap-structured DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
single-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
single-stranded DNA endodeoxyribonuclease activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
single-stranded DNA endodeoxyribonuclease activity	IMP Inferred from Mutant Phenotype more info	PubMed
transcription corepressor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
DNA double-strand break processing	TAS Traceable Author Statement more info
DNA double-strand break processing involved in repair via single-strand annealing	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA double-strand break processing involved in repair via single-strand annealing	IMP Inferred from Mutant Phenotype more info	PubMed
DNA repair	TAS Traceable Author Statement more info	PubMed
DNA replication	TAS Traceable Author Statement more info
G1/S transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
blastocyst hatching	IEA Inferred from Electronic Annotation more info
cell division	IEA Inferred from Electronic Annotation more info
double-strand break repair via homologous recombination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
double-strand break repair via homologous recombination	TAS Traceable Author Statement more info
meiotic cell cycle	IEA Inferred from Electronic Annotation more info
negative regulation of G0 to G1 transition	TAS Traceable Author Statement more info
negative regulation of nucleic acid-templated transcription	IEA Inferred from Electronic Annotation more info
nucleic acid phosphodiester bond hydrolysis	IEA Inferred from Electronic Annotation more info
nucleotide-excision repair	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleotide-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of signal transduction by p53 class mediator	TAS Traceable Author Statement more info
regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
response to estradiol	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	TAS Traceable Author Statement more info	PubMed
site of double-strand break	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transcriptional repressor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA endonuclease RBBP8

Names: CTBP-interacting protein; RBBP-8; retinoblastoma binding protein 8; sporulation in the absence of SPO11 protein 2 homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012121.1 RefSeqGene

Range

4997..98155

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002894.3 → NP_002885.1 DNA endonuclease RBBP8 isoform a

See identical proteins and their annotated locations for NP_002885.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 2 both encode isoform a.

Source sequence(s)

AC091147, AF043431, BG723261

Consensus CDS

CCDS11875.1

UniProtKB/Swiss-Prot

Q99708

UniProtKB/TrEMBL

A0A024RC34

Related

ENSP00000323050.5, ENST00000327155.10

Conserved Domains (2) summary

pfam08573
Location:797 → 857

SAE2; DNA repair protein endonuclease SAE2/CtIP C-terminus

pfam10482
Location:20 → 138

CtIP_N; tumor-suppressor protein CtIP N-terminal domain
NM_203291.1 → NP_976036.1 DNA endonuclease RBBP8 isoform a

See identical proteins and their annotated locations for NP_976036.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode isoform a.

Source sequence(s)

AF043431, BC001170, BU187672, U72066

Consensus CDS

CCDS11875.1

UniProtKB/Swiss-Prot

Q99708

UniProtKB/TrEMBL

A0A024RC34

Related

ENSP00000382628.2, ENST00000399722.6

Conserved Domains (2) summary

pfam08573
Location:797 → 857

SAE2; DNA repair protein endonuclease SAE2/CtIP C-terminus

pfam10482
Location:20 → 138

CtIP_N; tumor-suppressor protein CtIP N-terminal domain
NM_203292.1 → NP_976037.1 DNA endonuclease RBBP8 isoform b

See identical proteins and their annotated locations for NP_976037.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and lacks an alternate exon compared to variant 1, that causes a frameshift. The resulting isoform (b) is shorter and has a distinct C-terminus compared to isoform a.

Source sequence(s)

BC001170, BX648221, U72066

Consensus CDS

CCDS11874.1

UniProtKB/Swiss-Prot

Q99708

Related

ENSP00000382630.2, ENST00000399725.6

Conserved Domains (1) summary

pfam10482
Location:20 → 138

CtIP_N; Tumour-suppressor protein CtIP N-terminal domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000018.10 Reference GRCh38.p13 Primary Assembly

Range

22914121..23026486

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526132.2 → XP_011524434.1 DNA endonuclease RBBP8 isoform X1

See identical proteins and their annotated locations for XP_011524434.1

UniProtKB/Swiss-Prot

Q99708

UniProtKB/TrEMBL

A0A024RC34

Conserved Domains (2) summary

pfam08573
Location:797 → 857

SAE2; DNA repair protein endonuclease SAE2/CtIP C-terminus

pfam10482
Location:20 → 138

CtIP_N; tumor-suppressor protein CtIP N-terminal domain
XM_006722520.2 → XP_006722583.1 DNA endonuclease RBBP8 isoform X1

See identical proteins and their annotated locations for XP_006722583.1

UniProtKB/Swiss-Prot

Q99708

UniProtKB/TrEMBL

A0A024RC34

Conserved Domains (2) summary

pfam08573
Location:797 → 857

SAE2; DNA repair protein endonuclease SAE2/CtIP C-terminus

pfam10482
Location:20 → 138

CtIP_N; tumor-suppressor protein CtIP N-terminal domain
XM_006722519.2 → XP_006722582.1 DNA endonuclease RBBP8 isoform X1

See identical proteins and their annotated locations for XP_006722582.1

UniProtKB/Swiss-Prot

Q99708

UniProtKB/TrEMBL

A0A024RC34

Conserved Domains (2) summary

pfam08573
Location:797 → 857

SAE2; DNA repair protein endonuclease SAE2/CtIP C-terminus

pfam10482
Location:20 → 138

CtIP_N; tumor-suppressor protein CtIP N-terminal domain
XM_005258325.3 → XP_005258382.1 DNA endonuclease RBBP8 isoform X2

Conserved Domains (1) summary

pfam10482
Location:20 → 138

CtIP_N; Tumour-suppressor protein CtIP N-terminal domain
XM_024451233.1 → XP_024307001.1 DNA endonuclease RBBP8 isoform X3

Conserved Domains (2) summary

pfam08573
Location:699 → 759

SAE2; DNA repair protein endonuclease SAE2/CtIP C-terminus

pfam10482
Location:1 → 40

CtIP_N; tumor-suppressor protein CtIP N-terminal domain
XM_017025916.1 → XP_016881405.1 DNA endonuclease RBBP8 isoform X5
XM_006722521.2 → XP_006722584.1 DNA endonuclease RBBP8 isoform X1

See identical proteins and their annotated locations for XP_006722584.1

UniProtKB/Swiss-Prot

Q99708

UniProtKB/TrEMBL

A0A024RC34

Conserved Domains (2) summary

pfam08573
Location:797 → 857

SAE2; DNA repair protein endonuclease SAE2/CtIP C-terminus

pfam10482
Location:20 → 138

CtIP_N; tumor-suppressor protein CtIP N-terminal domain
XM_005258326.4 → XP_005258383.1 DNA endonuclease RBBP8 isoform X4

Conserved Domains (1) summary

pfam08573
Location:523 → 583

SAE2; DNA repair protein endonuclease SAE2/CtIP C-terminus