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Protein

DNA endonuclease RBBP8

Gene

RBBP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (PubMed:10764811, PubMed:10910365, PubMed:15485915, PubMed:16581787, PubMed:16818604, PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:20829486). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity).By similarity10 Publications

GO - Molecular functioni

  • damaged DNA binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • RNA polymerase II transcription corepressor activity Source: BHF-UCL
  • single-stranded DNA endodeoxyribonuclease activity Source: UniProtKB

GO - Biological processi

  • blastocyst hatching Source: Ensembl
  • cell cycle checkpoint Source: ProtInc
  • cell division Source: UniProtKB-KW
  • DNA double-strand break processing Source: Reactome
  • DNA double-strand break processing involved in repair via single-strand annealing Source: UniProtKB
  • DNA repair Source: ProtInc
  • DNA replication Source: Reactome
  • DNA synthesis involved in DNA repair Source: Reactome
  • double-strand break repair via homologous recombination Source: UniProtKB
  • G1/S transition of mitotic cell cycle Source: Ensembl
  • G2 DNA damage checkpoint Source: UniProtKB
  • meiotic cell cycle Source: UniProtKB-KW
  • nucleotide-excision repair Source: CACAO
  • regulation of signal transduction by p53 class mediator Source: Reactome
  • regulation of transcription from RNA polymerase II promoter Source: ProtInc
  • response to estradiol Source: Ensembl
  • strand displacement Source: Reactome

Keywordsi

Molecular functionDNA-binding, Endonuclease, Hydrolase, Nuclease
Biological processCell cycle, Cell division, DNA damage, DNA repair, Meiosis, Mitosis

Enzyme and pathway databases

ReactomeiR-HSA-5685938. HDR through Single Strand Annealing (SSA).
R-HSA-5685939. HDR through MMEJ (alt-NHEJ).
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-HSA-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-HSA-5693579. Homologous DNA Pairing and Strand Exchange.
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-69473. G2/M DNA damage checkpoint.
R-HSA-8953750. Transcriptional Regulation by E2F6.
R-HSA-912446. Meiotic recombination.
SIGNORiQ99708.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA endonuclease RBBP8 (EC:3.1.-.-)
Alternative name(s):
CtBP-interacting protein
Short name:
CtIP
Retinoblastoma-binding protein 8
Short name:
RBBP-8
Retinoblastoma-interacting protein and myosin-like
Short name:
RIM
Sporulation in the absence of SPO11 protein 2 homolog
Short name:
SAE2
Gene namesi
Name:RBBP8
Synonyms:CTIP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000101773.16.
HGNCiHGNC:9891. RBBP8.

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

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Seckel syndrome 2 (SCKL2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation.
See also OMIM:606744
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075824100R → W in SCKL2. 1 PublicationCorresponds to variant dbSNP:rs373804633Ensembl.1
Jawad syndrome (JWDS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by congenital microcephaly, moderately severe mental retardation, and symmetrical digital anomalies. Digital malformations of variable degree include hallux valgus, syndactyly of toes 4 and 5, short fifth fingers, single flexion crease of fifth fingers, polydactyly and synpolydactyly.
See also OMIM:251255
Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk (PubMed:21799032). Associated with sensitivity to tamoxifen in certain breast cancer cell lines (PubMed:18171986).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi31H → A: No effect on RPA focus formation on DNA damage. 1 Publication1
Mutagenesisi35V → A: No effect on RPA focus formation on DNA damage. 1 Publication1
Mutagenesisi41K → A: No effect on RPA focus formation on DNA damage. 1 Publication1
Mutagenesisi45L → A: No effect on RPA focus formation on DNA damage. 1 Publication1
Mutagenesisi62K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-78; R-115; R-132 and R-133. 1 Publication1
Mutagenesisi78K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-115; R-132 and R-133. 1 Publication1
Mutagenesisi115K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-132 and R-133. 1 Publication1
Mutagenesisi132K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115 and R-133. 1 Publication1
Mutagenesisi133K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115 and R-132. 1 Publication1
Mutagenesisi179K → A: No effect on FZR1-binding. 1 Publication1
Mutagenesisi276S → A: No effect on PIN1-binding. Impaired PIN1-binding, partially decreased CUL3/KLHL15-mediated proteasomal degradation, no effect on BRCA1-, MRE11-, nor on KLHL15-binding; when associated with A-315. 2 Publications1
Mutagenesisi315T → A: Decreased PIN1-binding. Impaired PIN1-binding, partially decreased CUL3/KLHL15-mediated proteasomal degradation, no effect on BRCA1-, MRE11-, nor on KLHL15-binding; when associated with A-276. 2 Publications1
Mutagenesisi327S → A: Abolishes BRCA1 interaction and ubiquitination. No activation of CHEK1 after DNA damage. 2 Publications1
Mutagenesisi404K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-572; R-578; R-640; R-759; R-760 and R-782. 1 Publication1
Mutagenesisi432K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-526 and R-604. 1 Publication1
Mutagenesisi467K → A: Impaired FZR1-binding and APC/C-mediated polyubiquitination. Increased stability. No effect on MRE11-binding, nor on CUL3/KLHL15-mediated proteasomal degradation. No effect on DNA-en resection activity. 2 Publications1
Mutagenesisi513K → A: Abolishes damage recruitment capability. 1 Publication1
Mutagenesisi515K → A: Abolishes damage recruitment capability. 1 Publication1
Mutagenesisi526K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-432 and R-604. 1 Publication1
Mutagenesisi572K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-578; R-640; R-759; R-760 and R-782. 1 Publication1
Mutagenesisi578K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-640; R-759; R-760 and R-782. 1 Publication1
Mutagenesisi604K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-432 and R-526. 1 Publication1
Mutagenesisi640K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-759; R-760 and R-782. 1 Publication1
Mutagenesisi664S → A: Abrogates dissociation of BRCA1. 1 Publication1
Mutagenesisi745S → A: Abrogates dissociation of BRCA1. 1 Publication1
Mutagenesisi759K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-760 and R-782. 1 Publication1
Mutagenesisi760K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759 and R-782. 1 Publication1
Mutagenesisi782K → R in K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759 and R-760. 1 Publication1
Mutagenesisi839R → A: No effect on CUL3/KLHL15-mediated proteasomal degradation. 1 Publication1
Mutagenesisi840F → A: Decreased CUL3/KLHL15-mediated proteasomal degradation. 1 Publication1
Mutagenesisi842Y → A: Decreased interaction with KLHL15, decreased polyubiquitination and CUL3/KLHL15-mediated proteasomal degradation. No effect on DNA-end resection activity. 1 Publication1
Mutagenesisi842Y → F: No effect on KLHL15-binding, nor on CUL3/KLHL15-mediated proteasomal degradation. 1 Publication1
Mutagenesisi847T → A: Impairs DNA resection. 1 Publication1
Mutagenesisi847T → E: Mimics constitutive phosphorylation. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism, Mental retardation

Organism-specific databases

DisGeNETi5932.
GeneReviewsiRBBP8.
MalaCardsiRBBP8.
MIMi251255. phenotype.
606744. phenotype.
OpenTargetsiENSG00000101773.
Orphaneti313795. Jawad syndrome.
808. Seckel syndrome.
PharmGKBiPA34255.

Polymorphism and mutation databases

BioMutaiRBBP8.
DMDMi116242745.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000971791 – 897DNA endonuclease RBBP8Add BLAST897

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki62Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki115Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei233PhosphoserineCombined sources1
Modified residuei276Phosphoserine1 Publication1
Modified residuei315Phosphothreonine; by CDK2Combined sources1 Publication1
Modified residuei326Phosphoserine1 Publication1
Modified residuei327PhosphoserineCombined sources1 Publication1
Modified residuei349Phosphoserine1 Publication1
Cross-linki360Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki378Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei379PhosphoserineCombined sources1
Cross-linki396Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki404Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki410Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei432N6-acetyllysine1 Publication1
Cross-linki438Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki449Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei526N6-acetyllysine; alternate1 Publication1
Cross-linki526Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki530Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki572Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki578Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei604N6-acetyllysine; alternate1 Publication1
Cross-linki604Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki613Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki638Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki640Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei664Phosphoserine; by ATM1 Publication1
Cross-linki676Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei679Phosphoserine1 Publication1
Cross-linki719Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei723PhosphoserineCombined sources1
Modified residuei745Phosphoserine; by ATM1 Publication1
Cross-linki782Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei847Phosphothreonine; by CDK11 Publication1
Cross-linki869Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Acetylated. Deacetylation by SIRT6 upon DNA damage promotes DNA end resection.1 Publication
Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Phosphorylation at Thr-847 by CDK1 is essential for the recruitment to DNA and the DNA repair function. Phosphorylated on Ser-327 as cells enter G2 phase. This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control. Phosphorylation at Thr-315, probably catalyzed by CDK2, is required for PIN1-binding, while phosphorylation at Ser-276 serves as a PIN1 isomerization site. Phosphorylation at Thr-315 is cell-cycle dependent. It steadily increases during S phase, peaks at late S/G2 phase, and drops at G1 (PubMed:23623683).5 Publications
Ubiquitinated (PubMed:14654780, PubMed:16818604, PubMed:27561354). Ubiquitination at multiple sites by BRCA1 (via its N-terminal RING domain) does not lead to its proteosomal degradation but instead the ubiquitinated RBBP8 binds to chromatin following DNA damage and may play a role in G2/M checkpoint control (PubMed:16818604). Ubiquitinated by RNF138 at its N-terminus (PubMed:26502057). Ubiquitinated through 'Lys-48' by the E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation (PubMed:27561354). Ubiquitinated by the E3 FZR1/APC/C complex; this modification leads to proteasomal degradation (PubMed:25349192).5 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99708.
MaxQBiQ99708.
PaxDbiQ99708.
PeptideAtlasiQ99708.
PRIDEiQ99708.

PTM databases

iPTMnetiQ99708.
PhosphoSitePlusiQ99708.

Expressioni

Tissue specificityi

Expressed in ER-positive breast cancer lines, but tends to be down-regulated ER-negative cells (at protein level).1 Publication

Inductioni

Expression is cell-cycle regulated. Levels increase as dividing cells traverse the G1/S boundary (PubMed:18171986). The protein is degraded by the proteasome pathway during mitotic exit. Also degraded in response to DNA damage in G2 cells; this degradation is mediated by the E3 FZR1/APC/C complex (PubMed:25349192).2 Publications

Gene expression databases

BgeeiENSG00000101773.
CleanExiHS_RBBP8.
ExpressionAtlasiQ99708. baseline and differential.
GenevisibleiQ99708. HS.

Organism-specific databases

HPAiHPA039890.
HPA052946.

Interactioni

Subunit structurei

Homodimer; dimerizes via the coiled coil domain (PubMed:15084581). Interacts (via the PXDLS motif) with CTBP1; the interaction is disrupted via binding of the adenovirus E1A to CTBP1 (PubMed:9535825). Component of the BRCA1-RBBP8 complex. Interacts (the Ser-327 phosphorylated form) with BRCA1 (via the C-terminal BRCA1 domains): the interaction occurs in the G2 phase, ubiquitinates RBBP8 and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage (PubMed:10764811, PubMed:15485915, PubMed:16818604, PubMed:17965729, PubMed:23623683). Interacts with RB1 (PubMed:9721205). Interacts with the MRN complex. Interacts directly with MRE11; the interaction is required for efficient homologous recombination (HR) and regulation of the MRN complex (PubMed:19759395, PubMed:23623683). Interacts directly with RAD50 (PubMed:19759395). Interacts directly with NBN (PubMed:19759395). Interacts with SIRT6; the interaction deacetylates RBBP8 upon DNA damage (PubMed:20829486). Interacts with LM04 (via the LIM zinc-binding 1 domain) (PubMed:11751867). Interacts with SIAH1 (PubMed:14654780). Interacts with RNF138 (PubMed:26502057). Interacts with EXD2 (PubMed:26807646). Interacts with CUL3 and KLHL15; this interaction leads to RBBP8 proteasomal degradation (PubMed:27561354). Directly interacts with PIN1; this interaction depends upon RBBP8 phosphorylation, predominantly at Thr-315 (PubMed:23623683). Interacts with FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal degradation (PubMed:25349192).16 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi111867. 61 interactors.
CORUMiQ99708.
DIPiDIP-24244N.
ELMiQ99708.
IntActiQ99708. 42 interactors.
MINTiMINT-102295.
STRINGi9606.ENSP00000323050.

Structurei

Secondary structure

1897
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi18 – 50Combined sources33
Beta strandi648 – 650Combined sources3
Helixi651 – 653Combined sources3
Turni662 – 666Combined sources5
Beta strandi677 – 679Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L4ZNMR-A641-685[»]
4D2HX-ray1.90A/B/C/D/E/F/G/H18-52[»]
ProteinModelPortaliQ99708.
SMRiQ99708.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99708.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni22 – 45Essential for binding to the MRN complex and for RPA focus formation on DNA damageAdd BLAST24
Regioni509 – 557Damage-recruitment motifAdd BLAST49

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili28 – 157Sequence analysisAdd BLAST130

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi490 – 494PXDLS motif5
Motifi840 – 842KLHL15-binding1 Publication3

Domaini

The PXDLS motif binds to a cleft in CtBP proteins.
The damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage.

Sequence similaritiesi

Belongs to the COM1/SAE2/CtIP family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IJ39. Eukaryota.
ENOG410ZSBE. LUCA.
GeneTreeiENSGT00530000063835.
HOGENOMiHOG000293331.
HOVERGENiHBG057046.
InParanoidiQ99708.
KOiK20773.
PhylomeDBiQ99708.
TreeFamiTF106469.

Family and domain databases

InterProiView protein in InterPro
IPR019518. CtIP_N.
IPR013882. Ctp1_C.
IPR033594. RBBP8.
IPR033316. RBBP8-like.
PANTHERiPTHR15107. PTHR15107. 1 hit.
PTHR15107:SF4. PTHR15107:SF4. 1 hit.
PfamiView protein in Pfam
PF10482. CtIP_N. 1 hit.
PF08573. SAE2. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99708-1) [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
MNISGSSCGS PNSADTSSDF KDLWTKLKEC HDREVQGLQV KVTKLKQERI
60 70 80 90 100
LDAQRLEEFF TKNQQLREQQ KVLHETIKVL EDRLRAGLCD RCAVTEEHMR
110 120 130 140 150
KKQQEFENIR QQNLKLITEL MNERNTLQEE NKKLSEQLQQ KIENDQQHQA
160 170 180 190 200
AELECEEDVI PDSPITAFSF SGVNRLRRKE NPHVRYIEQT HTKLEHSVCA
210 220 230 240 250
NEMRKVSKSS THPQHNPNEN EILVADTYDQ SQSPMAKAHG TSSYTPDKSS
260 270 280 290 300
FNLATVVAET LGLGVQEESE TQGPMSPLGD ELYHCLEGNH KKQPFEESTR
310 320 330 340 350
NTEDSLRFSD STSKTPPQEE LPTRVSSPVF GATSSIKSGL DLNTSLSPSL
360 370 380 390 400
LQPGKKKHLK TLPFSNTCIS RLEKTRSKSE DSALFTHHSL GSEVNKIIIQ
410 420 430 440 450
SSNKQILINK NISESLGEQN RTEYGKDSNT DKHLEPLKSL GGRTSKRKKT
460 470 480 490 500
EEESEHEVSC PQASFDKENA FPFPMDNQFS MNGDCVMDKP LDLSDRFSAI
510 520 530 540 550
QRQEKSQGSE TSKNKFRQVT LYEALKTIPK GFSSSRKASD GNCTLPKDSP
560 570 580 590 600
GEPCSQECII LQPLNKCSPD NKPSLQIKEE NAVFKIPLRP RESLETENVL
610 620 630 640 650
DDIKSAGSHE PIKIQTRSDH GGCELASVLQ LNPCRTGKIK SLQNNQDVSF
660 670 680 690 700
ENIQWSIDPG ADLSQYKMDV TVIDTKDGSQ SKLGGETVDM DCTLVSETVL
710 720 730 740 750
LKMKKQEQKG EKSSNEERKM NDSLEDMFDR TTHEEYESCL ADSFSQAADE
760 770 780 790 800
EEELSTATKK LHTHGDKQDK VKQKAFVEPY FKGDERETSL QNFPHIEVVR
810 820 830 840 850
KKEERRKLLG HTCKECEIYY ADMPAEEREK KLASCSRHRF RYIPPNTPEN
860 870 880 890
FWEVGFPSTQ TCMERGYIKE DLDPCPRPKR RQPYNAIFSP KGKEQKT
Length:897
Mass (Da):101,942
Last modified:October 17, 2006 - v2
Checksum:iE028DE56DE55C0F2
GO
Isoform 2 (identifier: Q99708-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     714-714: S → SMLFYI

Show »
Length:902
Mass (Da):102,610
Checksum:i43DEA11A0349322B
GO
Isoform 3 (identifier: Q99708-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     786-867: RETSLQNFPH...STQTCMERGY → SIMQICQQKK...QKARSRRHRR
     868-897: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:867
Mass (Da):98,434
Checksum:iA8CFDB72587619E3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4S → L in AAC14371 (PubMed:9721205).Curated1
Sequence conflicti74H → Q in BX648221 (PubMed:17974005).Curated1
Sequence conflicti92C → Y in BAF85170 (PubMed:14702039).Curated1
Sequence conflicti123E → G in BAF85170 (PubMed:14702039).Curated1
Sequence conflicti341D → G in BX648221 (PubMed:17974005).Curated1
Sequence conflicti515K → R in BX648221 (PubMed:17974005).Curated1
Sequence conflicti521L → P in BAF85170 (PubMed:14702039).Curated1
Sequence conflicti642L → P in BX648221 (PubMed:17974005).Curated1
Isoform 3 (identifier: Q99708-3)
Sequence conflicti862S → G in BX648221 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075824100R → W in SCKL2. 1 PublicationCorresponds to variant dbSNP:rs373804633Ensembl.1
Natural variantiVAR_051308357K → N. Corresponds to variant dbSNP:rs34678569Ensembl.1
Natural variantiVAR_028308387H → Y. Corresponds to variant dbSNP:rs1804732Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043220714S → SMLFYI in isoform 2. 1 Publication1
Alternative sequenceiVSP_045247786 – 867RETSL…MERGY → SIMQICQQKKEKRNWLPAQD TDSATFHPTHQRIFGKLVFL PLRLVWKEVILRKILILVLV QKDVSLTTQYFLQKARSRRH RR in isoform 3. 1 PublicationAdd BLAST82
Alternative sequenceiVSP_045248868 – 897Missing in isoform 3. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043431 mRNA. Translation: AAC34368.1.
U72066 mRNA. Translation: AAC14371.1.
AK292481 mRNA. Translation: BAF85170.1.
BX648221 mRNA. No translation available.
AC091147 Genomic DNA. No translation available.
AC106033 Genomic DNA. No translation available.
CH471088 Genomic DNA. Translation: EAX01144.1.
BC030590 mRNA. Translation: AAH30590.1.
CCDSiCCDS11874.1. [Q99708-3]
CCDS11875.1. [Q99708-1]
RefSeqiNP_002885.1. NM_002894.2. [Q99708-1]
NP_976036.1. NM_203291.1. [Q99708-1]
NP_976037.1. NM_203292.1. [Q99708-3]
XP_006722582.1. XM_006722519.2. [Q99708-1]
XP_006722583.1. XM_006722520.2. [Q99708-1]
XP_006722584.1. XM_006722521.2. [Q99708-1]
XP_011524434.1. XM_011526132.2. [Q99708-1]
UniGeneiHs.546282.

Genome annotation databases

EnsembliENST00000327155; ENSP00000323050; ENSG00000101773. [Q99708-1]
ENST00000399722; ENSP00000382628; ENSG00000101773. [Q99708-1]
ENST00000399725; ENSP00000382630; ENSG00000101773. [Q99708-3]
GeneIDi5932.
KEGGihsa:5932.
UCSCiuc002ktw.4. human. [Q99708-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCTIP_HUMAN
AccessioniPrimary (citable) accession number: Q99708
Secondary accession number(s): A6NKN2
, A8K8W6, E7ETY1, O75371, Q8NHQ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 17, 2006
Last modified: November 22, 2017
This is version 167 of the entry and version 2 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. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families