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Protein

Cell cycle and apoptosis regulator protein 2

Gene

CCAR2

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

Functioni

Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions. Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis. Inhibits SUV39H1 methyltransferase activity. As part of a histone H3-specific methyltransferase complex may mediate ligand-dependent transcriptional activation by nuclear hormone receptors. Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress. Regulates the circadian expression of the core clock components NR1D1 and ARNTL/BMAL1. Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:18235501, PubMed:18235502, PubMed:19131338, PubMed:19218236, PubMed:22446626, PubMed:23352644, PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed:20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed:24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (PubMed:25361978).15 Publications

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • enzyme inhibitor activity Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • RNA polymerase II core binding Source: UniProtKB

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB-KW
  • cellular response to heat Source: Reactome
  • mitochondrial fragmentation involved in apoptotic process Source: UniProtKB
  • mRNA processing Source: UniProtKB-KW
  • negative regulation of catalytic activity Source: GOC
  • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of DNA damage checkpoint Source: UniProtKB
  • regulation of cellular response to heat Source: Reactome
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of DNA-templated transcription, elongation Source: UniProtKB
  • regulation of protein stability Source: UniProtKB
  • response to UV Source: UniProtKB
  • rhythmic process Source: UniProtKB-KW
  • RNA splicing Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Metalloenzyme inhibitor, Repressor

Keywords - Biological processi

Apoptosis, Biological rhythms, Cell cycle, DNA damage, mRNA processing, mRNA splicing, Transcription, Transcription regulation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_264487. Regulation of HSF1-mediated heat shock response.

Names & Taxonomyi

Protein namesi
Recommended name:
Cell cycle and apoptosis regulator protein 2
Alternative name(s):
Cell division cycle and apoptosis regulator protein 2
DBIRD complex subunit KIAA1967
Deleted in breast cancer gene 1 protein
Short name:
DBC-1
Short name:
DBC.1
NET35
p30 DBC
Gene namesi
Name:CCAR2
Synonyms:DBC1, KIAA1967
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:23360. CCAR2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • DBIRD complex Source: UniProtKB
  • mitochondrial matrix Source: UniProtKB
  • nuclear chromatin Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi243 – 26422Missing : Abolishes binding to SIRT1. 1 PublicationAdd
BLAST
Mutagenesisi454 – 4541T → A: Significantly reduces association with SIRT1. Decreases sumoylation and the interaction of the sumoylated form with SIRT1. Inhibits CCAR2-PSIA3 interaction. Increases CCAR2-SENP1 interaction. Down-regulation of the signals related with the epithelial-mesenchymal transition of gastric cancer cells. 3 Publications
Mutagenesisi454 – 4541T → D: Significantly increases association with SIRT1 and induces p53 acetylation and apoptosis. Increases sumoylation and the interaction of the sumoylated form with SIRT1. Promotes CCAR2-PSIA3 interaction. Decreases CCAR2-SENP1 interaction. 2 Publications
Mutagenesisi591 – 5911K → R: Loss of sumoylation. 1 Publication
Mutagenesisi667 – 6671K → R: No effect on sumoylation. 1 Publication
Mutagenesisi839 – 8391K → R: No effect on sumoylation. 1 Publication

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

PharmGKBiPA134993792.

Polymorphism and mutation databases

BioMutaiKIAA1967.
DMDMi85701135.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 923923Cell cycle and apoptosis regulator protein 2PRO_0000050813Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei35 – 351Phosphothreonine2 Publications
Modified residuei112 – 1121N6-acetyllysine; by KAT81 Publication
Modified residuei124 – 1241Phosphoserine2 Publications
Modified residuei215 – 2151N6-acetyllysine; by KAT82 Publications
Modified residuei454 – 4541Phosphothreonine; by ATM, ATR and CK22 Publications
Modified residuei484 – 4841Phosphothreonine1 Publication
Modified residuei569 – 5691Phosphoserine1 Publication
Cross-linki591 – 591Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3)1 Publication
Modified residuei627 – 6271Phosphoserine1 Publication
Modified residuei675 – 6751Phosphoserine4 Publications
Modified residuei678 – 6781Phosphoserine5 Publications
Modified residuei681 – 6811Phosphoserine4 Publications
Modified residuei687 – 6871Phosphoserine1 Publication

Post-translational modificationi

ATM/ATR-mediated phosphorylation at Thr-454 upon DNA damage promotes binding to SIRT1. Phosphorylation at Thr-454 promotes its sumoylation by switching the binding partner of CCAR2 from SENP1 to PIAS3.2 Publications
Acetylation at Lys-112 and Lys-215 by KAT8 prevents inhibitory binding to SIRT1 and increases its deacetylase activity.1 Publication
Genotoxic stress induces its sumoylation and sumoylation promotes the SIRT1-CCAR2 interaction which in turn inhibits SIRT1-mediated deacetylation of p53/TP53. Sumoylation leads to transcriptional activation of p53/TP53 by sequestering SIRT1 from p53/TP53. Desumoylated by SENP1.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ8N163.
PaxDbiQ8N163.
PRIDEiQ8N163.

PTM databases

PhosphoSiteiQ8N163.

Expressioni

Tissue specificityi

Expressed in gastric carcinoma tissue and the expression gradually increases with the progression of the carcinoma (at protein level). Expressed ubiquitously in normal tissues. Expressed in 84 to 100% of neoplastic breast, lung, and colon tissues.2 Publications

Gene expression databases

BgeeiQ8N163.
CleanExiHS_DBC1.
ExpressionAtlasiQ8N163. baseline and differential.
GenevisibleiQ8N163. HS.

Organism-specific databases

HPAiCAB072827.
HPA019907.
HPA019943.

Interactioni

Subunit structurei

Component of the DBIRD complex. Interacts with ZNF326/ZIRD; the interaction is direct. Interacts (via N-terminus) with SIRT1, which inhibits the deacetylation of substrates. Interacts (via N-terminus) with SUV39H1; this interaction abolishes the interaction with SIRT1. Part of a complex composed at least of ASCL2, C11orf30/EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with NR1D1. Interacts (via N-terminus) with ESR1 and ESR2. Interacts (via N-terminus) with HDAC3 (via C-terminus). Interacts with HDAC1 and MED2F. Interacts with MCC. Interacts (via N-terminus) with NR1H2 and NR1H3 in a ligand-independent manner. Interacts with CSNK2A1. Interacts (via N-terminus) with p53/TP53. Interacts (via N-terminus) with BRCA1 (via the BRCT domains). Interacts (via N-terminus) with CHEK2 (via protein kinase domain). Interacts with PSEM3. Interacts (via N-terminus) with PSIA3 and SENP1. The sumoylated form shows a preferential interaction with SIRT1 as compared to its unmodified form.18 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MYCP011068EBI-355410,EBI-447544
ORFQ9Q2G45EBI-355410,EBI-6248094From a different organism.
SIRT1Q96EB69EBI-355410,EBI-1802965

Protein-protein interaction databases

BioGridi121775. 81 interactions.
DIPiDIP-38122N.
IntActiQ8N163. 38 interactions.
MINTiMINT-5003338.

Structurei

3D structure databases

ProteinModelPortaliQ8N163.
SMRiQ8N163. Positions 58-117.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni610 – 67061Interaction with MCC1 PublicationAdd
BLAST
Regioni704 – 923220Interaction with NR1D11 PublicationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili829 – 90981Sequence AnalysisAdd
BLAST

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiNOG307741.
GeneTreeiENSGT00530000063672.
HOVERGENiHBG081843.
InParanoidiQ8N163.
OMAiMSQFKRQ.
OrthoDBiEOG7CK365.
PhylomeDBiQ8N163.
TreeFamiTF316387.

Family and domain databases

InterProiIPR025224. CCAR1/CCAR2.
IPR028811. CCAR2.
IPR025954. DBC1/CARP1_inactive_NUDIX_dom.
IPR025223. S1-like_RNA-bd_dom.
[Graphical view]
PANTHERiPTHR14304. PTHR14304. 1 hit.
PTHR14304:SF12. PTHR14304:SF12. 1 hit.
PfamiPF14443. DBC1. 1 hit.
PF14444. S1-like. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N163-1) [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
MSQFKRQRIN PLPGGRNFSG TASTSLLGPP PGLLTPPVAT ELSQNARHLQ
60 70 80 90 100
GGEKQRVFTG IVTSLHDYFG VVDEEVFFQL SVVKGRLPQL GEKVLVKAAY
110 120 130 140 150
NPGQAVPWNA VKVQTLSNQP LLKSPAPPLL HVAALGQKQG ILGAQPQLIF
160 170 180 190 200
QPHRIPPLFP QKPLSLFQTS HTLHLSHLNR FPARGPHGRL DQGRSDDYDS
210 220 230 240 250
KKRKQRAGGE PWGAKKPRHD LPPYRVHLTP YTVDSPICDF LELQRRYRSL
260 270 280 290 300
LVPSDFLSVH LSWLSAFPLS QPFSLHHPSR IQVSSEKEAA PDAGAEPITA
310 320 330 340 350
DSDPAYSSKV LLLSSPGLEE LYRCCMLFVD DMAEPRETPE HPLKQIKFLL
360 370 380 390 400
GRKEEEAVLV GGEWSPSLDG LDPQADPQVL VRTAIRCAQA QTGIDLSGCT
410 420 430 440 450
KWWRFAEFQY LQPGPPRRLQ TVVVYLPDVW TIMPTLEEWE ALCQQKAAEA
460 470 480 490 500
APPTQEAQGE TEPTEQAPDA LEQAADTSRR NAETPEATTQ QETDTDLPEA
510 520 530 540 550
PPPPLEPAVI ARPGCVNLSL HGIVEDRRPK ERISFEVMVL AELFLEMLQR
560 570 580 590 600
DFGYRVYKML LSLPEKVVSP PEPEKEEAAK EEATKEEEAI KEEVVKEPKD
610 620 630 640 650
EAQNEGPATE SEAPLKEDGL LPKPLSSGGE EEEKPRGEAS EDLCEMALDP
660 670 680 690 700
ELLLLRDDGE EEFAGAKLED SEVRSVASNQ SEMEFSSLQD MPKELDPSAV
710 720 730 740 750
LPLDCLLAFV FFDANWCGYL HRRDLERILL TLGIRLSAEQ AKQLVSRVVT
760 770 780 790 800
QNICQYRSLQ YSRQEGLDGG LPEEVLFGNL DLLPPPGKST KPGAAPTEHK
810 820 830 840 850
ALVSHNGSLI NVGSLLQRAE QQDSGRLYLE NKIHTLELKL EESHNRFSAT
860 870 880 890 900
EVTNKTLAAE MQELRVRLAE AEETARTAER QKSQLQRLLQ ELRRRLTPLQ
910 920
LEIQRVVEKA DSWVEKEEPA PSN
Length:923
Mass (Da):102,902
Last modified:January 24, 2006 - v2
Checksum:i1733934377E35D21
GO
Isoform 2 (identifier: Q8N163-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     910-923: ADSWVEKEEPAPSN → VRWGWTRRQHSSFP

Note: No experimental confirmation available.
Show »
Length:923
Mass (Da):103,143
Checksum:i3C1BB0DE06A20926
GO

Sequence cautioni

The sequence AAG02472.1 differs from that shown. Reason: Frameshift at positions 610, 622, 794 and 810. Curated
The sequence BAB85553.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti47 – 471R → S in CAD38866 (PubMed:17974005).Curated
Sequence conflicti47 – 471R → S in CAD39017 (PubMed:17974005).Curated
Sequence conflicti850 – 8501T → S in AAH65495 (PubMed:15489334).Curated
Sequence conflicti908 – 9081E → G in CAD38866 (PubMed:17974005).Curated
Sequence conflicti908 – 9081E → G in CAD39017 (PubMed:17974005).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei910 – 92314ADSWV…PAPSN → VRWGWTRRQHSSFP in isoform 2. 1 PublicationVSP_017092Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK096547 mRNA. No translation available.
AK314535 mRNA. Translation: BAG37126.1.
AL834162 mRNA. Translation: CAD38866.1.
AL834351 mRNA. Translation: CAD39016.1.
AL834352 mRNA. Translation: CAD39017.1.
BX640952 mRNA. Translation: CAE45976.1.
AL137523 mRNA. Translation: CAB70788.3.
AC037459 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63658.1.
CH471080 Genomic DNA. Translation: EAW63661.1.
BC018269 mRNA. Translation: AAH18269.2.
BC065495 mRNA. Translation: AAH65495.1.
AB075847 mRNA. Translation: BAB85553.1. Different initiation.
AF293335 mRNA. Translation: AAG02472.1. Frameshift.
CCDSiCCDS34863.1. [Q8N163-1]
PIRiT46368.
RefSeqiNP_066997.3. NM_021174.5. [Q8N163-1]
UniGeneiHs.744848.

Genome annotation databases

EnsembliENST00000308511; ENSP00000310670; ENSG00000158941. [Q8N163-1]
ENST00000389279; ENSP00000373930; ENSG00000158941. [Q8N163-1]
GeneIDi57805.
KEGGihsa:57805.
UCSCiuc003xch.3. human. [Q8N163-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK096547 mRNA. No translation available.
AK314535 mRNA. Translation: BAG37126.1.
AL834162 mRNA. Translation: CAD38866.1.
AL834351 mRNA. Translation: CAD39016.1.
AL834352 mRNA. Translation: CAD39017.1.
BX640952 mRNA. Translation: CAE45976.1.
AL137523 mRNA. Translation: CAB70788.3.
AC037459 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63658.1.
CH471080 Genomic DNA. Translation: EAW63661.1.
BC018269 mRNA. Translation: AAH18269.2.
BC065495 mRNA. Translation: AAH65495.1.
AB075847 mRNA. Translation: BAB85553.1. Different initiation.
AF293335 mRNA. Translation: AAG02472.1. Frameshift.
CCDSiCCDS34863.1. [Q8N163-1]
PIRiT46368.
RefSeqiNP_066997.3. NM_021174.5. [Q8N163-1]
UniGeneiHs.744848.

3D structure databases

ProteinModelPortaliQ8N163.
SMRiQ8N163. Positions 58-117.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121775. 81 interactions.
DIPiDIP-38122N.
IntActiQ8N163. 38 interactions.
MINTiMINT-5003338.

PTM databases

PhosphoSiteiQ8N163.

Polymorphism and mutation databases

BioMutaiKIAA1967.
DMDMi85701135.

Proteomic databases

MaxQBiQ8N163.
PaxDbiQ8N163.
PRIDEiQ8N163.

Protocols and materials databases

DNASUi57805.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308511; ENSP00000310670; ENSG00000158941. [Q8N163-1]
ENST00000389279; ENSP00000373930; ENSG00000158941. [Q8N163-1]
GeneIDi57805.
KEGGihsa:57805.
UCSCiuc003xch.3. human. [Q8N163-1]

Organism-specific databases

CTDi57805.
GeneCardsiGC08P022463.
HGNCiHGNC:23360. CCAR2.
HPAiCAB072827.
HPA019907.
HPA019943.
MIMi607359. gene.
neXtProtiNX_Q8N163.
PharmGKBiPA134993792.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG307741.
GeneTreeiENSGT00530000063672.
HOVERGENiHBG081843.
InParanoidiQ8N163.
OMAiMSQFKRQ.
OrthoDBiEOG7CK365.
PhylomeDBiQ8N163.
TreeFamiTF316387.

Enzyme and pathway databases

ReactomeiREACT_264487. Regulation of HSF1-mediated heat shock response.

Miscellaneous databases

ChiTaRSiCCAR2. human.
GeneWikiiKIAA1967.
GenomeRNAii57805.
NextBioi64756.
PROiQ8N163.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N163.
CleanExiHS_DBC1.
ExpressionAtlasiQ8N163. baseline and differential.
GenevisibleiQ8N163. HS.

Family and domain databases

InterProiIPR025224. CCAR1/CCAR2.
IPR028811. CCAR2.
IPR025954. DBC1/CARP1_inactive_NUDIX_dom.
IPR025223. S1-like_RNA-bd_dom.
[Graphical view]
PANTHERiPTHR14304. PTHR14304. 1 hit.
PTHR14304:SF12. PTHR14304:SF12. 1 hit.
PfamiPF14443. DBC1. 1 hit.
PF14444. S1-like. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Placenta.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Amygdala and Testis.
  3. "DNA sequence and analysis of human chromosome 8."
    Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
    , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
    Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Lymph and Placenta.
  6. "Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins."
    Nagase T., Kikuno R., Ohara O.
    DNA Res. 8:319-327(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 133-923 (ISOFORM 2).
    Tissue: Brain.
  7. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 439-845, TISSUE SPECIFICITY.
  8. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-675; SER-678 AND SER-681, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  9. "DBC1 is a negative regulator of SIRT1."
    Kim J.-E., Chen J., Lou Z.
    Nature 451:583-586(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS SIRT1 INHIBITOR, INTERACTION WITH SIRT1, MUTAGENESIS OF 243-LEU--LEU-264, IDENTIFICATION BY MASS SPECTROMETRY.
  10. "Negative regulation of the deacetylase SIRT1 by DBC1."
    Zhao W., Kruse J.-P., Tang Y., Jung S.Y., Qin J., Gu W.
    Nature 451:587-590(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN APOPTOSIS, INTERACTION WITH SIRT1.
  11. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-675; SER-678 AND SER-681, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  12. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  13. "Identification and characterization of a novel nuclear protein complex involved in nuclear hormone receptor-mediated gene regulation."
    Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A., Samuels H.H.
    J. Biol. Chem. 284:7542-7552(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN TRANSCRIPTIONAL REGULATION, IDENTIFICATION IN A COMPLEX WITH HCFC1; MKI67; C11ORF30; MATR3; HSPA8; TUBB2A; ZNF335; ASCL2; RBBP5 AND WDR5.
  14. "Inhibition of SUV39H1 methyltransferase activity by DBC1."
    Li Z., Chen L., Kabra N., Wang C., Fang J., Chen J.
    J. Biol. Chem. 284:10361-10366(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS SUV39H1 INHIBITOR, INTERACTION WITH SUV39H1.
  15. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-35; SER-675; SER-678 AND SER-681, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  16. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-215, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  17. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ESR1 AND ESR2.
  18. Cited for: FUNCTION, INTERACTION WITH BRCA1, SUBCELLULAR LOCATION.
  19. "HDAC3 is negatively regulated by the nuclear protein DBC1."
    Chini C.C., Escande C., Nin V., Chini E.N.
    J. Biol. Chem. 285:40830-40837(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HDAC1; HDAC3; SIRT1 AND MEF2D.
  20. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-35; SER-124; SER-675; SER-678 AND SER-681, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  21. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  22. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-678, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. "DBC1 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage."
    Zannini L., Buscemi G., Kim J.E., Fontanella E., Delia D.
    J. Mol. Cell Biol. 4:294-303(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-454, MUTAGENESIS OF THR-454, INTERACTION WITH SIRT1.
  24. "DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation."
    Close P., East P., Dirac-Svejstrup A.B., Hartmann H., Heron M., Maslen S., Chariot A., Soding J., Skehel M., Svejstrup J.Q.
    Nature 484:386-389(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN THE DBIRD COMPLEX, FUNCTION, INTERACTION WITH ZNF326.
  25. "DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbalpha."
    Chini C.C., Escande C., Nin V., Chini E.N.
    Biochem. J. 451:453-461(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH NR1D1.
  26. "Deleted in breast cancer-1 (DBC-1) in the interface between metabolism, aging and cancer."
    Chini E.N., Chini C.C., Nin V., Escande C.
    Biosci. Rep. 33:0-0(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  27. "Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of breast cancer cells through impaired responses to UV-induced DNA damage."
    Kim W., Kim J.E.
    Cancer Lett. 333:180-186(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SIRT1.
  28. "A functional proteomics perspective of dbc1 as a regulator of transcription."
    Joshi P., Quach O.L., Giguere S.S., Cristea I.M.
    J. Proteomics. Bioinform. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  29. "hMOF acetylation of DBC1/CCAR2 prevents binding and inhibition of SirT1."
    Zheng H., Yang L., Peng L., Izumi V., Koomen J., Seto E., Chen J.
    Mol. Cell. Biol. 33:4960-4970(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT LYS-112 AND LYS-215, INTERACTION WITH SIRT1.
  30. "Deleted in breast cancer 1 (DBC1) protein regulates hepatic gluconeogenesis."
    Nin V., Chini C.C., Escande C., Capellini V., Chini E.N.
    J. Biol. Chem. 289:5518-5527(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  31. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-484; SER-569; SER-627 AND SER-687, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  32. "Modification of DBC1 by SUMO2/3 is crucial for p53-mediated apoptosis in response to DNA damage."
    Park J.H., Lee S.W., Yang S.W., Yoo H.M., Park J.M., Seong M.W., Ka S.H., Oh K.H., Jeon Y.J., Chung C.H.
    Nat. Commun. 5:5483-5483(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION AT LYS-591, DESUMOYLATION, PHOSPHORYLATION AT THR-454, MUTAGENESIS OF THR-454; LYS-591; LYS-667 AND LYS-839, INTERACTION WITH SIRT1; PSIA3 AND SENP1.
  33. "Chk2 and REGgamma-dependent DBC1 regulation in DNA damage induced apoptosis."
    Magni M., Ruscica V., Buscemi G., Kim J.E., Nachimuthu B.T., Fontanella E., Delia D., Zannini L.
    Nucleic Acids Res. 42:13150-13160(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CHEK2 AND PSEM3.
  34. "DBC1 functions as a tumor suppressor by regulating p53 stability."
    Qin B., Minter-Dykhouse K., Yu J., Zhang J., Liu T., Zhang H., Lee S., Kim J., Wang L., Lou Z.
    Cell Rep. 10:1324-1334(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TP53.
  35. "MCC inhibits beta-catenin transcriptional activity by sequestering DBC1 in the cytoplasm."
    Pangon L., Mladenova D., Watkins L., Van Kralingen C., Currey N., Al-Sohaily S., Lecine P., Borg J.P., Kohonen-Corish M.R.
    Int. J. Cancer 136:55-64(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MCC.
  36. "CK2alpha phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients."
    Bae J.S., Park S.H., Kim K.M., Kwon K.S., Kim C.Y., Lee H.K., Park B.H., Park H.S., Lee H., Moon W.S., Chung M.J., Sylvester K.G., Jang K.Y.
    Int. J. Cancer 136:797-809(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-454, MUTAGENESIS OF THR-454, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH CSNK2A1.
  37. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NR1H2 AND NR1H3.

Entry informationi

Entry nameiCCAR2_HUMAN
AccessioniPrimary (citable) accession number: Q8N163
Secondary accession number(s): A6NL03
, B2RB79, D3DSR6, Q6P0Q9, Q8N3G7, Q8N8M1, Q8TF34, Q9H9Q9, Q9HD12, Q9NT55
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: January 24, 2006
Last modified: June 24, 2015
This is version 128 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.