Q13352 (CENPR_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 86.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Centromere protein R Short name=CENP-R Alternative name(s): Beta-3-endonexin Integrin beta-3-binding protein Nuclear receptor-interacting factor 3 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 177 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Transcription coregulator that can have both coactivator and corepressor functions. Isoform 1, but not other isoforms, is involved in the coactivation of nuclear receptors for retinoid X (RXRs) and thyroid hormone (TRs) in a ligand-dependent fashion. In contrast, it does not coactivate nuclear receptors for retinoic acid, vitamin D, progesterone receptor, nor glucocorticoid. Acts as a coactivator for estrogen receptor alpha. Acts as a transcriptional corepressor via its interaction with the NFKB1 NF-kappa-B subunit, possibly by interfering with the transactivation domain of NFKB1. Induces apoptosis in breast cancer cells, but not in other cancer cells, via a caspase-2 mediated pathway that involves mitochondrial membrane permeabilization but does not require other caspases. May also act as an inhibitor of cyclin A-associated kinase. Also acts a component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Ref.2 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 |
| Subunit structure | Homodimer; mediated by the coiled coil domain. Isoform 3, but not other isoforms, interacts with the cytoplasmic tail of integrin ITGB3. The relevance of the interaction with ITGB3 is however uncertain, since isoform 3 is mainly nuclear. Interacts with CCNA2 and MTA1. Interacts with NFKB1 NF-kappa-B subunit. Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and MLF1IP/CENPU. Ref.1 Ref.2 Ref.8 Ref.9 Ref.10 Ref.12 |
| Subcellular location | Isoform 1: Nucleus. Chromosome › centromere Ref.2 Ref.6 Ref.7 Ref.9 Ref.10 Ref.13. Isoform 2: Nucleus Ref.2 Ref.6 Ref.7 Ref.9 Ref.10 Ref.13. Isoform 3: Nucleus. Cytoplasm. Note: Isoform 3 is predominantly nuclear and weakly cytoplasmic. Ref.2 Ref.6 Ref.7 Ref.9 Ref.10 Ref.13 |
| Tissue specificity | Widely expressed. Expressed in spleen, thymus, prostate, ovary, small intestine and white blood cells. Highly expressed in testis and colon. Isoform 4 is expressed in platelets, lymphocytes and granulocytes. Ref.1 Ref.6 |
| Induction | By estrogen. Ref.12 |
| Domain | The DD1 domain (also called RepD1 domain) mediates the corepressor function and is essential in the triggering of apoptosis. Ref.11 Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, a motif known to be important for the association with nuclear receptors. Such motif, which is required for an efficient association with nuclear receptors, is however not essential. Ref.11 Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, which is essential for the association with nuclear receptors. Ref.11 |
| Sequence caution | The sequence AAH14385.1 differs from that shown. Reason: Erroneous initiation. |
Ontologies
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q13352-1) 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. | ||||||
| Isoform 2 (identifier: Q13352-2) Also known as: Long; EnL; En-L; The sequence of this isoform differs from the canonical sequence as follows: 162-177: ASRHLDSYEFLKAILN → GQPQMSQPL | ||||||
| Isoform 3 (identifier: Q13352-3) Also known as: Short; EnS; En-S; The sequence of this isoform differs from the canonical sequence as follows: 112-177: Missing. | ||||||
| Isoform 4 (identifier: Q13352-4) The sequence of this isoform differs from the canonical sequence as follows: 63-177: Missing. | ||||||
| Isoform 5 (identifier: Q13352-5) The sequence of this isoform differs from the canonical sequence as follows: 1-2: MP → MPFAPVAQAGVQWHDFRSLQHLLPAFKRFSCLSLGSSWDYS | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 177 | 177 | Centromere protein R | PRO_0000057949 | |||||
Regions | |||||||||
| Region | 20 – 50 | 31 | DD1 | ||||||
| Coiled coil | 83 – 113 | 31 | Potential | ||||||
| Motif | 9 – 13 | 5 | LXXLL motif | ||||||
| Motif | 63 – 66 | 4 | Nuclear localization signal | ||||||
| Motif | 172 – 176 | 5 | LXXIL motif | ||||||
Amino acid modifications | |||||||||
| Modified residue | 17 | 1 | Phosphoserine Ref.15 Ref.16 | ||||||
| Modified residue | 28 | 1 | Phosphoserine Probable | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 2 | 2 | MP → MPFAPVAQAGVQWHDFRSLQ HLLPAFKRFSCLSLGSSWDY S in isoform 5. | VSP_010831 | |||||
| Alternative sequence | 63 – 177 | 115 | Missing in isoform 4. | VSP_010832 | |||||
| Alternative sequence | 112 – 177 | 66 | Missing in isoform 3. | VSP_010833 | |||||
| Alternative sequence | 162 – 177 | 16 | ASRHL…KAILN → GQPQMSQPL in isoform 2. | VSP_010834 | |||||
| Natural variant | 30 | 1 | I → V. Corresponds to variant rs1058057 [ dbSNP | Ensembl ]. | VAR_048691 | |||||
Experimental info | |||||||||
| Mutagenesis | 9 | 1 | L → A: Decreased interaction with nuclear receptors. Ref.2 | ||||||
| Mutagenesis | 28 | 1 | S → A: Loss of repressor function. Ref.9 Ref.11 | ||||||
| Mutagenesis | 63 – 66 | 4 | Missing: Abolishes localization to nucleus. Ref.10 | ||||||
| Mutagenesis | 63 – 65 | 3 | KRK → AAA: Abolishes localization to nucleus. Ref.6 | ||||||
| Mutagenesis | 89 | 1 | L → R: Abolishes dimerization, but not interactions with nuclear receptors; when associated with R-96. Ref.9 | ||||||
| Mutagenesis | 96 | 1 | L → R: Abolishes dimerization, but not interactions with nuclear receptors; when associated with R-89. Ref.9 | ||||||
| Mutagenesis | 172 – 176 | 5 | LKAIL → AKAAA: Abolishes interaction with nuclear receptors. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Beta 3-endonexin, a novel polypeptide that interacts specifically with the cytoplasmic tail of the integrin beta 3 subunit." Shattil S.J., O'Toole T.E., Eigenthaler M.J., Thon V., Williams M.J., Babior B.M., Ginsberg M.H. J. Cell Biol. 131:807-816(1995) [PubMed: 7593198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY, INTERACTION WITH ITGB3. Tissue: B-cell. |
| [2] | "NRIF3 is a novel coactivator mediating functional specificity of nuclear hormone receptors." Li D., Desai-Yajnik V., Lo E., Schapira M., Abagyan R., Samuels H.H. Mol. Cell. Biol. 19:7191-7202(1999) [PubMed: 10490654] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), COACTIVATOR FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RXRA AND THRA, MUTAGENESIS OF LEU-9 AND 172-LEU--LEU-176. Tissue: Cervix carcinoma. |
| [3] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis. |
| [4] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5). Tissue: Bone marrow and Placenta. |
| [6] | "Novel alternatively spliced form of beta(3)-endonexin." Fujimoto T.-T., Katsutani S., Shimomura T., Fujimura K. Thromb. Res. 105:63-70(2002) [PubMed: 11864709] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 4), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF 63-LYS--LYS-65. |
| [7] | "Affinity modulation of platelet integrin alphaIIbbeta3 by beta3-endonexin, a selective binding partner of the beta3 integrin cytoplasmic tail." Kashiwagi H., Schwartz M.A., Eigenthaler M., Davis K.A., Ginsberg M.H., Shattil S.J. J. Cell Biol. 137:1433-1443(1997) [PubMed: 9182673] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [8] | "Beta3-endonexin as a novel inhibitor of cyclin A-associated kinase." Ohtoshi A., Maeda T., Higashi H., Ashizawa S., Yamada M., Hatakeyama M. Biochem. Biophys. Res. Commun. 267:947-952(2000) [PubMed: 10673397] [Abstract] Cited for: INTERACTION WITH CCNA2. |
| [9] | "Domain structure of the NRIF3 family of coregulators suggests potential dual roles in transcriptional regulation." Li D., Wang F., Samuels H.H. Mol. Cell. Biol. 21:8371-8384(2001) [PubMed: 11713274] [Abstract] Cited for: FUNCTION AS A COREPRESSOR, SUBCELLULAR LOCATION, HOMODIMERIZATION, PHOSPHORYLATION, MUTAGENESIS OF SER-28; LEU-89 AND LEU-96. |
| [10] | "Role of beta(3)-endonexin in the regulation of NF-kappaB-dependent expression of urokinase-type plasminogen activator receptor." Besta F., Massberg S., Brand K., Mueller E., Page S., Gruener S., Lorenz M., Sadoul K., Kolanus W., Lengyel E., Gawaz M. J. Cell Sci. 115:3879-3888(2002) [PubMed: 12244126] [Abstract] Cited for: FUNCTION AS A COREPRESSOR, SUBCELLULAR LOCATION, INTERACTION WITH NFKB1, MUTAGENESIS OF 63-LYS--LYS-66. |
| [11] | "The NRIF3 family of transcriptional coregulators induces rapid and profound apoptosis in breast cancer cells." Li D., Das S., Yamada T., Samuels H.H. Mol. Cell. Biol. 24:3838-3848(2004) [PubMed: 15082778] [Abstract] Cited for: FUNCTION, DOMAIN, MUTAGENESIS OF SER-28. |
| [12] | "Metastasis-associated protein 1 interacts with NRIF3, an estrogen-inducible nuclear receptor coregulator." Talukder A.H., Gururaj A., Mishra S.K., Vadlamudi R.K., Kumar R. Mol. Cell. Biol. 24:6581-6591(2004) [PubMed: 15254226] [Abstract] Cited for: FUNCTION, INDUCTION, INTERACTION WITH MTA1. |
| [13] | "The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres." Okada M., Cheeseman I.M., Hori T., Okawa K., McLeod I.X., Yates J.R. III, Desai A., Fukagawa T. Nat. Cell Biol. 8:446-457(2006) [PubMed: 16622420] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH CENPH; CENPI; CENPK; CENPN; CENPO; CENPP; CENPQ AND CENPU, FUNCTION, SUBCELLULAR LOCATION. |
| [14] | "The human CENP-A centromeric nucleosome-associated complex." Foltz D.R., Jansen L.E.T., Black B.E., Bailey A.O., Yates J.R. III, Cleveland D.W. Nat. Cell Biol. 8:458-469(2006) [PubMed: 16622419] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE CENPA-CAD COMPLEX WITH CENPI; CENPK; CENPL; CENPO; CENPP; CENPQ AND CENPS. |
| [15] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [16] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U37139 mRNA. Translation: AAC50295.1. U37139 mRNA. Translation: AAC50294.1. AF175306 mRNA. Translation: AAF00239.1. AK312944 mRNA. Translation: BAG35785.1. BX004807, AL592218 Genomic DNA. Translation: CAI15771.1. BX004807, AL592218 Genomic DNA. Translation: CAI15772.1. AL592218, BX004807 Genomic DNA. Translation: CAI18958.1. AL592218, BX004807 Genomic DNA. Translation: CAI18959.1. BC009929 mRNA. Translation: AAH09929.1. BC014385 mRNA. Translation: AAH14385.1. Different initiation. |
| IPI | IPI00439184. IPI00439185. IPI00439186. IPI00439187. IPI00555934. |
| PIR | A57277. |
| RefSeq | NP_001193668.1. NM_001206739.1. NP_055103.3. NM_014288.4. |
| UniGene | Hs.166539. |
3D structure databases | |
| ProteinModelPortal | Q13352. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q13352. 28 interactions. |
| MINT | MINT-1378371. |
| STRING | Q13352. |
PTM databases | |
| PhosphoSite | Q13352. |
Polymorphism databases | |
| DMDM | 50400855. |
Proteomic databases | |
| PRIDE | Q13352. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000271002; ENSP00000271002; ENSG00000142856. |
| GeneID | 23421. |
| KEGG | hsa:23421. |
| UCSC | uc001dba.1. human. uc009wak.1. human. |
Organism-specific databases | |
| CTD | 23421. |
| GeneCards | GC01M063906. |
| H-InvDB | HIX0019635. |
| HGNC | HGNC:6157. ITGB3BP. |
| HPA | HPA028463. |
| MIM | 605494. gene. |
| neXtProt | NX_Q13352. |
| PharmGKB | PA29956. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG04879. |
| GeneTree | ENSGT00390000004336. |
| HOVERGEN | HBG080553. |
| OrthoDB | EOG4Z36G0. |
| PhylomeDB | Q13352. |
Enzyme and pathway databases | |
| Reactome | REACT_111102. Signal Transduction. REACT_152. Cell Cycle, Mitotic. REACT_22172. Chromosome Maintenance. REACT_383. DNA Replication. |
Gene expression databases | |
| ArrayExpress | Q13352. |
| Bgee | Q13352. |
| Genevestigator | Q13352. |
| GermOnline | ENSG00000142856. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR009601. NRIF3_coact_rcpt. [Graphical view] |
| KO | K11510. |
| PANTHER | PTHR15581. PTHR15581. 1 hit. |
| Pfam | PF06729. NRIF3. 1 hit. [Graphical view] |
| PIRSF | PIRSF011860. NRIF3_coact_rcpt. 1 hit. |
| ProtoNet | Search... |
Other | |
| NextBio | 45639. |
| SOURCE | Search... |
Entry information
| Entry name | CENPR_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13352 Secondary accession number(s): B2R7D8 Q9UKB6 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |

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