| General information | | DisProt: | DP00712 | | Name: | Lysine-specific demethylase 5B | | Synonym(s): | KDM5B_HUMAN
Cancer/testis antigen 31
Histone demethylase JARID1B
Jumonji/ARID domain-containing protein 1B
PLU-1
Retinoblastoma-binding protein 2 homolog 1
CT31
RBP2-H1
| | First appeared in release: | Release 6.00 (07/01/2012) | | UniProt: | Q9UGL1 | | UniGene: | | | SwissProt: | KDM5B_HUMAN | | TrEMBL: | | | NCBI (GI): | | | Source organism: | Homo sapiens (Human) | | Sequence length: | 1544 | | Percent disordered: | 2% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
| | | | | |
MEAATTLHPG PRPALPLGGP GPLGEFLPPP ECPVFEPSWE EFADPFAFIH KIRPIAEQTG - 60
ICKVRPPPDW QPPFACDVDK LHFTPRIQRL NELEAQTRVK LNFLDQIAKY WELQGSTLKI - 120
PHVERKILDL FQLNKLVAEE GGFAVVCKDR KWTKIATKMG FAPGKAVGSH IRGHYERILN - 180
PYNLFLSGDS LRCLQKPNLT TDTKDKEYKP HDIPQRQSVQ PSETCPPARR AKRMRAEAMN - 240
IKIEPEETTE ARTHNLRRRM GCPTPKCENE KEMKSSIKQE PIERKDYIVE NEKEKPKSRS - 300
KKATNAVDLY VCLLCGSGND EDRLLLCDGC DDSYHTFCLI PPLHDVPKGD WRCPKCLAQE - 360
CSKPQEAFGF EQAARDYTLR TFGEMADAFK SDYFNMPVHM VPTELVEKEF WRLVSTIEED - 420
VTVEYGADIA SKEFGSGFPV RDGKIKLSPE EEEYLDSGWN LNNMPVMEQS VLAHITADIC - 480
GMKLPWLYVG MCFSSFCWHI EDHWSYSINY LHWGEPKTWY GVPGYAAEQL ENVMKKLAPE - 540
LFVSQPDLLH QLVTIMNPNT LMTHEVPVYR TNQCAGEFVI TFPRAYHSGF NQGFNFAEAV - 600
NFCTVDWLPL GRQCVEHYRL LHRYCVFSHD EMICKMASKA DVLDVVVAST VQKDMAIMIE - 660
DEKALRETVR KLGVIDSERM DFELLPDDER QCVKCKTTCF MSAISCSCKP GLLVCLHHVK - 720
ELCSCPPYKY KLRYRYTLDD LYPMMNALKL RAESYNEWAL NVNEALEAKI NKKKSLVSFK - 780
ALIEESEMKK FPDNDLLRHL RLVTQDAEKC ASVAQQLLNG KRQTRYRSGG GKSQNQLTVN - 840
ELRQFVTQLY ALPCVLSQTP LLKDLLNRVE DFQQHSQKLL SEETPSAAEL QDLLDVSFEF - 900
DVELPQLAEM RIRLEQARWL EEVQQACLDP SSLTLDDMRR LIDLGVGLAP YSAVEKAMAR - 960
LQELLTVSEH WDDKAKSLLK ARPRHSLNSL ATAVKEIEEI PAYLPNGAAL KDSVQRARDW - 1020
LQDVEGLQAG GRVPVLDTLI ELVTRGRSIP VHLNSLPRLE TLVAEVQAWK ECAVNTFLTE - 1080
NSPYSLLEVL CPRCDIGLLG LKRKQRKLKE PLPNGKKKST KLESLSDLER ALTESKETAS - 1140
AMATLGEARL REMEALQSLR LANEGKLLSP LQDVDIKICL CQKAPAAPMI QCELCRDAFH - 1200
TSCVAVPSIS QGLRIWLCPH CRRSEKPPLE KILPLLASLQ RIRVRLPEGD ALRYMIERTV - 1260
NWQHRAQQLL SSGNLKFVQD RVGSGLLYSR WQASAGQVSD TNKVSQPPGT TSFSLPDDWD - 1320
NRTSYLHSPF STGRSCIPLH GVSPEVNELL MEAQLLQVSL PEIQELYQTL LAKPSPAQQT - 1380
DRSSPVRPSS EKNDCCRGKR DGINSLERKL KRRLEREGLS SERWERVKKM RTPKKKKIKL - 1440
SHPKDMNNFK LERERSYELV RSAETHSLPS DTSYSEQEDS EDEDAICPAV SCLQPEGDEV - 1500
DWVQCDGSCN QWFHQVCVGV SPEMAEKEDY ICVRCTVKDA PSRK
|
| Functional narrative |
Function: Histone demethylase that demethylates \'Lys-4\' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 \'Lys-9\' or H3 \'Lys-27\'. Demethylates trimethylated, dimethylated and monomethylated H3 \'Lys-4\'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5. In contrast, may act as a tumor suppressor for melanoma.
COFACTOR: Binds 1 Fe(2+) ion per subunit (By similarity).
SUBUNIT: Interacts with FOXG1B, PAX9, MYC, MYCN and RB1. Interacts with HDAC1, HDAC4, HDAC5 and HDAC7 (By similarity).
Subcellular Location: Nucleus. Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9UGL1-1; Sequence=Displayed; Name=2; IsoId=Q9UGL1-2; Sequence=VSP_026408;
TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in testis. Down-regulated in melanoma and glioblastoma. Up-regulated in breast cancer (at protein level).
DOMAIN: Both the JmjC domain and the JmjN domain are required for enzymatic activity.
DOMAIN: The 2 first PHD-type zinc finger domains are required for transcription repression activity.
SIMILARITY: Belongs to the JARID1 histone demethylase family.
SIMILARITY: Contains 1 ARID domain.
SIMILARITY: Contains 1 JmjC domain.
SIMILARITY: Contains 1 JmjN domain.
SIMILARITY: Contains 3 PHD-type zinc fingers. Sequence=CAB63108.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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|
| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
|
| Region 1 | | Type: | Disordered | | Name: | Loop L1 of ARID domain | | Location: | 115 - 129 | | Length: | 15 | | Region sequence: |
GSTLKIPHVERKILD | | Modification type: | Complex
Fragment
| | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-DNA binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.5; protein 0.5 mM; phosphate 20 mM; NaCl 50 mM; DTT 5 mM; NaN3 0.5 mM; D2O 10%)
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.5; ARID domain protein 0.4 mM; Buffer A (20 mM phosphate, 0.5 mM EDTA, 50 mM NaCl); duplex DNA (synthetic, in Buffer A) 1 mM)
| References:
- Yao W, Peng Y, Chen Q, Lin D. "1H, 13C, 15N backbone and side-chain resonance assignments of the Bright/ARID domain from the human histone demethylase JARID1B." Biomol NMR Assign. 2009; 3(1): 85-7. PubMed: 19636953
- Yao W, Peng Y, Lin D. "The flexible loop L1 of the H3K4 demethylase JARID1B ARID domain has a crucial role in DNA-binding activity." Biochem. Biophys. Res. Commun.. 2010; 396(2): 323-8. PubMed: 20403335
| Comments:According to Yao et al (2010), Loop L1 is "the main interface between the human JARID1B ARID domain and DNA," and is "very important for maintaining H3K4 demethylase activity."
The DNA-binding interaction appears to be salt-dependent, and the Loop L1 residues involved are K119, H122, E124, R125, L128, of which R125 is the most important. Other residues involved in DNA binding are W152 and K165.
The entire ARID domain (aa 88-199) is highly conserved. See also, DP00711 Mouse JARID1B for which there is an x-ray crystal structure of the ARID domain (PDB 2EQY:A).
|
| Region 2 | | Type: | Disordered | | Name: | Loop L2 of ARID domain | | Location: | 159 - 165 | | Length: | 7 | | Region sequence: |
MGFAPGK | | Modification type: | Complex
Fragment
| | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-DNA binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.5; ARID domain protein 0.5 mM; D2O 10%; DTT 5 mM; NaCl 50 mM; NaN3 0.5 mM; phosphate 20 mM)
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.5; ARID domain protein 0.4 mM; Buffer A (20 mM phosphate, 0.5 mM EDTA, 50 mM NaCl); duplex DNA (synthetic, in Buffer A) 1 mM)
| References:
- Yao W, Peng Y, Chen Q, Lin D. "1H, 13C, 15N backbone and side-chain resonance assignments of the Bright/ARID domain from the human histone demethylase JARID1B." Biomol NMR Assign. 2009; 3(1): 85-7. PubMed: 19636953
- Yao W, Peng Y, Lin D. "The flexible loop L1 of the H3K4 demethylase JARID1B ARID domain has a crucial role in DNA-binding activity." Biochem. Biophys. Res. Commun.. 2010; 396(2): 323-8. PubMed: 20403335
| Comments:Yao et al (2010) describe Loop L2 as shorter than in other ARID domains, and speculate "that the length and flexibility of Loop L1 may affect may affect interaction between Loop L2 and DNA."
Residue K165, found in Loop L2, participates in DNA-binding.
The entire ARID domain (aa 88-199) is highly conserved. See also, DP00711 Mouse JARID1B for which there is an x-ray crystal structure of the ARID domain (PDB 2EQY:A).
|
| Region 3 | | Type: | Disordered | | Name: | C-tail of ARID domain | | Location: | 188 - 199 | | Length: | 12 | | Region sequence: |
GDSLRCLQKPNL | | Modification type: | Complex
Fragment
| | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | | Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.5; ARID domain protein 0.5 mM; D2O 10%; DTT 5 mM; NaCl 50 mM; NaN3 0.5 mM; phosphate 20 mM)
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.5; ARID domain protein 0.4 mM; Buffer A (20 mM phosphate, 0.5 mM EDTA, 50 mM NaCl); duplex DNA (synthetic, in Buffer A) 1 mM)
| References:
- Yao W, Peng Y, Chen Q, Lin D. "1H, 13C, 15N backbone and side-chain resonance assignments of the Bright/ARID domain from the human histone demethylase JARID1B." Biomol NMR Assign. 2009; 3(1): 85-7. PubMed: 19636953
- Yao W, Peng Y, Lin D. "The flexible loop L1 of the H3K4 demethylase JARID1B ARID domain has a crucial role in DNA-binding activity." Biochem. Biophys. Res. Commun.. 2010; 396(2): 323-8. PubMed: 20403335
| Comments:Yao et al (2010) state that the C-terminal tail (aa 106-111) "does not appear in the [NMR] spectrum."
The entire ARID domain (aa 88-199) is highly conserved. See also, DP00711 Mouse JARID1B for which there is an x-ray crystal structure of the ARID domain (PDB 2EQY:A).
|
| Comments |
Yao et al (2009) BioMagResBank accession number 15732.
AV sent 6/19/2012 (PMID:20403335)
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