O15054 (KDM6B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lysine-specific demethylase 6B
EC=1.14.11.-

Alternative name(s):
JmjC domain-containing protein 3
Jumonji domain-containing protein 3
Lysine demethylase 6B

Gene names

Name:	KDM6B
Synonyms:	JMJD3, KIAA0346

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1643 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation. Ref.6 Ref.7
Cofactor	Ascorbate By similarity. Ref.6 Fe2+. Ref.6
Subunit structure	Interacts with TLE1 By similarity. Component of the MLL4 complex, at least composed of MLL4, ASH2L, RBBP5, WDR5, and KDM6B. Ref.6
Subcellular location	Nucleus Probable Ref.6.
Induction	By 12-O-tetradecanoylphorbol-13-acetate (TPA) in myeloid leukemia cells. Ref.5
Sequence similarities	Belongs to the UTX family. Contains 1 JmjC domain.
Sequence caution	The sequence BAA21572.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Inflammatory response
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Iron Metal-binding
Molecular function	Chromatin regulator Dioxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	histone demethylation Inferred from electronic annotation. Source: Compara inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: O15054-2)

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.

Note: Gene prediction based on similarity to mouse ortholog.

Isoform 1 (identifier: O15054-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1636-1636: L → LVRARRARGQRRRALGQAAGTGFGSPAAPFPEPPPAFSPQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1643

1643

Lysine-specific demethylase 6B

PRO_0000292007

Regions

Domain

1339 – 1502

164

JmjC

Compositional bias

32 – 85

54

Pro-rich

Compositional bias

195 – 906

712

Pro-rich

Compositional bias

738 – 764

27

Thr-rich

Compositional bias

1046 – 1082

37

Pro-rich

Sites

Metal binding

1390

1

Iron Probable

Metal binding

1392

1

Iron Probable

Natural variations

Alternative sequence

1636

1

L → LVRARRARGQRRRALGQAAG TGFGSPAAPFPEPPPAFSPQ in isoform 1.

VSP_040102

Natural variant

203

1

P → A.
Corresponds to variant rs60738318 [ dbSNP | Ensembl ].

VAR_061670

Natural variant

308

1

S → L.
Corresponds to variant rs2270516 [ dbSNP | Ensembl ].

VAR_032927

Experimental info

Sequence conflict

252 – 254

3

Missing in BAA21572. Ref.1

Sequence conflict

252 – 254

3

Missing in AAH09994. Ref.3

Secondary structure

1

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1643

Helix Strand Turn

Details...

Helix

1178 – 1181

4

Beta strand

1187 – 1189

3

Helix

1193 – 1195

3

Helix

1199 – 1206

8

Beta strand

1211 – 1217

7

Helix

1218 – 1222

5

Helix

1226 – 1229

4

Helix

1231 – 1238

8

Beta strand

1242 – 1249

8

Beta strand

1261 – 1264

4

Beta strand

1271 – 1276

6

Helix

1277 – 1289

13

Beta strand

1325 – 1333

9

Helix

1337 – 1347

11

Helix

1352 – 1354

3

Turn

1356 – 1359

4

Beta strand

1363 – 1365

3

Beta strand

1366 – 1368

3

Turn

1371 – 1373

3

Beta strand

1375 – 1381

7

Beta strand

1386 – 1390

5

Helix

1393 – 1395

3

Beta strand

1397 – 1406

10

Beta strand

1408 – 1413

6

Helix

1415 – 1417

3

Helix

1418 – 1427

10

Turn

1432 – 1434

3

Helix

1441 – 1446

6

Beta strand

1452 – 1456

5

Beta strand

1461 – 1464

4

Beta strand

1469 – 1487

19

Helix

1491 – 1495

5

Helix

1514 – 1524

11

Helix

1530 – 1557

28

Beta strand

1561 – 1563

3

Turn

1576 – 1578

3

Beta strand

1584 – 1590

7

Beta strand

1598 – 1601

4

Helix

1603 – 1608

6

Turn

1610 – 1615

6

Beta strand

1617 – 1622

6

Helix

1624 – 1633

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified November 30, 2010. Version 4. Checksum: 8CE32AE602683BA3	FASTA	1,643	176,632
	10 20 30 40 50 60 MHRAVDPPGA RAAREAFALG GLSCAGAWSS CPPHPPPRSA WLPGGRCSAS IGQPPLPAPL 70 80 90 100 110 120 PPSHGSSSGH PSKPYYAPGA PTPRPLHGKL ESLHGCVQAL LREPAQPGLW EQLGQLYESE 130 140 150 160 170 180 HDSEEATRCY HSALRYGGSF AELGPRIGRL QQAQLWNFHT GSCQHRAKVL PPLEQVWNLL 190 200 210 220 230 240 HLEHKRNYGA KRGGPPVKRA AEPPVVQPVP PAALSGPSGE EGLSPGGKRR RGCNSEQTGL 250 260 270 280 290 300 PPGLPLPPPP LPPPPPPPPP PPPPLPGLAT SPPFQLTKPG LWSTLHGDAW GPERKGSAPP 310 320 330 340 350 360 ERQEQRHSLP HPYPYPAPAY TAHPPGHRLV PAAPPGPGPR PPGAESHGCL PATRPPGSDL 370 380 390 400 410 420 RESRVQRSRM DSSVSPAATT ACVPYAPSRP PGLPGTTTSS SSSSSSNTGL RGVEPNPGIP 430 440 450 460 470 480 GADHYQTPAL EVSHHGRLGP SAHSSRKPFL GAPAATPHLS LPPGPSSPPP PPCPRLLRPP 490 500 510 520 530 540 PPPAWLKGPA CRAAREDGEI LEELFFGTEG PPRPAPPPLP HREGFLGPPA SRFSVGTQDS 550 560 570 580 590 600 HTPPTPPTPT TSSSNSNSGS HSSSPAGPVS FPPPPYLARS IDPLPRPPSP AQNPQDPPLV 610 620 630 640 650 660 PLTLALPPAP PSSCHQNTSG SFRRPESPRP RVSFPKTPEV GPGPPPGPLS KAPQPVPPGV 670 680 690 700 710 720 GELPARGPRL FDFPPTPLED QFEEPAEFKI LPDGLANIMK MLDESIRKEE EQQQHEAGVA 730 740 750 760 770 780 PQPPLKEPFA SLQSPFPTDT APTTTAPAVA VTTTTTTTTT TTATQEEEKK PPPALPPPPP 790 800 810 820 830 840 LAKFPPPSQP QPPPPPPPSP ASLLKSLASV LEGQKYCYRG TGAAVSTRPG PLPTTQYSPG 850 860 870 880 890 900 PPSGATALPP TSAAPSAQGS PQPSASSSSQ FSTSGGPWAR ERRAGEEPVP GPMTPTQPPP 910 920 930 940 950 960 PLSLPPARSE SEVLEEISRA CETLVERVGR SATDPADPVD TAEPADSGTE RLLPPAQAKE 970 980 990 1000 1010 1020 EAGGVAAVSG SCKRRQKEHQ KEHRRHRRAC KDSVGRRPRE GRAKAKAKVP KEKSRRVLGN 1030 1040 1050 1060 1070 1080 LDLQSEEIQG REKSRPDLGG ASKAKPPTAP APPSAPAPSA QPTPPSASVP GKKAREEAPG 1090 1100 1110 1120 1130 1140 PPGVSRADML KLRSLSEGPP KELKIRLIKV ESGDKETFIA SEVEERRLRM ADLTISHCAA 1150 1160 1170 1180 1190 1200 DVVRASRNAK VKGKFRESYL SPAQSVKPKI NTEEKLPREK LNPPTPSIYL ESKRDAFSPV 1210 1220 1230 1240 1250 1260 LLQFCTDPRN PITVIRGLAG SLRLNLGLFS TKTLVEASGE HTVEVRTQVQ QPSDENWDLT 1270 1280 1290 1300 1310 1320 GTRQIWPCES SRSHTTIAKY AQYQASSFQE SLQEEKESED EESEEPDSTT GTPPSSAPDP 1330 1340 1350 1360 1370 1380 KNHHIIKFGT NIDLSDAKRW KPQLQELLKL PAFMRVTSTG NMLSHVGHTI LGMNTVQLYM 1390 1400 1410 1420 1430 1440 KVPGSRTPGH QENNNFCSVN INIGPGDCEW FAVHEHYWET ISAFCDRHGV DYLTGSWWPI 1450 1460 1470 1480 1490 1500 LDDLYASNIP VYRFVQRPGD LVWINAGTVH WVQATGWCNN IAWNVGPLTA YQYQLALERY 1510 1520 1530 1540 1550 1560 EWNEVKNVKS IVPMIHVSWN VARTVKISDP DLFKMIKFCL LQSMKHCQVQ RESLVRAGKK 1570 1580 1590 1600 1610 1620 IAYQGRVKDE PAYYCNECDV EVFNILFVTS ENGSRNTYLV HCEGCARRRS AGLQGVVVLE 1630 1640 QYRTEELAQA YDAFTLAPAS TSR
	Isoform 1 [UniParc]. Checksum: E4264890580649AB	FASTA	1,682	180,702
	10 20 30 40 50 60 MHRAVDPPGA RAAREAFALG GLSCAGAWSS CPPHPPPRSA WLPGGRCSAS IGQPPLPAPL 70 80 90 100 110 120 PPSHGSSSGH PSKPYYAPGA PTPRPLHGKL ESLHGCVQAL LREPAQPGLW EQLGQLYESE 130 140 150 160 170 180 HDSEEATRCY HSALRYGGSF AELGPRIGRL QQAQLWNFHT GSCQHRAKVL PPLEQVWNLL 190 200 210 220 230 240 HLEHKRNYGA KRGGPPVKRA AEPPVVQPVP PAALSGPSGE EGLSPGGKRR RGCNSEQTGL 250 260 270 280 290 300 PPGLPLPPPP LPPPPPPPPP PPPPLPGLAT SPPFQLTKPG LWSTLHGDAW GPERKGSAPP 310 320 330 340 350 360 ERQEQRHSLP HPYPYPAPAY TAHPPGHRLV PAAPPGPGPR PPGAESHGCL PATRPPGSDL 370 380 390 400 410 420 RESRVQRSRM DSSVSPAATT ACVPYAPSRP PGLPGTTTSS SSSSSSNTGL RGVEPNPGIP 430 440 450 460 470 480 GADHYQTPAL EVSHHGRLGP SAHSSRKPFL GAPAATPHLS LPPGPSSPPP PPCPRLLRPP 490 500 510 520 530 540 PPPAWLKGPA CRAAREDGEI LEELFFGTEG PPRPAPPPLP HREGFLGPPA SRFSVGTQDS 550 560 570 580 590 600 HTPPTPPTPT TSSSNSNSGS HSSSPAGPVS FPPPPYLARS IDPLPRPPSP AQNPQDPPLV 610 620 630 640 650 660 PLTLALPPAP PSSCHQNTSG SFRRPESPRP RVSFPKTPEV GPGPPPGPLS KAPQPVPPGV 670 680 690 700 710 720 GELPARGPRL FDFPPTPLED QFEEPAEFKI LPDGLANIMK MLDESIRKEE EQQQHEAGVA 730 740 750 760 770 780 PQPPLKEPFA SLQSPFPTDT APTTTAPAVA VTTTTTTTTT TTATQEEEKK PPPALPPPPP 790 800 810 820 830 840 LAKFPPPSQP QPPPPPPPSP ASLLKSLASV LEGQKYCYRG TGAAVSTRPG PLPTTQYSPG 850 860 870 880 890 900 PPSGATALPP TSAAPSAQGS PQPSASSSSQ FSTSGGPWAR ERRAGEEPVP GPMTPTQPPP 910 920 930 940 950 960 PLSLPPARSE SEVLEEISRA CETLVERVGR SATDPADPVD TAEPADSGTE RLLPPAQAKE 970 980 990 1000 1010 1020 EAGGVAAVSG SCKRRQKEHQ KEHRRHRRAC KDSVGRRPRE GRAKAKAKVP KEKSRRVLGN 1030 1040 1050 1060 1070 1080 LDLQSEEIQG REKSRPDLGG ASKAKPPTAP APPSAPAPSA QPTPPSASVP GKKAREEAPG 1090 1100 1110 1120 1130 1140 PPGVSRADML KLRSLSEGPP KELKIRLIKV ESGDKETFIA SEVEERRLRM ADLTISHCAA 1150 1160 1170 1180 1190 1200 DVVRASRNAK VKGKFRESYL SPAQSVKPKI NTEEKLPREK LNPPTPSIYL ESKRDAFSPV 1210 1220 1230 1240 1250 1260 LLQFCTDPRN PITVIRGLAG SLRLNLGLFS TKTLVEASGE HTVEVRTQVQ QPSDENWDLT 1270 1280 1290 1300 1310 1320 GTRQIWPCES SRSHTTIAKY AQYQASSFQE SLQEEKESED EESEEPDSTT GTPPSSAPDP 1330 1340 1350 1360 1370 1380 KNHHIIKFGT NIDLSDAKRW KPQLQELLKL PAFMRVTSTG NMLSHVGHTI LGMNTVQLYM 1390 1400 1410 1420 1430 1440 KVPGSRTPGH QENNNFCSVN INIGPGDCEW FAVHEHYWET ISAFCDRHGV DYLTGSWWPI 1450 1460 1470 1480 1490 1500 LDDLYASNIP VYRFVQRPGD LVWINAGTVH WVQATGWCNN IAWNVGPLTA YQYQLALERY 1510 1520 1530 1540 1550 1560 EWNEVKNVKS IVPMIHVSWN VARTVKISDP DLFKMIKFCL LQSMKHCQVQ RESLVRAGKK 1570 1580 1590 1600 1610 1620 IAYQGRVKDE PAYYCNECDV EVFNILFVTS ENGSRNTYLV HCEGCARRRS AGLQGVVVLE 1630 1640 1650 1660 1670 1680 QYRTEELAQA YDAFTLVRAR RARGQRRRAL GQAAGTGFGS PAAPFPEPPP AFSPQAPAST SR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] OF 1000-1643 (ISOFORM 2). Tissue: Brain.
[5]	"An efficient strategy to identify early TPA-responsive genes during differentiation of HL-60 cells." Hu L.Y., Tepper C.G., Lo S.H., Lin W.C. Gene Expr. 13:179-189(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY TPA.
[6]	"The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing." De Santa F., Totaro M.G., Prosperini E., Notarbartolo S., Testa G., Natoli G. Cell 130:1083-1094(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, IDENTIFICATION IN THE MLL4 COMPLEX.
[7]	"A histone H3 lysine 27 demethylase regulates animal posterior development." Lan F., Bayliss P.E., Rinn J.L., Whetstine J.R., Wang J.K., Chen S., Iwase S., Alpatov R., Issaeva I., Canaani E., Roberts T.M., Chang H.Y., Shi Y. Nature 449:689-694(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY.
[8]	"Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases." Hong S., Cho Y.W., Yu L.-R., Yu H., Veenstra T.D., Ge K. Proc. Natl. Acad. Sci. U.S.A. 104:18439-18444(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME ACTIVITY.
[9]	"Crystal structure of the human JMJD3 Jumonji domain." Structural genomics consortium (SGC) Submitted (DEC-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1176-1502 IN COMPLEX WITH NICKEL IONS AND 8-HYDROXYQUINOLINE-5-CARBOXYLIC ACID.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB002344 mRNA. Translation: BAA21572.2. Different initiation.
AC104581 Genomic DNA. No translation available.
BC009994 mRNA. Translation: AAH09994.1.

IPI

IPI00550090.
IPI00848052.

RefSeq

NP_001073893.1. NM_001080424.1.

UniGene

Hs.730881.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XUE	X-ray	2.00	A/B	1141-1643	[»]
2XXZ	X-ray	1.80	A/B	1176-1502	[»]
4ASK	X-ray	1.86	A/B	1141-1643	[»]

ProteinModelPortal

O15054.

SMR

O15054. Positions 1157-1638.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59912N.

IntAct

O15054. 2 interactions.

STRING

9606.ENSP00000254846.

PTM databases

PhosphoSite

O15054.

Proteomic databases

PaxDb

O15054.

PRIDE

O15054.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000254846; ENSP00000254846; ENSG00000132510.
ENST00000448097; ENSP00000412513; ENSG00000132510.

GeneID

23135.

KEGG

hsa:23135.

UCSC

uc002giw.1. human.
uc002gix.3. human.

Organism-specific databases

CTD

23135.

GeneCards

GC17P007686.

HGNC

HGNC:29012. KDM6B.

HPA

HPA037988.

MIM

611577. gene.

neXtProt

NX_O15054.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG246325.

HOGENOM

HOG000113217.

InParanoid

O15054.

KO

K11448.

OMA

LSCAGAW.

OrthoDB

EOG402WRG.

Gene expression databases

ArrayExpress

O15054.

Bgee

O15054.

CleanEx

HS_JMJD3.

Genevestigator

O15054.

Family and domain databases

InterPro

IPR003347. JmjC_dom.
[Graphical view]

Pfam

PF02373. JmjC. 1 hit.
[Graphical view]

SMART

SM00558. JmjC. 1 hit.
[Graphical view]

PROSITE

PS51184. JMJC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O15054.

ChEMBL

CHEMBL1938211.

EvolutionaryTrace

O15054.

GenomeRNAi

23135.

NextBio

44391.

SOURCE

Search...

Entry information

Entry name

KDM6B_HUMAN

Accession

Primary (citable) accession number: O15054
Secondary accession number(s): C9IZ40, Q96G33

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 26, 2007
Last sequence update:	November 30, 2010
Last modified:	April 3, 2013
This is version 93 of the entry and version 4 of the sequence. [Complete history]

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.