Q6B0I6 (KDM4D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lysine-specific demethylase 4D
EC=1.14.11.-

Alternative name(s):
JmjC domain-containing histone demethylation protein 3D
Jumonji domain-containing protein 2D

Gene names

Name:	KDM4D
Synonyms:	JHDM3D, JMJD2D

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	523 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Demethylates both di- and trimethylated H3 'Lys-9' residue, while it has no activity on monomethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Ref.7
Cofactor	Binds 1 Fe2+ ion per subunit By similarity.
Subcellular location	Nucleus By similarity.
Sequence similarities	Belongs to the JHDM3 histone demethylase family. Contains 1 JmjC domain. Contains 1 JmjN domain.
Caution	It is uncertain whether Met-1 or Met-4 is the initiator.
Sequence caution	The sequence BAA91508.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	Iron Metal-binding Zinc
Molecular function	Chromatin regulator Dioxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
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
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 523

523

Lysine-specific demethylase 4D

PRO_0000234376

Regions

Domain

18 – 60

43

JmjN

Domain

146 – 312

167

JmjC

Compositional bias

91 – 94

4

Poly-Lys

Sites

Metal binding

192

1

Iron; catalytic By similarity

Metal binding

194

1

Iron; catalytic By similarity

Metal binding

238

1

Zinc By similarity

Metal binding

244

1

Zinc By similarity

Metal binding

280

1

Iron; catalytic By similarity

Metal binding

310

1

Zinc By similarity

Metal binding

312

1

Zinc By similarity

Binding site

136

1

Alpha-ketoglutarate By similarity

Binding site

202

1

Alpha-ketoglutarate By similarity

Binding site

210

1

Alpha-ketoglutarate By similarity

Amino acid modifications

Modified residue

409

1

Phosphoserine Ref.8

Natural variations

Natural variant

355

1

S → R.
Corresponds to variant rs35631512 [ dbSNP | Ensembl ].

VAR_057882

Natural variant

408

1

R → Q. Ref.1 Ref.4
Corresponds to variant rs3740853 [ dbSNP | Ensembl ].

VAR_026225

Natural variant

471

1

A → S.
Corresponds to variant rs34366036 [ dbSNP | Ensembl ].

VAR_057883

Experimental info

Sequence conflict

510

1

H → R in AAH74739. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

523

Helix Strand Turn

Details...

Helix

27 – 29

3

Helix

31 – 40

10

Beta strand

49 – 51

3

Beta strand

59 – 61

3

Beta strand

70 – 73

4

Beta strand

75 – 80

6

Beta strand

86 – 92

7

Helix

101 – 105

5

Turn

108 – 110

3

Helix

118 – 128

11

Helix

129 – 131

3

Helix

160 – 167

8

Beta strand

179 – 181

3

Helix

195 – 197

3

Beta strand

199 – 206

8

Beta strand

210 – 214

5

Helix

222 – 230

9

Helix

241 – 244

4

Helix

251 – 256

6

Beta strand

262 – 266

5

Beta strand

271 – 274

4

Beta strand

289 – 295

7

Helix

298 – 300

3

Helix

321 – 328

8

Helix

330 – 337

8

Sequences

	Sequence		Length	Mass (Da)
	Q6B0I6 [UniParc]. Last modified June 16, 2009. Version 3. Checksum: 5303A0846ECEBA58	FASTA	523	58,603
	10 20 30 40 50 60 METMKSKANC AQNPNCNIMI FHPTKEEFND FDKYIAYMES QGAHRAGLAK IIPPKEWKAR 70 80 90 100 110 120 ETYDNISEIL IATPLQQVAS GRAGVFTQYH KKKKAMTVGE YRHLANSKKY QTPPHQNFED 130 140 150 160 170 180 LERKYWKNRI YNSPIYGADI SGSLFDENTK QWNLGHLGTI QDLLEKECGV VIEGVNTPYL 190 200 210 220 230 240 YFGMWKTTFA WHTEDMDLYS INYLHLGEPK TWYVVPPEHG QRLERLAREL FPGSSRGCGA 250 260 270 280 290 300 FLRHKVALIS PTVLKENGIP FNRITQEAGE FMVTFPYGYH AGFNHGFNCA EAINFATPRW 310 320 330 340 350 360 IDYGKMASQC SCGEARVTFS MDAFVRILQP ERYDLWKRGQ DRAVVDHMEP RVPASQELST 370 380 390 400 410 420 QKEVQLPRRA ALGLRQLPSH WARHSPWPMA ARSGTRCHTL VCSSLPRRSA VSGTATQPRA 430 440 450 460 470 480 AAVHSSKKPS STPSSTPGPS AQIIHPSNGR RGRGRPPQKL RAQELTLQTP AKRPLLAGTT 490 500 510 520 CTASGPEPEP LPEDGALMDK PVPLSPGLQH PVKASGCSWA PVP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-408. Tissue: Embryo and Teratocarcinoma.
[2]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-408. Tissue: Brain.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 395-523. Tissue: Testis.
[6]	"Identification and characterization of JMJD2 family genes in silico." Katoh M., Katoh M. Int. J. Oncol. 24:1623-1628(2004) [PubMed: 15138608] [Abstract] Cited for: IDENTIFICATION.
[7]	"Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases." Whetstine J.R., Nottke A., Lan F., Huarte M., Smolikov S., Chen Z., Spooner E., Li E., Zhang G., Colaiacovo M., Shi Y. Cell 125:467-481(2006) [PubMed: 16603238] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY.
[8]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK001113 mRNA. Translation: BAA91508.1. Different initiation.
AK056162 mRNA. Translation: BAG51636.1.
AP002383 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW66952.1.
BC074739 mRNA. Translation: AAH74739.1.
BC119010 mRNA. Translation: AAI19011.1.
BC122858 mRNA. Translation: AAI22859.1.
AL137545 mRNA. Translation: CAB70803.1.

IPI

IPI00017991.

PIR

T46388.

RefSeq

NP_060509.2. NM_018039.2.

UniGene

Hs.503598.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DXT	X-ray	1.80	A	1-354	[»]
3DXU	X-ray	2.20	A	11-341	[»]

ProteinModelPortal

Q6B0I6.

SMR

Q6B0I6. Positions 11-341.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29606N.

STRING

Q6B0I6.

Polymorphism databases

DMDM

239938885.

Proteomic databases

PRIDE

Q6B0I6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000335080; ENSP00000334181; ENSG00000186280.

GeneID

55693.

KEGG

hsa:55693.

UCSC

uc001pfe.1. human.

Organism-specific databases

CTD

55693.

GeneCards

GC11P094706.

H-InvDB

HIX0010037.

HGNC

HGNC:25498. KDM4D.

MIM

609766. gene.

neXtProt

NX_Q6B0I6.

PharmGKB

PA164721552.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00530000063342.

HOGENOM

HBG505384.

InParanoid

Q6B0I6.

OMA

NSPIYGA.

OrthoDB

EOG4F7NJR.

PhylomeDB

Q6B0I6.

Gene expression databases

ArrayExpress

Q6B0I6.

Bgee

Q6B0I6.

CleanEx

HS_JMJD2D.

Genevestigator

Q6B0I6.

GermOnline

ENSG00000186280. Homo sapiens.

Family and domain databases

InterPro

IPR013129. TF_JmjC.
IPR003347. TF_JmjC_AAH.
IPR003349. TF_JmjN.
[Graphical view]

KO

K06709.

Pfam

PF02373. JmjC. 1 hit.
PF02375. JmjN. 1 hit.
[Graphical view]

SMART

SM00558. JmjC. 1 hit.
[Graphical view]

PROSITE

PS51184. JMJC. 1 hit.
PS51183. JMJN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

SOURCE

Search...

Entry information

Entry name

KDM4D_HUMAN

Accession

Primary (citable) accession number: Q6B0I6
Secondary accession number(s): B3KPC4 , Q0VF39, Q9NT41, Q9NW76

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	June 16, 2009
Last modified:	January 25, 2012
This is version 66 of the entry and version 3 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.