Reviewed, UniProtKB/Swiss-Prot Q6B0I6 (KDM4D_HUMAN)

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) [Complete proteome]

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.
Sequence processing	The displayed sequence is not processed.
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.

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
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	iron 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 zinc ion binding 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: dbSNP rs35631512.		VAR_057882
	Natural variant	408	1	R → Q: dbSNP rs3740853. Ref.1 Ref.4		VAR_026225
	Natural variant	471	1	A → S: dbSNP rs34366036.		VAR_057883
Experimental info
	Sequence conflict	510	1	H → R in AAH74739. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q6B0I6-1 [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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Hs.503598

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

STRING

Q6B0I6.

Proteomic databases

PRIDE

Q6B0I6.

Genome annotation databases

Ensembl

ENST00000335080; ENSP00000334181; ENSG00000186280; Homo sapiens. [Genome view]

GeneID

55693.

KEGG

hsa:55693.

UCSC

uc001pfe.1. human.

Organism-specific databases

GeneCards

GC11P094346.

H-InvDB

HIX0010037.

HGNC

HGNC:25498. KDM4D.

MIM

609766. gene.

PharmGKB

PA134895886.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

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]

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 Resources

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:	November 3, 2009
This is version 46 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.