Reviewed, UniProtKB/Swiss-Prot Q9H3R0 (KDM4C_HUMAN)

Names and origin

Protein names

Recommended name:
    Lysine-specific demethylase 4C
    EC=1.14.11.-
Alternative name(s):
    JmjC domain-containing histone demethylation protein 3C
    Jumonji domain-containing protein 2C
    Gene amplified in squamous cell carcinoma 1 protein
      Short name=GASC-1 protein

Gene names

Name:	KDM4C
Synonyms:	GASC1, JHDM3C, JMJD2C, KIAA0780

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	1056 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Ref.5
Cofactor	Binds 1 Fe2+ ion per subunit By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	Overexpressed in several esophageal squamous cell carcinomas (ESCs). Ref.1
Domain	The 2 Tudor domains recognize and bind methylated histones. Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails By similarity.
Sequence similarities	Belongs to the JHDM3 histone demethylase family. Contains 1 JmjC domain. Contains 1 JmjN domain. Contains 2 PHD-type zinc fingers. Contains 2 Tudor domains.
Sequence caution	The sequence CAI39533.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI39608.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	Iron Metal-binding Zinc
Molecular function	Chromatin regulator Dioxygenase Oxidoreductase
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, DNA-dependent 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 nucleic acid binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9H3R0-1)

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: Q9H3R0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     999-1056: STASDMRFED...SFQKKCQKRQ → VSAGRCHLGT...QCNIFLSGTY

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1056	1056	Lysine-specific demethylase 4C		PRO_0000183177
Regions
	Domain	16 – 58	43	JmjN
	Domain	144 – 310	167	JmjC
	Domain	877 – 934	58	Tudor 1
	Domain	935 – 991	57	Tudor 2
	Zinc finger	689 – 747	59	PHD-type 1
	Zinc finger	809 – 865	57	PHD-type 2
Sites
	Metal binding	190	1	Iron; catalytic By similarity
	Metal binding	192	1	Iron; catalytic By similarity
	Metal binding	236	1	Zinc By similarity
	Metal binding	242	1	Zinc By similarity
	Metal binding	278	1	Iron; catalytic By similarity
	Metal binding	308	1	Zinc By similarity
	Metal binding	310	1	Zinc By similarity
	Binding site	134	1	Alpha-ketoglutarate By similarity
	Binding site	200	1	Alpha-ketoglutarate By similarity
	Binding site	208	1	Alpha-ketoglutarate By similarity
Natural variations
	Alternative sequence	999 – 1056	58	STASD…CQKRQ → VSAGRCHLGTCQVNSLSSPH VSQAQQETYLGFWINSKKSQ CNIFLSGTY in isoform 2.		VSP_018311
	Natural variant	206	1	E → D: dbSNP rs7864351.		VAR_049660
	Natural variant	396	1	D → N: dbSNP rs2296067.		VAR_020340
	Natural variant	492	1	S → T: dbSNP rs35826653. Ref.1 Ref.2		VAR_049661
	Natural variant	697	1	N → S: dbSNP rs35389625.		VAR_049662
	Natural variant	767	1	Q → E: dbSNP rs1407856.		VAR_024681
	Natural variant	772	1	K → R: dbSNP rs1417290. Ref.1		VAR_049663
	Natural variant	1039	1	V → I: dbSNP rs913588. Ref.4		VAR_024682
Experimental info
	Sequence conflict	155	1	L → I in BAB16102. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 16, 2006. Version 2. Checksum: CBE871D4FAADD06D	FASTA	1,056	119,982
	10 20 30 40 50 60 MEVAEVESPL NPSCKIMTFR PSMEEFREFN KYLAYMESKG AHRAGLAKVI PPKEWKPRQC 70 80 90 100 110 120 YDDIDNLLIP APIQQMVTGQ SGLFTQYNIQ KKAMTVKEFR QLANSGKYCT PRYLDYEDLE 130 140 150 160 170 180 RKYWKNLTFV APIYGADING SIYDEGVDEW NIARLNTVLD VVEEECGISI EGVNTPYLYF 190 200 210 220 230 240 GMWKTTFAWH TEDMDLYSIN YLHFGEPKSW YAIPPEHGKR LERLAQGFFP SSSQGCDAFL 250 260 270 280 290 300 RHKMTLISPS VLKKYGIPFD KITQEAGEFM ITFPYGYHAG FNHGFNCAES TNFATVRWID 310 320 330 340 350 360 YGKVAKLCTC RKDMVKISMD IFVRKFQPDR YQLWKQGKDI YTIDHTKPTP ASTPEVKAWL 370 380 390 400 410 420 QRRRKVRKAS RSFQCARSTS KRPKADEEEE VSDEVDGAEV PNPDSVTDDL KVSEKSEAAV 430 440 450 460 470 480 KLRNTEASSE EESSASRMQV EQNLSDHIKL SGNSCLSTSV TEDIKTEDDK AYAYRSVPSI 490 500 510 520 530 540 SSEADDSIPL SSGYEKPEKS DPSELSWPKS PESCSSVAES NGVLTEGEES DVESHGNGLE 550 560 570 580 590 600 PGEIPAVPSG ERNSFKVPSI AEGENKTSKS WRHPLSRPPA RSPMTLVKQQ APSDEELPEV 610 620 630 640 650 660 LSIEEEVEET ESWAKPLIHL WQTKSPNFAA EQEYNATVAR MKPHCAICTL LMPYHKPDSS 670 680 690 700 710 720 NEENDARWET KLDEVVTSEG KTKPLIPEMC FIYSEENIEY SPPNAFLEED GTSLLISCAK 730 740 750 760 770 780 CCVRVHASCY GIPSHEICDG WLCARCKRNA WTAECCLCNL RGGALKQTKN NKWAHVMCAV 790 800 810 820 830 840 AVPEVRFTNV PERTQIDVGR IPLQRLKLKC IFCRHRVKRV SGACIQCSYG RCPASFHVTC 850 860 870 880 890 900 AHAAGVLMEP DDWPYVVNIT CFRHKVNPNV KSKACEKVIS VGQTVITKHR NTRYYSCRVM 910 920 930 940 950 960 AVTSQTFYEV MFDDGSFSRD TFPEDIVSRD CLKLGPPAEG EVVQVKWPDG KLYGAKYFGS 970 980 990 1000 1010 1020 NIAHMYQVEF EDGSQIAMKR EDIYTLDEEL PKRVKARFST ASDMRFEDTF YGADIIQGER 1030 1040 1050 KRQRVLSSRF KNEYVADPVY RTFLKSSFQK KCQKRQ
	Isoform 2. Checksum: 5A6E06262786B259	FASTA	1,047	118,416
	10 20 30 40 50 60 MEVAEVESPL NPSCKIMTFR PSMEEFREFN KYLAYMESKG AHRAGLAKVI PPKEWKPRQC 70 80 90 100 110 120 YDDIDNLLIP APIQQMVTGQ SGLFTQYNIQ KKAMTVKEFR QLANSGKYCT PRYLDYEDLE 130 140 150 160 170 180 RKYWKNLTFV APIYGADING SIYDEGVDEW NIARLNTVLD VVEEECGISI EGVNTPYLYF 190 200 210 220 230 240 GMWKTTFAWH TEDMDLYSIN YLHFGEPKSW YAIPPEHGKR LERLAQGFFP SSSQGCDAFL 250 260 270 280 290 300 RHKMTLISPS VLKKYGIPFD KITQEAGEFM ITFPYGYHAG FNHGFNCAES TNFATVRWID 310 320 330 340 350 360 YGKVAKLCTC RKDMVKISMD IFVRKFQPDR YQLWKQGKDI YTIDHTKPTP ASTPEVKAWL 370 380 390 400 410 420 QRRRKVRKAS RSFQCARSTS KRPKADEEEE VSDEVDGAEV PNPDSVTDDL KVSEKSEAAV 430 440 450 460 470 480 KLRNTEASSE EESSASRMQV EQNLSDHIKL SGNSCLSTSV TEDIKTEDDK AYAYRSVPSI 490 500 510 520 530 540 SSEADDSIPL SSGYEKPEKS DPSELSWPKS PESCSSVAES NGVLTEGEES DVESHGNGLE 550 560 570 580 590 600 PGEIPAVPSG ERNSFKVPSI AEGENKTSKS WRHPLSRPPA RSPMTLVKQQ APSDEELPEV 610 620 630 640 650 660 LSIEEEVEET ESWAKPLIHL WQTKSPNFAA EQEYNATVAR MKPHCAICTL LMPYHKPDSS 670 680 690 700 710 720 NEENDARWET KLDEVVTSEG KTKPLIPEMC FIYSEENIEY SPPNAFLEED GTSLLISCAK 730 740 750 760 770 780 CCVRVHASCY GIPSHEICDG WLCARCKRNA WTAECCLCNL RGGALKQTKN NKWAHVMCAV 790 800 810 820 830 840 AVPEVRFTNV PERTQIDVGR IPLQRLKLKC IFCRHRVKRV SGACIQCSYG RCPASFHVTC 850 860 870 880 890 900 AHAAGVLMEP DDWPYVVNIT CFRHKVNPNV KSKACEKVIS VGQTVITKHR NTRYYSCRVM 910 920 930 940 950 960 AVTSQTFYEV MFDDGSFSRD TFPEDIVSRD CLKLGPPAEG EVVQVKWPDG KLYGAKYFGS 970 980 990 1000 1010 1020 NIAHMYQVEF EDGSQIAMKR EDIYTLDEEL PKRVKARFVS AGRCHLGTCQ VNSLSSPHVS 1030 1040 QAQQETYLGF WINSKKSQCN IFLSGTY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines." Yang Z.Q., Imoto I., Fukuda Y., Pimkhaokham A., Shimada Y., Imamura M., Sugano S., Nakamura Y., Inazawa J. Cancer Res. 60:4735-4739(2000) [PubMed: 10987278] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS THR-492 AND ARG-772.
[2]	"Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:277-286(1998) [PubMed: 9872452] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT THR-492. Tissue: Brain.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-1039. Tissue: Liver.
[5]	"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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB037901 mRNA. Translation: BAB16102.1. AB018323 mRNA. Translation: BAA34500.1. Different initiation. AL354707 , AL137020, AL161443, AL445592, AL513412 Genomic DNA. Translation: CAH73283.1. AL354707 , AL137020, AL161443, AL513412, AL445592 Genomic DNA. Translation: CAH73284.1. AL445592 , AL161443, AL513412, AL354707, AL137020 Genomic DNA. Translation: CAI16322.1. AL445592 , AL137020, AL354707, AL513412, AL161443 Genomic DNA. Translation: CAI16323.1. AL137020 , AL161443, AL513412, AL445592, AL354707 Genomic DNA. Translation: CAI39531.1. AL137020 , AL354707, AL513412, AL445592, AL161443 Genomic DNA. Translation: CAI39532.1. AL137020, AL161443, AL513412 Genomic DNA. Translation: CAI39533.1. Sequence problems. AL161443 , AL137020, AL354707, AL513412, AL445592 Genomic DNA. Translation: CAI39606.1. AL161443 , AL513412, AL445592, AL354707, AL137020 Genomic DNA. Translation: CAI39607.1. AL161443, AL137020, AL513412 Genomic DNA. Translation: CAI39608.1. Sequence problems. BC104859 mRNA. Translation: AAI04860.1. BC104861 mRNA. Translation: AAI04862.1.
IPI	IPI00027642. IPI00645825.
RefSeq	NP_055876.2.
UniGene	Hs.709425
3D structure databases
SMR	Q9H3R0. Positions 10-357.
ModBase	Search...
Proteomic databases
PRIDE	Q9H3R0.
Genome annotation databases
Ensembl	ENSG00000107077. Homo sapiens. [Contig view]
GeneID	23081.
KEGG	hsa:23081.
NMPDR	fig|9606.3.peg.31026.
Organism-specific databases
GeneCards	GC09P006731.
H-InvDB	HIX0017555.
HGNC	HGNC:17071. KDM4C.
MIM	605469. gene.
PharmGKB	PA134923378.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9H3R0.
HOVERGEN	Q9H3R0.
OMA	Q9H3R0. NIAHMYQ.
Enzyme and pathway databases
Pathway_Interaction_DB	ar_pathway. Coregulation of Androgen receptor activity.
Gene expression databases
ArrayExpress	Q9H3R0.
Bgee	Q9H3R0.
CleanEx	HS_JMJD2C.
GermOnline	ENSG00000107077. Homo sapiens.
Family and domain databases
InterPro	IPR013129. TF_JmjC. IPR003347. TF_JmjC_AAH. IPR003349. TF_JmjN. IPR002999. Tudor. IPR019786. Zinc_finger_PHD-type_CS. IPR001965. Znf_PHD. [Graphical view]
Pfam	PF02373. JmjC. 1 hit. PF02375. JmjN. 1 hit. [Graphical view]
SMART	SM00558. JmjC. 1 hit. SM00545. JmjN. 1 hit. SM00249. PHD. 2 hits. SM00333. TUDOR. 2 hits. [Graphical view]
PROSITE	PS51184. JMJC. 1 hit. PS51183. JMJN. 1 hit. PS50304. TUDOR. False negative. PS01359. ZF_PHD_1. False negative. PS50016. ZF_PHD_2. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	44205.
SOURCE	Search...

Entry information

Entry name

KDM4C_HUMAN

Accession

Primary (citable) accession number: Q9H3R0
Secondary accession number(s): O94877 , Q2M3M0, Q5JUC9, Q5VYJ2, Q5VYJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 16, 2004
Last sequence update:	May 16, 2006
Last modified:	June 16, 2009
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)