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Protein

Lysine-specific demethylase 4C

Gene

KDM4C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.2 Publications

Cofactori

Fe2+1 PublicationNote: Binds 1 Fe2+ ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1342-oxoglutarateBy similarity1
Metal bindingi190Iron; catalytic1
Metal bindingi192Iron; catalytic1
Binding sitei2002-oxoglutarateBy similarity1
Binding sitei2082-oxoglutarateBy similarity1
Metal bindingi236Zinc1 Publication1
Metal bindingi242Zinc1 Publication1
Binding sitei2432-oxoglutarateBy similarity1
Metal bindingi278Iron; catalytic1
Metal bindingi308Zinc1 Publication1
Metal bindingi310Zinc1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri689 – 747PHD-type 1Add BLAST59
Zinc fingeri752 – 785C2HC pre-PHD-typePROSITE-ProRule annotationAdd BLAST34
Zinc fingeri808 – 865PHD-type 2PROSITE-ProRule annotationAdd BLAST58

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Dioxygenase, Oxidoreductase
Biological processTranscription, Transcription regulation
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi1.14.11.27 2681
1.14.11.B1 2681
ReactomeiR-HSA-3214842 HDMs demethylate histones
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
SIGNORiQ9H3R0

Names & Taxonomyi

Protein namesi
Recommended name:
Lysine-specific demethylase 4C (EC:1.14.11.-)
Alternative name(s):
Gene amplified in squamous cell carcinoma 1 protein
Short name:
GASC-1 protein
JmjC domain-containing histone demethylation protein 3C
Jumonji domain-containing protein 2C
Gene namesi
Name:KDM4C
Synonyms:GASC1, JHDM3C, JMJD2C, KIAA0780
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000107077.17
HGNCiHGNC:17071 KDM4C
MIMi605469 gene
neXtProtiNX_Q9H3R0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi190 – 192HTE → ATA: Abolishes lysine-specific histone demethylase activity. 1 Publication3

Organism-specific databases

DisGeNETi23081
OpenTargetsiENSG00000107077
PharmGKBiPA164721503

Chemistry databases

ChEMBLiCHEMBL6175
GuidetoPHARMACOLOGYi2677

Polymorphism and mutation databases

BioMutaiKDM4C
DMDMi97536525

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001831771 – 1056Lysine-specific demethylase 4CAdd BLAST1056

Proteomic databases

EPDiQ9H3R0
MaxQBiQ9H3R0
PaxDbiQ9H3R0
PeptideAtlasiQ9H3R0
PRIDEiQ9H3R0
ProteomicsDBi80741
80742 [Q9H3R0-2]

PTM databases

iPTMnetiQ9H3R0
PhosphoSitePlusiQ9H3R0

Expressioni

Tissue specificityi

Overexpressed in several esophageal squamous cell carcinomas (ESCs).1 Publication

Gene expression databases

BgeeiENSG00000107077 Expressed in 203 organ(s), highest expression level in cerebellar hemisphere
CleanExiHS_JMJD2C
ExpressionAtlasiQ9H3R0 baseline and differential
GenevisibleiQ9H3R0 HS

Organism-specific databases

HPAiHPA069357

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116712, 13 interactors
DIPiDIP-60098N
IntActiQ9H3R0, 1 interactor
STRINGi9606.ENSP00000370710

Chemistry databases

BindingDBiQ9H3R0

Structurei

Secondary structure

11056
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9H3R0
SMRiQ9H3R0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H3R0

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 58JmjNPROSITE-ProRule annotationAdd BLAST43
Domaini144 – 310JmjCPROSITE-ProRule annotationAdd BLAST167
Domaini877 – 934Tudor 1Add BLAST58
Domaini935 – 991Tudor 2Add BLAST57

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the JHDM3 histone demethylase family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri689 – 747PHD-type 1Add BLAST59
Zinc fingeri752 – 785C2HC pre-PHD-typePROSITE-ProRule annotationAdd BLAST34
Zinc fingeri808 – 865PHD-type 2PROSITE-ProRule annotationAdd BLAST58

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IT40 Eukaryota
COG5141 LUCA
GeneTreeiENSGT00530000063342
HOGENOMiHOG000231125
HOVERGENiHBG080483
InParanoidiQ9H3R0
KOiK06709
OMAiDGSQIAM
OrthoDBiEOG091G01FR
PhylomeDBiQ9H3R0
TreeFamiTF106449

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR034732 EPHD
IPR003347 JmjC_dom
IPR003349 JmjN
IPR002999 Tudor
IPR011011 Znf_FYVE_PHD
IPR001965 Znf_PHD
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF02373 JmjC, 1 hit
PF02375 JmjN, 1 hit
SMARTiView protein in SMART
SM00558 JmjC, 1 hit
SM00545 JmjN, 1 hit
SM00249 PHD, 2 hits
SM00333 TUDOR, 2 hits
SUPFAMiSSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS51805 EPHD, 1 hit
PS51184 JMJC, 1 hit
PS51183 JMJN, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9H3R0-1) [UniParc]FASTAAdd to basket

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.

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

KCQKRQ
Length:1,056
Mass (Da):119,982
Last modified:May 16, 2006 - v2
Checksum:iCBE871D4FAADD06D
GO
Isoform 2 (identifier: Q9H3R0-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:1,047
Mass (Da):118,416
Checksum:i5A6E06262786B259
GO
Isoform 3 (identifier: Q9H3R0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     809-813: KCIFC → GRLGI
     814-1056: Missing.

Note: No experimental confirmation available.
Show »
Length:813
Mass (Da):91,891
Checksum:i672012048DEE27AC
GO
Isoform 4 (identifier: Q9H3R0-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MKHYGLPWKRTEEAAADTALTIM
     809-813: KCIFC → GRLGI
     814-1056: Missing.

Note: No experimental confirmation available.
Show »
Length:835
Mass (Da):94,376
Checksum:iB08576383C57FE4B
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WCN1F8WCN1_HUMAN
Lysine-specific demethylase 4C
KDM4C
373Annotation score:
C9J879C9J879_HUMAN
Lysine-specific demethylase 4C
KDM4C
743Annotation score:
A0A0A0MSR6A0A0A0MSR6_HUMAN
Lysine-specific demethylase 4C
KDM4C
354Annotation score:
B0QZ60B0QZ60_HUMAN
Lysine-specific demethylase 4C
KDM4C
151Annotation score:

Sequence cautioni

The sequence BAA34500 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti155L → I in BAB16102 (PubMed:10987278).Curated1
Sequence conflicti514C → S in BAG64946 (PubMed:14702039).Curated1
Sequence conflicti807K → R in BAG64946 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049660206E → D. Corresponds to variant dbSNP:rs7864351Ensembl.1
Natural variantiVAR_020340396D → N. Corresponds to variant dbSNP:rs2296067Ensembl.1
Natural variantiVAR_049661492S → T3 PublicationsCorresponds to variant dbSNP:rs35826653Ensembl.1
Natural variantiVAR_049662697N → S. Corresponds to variant dbSNP:rs35389625Ensembl.1
Natural variantiVAR_024681767Q → E. Corresponds to variant dbSNP:rs1407856Ensembl.1
Natural variantiVAR_049663772K → R1 PublicationCorresponds to variant dbSNP:rs1417290Ensembl.1
Natural variantiVAR_0246821039V → I1 PublicationCorresponds to variant dbSNP:rs913588Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0461131M → MKHYGLPWKRTEEAAADTAL TIM in isoform 4. 1 Publication1
Alternative sequenceiVSP_045462809 – 813KCIFC → GRLGI in isoform 3 and isoform 4. 1 Publication5
Alternative sequenceiVSP_045463814 – 1056Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST243
Alternative sequenceiVSP_018311999 – 1056STASD…CQKRQ → VSAGRCHLGTCQVNSLSSPH VSQAQQETYLGFWINSKKSQ CNIFLSGTY in isoform 2. 1 PublicationAdd BLAST58

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037901 mRNA Translation: BAB16102.1
AB018323 mRNA Translation: BAA34500.1 Different initiation.
AK304032 mRNA Translation: BAG64946.1
AK310439 mRNA No translation available.
AL137020 Genomic DNA No translation available.
AL161443 Genomic DNA No translation available.
AL354707 Genomic DNA No translation available.
AL445592 Genomic DNA No translation available.
AL513412 Genomic DNA No translation available.
BC104859 mRNA Translation: AAI04860.1
BC104861 mRNA Translation: AAI04862.1
BC143571 mRNA Translation: AAI43572.1
CCDSiCCDS55285.1 [Q9H3R0-4]
CCDS55286.1 [Q9H3R0-3]
CCDS6471.1 [Q9H3R0-1]
RefSeqiNP_001140167.1, NM_001146695.1 [Q9H3R0-3]
NP_001140168.1, NM_001146696.1 [Q9H3R0-4]
NP_055876.2, NM_015061.3 [Q9H3R0-1]
UniGeneiHs.709425

Genome annotation databases

EnsembliENST00000381306; ENSP00000370707; ENSG00000107077 [Q9H3R0-2]
ENST00000381309; ENSP00000370710; ENSG00000107077 [Q9H3R0-1]
ENST00000536108; ENSP00000440656; ENSG00000107077 [Q9H3R0-4]
ENST00000543771; ENSP00000445427; ENSG00000107077 [Q9H3R0-3]
GeneIDi23081
KEGGihsa:23081
UCSCiuc003zkg.4 human [Q9H3R0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037901 mRNA Translation: BAB16102.1
AB018323 mRNA Translation: BAA34500.1 Different initiation.
AK304032 mRNA Translation: BAG64946.1
AK310439 mRNA No translation available.
AL137020 Genomic DNA No translation available.
AL161443 Genomic DNA No translation available.
AL354707 Genomic DNA No translation available.
AL445592 Genomic DNA No translation available.
AL513412 Genomic DNA No translation available.
BC104859 mRNA Translation: AAI04860.1
BC104861 mRNA Translation: AAI04862.1
BC143571 mRNA Translation: AAI43572.1
CCDSiCCDS55285.1 [Q9H3R0-4]
CCDS55286.1 [Q9H3R0-3]
CCDS6471.1 [Q9H3R0-1]
RefSeqiNP_001140167.1, NM_001146695.1 [Q9H3R0-3]
NP_001140168.1, NM_001146696.1 [Q9H3R0-4]
NP_055876.2, NM_015061.3 [Q9H3R0-1]
UniGeneiHs.709425

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XDPX-ray1.56A875-995[»]
2XMLX-ray2.55A/B1-347[»]
4XDOX-ray1.97A/B10-347[»]
4XDPX-ray2.07A/B10-347[»]
5FJHX-ray2.10A/B3-347[»]
5FJKX-ray1.66A3-347[»]
5KR7X-ray1.90A/B1-350[»]
ProteinModelPortaliQ9H3R0
SMRiQ9H3R0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116712, 13 interactors
DIPiDIP-60098N
IntActiQ9H3R0, 1 interactor
STRINGi9606.ENSP00000370710

Chemistry databases

BindingDBiQ9H3R0
ChEMBLiCHEMBL6175
GuidetoPHARMACOLOGYi2677

PTM databases

iPTMnetiQ9H3R0
PhosphoSitePlusiQ9H3R0

Polymorphism and mutation databases

BioMutaiKDM4C
DMDMi97536525

Proteomic databases

EPDiQ9H3R0
MaxQBiQ9H3R0
PaxDbiQ9H3R0
PeptideAtlasiQ9H3R0
PRIDEiQ9H3R0
ProteomicsDBi80741
80742 [Q9H3R0-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381306; ENSP00000370707; ENSG00000107077 [Q9H3R0-2]
ENST00000381309; ENSP00000370710; ENSG00000107077 [Q9H3R0-1]
ENST00000536108; ENSP00000440656; ENSG00000107077 [Q9H3R0-4]
ENST00000543771; ENSP00000445427; ENSG00000107077 [Q9H3R0-3]
GeneIDi23081
KEGGihsa:23081
UCSCiuc003zkg.4 human [Q9H3R0-1]

Organism-specific databases

CTDi23081
DisGeNETi23081
EuPathDBiHostDB:ENSG00000107077.17
GeneCardsiKDM4C
H-InvDBiHIX0017555
HGNCiHGNC:17071 KDM4C
HPAiHPA069357
MIMi605469 gene
neXtProtiNX_Q9H3R0
OpenTargetsiENSG00000107077
PharmGKBiPA164721503
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IT40 Eukaryota
COG5141 LUCA
GeneTreeiENSGT00530000063342
HOGENOMiHOG000231125
HOVERGENiHBG080483
InParanoidiQ9H3R0
KOiK06709
OMAiDGSQIAM
OrthoDBiEOG091G01FR
PhylomeDBiQ9H3R0
TreeFamiTF106449

Enzyme and pathway databases

BRENDAi1.14.11.27 2681
1.14.11.B1 2681
ReactomeiR-HSA-3214842 HDMs demethylate histones
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
SIGNORiQ9H3R0

Miscellaneous databases

ChiTaRSiKDM4C human
EvolutionaryTraceiQ9H3R0
GeneWikiiJMJD2C
GenomeRNAii23081
PROiPR:Q9H3R0
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107077 Expressed in 203 organ(s), highest expression level in cerebellar hemisphere
CleanExiHS_JMJD2C
ExpressionAtlasiQ9H3R0 baseline and differential
GenevisibleiQ9H3R0 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR034732 EPHD
IPR003347 JmjC_dom
IPR003349 JmjN
IPR002999 Tudor
IPR011011 Znf_FYVE_PHD
IPR001965 Znf_PHD
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF02373 JmjC, 1 hit
PF02375 JmjN, 1 hit
SMARTiView protein in SMART
SM00558 JmjC, 1 hit
SM00545 JmjN, 1 hit
SM00249 PHD, 2 hits
SM00333 TUDOR, 2 hits
SUPFAMiSSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS51805 EPHD, 1 hit
PS51184 JMJC, 1 hit
PS51183 JMJN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKDM4C_HUMAN
AccessioniPrimary (citable) accession number: Q9H3R0
Secondary accession number(s): B4E1Y4
, B7ZL46, F5H347, F5H7P0, O94877, Q2M3M0, Q5JUC9, Q5VYJ2, Q5VYJ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: May 16, 2006
Last modified: November 7, 2018
This is version 159 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
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