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Protein

Lysine-specific demethylase 5D

Gene

KDM5D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May play a role in spermatogenesis. Involved in transcriptional repression of diverse metastasis-associated genes; in this function seems to cooperate with ZMYND8. Suppresses prostate cancer cell invasion. Regulates androgen receptor (AR) transcriptional activity by demethylating H3K4me3 active transcription marks.7 Publications

Miscellaneous

Involved in sensitivity to docetaxel.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • L-ascorbate1 Publication
  • Fe2+1 PublicationNote: Binds 1 Fe2+ ion per subunit.1 Publication

Kineticsi

Kcat are 2.6 min(-1) and 3.0 min(-1) for 2-oxoglutarate and histone H3K4me3, respectively.1 Publication
  1. KM=10 µM for 2-oxoglutarate1 Publication
  2. KM=6.2 µM for histone H3K4me31 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei4302-oxoglutarateBy similarity1
    Metal bindingi504Iron; catalyticPROSITE-ProRule annotation1
    Metal bindingi506Iron; catalyticBy similarity1
    Binding sitei5122-oxoglutarateBy similarity1
    Binding sitei5142-oxoglutarateBy similarity1
    Binding sitei5222-oxoglutarateBy similarity1
    Metal bindingi592Iron; catalyticPROSITE-ProRule annotation1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri316 – 362PHD-type 1PROSITE-ProRule annotationAdd BLAST47
    Zinc fingeri697 – 749C5HC2By similarityAdd BLAST53
    Zinc fingeri1174 – 1235PHD-type 2PROSITE-ProRule annotationAdd BLAST62

    GO - Molecular functioni

    GO - Biological processi

    • histone H3-K4 demethylation Source: MGI
    • regulation of androgen receptor signaling pathway Source: UniProtKB
    • regulation of transcription, DNA-templated Source: UniProtKB-KW
    • T cell antigen processing and presentation Source: Ensembl
    • transcription, DNA-templated Source: UniProtKB-KW

    Keywordsi

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

    Enzyme and pathway databases

    ReactomeiR-HSA-3214842. HDMs demethylate histones.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Lysine-specific demethylase 5D (EC:1.14.11.-)
    Alternative name(s):
    Histocompatibility Y antigen
    Short name:
    H-Y
    Histone demethylase JARID1D
    Jumonji/ARID domain-containing protein 1D
    Protein SmcY
    Gene namesi
    Name:KDM5D
    Synonyms:HY, HYA, JARID1D, KIAA0234, SMCY
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome Y

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000012817.15.
    HGNCiHGNC:11115. KDM5D.

    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
    Mutagenesisi534H → A: Abolishes enzymatic activity; when associated with A-536. 1 Publication1
    Mutagenesisi536E → A: Abolishes enzymatic activity; when associated with A-534. 1 Publication1

    Organism-specific databases

    DisGeNETi8284.
    GeneReviewsiKDM5D.
    OpenTargetsiENSG00000012817.
    PharmGKBiPA35965.

    Chemistry databases

    DrugBankiDB00126. Vitamin C.

    Polymorphism and mutation databases

    BioMutaiKDM5D.
    DMDMi17368706.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002005881 – 1539Lysine-specific demethylase 5DAdd BLAST1539

    Proteomic databases

    MaxQBiQ9BY66.
    PaxDbiQ9BY66.
    PeptideAtlasiQ9BY66.
    PRIDEiQ9BY66.

    PTM databases

    iPTMnetiQ9BY66.
    PhosphoSitePlusiQ9BY66.

    Expressioni

    Tissue specificityi

    Expression is highly down-regulated in metastatic prostate tumors.1 Publication

    Gene expression databases

    BgeeiENSG00000012817.
    CleanExiHS_JARID1D.
    ExpressionAtlasiQ9BY66. baseline and differential.
    GenevisibleiQ9BY66. HS.

    Organism-specific databases

    HPAiHPA049086.
    HPA060807.

    Interactioni

    Subunit structurei

    Interacts with PCGF6, MSH5, ZMYND8, AR.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ARP102752EBI-1246860,EBI-608057

    GO - Molecular functioni

    • androgen receptor binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi113891. 2 interactors.
    IntActiQ9BY66. 2 interactors.
    STRINGi9606.ENSP00000444293.

    Chemistry databases

    BindingDBiQ9BY66.

    Structurei

    Secondary structure

    11539
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi81 – 96Combined sources16
    Beta strandi106 – 109Combined sources4
    Helixi112 – 122Combined sources11
    Helixi125 – 130Combined sources6
    Turni131 – 133Combined sources3
    Helixi134 – 140Combined sources7
    Helixi149 – 159Combined sources11
    Helixi161 – 167Combined sources7
    Beta strandi318 – 320Combined sources3
    Helixi324 – 328Combined sources5
    Turni333 – 335Combined sources3
    Beta strandi341 – 346Combined sources6
    Helixi359 – 366Combined sources8

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2E6RNMR-A306-384[»]
    2YQENMR-A79-171[»]
    ProteinModelPortaliQ9BY66.
    SMRiQ9BY66.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9BY66.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini14 – 55JmjNPROSITE-ProRule annotationAdd BLAST42
    Domaini79 – 169ARIDPROSITE-ProRule annotationAdd BLAST91
    Domaini458 – 624JmjCPROSITE-ProRule annotationAdd BLAST167

    Domaini

    The JmjC domain is required for enzymatic activity.

    Sequence similaritiesi

    Belongs to the JARID1 histone demethylase family.Curated

    Zinc finger

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri316 – 362PHD-type 1PROSITE-ProRule annotationAdd BLAST47
    Zinc fingeri697 – 749C5HC2By similarityAdd BLAST53
    Zinc fingeri1174 – 1235PHD-type 2PROSITE-ProRule annotationAdd BLAST62

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiKOG1246. Eukaryota.
    ENOG410XR9J. LUCA.
    GeneTreeiENSGT00530000063118.
    HOGENOMiHOG000290719.
    InParanoidiQ9BY66.
    KOiK11446.
    OMAiCILAECK.
    OrthoDBiEOG091G0RFR.
    PhylomeDBiQ9BY66.
    TreeFamiTF106476.

    Family and domain databases

    Gene3Di1.10.150.60. 1 hit.
    3.30.40.10. 2 hits.
    InterProiView protein in InterPro
    IPR001606. ARID_dom.
    IPR036431. ARID_dom_sf.
    IPR003347. JmjC_dom.
    IPR003349. JmjN.
    IPR013637. Lys_sp_deMease-like_dom.
    IPR019786. Zinc_finger_PHD-type_CS.
    IPR004198. Znf_C5HC2.
    IPR011011. Znf_FYVE_PHD.
    IPR001965. Znf_PHD.
    IPR019787. Znf_PHD-finger.
    IPR013083. Znf_RING/FYVE/PHD.
    PfamiView protein in Pfam
    PF01388. ARID. 1 hit.
    PF02373. JmjC. 1 hit.
    PF02375. JmjN. 1 hit.
    PF00628. PHD. 1 hit.
    PF08429. PLU-1. 1 hit.
    PF02928. zf-C5HC2. 1 hit.
    SMARTiView protein in SMART
    SM00501. BRIGHT. 1 hit.
    SM00558. JmjC. 1 hit.
    SM00545. JmjN. 1 hit.
    SM00249. PHD. 2 hits.
    SUPFAMiSSF46774. SSF46774. 1 hit.
    SSF57903. SSF57903. 2 hits.
    PROSITEiView protein in PROSITE
    PS51011. ARID. 1 hit.
    PS51184. JMJC. 1 hit.
    PS51183. JMJN. 1 hit.
    PS01359. ZF_PHD_1. 2 hits.
    PS50016. ZF_PHD_2. 1 hit.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Note: Additional isoforms seem to exist.
    Isoform 1 (identifier: Q9BY66-1) [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
    MEPGCDEFLP PPECPVFEPS WAEFQDPLGY IAKIRPIAEK SGICKIRPPA
    60 70 80 90 100
    DWQPPFAVEV DNFRFTPRVQ RLNELEAQTR VKLNYLDQIA KFWEIQGSSL
    110 120 130 140 150
    KIPNVERKIL DLYSLSKIVI EEGGYEAICK DRRWARVAQR LHYPPGKNIG
    160 170 180 190 200
    SLLRSHYERI IYPYEMFQSG ANHVQCNTHP FDNEVKDKEY KPHSIPLRQS
    210 220 230 240 250
    VQPSKFSSYS RRAKRLQPDP EPTEEDIEKH PELKKLQIYG PGPKMMGLGL
    260 270 280 290 300
    MAKDKDKTVH KKVTCPPTVT VKDEQSGGGN VSSTLLKQHL SLEPCTKTTM
    310 320 330 340 350
    QLRKNHSSAQ FIDSYICQVC SRGDEDDKLL FCDGCDDNYH IFCLLPPLPE
    360 370 380 390 400
    IPRGIWRCPK CILAECKQPP EAFGFEQATQ EYSLQSFGEM ADSFKSDYFN
    410 420 430 440 450
    MPVHMVPTEL VEKEFWRLVS SIEEDVTVEY GADIHSKEFG SGFPVSNSKQ
    460 470 480 490 500
    NLSPEEKEYA TSGWNLNVMP VLDQSVLCHI NADISGMKVP WLYVGMVFSA
    510 520 530 540 550
    FCWHIEDHWS YSINYLHWGE PKTWYGVPSL AAEHLEEVMK MLTPELFDSQ
    560 570 580 590 600
    PDLLHQLVTL MNPNTLMSHG VPVVRTNQCA GEFVITFPRA YHSGFNQGYN
    610 620 630 640 650
    FAEAVNFCTA DWLPAGRQCI EHYRRLRRYC VFSHEELICK MAAFPETLDL
    660 670 680 690 700
    NLAVAVHKEM FIMVQEERRL RKALLEKGVT EAEREAFELL PDDERQCIKC
    710 720 730 740 750
    KTTCFLSALA CYDCPDGLVC LSHINDLCKC SSSRQYLRYR YTLDELPTML
    760 770 780 790 800
    HKLKIRAESF DTWANKVRVA LEVEDGRKRS FEELRALESE ARERRFPNSE
    810 820 830 840 850
    LLQRLKNCLS EVEACIAQVL GLVSGQVARM DTPQLTLTEL RVLLEQMGSL
    860 870 880 890 900
    PCAMHQIGDV KDVLEQVEAY QAEAREALAT LPSSPGLLRS LLERGQQLGV
    910 920 930 940 950
    EVPEAHQLQQ QVEQAQWLDE VKQALAPSAH RGSLVIMQGL LVMGAKIASS
    960 970 980 990 1000
    PSVDKARAEL QELLTIAERW EEKAHFCLEA RQKHPPATLE AIIRETENIP
    1010 1020 1030 1040 1050
    VHLPNIQALK EALTKAQAWI ADVDEIQNGD HYPCLDDLEG LVAVGRDLPV
    1060 1070 1080 1090 1100
    GLEELRQLEL QVLTAHSWRE KASKTFLKKN SCYTLLEVLC PCADAGSDST
    1110 1120 1130 1140 1150
    KRSRWMEKAL GLYQCDTELL GLSAQDLRDP GSVIVAFKEG EQKEKEGILQ
    1160 1170 1180 1190 1200
    LRRTNSAKPS PLAPSLMASS PTSICVCGQV PAGVGVLQCD LCQDWFHGQC
    1210 1220 1230 1240 1250
    VSVPHLLTSP KPSLTSSPLL AWWEWDTKFL CPLCMRSRRP RLETILALLV
    1260 1270 1280 1290 1300
    ALQRLPVRLP EGEALQCLTE RAIGWQDRAR KALASEDVTA LLRQLAELRQ
    1310 1320 1330 1340 1350
    QLQAKPRPEE ASVYTSATAC DPIREGSGNN ISKVQGLLEN GDSVTSPENM
    1360 1370 1380 1390 1400
    APGKGSDLEL LSSLLPQLTG PVLELPEAIR APLEELMMEG DLLEVTLDEN
    1410 1420 1430 1440 1450
    HSIWQLLQAG QPPDLDRIRT LLELEKFEHQ GSRTRSRALE RRRRRQKVDQ
    1460 1470 1480 1490 1500
    GRNVENLVQQ ELQSKRARSS GIMSQVGREE EHYQEKADRE NMFLTPSTDH
    1510 1520 1530
    SPFLKGNQNS LQHKDSGSSA ACPSLMPLLQ LSYSDEQQL
    Length:1,539
    Mass (Da):174,073
    Last modified:October 24, 2001 - v2
    Checksum:iE58DAE374E3BD7AA
    GO
    Isoform 2 (identifier: Q9BY66-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         118-174: Missing.

    Show »
    Length:1,482
    Mass (Da):167,401
    Checksum:iF1A41999427CA63D
    GO
    Isoform 3 (identifier: Q9BY66-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         457-457: K → KRQSLTVLTRLISSFWAQAVLPPWPPKVLGLQ

    Note: No experimental confirmation available.
    Show »
    Length:1,570
    Mass (Da):177,558
    Checksum:i364A4C31873A1D57
    GO

    Sequence cautioni

    The sequence BAA13241 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti327D → N in AAC50806 (PubMed:8841177).Curated1
    Sequence conflicti327D → N in AAC51135 (PubMed:9060413).Curated1
    Sequence conflicti1285S → F in AAC50806 (PubMed:8841177).Curated1
    Sequence conflicti1352P → L in AAK27839 (Ref. 8) Curated1
    Sequence conflicti1391D → G in AAC50806 (PubMed:8841177).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0329911186V → L1 PublicationCorresponds to variant dbSNP:rs1050807Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_000317118 – 174Missing in isoform 2. 2 PublicationsAdd BLAST57
    Alternative sequenceiVSP_043320457K → KRQSLTVLTRLISSFWAQAV LPPWPPKVLGLQ in isoform 3. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U52191 mRNA. Translation: AAC50806.1.
    D87072 mRNA. Translation: BAA13241.2. Different initiation.
    AF273841 Genomic DNA. Translation: AAG00951.1.
    AC010889 Genomic DNA. No translation available.
    CH471202 Genomic DNA. Translation: EAW54663.1.
    BC132721 mRNA. Translation: AAI32722.1.
    BC144102 mRNA. Translation: AAI44103.1.
    BC146767 mRNA. Translation: AAI46768.1.
    U52365 mRNA. Translation: AAC51135.1.
    AF134849 Genomic DNA. Translation: AAK27839.1.
    CCDSiCCDS14794.1. [Q9BY66-1]
    CCDS55554.1. [Q9BY66-2]
    CCDS55555.1. [Q9BY66-3]
    RefSeqiNP_001140177.1. NM_001146705.1. [Q9BY66-3]
    NP_001140178.1. NM_001146706.1. [Q9BY66-2]
    NP_004644.2. NM_004653.4. [Q9BY66-1]
    UniGeneiHs.80358.

    Genome annotation databases

    EnsembliENST00000317961; ENSP00000322408; ENSG00000012817. [Q9BY66-1]
    ENST00000382806; ENSP00000372256; ENSG00000012817. [Q9BY66-2]
    ENST00000541639; ENSP00000444293; ENSG00000012817. [Q9BY66-3]
    GeneIDi8284.
    KEGGihsa:8284.
    UCSCiuc004fug.4. human. [Q9BY66-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiKDM5D_HUMAN
    AccessioniPrimary (citable) accession number: Q9BY66
    Secondary accession number(s): A2RU19
    , A6H8V7, B7ZLX1, Q92509, Q92809, Q9HCU1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 24, 2001
    Last sequence update: October 24, 2001
    Last modified: October 25, 2017
    This is version 155 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. Human chromosome Y
      Human chromosome Y: entries, gene names and cross-references to MIM
    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. SIMILARITY comments
      Index of protein domains and families