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Overview

Uniprot IDP29375
Protein NameLysine-specific demethylase 5A
Gene NameKDM5A
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1422 TPRKQPRKSPLVPRS
238 SRNTELKKLQIFGAG

Function

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'. Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif (PubMed:18270511). May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation (PubMed:19430464). May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity). Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells (PubMed:27427228)

Protein Sequence

10 MAGVGPGGYA 20 AEFVPPPECP 30 VFEPSWEEFT 40 DPLSFIGRIR 50 PLAEKTGICK 60 IRPPKDWQPP 70 FACEVKSFRF 80 TPRVQRLNEL 90 EAMTRVRLDF 100 LDQLAKFWEL 110 QGSTLKIPVV 120 ERKILDLYAL 130 SKIVASKGGF 140 EMVTKEKKWS 150 KVGSRLGYLP 160 GKGTGSLLKS 170 HYERILYPYE 180 LFQSGVSLMG 190 VQMPNLDLKE 200 KVEPEVLSTD 210 TQTSPEPGTR 220 MNILPKRTRR 230 VKTQSESGDV 240 SRNTELKKLQ 250 IFGAGPKVVG 260 LAMGTKDKED 270 EVTRRRKVTN 280 RSDAFNMQMR 290 QRKGTLSVNF 300 VDLYVCMFCG 310 RGNNEDKLLL 320 CDGCDDSYHT 330 FCLIPPLPDV 340 PKGDWRCPKC 350 VAEECSKPRE 360 AFGFEQAVRE 370 YTLQSFGEMA 380 DNFKSDYFNM 390 PVHMVPTELV 400 EKEFWRLVSS 410 IEEDVIVEYG 420 ADISSKDFGS 430 GFPVKDGRRK 440 ILPEEEEYAL 450 SGWNLNNMPV 460 LEQSVLAHIN 470 VDISGMKVPW 480 LYVGMCFSSF 490 CWHIEDHWSY 500 SINYLHWGEP 510 KTWYGVPSHA 520 AEQLEEVMRE 530 LAPELFESQP 540 DLLHQLVTIM 550 NPNVLMEHGV 560 PVYRTNQCAG 570 EFVVTFPRAY 580 HSGFNQGYNF 590 AEAVNFCTAD 600 WLPIGRQCVN 610 HYRRLRRHCV 620 FSHEELIFKM 630 AADPECLDVG 640 LAAMVCKELT 650 LMTEEETRLR 660 ESVVQMGVLM 670 SEEEVFELVP 680 DDERQCSACR 690 TTCFLSALTC 700 SCNPERLVCL 710 YHPTDLCPCP 720 MQKKCLRYRY 730 PLEDLPSLLY 740 GVKVRAQSYD 750 TWVSRVTEAL 760 SANFNHKKDL 770 IELRVMLEDA 780 EDRKYPENDL 790 FRKLRDAVKE 800 AETCASVAQL 810 LLSKKQKHRQ 820 SPDSGRTRTK 830 LTVEELKAFV 840 QQLFSLPCVI 850 SQARQVKNLL 860 DDVEEFHERA 870 QEAMMDETPD 880 SSKLQMLIDM 890 GSSLYVELPE 900 LPRLKQELQQ 910 ARWLDEVRLT 920 LSDPQQVTLD 930 VMKKLIDSGV 940 GLAPHHAVEK 950 AMAELQELLT 960 VSERWEEKAK 970 VCLQARPRHS 980 VASLESIVNE 990 AKNIPAFLPN 1000 VLSLKEALQK 1010 AREWTAKVEA 1020 IQSGSNYAYL 1030 EQLESLSAKG 1040 RPIPVRLEAL 1050 PQVESQVAAA 1060 RAWRERTGRT 1070 FLKKNSSHTL 1080 LQVLSPRTDI 1090 GVYGSGKNRR 1100 KKVKELIEKE 1110 KEKDLDLEPL 1120 SDLEEGLEET 1130 RDTAMVVAVF 1140 KEREQKEIEA 1150 MHSLRAANLA 1160 KMTMVDRIEE 1170 VKFCICRKTA 1180 SGFMLQCELC 1190 KDWFHNSCVP 1200 LPKSSSQKKG 1210 SSWQAKEVKF 1220 LCPLCMRSRR 1230 PRLETILSLL 1240 VSLQKLPVRL 1250 PEGEALQCLT 1260 ERAMSWQDRA 1270 RQALATDELS 1280 SALAKLSVLS 1290 QRMVEQAARE 1300 KTEKIISAEL 1310 QKAAANPDLQ 1320 GHLPSFQQSA 1330 FNRVVSSVSS 1340 SPRQTMDYDD 1350 EETDSDEDIR 1360 ETYGYDMKDT 1370 ASVKSSSSLE 1380 PNLFCDEEIP 1390 IKSEEVVTHM 1400 WTAPSFCAEH 1410 AYSSASKSCS 1420 QGSSTPRKQP 1430 RKSPLVPRSL 1440 EPPVLELSPG 1450 AKAQLEELMM 1460 VGDLLEVSLD 1470 ETQHIWRILQ 1480 ATHPPSEDRF 1490 LHIMEDDSME 1500 EKPLKVKGKD 1510 SSEKKRKRKL 1520 EKVEQLFGEG 1530 KQKSKELKKM 1540 DKPRKKKLKL 1550 GADKSKELNK 1560 LAKKLAKEEE 1570 RKKKKEKAAA 1580 AKVELVKEST 1590 EKKREKKVLD 1600 IPSKYDWSGA 1610 EESDDENAVC 1620 AAQNCQRPCK 1630 DKVDWVQCDG 1640 GCDEWFHQVC 1650 VGVSPEMAEN 1660 EDYICINCAK 1670 KQGPVSPGPA 1680 PPPSFIMSYK 1690 LPMEDLKETS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0016604 nuclear body
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032993 protein-DNA complex
Molecular Function GO:0031490 chromatin DNA binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0004857 enzyme inhibitor activity
Molecular Function GO:0042393 histone binding
Molecular Function GO:0032452 histone demethylase activity
Molecular Function GO:0034647 histone H3K4me/H3K4me2/H3K4me3 demethylase activity
Molecular Function GO:0000976 transcription cis-regulatory region binding
Molecular Function GO:0003713 transcription coactivator activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006338 chromatin remodeling
Biological Process GO:0032922 circadian regulation of gene expression
Biological Process GO:0140718 facultative heterochromatin formation
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0045815 transcription initiation-coupled chromatin remodeling

Reference

[1] Chao L, Xu Y, Yang Y, Ao X, Liang J. Identification of lactylation-related biomarkers for diagnosis, prognosis, and treatment responsiveness in triple-negative breast cancer.. World J Surg Oncol 24(1):77. 2026 Jan 22. PMID: 41566505.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.