HMGB3_HUMAN
ID HMGB3_HUMAN Reviewed; 200 AA.
AC O15347; O95556; Q6NS40;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=High mobility group protein B3;
DE AltName: Full=High mobility group protein 2a;
DE Short=HMG-2a;
DE AltName: Full=High mobility group protein 4;
DE Short=HMG-4;
GN Name=HMGB3; Synonyms=HMG2A, HMG4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9370291; DOI=10.1016/s0378-1119(97)00324-7;
RA Wilke K., Wiemann S., Gaul R., Gong W., Poustka A.;
RT "Isolation of human and mouse HMG2a cDNAs: evidence for an HMG2a-specific
RT 3' untranslated region.";
RL Gene 198:269-274(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [6]
RP STRUCTURE BY NMR OF 1-164.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first and second HMG-box domain from high
RT mobility group protein B3.";
RL Submitted (APR-2008) to the PDB data bank.
RN [7]
RP VARIANT GLN-56.
RX PubMed=20598277; DOI=10.1016/j.ajhg.2010.06.008;
RA Sun Y., Almomani R., Aten E., Celli J., van der Heijden J., Venselaar H.,
RA Robertson S.P., Baroncini A., Franco B., Basel-Vanagaite L., Horii E.,
RA Drut R., Ariyurek Y., den Dunnen J.T., Breuning M.H.;
RT "Terminal osseous dysplasia is caused by a single recurrent mutation in the
RT FLNA gene.";
RL Am. J. Hum. Genet. 87:146-153(2010).
RN [8]
RP INVOLVEMENT IN MCOPS13.
RX PubMed=24993872; DOI=10.1001/jamaophthalmol.2014.1731;
RA Scott A.F., Mohr D.W., Kasch L.M., Barton J.A., Pittiglio R., Ingersoll R.,
RA Craig B., Marosy B.A., Doheny K.F., Bromley W.C., Roderick T.H.,
RA Chassaing N., Calvas P., Prabhu S.S., Jabs E.W.;
RT "Identification of an HMGB3 frameshift mutation in a family with an X-
RT linked colobomatous microphthalmia syndrome using whole-genome and X-exome
RT sequencing.";
RL JAMA Ophthalmol. 132:1215-1220(2014).
RN [9]
RP NOMENCLATURE OF REDOX FORMS.
RX PubMed=24531895; DOI=10.2119/molmed.2014.00022;
RA Antoine D.J., Harris H.E., Andersson U., Tracey K.J., Bianchi M.E.;
RT "A systematic nomenclature for the redox states of high mobility group box
RT (HMGB) proteins.";
RL Mol. Med. 20:135-137(2014).
CC -!- FUNCTION: Multifunctional protein with various roles in different
CC cellular compartments. May act in a redox sensitive manner. Associates
CC with chromatin and binds DNA with a preference to non-canonical DNA
CC structures such as single-stranded DNA. Can bent DNA and enhance DNA
CC flexibility by looping thus providing a mechanism to promote activities
CC on various gene promoters (By similarity). Proposed to be involved in
CC the innate immune response to nucleic acids by acting as a cytoplasmic
CC promiscuous immunogenic DNA/RNA sensor (By similarity). Negatively
CC regulates B-cell and myeloid cell differentiation. In hematopoietic
CC stem cells may regulate the balance between self-renewal and
CC differentiation. Involved in negative regulation of canonical Wnt
CC signaling (By similarity). {ECO:0000250|UniProtKB:O54879,
CC ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P40618}.
CC -!- INTERACTION:
CC O15347; P50221: MEOX1; NbExp=3; IntAct=EBI-2214136, EBI-2864512;
CC O15347; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2214136, EBI-16439278;
CC O15347; Q02548: PAX5; NbExp=3; IntAct=EBI-2214136, EBI-296331;
CC O15347; P26367: PAX6; NbExp=3; IntAct=EBI-2214136, EBI-747278;
CC O15347; O00560: SDCBP; NbExp=7; IntAct=EBI-2214136, EBI-727004;
CC O15347; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-2214136, EBI-750109;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P40618,
CC ECO:0000255|PROSITE-ProRule:PRU00267}. Chromosome {ECO:0000305}.
CC Cytoplasm {ECO:0000250|UniProtKB:O54879}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in placenta.
CC -!- PTM: Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-
CC 104 and a possible intramolecular disulfide bond involving Cys-23 and
CC Cys-45 give rise to different redox forms with specific functional
CC activities in various cellular compartments: 1- fully reduced HMGB3
CC (HMGB3C23hC45hC104h), 2- disulfide HMGB3 (HMGB3C23-C45C104h) and
CC 3- sulfonyl HMGB3 (HMGB3C23soC45soC104so).
CC {ECO:0000250|UniProtKB:P09429, ECO:0000305|PubMed:24531895}.
CC -!- DISEASE: Microphthalmia, syndromic, 13 (MCOPS13) [MIM:300915]: A form
CC of microphthalmia, a disorder of eye formation, ranging from small size
CC of a single eye to complete bilateral absence of ocular tissues
CC (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in
CC association with syndromes that include non-ocular abnormalities.
CC MCOPS13 patients exhibit colobomatous microphthalmia with microcephaly,
CC short stature, and psychomotor retardation.
CC {ECO:0000269|PubMed:24993872}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the HMGB family. {ECO:0000305}.
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DR EMBL; Y10043; CAA71143.1; -; mRNA.
DR EMBL; AF003626; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC070482; AAH70482.1; -; mRNA.
DR CCDS; CCDS35428.1; -.
DR RefSeq; NP_001288157.1; NM_001301228.1.
DR RefSeq; NP_001288158.1; NM_001301229.1.
DR RefSeq; NP_001288160.1; NM_001301231.1.
DR RefSeq; NP_005333.2; NM_005342.3.
DR PDB; 2EQZ; NMR; -; A=1-79.
DR PDB; 2YQI; NMR; -; A=91-164.
DR PDBsum; 2EQZ; -.
DR PDBsum; 2YQI; -.
DR AlphaFoldDB; O15347; -.
DR SMR; O15347; -.
DR BioGRID; 109392; 55.
DR IntAct; O15347; 20.
DR MINT; O15347; -.
DR STRING; 9606.ENSP00000359393; -.
DR GlyGen; O15347; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15347; -.
DR PhosphoSitePlus; O15347; -.
DR SwissPalm; O15347; -.
DR BioMuta; HMGB3; -.
DR EPD; O15347; -.
DR jPOST; O15347; -.
DR MassIVE; O15347; -.
DR MaxQB; O15347; -.
DR PaxDb; O15347; -.
DR PeptideAtlas; O15347; -.
DR PRIDE; O15347; -.
DR ProteomicsDB; 48596; -.
DR TopDownProteomics; O15347; -.
DR Antibodypedia; 17019; 306 antibodies from 36 providers.
DR DNASU; 3149; -.
DR Ensembl; ENST00000325307.12; ENSP00000359393.3; ENSG00000029993.15.
DR Ensembl; ENST00000448905.6; ENSP00000442758.1; ENSG00000029993.15.
DR GeneID; 3149; -.
DR KEGG; hsa:3149; -.
DR MANE-Select; ENST00000325307.12; ENSP00000359393.3; NM_005342.4; NP_005333.2.
DR UCSC; uc004fep.4; human.
DR CTD; 3149; -.
DR DisGeNET; 3149; -.
DR GeneCards; HMGB3; -.
DR HGNC; HGNC:5004; HMGB3.
DR HPA; ENSG00000029993; Tissue enhanced (placenta).
DR MalaCards; HMGB3; -.
DR MIM; 300193; gene.
DR MIM; 300915; phenotype.
DR neXtProt; NX_O15347; -.
DR OpenTargets; ENSG00000029993; -.
DR PharmGKB; PA35092; -.
DR VEuPathDB; HostDB:ENSG00000029993; -.
DR eggNOG; KOG0381; Eukaryota.
DR GeneTree; ENSGT00940000153299; -.
DR InParanoid; O15347; -.
DR OMA; DMKNTEL; -.
DR OrthoDB; 1641977at2759; -.
DR PhylomeDB; O15347; -.
DR TreeFam; TF105371; -.
DR PathwayCommons; O15347; -.
DR SignaLink; O15347; -.
DR BioGRID-ORCS; 3149; 120 hits in 655 CRISPR screens.
DR ChiTaRS; HMGB3; human.
DR EvolutionaryTrace; O15347; -.
DR GeneWiki; HMGB3; -.
DR GenomeRNAi; 3149; -.
DR Pharos; O15347; Tbio.
DR PRO; PR:O15347; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O15347; protein.
DR Bgee; ENSG00000029993; Expressed in secondary oocyte and 162 other tissues.
DR ExpressionAtlas; O15347; baseline and differential.
DR Genevisible; O15347; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0008301; F:DNA binding, bending; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0000400; F:four-way junction DNA binding; ISS:AgBase.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0032392; P:DNA geometric change; ISS:AgBase.
DR GO; GO:0006310; P:DNA recombination; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045578; P:negative regulation of B cell differentiation; IEA:Ensembl.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.30.10; -; 2.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR017967; HMG_boxA_CS.
DR InterPro; IPR031077; HMGB3.
DR PANTHER; PTHR48112:SF14; PTHR48112:SF14; 1.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF09011; HMG_box_2; 1.
DR SMART; SM00398; HMG; 2.
DR SUPFAM; SSF47095; SSF47095; 2.
DR PROSITE; PS00353; HMG_BOX_1; 1.
DR PROSITE; PS50118; HMG_BOX_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosome; Cytoplasm; Disulfide bond;
KW DNA-binding; Immunity; Innate immunity; Microphthalmia; Nucleus; Oxidation;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN 1..200
FT /note="High mobility group protein B3"
FT /id="PRO_0000048539"
FT DNA_BIND 9..79
FT /note="HMG box 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT DNA_BIND 93..161
FT /note="HMG box 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 71..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 71..93
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..181
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..200
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 3
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT MOD_RES 23
FT /note="Cysteine sulfonic acid (-SO3H); alternate"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT MOD_RES 30
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT MOD_RES 43
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63158"
FT MOD_RES 45
FT /note="Cysteine sulfonic acid (-SO3H); alternate"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT MOD_RES 104
FT /note="Cysteine sulfonic acid (-SO3H)"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT MOD_RES 112
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P30681"
FT MOD_RES 139
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63158"
FT DISULFID 23..45
FT /note="In disulfide HMGB3; alternate"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT VARIANT 51
FT /note="T -> A (in dbSNP:rs16995792)"
FT /id="VAR_049558"
FT VARIANT 56
FT /note="E -> Q"
FT /evidence="ECO:0000269|PubMed:20598277"
FT /id="VAR_064162"
FT CONFLICT 13
FT /note="M -> T (in Ref. 1; CAA71143)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="M -> V (in Ref. 1; CAA71143)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="E -> Q (in Ref. 1; CAA71143)"
FT /evidence="ECO:0000305"
FT STRAND 6..8
FT /evidence="ECO:0007829|PDB:2EQZ"
FT HELIX 15..30
FT /evidence="ECO:0007829|PDB:2EQZ"
FT HELIX 38..50
FT /evidence="ECO:0007829|PDB:2EQZ"
FT HELIX 54..78
FT /evidence="ECO:0007829|PDB:2EQZ"
FT HELIX 99..114
FT /evidence="ECO:0007829|PDB:2YQI"
FT HELIX 120..133
FT /evidence="ECO:0007829|PDB:2YQI"
FT HELIX 136..160
FT /evidence="ECO:0007829|PDB:2YQI"
SQ SEQUENCE 200 AA; 22980 MW; 31C090FAA4D581E6 CRC64;
MAKGDPKKPK GKMSAYAFFV QTCREEHKKK NPEVPVNFAE FSKKCSERWK TMSGKEKSKF
DEMAKADKVR YDREMKDYGP AKGGKKKKDP NAPKRPPSGF FLFCSEFRPK IKSTNPGISI
GDVAKKLGEM WNNLNDSEKQ PYITKAAKLK EKYEKDVADY KSKGKFDGAK GPAKVARKKV
EEEDEEEEEE EEEEEEEEDE
