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Protein

High mobility group protein B2

Gene

HMGB2

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

Functioni

Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. In the nucleus is an abundant chromatin-associated non-histone protein involved in transcription, chromatin remodeling and V(D)J recombination and probably other processes. Binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:7797075, PubMed:11909973, PubMed:19522541, PubMed:18413230, PubMed:19965638, PubMed:20123072). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). Proposed to be involved in the innate immune response to nucleic acids by acting as a promiscuous immunogenic DNA/RNA sensor which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). In the extracellular compartment acts as a chemokine. Promotes proliferation and migration of endothelial cells implicating AGER/RAGE (PubMed:19811285). Has antimicrobial activity in gastrointestinal epithelial tissues (PubMed:23877675). Involved in inflammatory response to antigenic stimulus coupled with proinflammatory activity (By similarity). Involved in modulation of neurogenesis probably by regulation of neural stem proliferation (By similarity). Involved in articular cartilage surface maintenance implicating LEF1 and the Wnt/beta-catenin pathway (By similarity).By similarity1 Publication7 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi9 – 79HMG box 1PROSITE-ProRule annotationAdd BLAST71
DNA bindingi95 – 163HMG box 2PROSITE-ProRule annotationAdd BLAST69

GO - Molecular functioni

  • chemoattractant activity Source: UniProtKB
  • damaged DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • DNA binding, bending Source: UniProtKB
  • DNA binding transcription factor activity Source: UniProtKB
  • double-stranded DNA binding Source: UniProtKB
  • drug binding Source: AgBase
  • enhancer sequence-specific DNA binding Source: AgBase
  • four-way junction DNA binding Source: AgBase
  • non-sequence-specific DNA binding, bending Source: AgBase
  • protein domain specific binding Source: Ensembl
  • RAGE receptor binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • single-stranded DNA binding Source: UniProtKB
  • supercoiled DNA binding Source: AgBase
  • transcription factor binding Source: AgBase
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • apoptotic DNA fragmentation Source: Reactome
  • cell chemotaxis Source: UniProtKB
  • cellular response to lipopolysaccharide Source: UniProtKB
  • chromatin organization Source: UniProtKB
  • defense response to Gram-negative bacterium Source: AgBase
  • defense response to Gram-positive bacterium Source: AgBase
  • DNA geometric change Source: AgBase
  • DNA ligation involved in DNA repair Source: UniProtKB
  • DNA topological change Source: UniProtKB
  • inflammatory response to antigenic stimulus Source: AgBase
  • innate immune response Source: UniProtKB-KW
  • male gonad development Source: Ensembl
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • nucleosome assembly Source: UniProtKB
  • positive regulation of DNA binding Source: UniProtKB
  • positive regulation of endothelial cell proliferation Source: UniProtKB
  • positive regulation of erythrocyte differentiation Source: UniProtKB
  • positive regulation of innate immune response Source: Ensembl
  • positive regulation of interferon-beta production Source: Ensembl
  • positive regulation of megakaryocyte differentiation Source: UniProtKB
  • positive regulation of nuclease activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • regulation of neurogenesis Source: AgBase
  • regulation of stem cell proliferation Source: AgBase
  • regulation of transcription by RNA polymerase II Source: UniProtKB
  • response to drug Source: AgBase
  • response to lipopolysaccharide Source: AgBase
  • response to steroid hormone Source: Ensembl
  • spermatid nucleus differentiation Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
  • V(D)J recombination Source: UniProtKB

Keywordsi

Molecular functionDNA-binding
Biological processChemotaxis, DNA recombination, Immunity, Inflammatory response, Innate immunity, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-211227 Activation of DNA fragmentation factor
SIGNORiP26583

Names & Taxonomyi

Protein namesi
Recommended name:
High mobility group protein B2
Alternative name(s):
High mobility group protein 2
Short name:
HMG-2
Gene namesi
Name:HMGB2
Synonyms:HMG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000164104.11
HGNCiHGNC:5000 HMGB2
MIMi163906 gene
neXtProtiNX_P26583

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

Chromosome, Cytoplasm, Nucleus, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3148
OpenTargetsiENSG00000164104
PharmGKBiPA35091

Polymorphism and mutation databases

BioMutaiHMGB2
DMDMi123374

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000485341 – 209High mobility group protein B2Add BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3N6-acetyllysineBy similarity1
Disulfide bondi23 ↔ 45In disulfide HMGB2; alternateBy similarity
Modified residuei23Cysteine sulfonic acid (-SO3H); alternateBy similarity1
Modified residuei30N6-acetyllysineCombined sources1
Modified residuei35PhosphoserineCombined sources1
Modified residuei43N6-acetyllysineBy similarity1
Modified residuei45Cysteine sulfonic acid (-SO3H); alternateBy similarity1
Modified residuei90N6-acetyllysineBy similarity1
Modified residuei100PhosphoserineBy similarity1
Modified residuei106Cysteine sulfonic acid (-SO3H)By similarity1
Modified residuei114N6-acetyllysineBy similarity1
Modified residuei141N6-acetyllysineBy similarity1

Post-translational modificationi

Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB2 (HMGB2C23hC45hC106h), 2- disulfide HMGB2 (HMGB2C23-C45C106h) and 3- sulfonyl HMGB2 (HMGB2C23soC45soC106so).By similarity1 Publication
Acetylation enhances nucleosome binding and chromation remodeling activity.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, Oxidation, Phosphoprotein

Proteomic databases

EPDiP26583
MaxQBiP26583
PaxDbiP26583
PeptideAtlasiP26583
PRIDEiP26583
ProteomicsDBi54353
TopDownProteomicsiP26583

PTM databases

iPTMnetiP26583
PhosphoSitePlusiP26583
SwissPalmiP26583

Miscellaneous databases

PMAP-CutDBiP26583

Expressioni

Tissue specificityi

Expressed in gastric and intestinal tissues (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000164104
CleanExiHS_HMGB2
ExpressionAtlasiP26583 baseline and differential
GenevisibleiP26583 HS

Organism-specific databases

HPAiCAB037206
HPA003506
HPA053314

Interactioni

Subunit structurei

Interacts with POU2F2, POU2F1 and POU3F1 (By similarity). Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By similarity). Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Directly interacts with SET (PubMed:11909973). Interacts with LEF1 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
PKNOX1Q96I873EBI-1057009,EBI-10173774

GO - Molecular functioni

  • chemoattractant activity Source: UniProtKB
  • protein domain specific binding Source: Ensembl
  • RAGE receptor binding Source: UniProtKB
  • transcription factor binding Source: AgBase

Protein-protein interaction databases

BioGridi109391, 51 interactors
CORUMiP26583
IntActiP26583, 24 interactors
MINTiP26583
STRINGi9606.ENSP00000296503

Structurei

3D structure databases

ProteinModelPortaliP26583
SMRiP26583
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni165 – 180Required for chemotactic activity1 PublicationAdd BLAST16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi186 – 209Asp/Glu-rich (acidic)Add BLAST24

Domaini

Both, HMG box 1 and HMG box 2, show antimicrobial activity.1 Publication

Sequence similaritiesi

Belongs to the HMGB family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0381 Eukaryota
COG5648 LUCA
GeneTreeiENSGT00760000119164
HOGENOMiHOG000197861
HOVERGENiHBG009000
InParanoidiP26583
KOiK11295
OMAiADDTWRA
OrthoDBiEOG091G0P81
PhylomeDBiP26583
TreeFamiTF105371

Family and domain databases

Gene3Di1.10.30.10, 2 hits
InterProiView protein in InterPro
IPR009071 HMG_box_dom
IPR036910 HMG_box_dom_sf
IPR017967 HMG_boxA_CS
IPR031075 HMGB2
PANTHERiPTHR13711:SF181 PTHR13711:SF181, 1 hit
PfamiView protein in Pfam
PF00505 HMG_box, 1 hit
PF09011 HMG_box_2, 1 hit
SMARTiView protein in SMART
SM00398 HMG, 2 hits
SUPFAMiSSF47095 SSF47095, 2 hits
PROSITEiView protein in PROSITE
PS00353 HMG_BOX_1, 1 hit
PS50118 HMG_BOX_2, 2 hits

Sequencei

Sequence statusi: Complete.

P26583-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKGDPNKPR GKMSSYAFFV QTCREEHKKK HPDSSVNFAE FSKKCSERWK
60 70 80 90 100
TMSAKEKSKF EDMAKSDKAR YDREMKNYVP PKGDKKGKKK DPNAPKRPPS
110 120 130 140 150
AFFLFCSEHR PKIKSEHPGL SIGDTAKKLG EMWSEQSAKD KQPYEQKAAK
160 170 180 190 200
LKEKYEKDIA AYRAKGKSEA GKKGPGRPTG SKKKNEPEDE EEEEEEEDED

EEEEDEDEE
Length:209
Mass (Da):24,034
Last modified:January 23, 2007 - v2
Checksum:i5E65292BC4AD8373
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti163R → G in CAA78938 (PubMed:1475204).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83665 Genomic DNA Translation: AAA58659.1
X62534 mRNA Translation: CAA44395.1
BT019782 mRNA Translation: AAV38585.1
AK311864 mRNA Translation: BAG34805.1
CH471056 Genomic DNA Translation: EAX04758.1
CH471056 Genomic DNA Translation: EAX04759.1
BC001063 mRNA Translation: AAH01063.1
BC100019 mRNA Translation: AAI00020.1
Z17240 mRNA Translation: CAA78938.1
CCDSiCCDS3816.1
PIRiA42425 NSHUH2
S30221
RefSeqiNP_001124160.1, NM_001130688.1
NP_001124161.1, NM_001130689.1
NP_002120.1, NM_002129.3
UniGeneiHs.434953

Genome annotation databases

EnsembliENST00000296503; ENSP00000296503; ENSG00000164104
ENST00000438704; ENSP00000404912; ENSG00000164104
ENST00000446922; ENSP00000393448; ENSG00000164104
GeneIDi3148
KEGGihsa:3148
UCSCiuc003ita.4 human

Similar proteinsi

Entry informationi

Entry nameiHMGB2_HUMAN
AccessioniPrimary (citable) accession number: P26583
Secondary accession number(s): B2R4K8, D3DP37, Q5U072
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 187 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

Complete proteome, Reference proteome

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