UniProtKB - P26583 (HMGB2_HUMAN)
Protein
High mobility group protein B2
Gene
HMGB2
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 9 – 79 | HMG box 1PROSITE-ProRule annotationAdd BLAST | 71 | |
DNA bindingi | 95 – 163 | HMG box 2PROSITE-ProRule annotationAdd BLAST | 69 |
GO - Molecular functioni
- chemoattractant activity Source: UniProtKB
- chromatin binding Source: GO_Central
- cis-regulatory region sequence-specific DNA binding Source: AgBase
- damaged DNA binding Source: UniProtKB
- DNA binding Source: UniProtKB
- DNA binding, bending Source: UniProtKB
- double-stranded DNA binding Source: UniProtKB
- 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 coactivator activity Source: UniProtKB
- transcription factor binding Source: AgBase
- transcription regulatory region sequence-specific 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
- chromatin remodeling Source: GO_Central
- 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 recombination Source: GO_Central
- 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: GO_Central
- 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, DNA-templated Source: GO_Central
- regulation of transcription by RNA polymerase II Source: UniProtKB
- response to lipopolysaccharide Source: AgBase
- response to steroid hormone Source: Ensembl
- spermatid nucleus differentiation Source: Ensembl
- V(D)J recombination Source: UniProtKB
Keywordsi
Molecular function | DNA-binding |
Biological process | Chemotaxis, DNA recombination, Immunity, Inflammatory response, Innate immunity, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P26583 |
Reactomei | R-HSA-140342, Apoptosis induced DNA fragmentation |
SIGNORi | P26583 |
Names & Taxonomyi
Protein namesi | Recommended name: High mobility group protein B2Alternative name(s): High mobility group protein 2 Short name: HMG-2 |
Gene namesi | Name:HMGB2 Synonyms:HMG2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000164104.11 |
HGNCi | HGNC:5000, HMGB2 |
MIMi | 163906, gene |
neXtProti | NX_P26583 |
Subcellular locationi
Extracellular region or secreted
- Secreted 2 Publications
Nucleus
- Nucleus 3 Publications
Other locations
- Chromosome 1 Publication
- Cytoplasm 2 Publications
Note: In basal state predominantly nuclear.Curated
Extracellular region or secreted
- extracellular space Source: UniProtKB
Nucleus
- nuclear chromatin Source: AgBase
- nucleolus Source: HPA
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- condensed chromosome Source: UniProtKB
- cytoplasm Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Chromosome, Cytoplasm, Nucleus, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 3148 |
OpenTargetsi | ENSG00000164104 |
PharmGKBi | PA35091 |
Miscellaneous databases
Pharosi | P26583, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4295734 |
Polymorphism and mutation databases
BioMutai | HMGB2 |
DMDMi | 123374 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000048534 | 1 – 209 | High mobility group protein B2Add BLAST | 209 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 3 | N6-acetyllysineBy similarity | 1 | |
Disulfide bondi | 23 ↔ 45 | In disulfide HMGB2; alternateBy similarity | ||
Modified residuei | 23 | Cysteine sulfonic acid (-SO3H); alternateBy similarity | 1 | |
Modified residuei | 30 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 35 | PhosphoserineCombined sources | 1 | |
Modified residuei | 43 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 45 | Cysteine sulfonic acid (-SO3H); alternateBy similarity | 1 | |
Modified residuei | 90 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 100 | PhosphoserineBy similarity | 1 | |
Modified residuei | 106 | Cysteine sulfonic acid (-SO3H)By similarity | 1 | |
Modified residuei | 114 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 141 | N6-acetyllysineBy similarity | 1 |
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, PhosphoproteinProteomic databases
EPDi | P26583 |
jPOSTi | P26583 |
MassIVEi | P26583 |
MaxQBi | P26583 |
PaxDbi | P26583 |
PeptideAtlasi | P26583 |
PRIDEi | P26583 |
ProteomicsDBi | 54353 |
TopDownProteomicsi | P26583 |
PTM databases
iPTMneti | P26583 |
MetOSitei | P26583 |
PhosphoSitePlusi | P26583 |
SwissPalmi | P26583 |
Expressioni
Tissue specificityi
Expressed in gastric and intestinal tissues (at protein level).1 Publication
Gene expression databases
Bgeei | ENSG00000164104, Expressed in ventricular zone and 244 other tissues |
ExpressionAtlasi | P26583, baseline and differential |
Genevisiblei | P26583, HS |
Organism-specific databases
HPAi | ENSG00000164104, Group enriched (blood, bone marrow, lymphoid tissue) |
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 PublicationBinary interactionsi
Hide detailsP26583
With | #Exp. | IntAct |
---|---|---|
PKNOX1 [P55347] | 4 | EBI-1057009,EBI-1373569 |
PKNOX1 [Q96I87] | 3 | EBI-1057009,EBI-10173774 |
TSNAX [Q99598] | 3 | EBI-1057009,EBI-742638 |
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
BioGRIDi | 109391, 82 interactors |
CORUMi | P26583 |
IntActi | P26583, 50 interactors |
MINTi | P26583 |
STRINGi | 9606.ENSP00000296503 |
Miscellaneous databases
RNActi | P26583, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 165 – 180 | Required for chemotactic activity1 PublicationAdd BLAST | 16 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 186 – 209 | Asp/Glu-rich (acidic)Add BLAST | 24 |
Domaini
Both, HMG box 1 and HMG box 2, show antimicrobial activity.1 Publication
Sequence similaritiesi
Belongs to the HMGB family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0381, Eukaryota |
GeneTreei | ENSGT00940000154466 |
HOGENOMi | CLU_082854_0_0_1 |
InParanoidi | P26583 |
OMAi | QPFEQKA |
OrthoDBi | 1641977at2759 |
PhylomeDBi | P26583 |
TreeFami | TF105371 |
Family and domain databases
Gene3Di | 1.10.30.10, 2 hits |
InterProi | View protein in InterPro IPR009071, HMG_box_dom IPR036910, HMG_box_dom_sf IPR017967, HMG_boxA_CS |
Pfami | View protein in Pfam PF00505, HMG_box, 1 hit PF09011, HMG_box_2, 1 hit |
SMARTi | View protein in SMART SM00398, HMG, 2 hits |
SUPFAMi | SSF47095, SSF47095, 2 hits |
PROSITEi | View protein in PROSITE PS00353, HMG_BOX_1, 1 hit PS50118, HMG_BOX_2, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P26583-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketD6R9A6 | D6R9A6_HUMAN | High mobility group protein B2 | HMGB2 | 134 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 163 | R → G in CAA78938 (PubMed:1475204).Curated | 1 |
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 |
CCDSi | CCDS3816.1 |
PIRi | A42425, NSHUH2 S30221 |
RefSeqi | NP_001124160.1, NM_001130688.1 NP_001124161.1, NM_001130689.1 NP_002120.1, NM_002129.3 |
Genome annotation databases
Ensembli | ENST00000296503; ENSP00000296503; ENSG00000164104 ENST00000438704; ENSP00000404912; ENSG00000164104 ENST00000446922; ENSP00000393448; ENSG00000164104 |
GeneIDi | 3148 |
KEGGi | hsa:3148 |
UCSCi | uc003ita.4, human |
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS3816.1 |
PIRi | A42425, NSHUH2 S30221 |
RefSeqi | NP_001124160.1, NM_001130688.1 NP_001124161.1, NM_001130689.1 NP_002120.1, NM_002129.3 |
3D structure databases
SMRi | P26583 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109391, 82 interactors |
CORUMi | P26583 |
IntActi | P26583, 50 interactors |
MINTi | P26583 |
STRINGi | 9606.ENSP00000296503 |
Chemistry databases
ChEMBLi | CHEMBL4295734 |
PTM databases
iPTMneti | P26583 |
MetOSitei | P26583 |
PhosphoSitePlusi | P26583 |
SwissPalmi | P26583 |
Polymorphism and mutation databases
BioMutai | HMGB2 |
DMDMi | 123374 |
Proteomic databases
EPDi | P26583 |
jPOSTi | P26583 |
MassIVEi | P26583 |
MaxQBi | P26583 |
PaxDbi | P26583 |
PeptideAtlasi | P26583 |
PRIDEi | P26583 |
ProteomicsDBi | 54353 |
TopDownProteomicsi | P26583 |
Protocols and materials databases
ABCDi | P26583, 1 sequenced antibody |
Antibodypediai | 1112, 379 antibodies |
DNASUi | 3148 |
Genome annotation databases
Ensembli | ENST00000296503; ENSP00000296503; ENSG00000164104 ENST00000438704; ENSP00000404912; ENSG00000164104 ENST00000446922; ENSP00000393448; ENSG00000164104 |
GeneIDi | 3148 |
KEGGi | hsa:3148 |
UCSCi | uc003ita.4, human |
Organism-specific databases
CTDi | 3148 |
DisGeNETi | 3148 |
EuPathDBi | HostDB:ENSG00000164104.11 |
GeneCardsi | HMGB2 |
HGNCi | HGNC:5000, HMGB2 |
HPAi | ENSG00000164104, Group enriched (blood, bone marrow, lymphoid tissue) |
MIMi | 163906, gene |
neXtProti | NX_P26583 |
OpenTargetsi | ENSG00000164104 |
PharmGKBi | PA35091 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0381, Eukaryota |
GeneTreei | ENSGT00940000154466 |
HOGENOMi | CLU_082854_0_0_1 |
InParanoidi | P26583 |
OMAi | QPFEQKA |
OrthoDBi | 1641977at2759 |
PhylomeDBi | P26583 |
TreeFami | TF105371 |
Enzyme and pathway databases
PathwayCommonsi | P26583 |
Reactomei | R-HSA-140342, Apoptosis induced DNA fragmentation |
SIGNORi | P26583 |
Miscellaneous databases
BioGRID-ORCSi | 3148, 7 hits in 873 CRISPR screens |
ChiTaRSi | HMGB2, human |
GeneWikii | HMGB2 |
GenomeRNAii | 3148 |
Pharosi | P26583, Tbio |
PROi | PR:P26583 |
RNActi | P26583, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164104, Expressed in ventricular zone and 244 other tissues |
ExpressionAtlasi | P26583, baseline and differential |
Genevisiblei | P26583, HS |
Family and domain databases
Gene3Di | 1.10.30.10, 2 hits |
InterProi | View protein in InterPro IPR009071, HMG_box_dom IPR036910, HMG_box_dom_sf IPR017967, HMG_boxA_CS |
Pfami | View protein in Pfam PF00505, HMG_box, 1 hit PF09011, HMG_box_2, 1 hit |
SMARTi | View protein in SMART SM00398, HMG, 2 hits |
SUPFAMi | SSF47095, SSF47095, 2 hits |
PROSITEi | View protein in PROSITE PS00353, HMG_BOX_1, 1 hit PS50118, HMG_BOX_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HMGB2_HUMAN | |
Accessioni | P26583Primary (citable) accession number: P26583 Secondary accession number(s): B2R4K8, D3DP37, Q5U072 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1992 |
Last sequence update: | January 23, 2007 | |
Last modified: | December 2, 2020 | |
This is version 205 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families