HMGB2

Protein identityUniProt · HPA

UniProt accession

P26583

Gene

HMGB2

Ensembl

ENSG00000164104

Chromosome

4

Canonical length

209 aa

Protein class

Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Nucleoplasm,Nucleoli,Principal piece,Annulus

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a member of the non-histone chromosomal high mobility group protein family. The proteins of this family are chromatin-associated and ubiquitously distributed in the nucleus of higher eukaryotic cells. In vitro studies have demonstrated that this protein is able to efficiently bend DNA and form DNA circles. These studies suggest a role in facilitating cooperative interactions between cis-acting proteins by promoting DNA flexibility. This protein was also reported to be involved in the final ligation step in DNA end-joining processes of DNA double-strand breaks repair and V(D)J recombination. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

209 residues, UniProt reviewed canonical sequence.

>P26583|HMGB2
     1  MGKGDPNKPR GKMSSYAFFV QTCREEHKKK HPDSSVNFAE FSKKCSERWK TMSAKEKSKF
    61  EDMAKSDKAR YDREMKNYVP PKGDKKGKKK DPNAPKRPPS AFFLFCSEHR PKIKSEHPGL
   121  SIGDTAKKLG EMWSEQSAKD KQPYEQKAAK LKEKYEKDIA AYRAKGKSEA GKKGPGRPTG
   181  SKKKNEPEDE EEEEEEEDED EEEEDEDEE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HMGB2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.48

Highest tissue expression

2,215 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HMGB2.

Disease | ImmuneIEDB

Conditions an epitope on HMGB2 was assayed in.

• rheumatoid arthritis B cell

ReferencesPubMed · IEDB

Publications for HMGB2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.32

gnomAD pLI

0.95

gnomAD missense Z

1.61

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell chemotaxis
• cellular response to lipopolysaccharide
• chromatin organization
• chromatin remodeling
• defense response to Gram-negative bacterium
• defense response to Gram-positive bacterium
• DNA geometric change
• DNA topological change
• double-strand break repair via nonhomologous end joining
• extrinsic apoptotic signaling pathway via death domain receptors
• inflammatory response to antigenic stimulus
• innate immune response
• male gonad development
• negative regulation of DNA-templated transcription
• negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• negative regulation of gene expression
• negative regulation of transcription by RNA polymerase II
• nucleosome assembly
• positive regulation of DNA-templated transcription
• positive regulation of endothelial cell proliferation
• positive regulation of erythrocyte differentiation
• positive regulation of innate immune response
• positive regulation of interferon-beta production
• positive regulation of megakaryocyte differentiation
• positive regulation of transcription by RNA polymerase II
• regulation of neurogenesis
• regulation of stem cell proliferation
• regulation of transcription by RNA polymerase II
• response to lipopolysaccharide
• response to steroid hormone
• spermatid nucleus differentiation
• V(D)J recombination

Molecular functions

• chemoattractant activity
• cis-regulatory region sequence-specific DNA binding
• damaged DNA binding
• DNA binding
• DNA binding, bending
• DNA-binding transcription factor binding
• double-stranded DNA binding
• four-way junction DNA binding
• non-sequence-specific DNA binding, bending
• protein domain specific binding
• RAGE receptor binding
• RNA binding
• single-stranded DNA binding
• supercoiled DNA binding
• transcription cis-regulatory region binding
• transcription coactivator activity
• transcription factor binding

Cellular components

• chromatin
• condensed chromosome
• cytoplasm
• extracellular space
• nucleolus
• nucleoplasm
• nucleus
• perinuclear region of cytoplasm
• protein-containing complex
• sperm annulus
• sperm principal piece

Protein domainsUniProt · Pfam · InterPro

• High mobility group box domain
• HMG box A DNA-binding domain, conserved site
• High mobility group box domain superfamily
• High Mobility Group Box (HMGB)
• HMG (high mobility group) box
• HMG-box domain

KeywordsUniProt

• Acetylation
• Chemotaxis
• Chromosome
• Cytoplasm
• Disulfide bond
• DNA recombination
• DNA-binding
• Immunity
• Inflammatory response
• Innate immunity
• Nucleus
• Oxidation
• Phosphoprotein
• Repeat
• Secreted
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of HMGB2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LEF1
• POU2F1
• POU2F2
• POU3F1
• SET
• COMMD1
• FLNA
• MIEN1
• NOP53
• RPL14
• RPL24
• RPS16
• RPS28
• ZNF428
• ZNF668