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Protein

High mobility group protein B2

Gene

HMGB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi9 – 7971HMG box 1PROSITE-ProRule annotationAdd
BLAST
DNA bindingi95 – 16369HMG box 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • chemoattractant activity Source: UniProtKB
  • damaged DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • DNA binding, bending 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
  • poly(A) RNA binding Source: UniProtKB
  • RAGE receptor binding Source: UniProtKB
  • single-stranded DNA binding Source: UniProtKB
  • supercoiled DNA binding Source: AgBase
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: AgBase
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Chemotaxis, DNA recombination, Immunity, Inflammatory response, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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

HGNCiHGNC:5000. HMGB2.

Subcellular locationi

GO - Cellular componenti

  • cell Source: AgBase
  • condensed chromosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • extracellular space Source: UniProtKB
  • nuclear chromatin Source: AgBase
  • nucleolus Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35091.

Polymorphism and mutation databases

BioMutaiHMGB2.
DMDMi123374.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 209208High mobility group protein B2PRO_0000048534Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi23 ↔ 45In disulfide HMGB2By similarity
Modified residuei23 – 231Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB2; alternateBy similarity
Modified residuei30 – 301N6-acetyllysineCombined sources
Modified residuei35 – 351PhosphoserineCombined sources
Modified residuei45 – 451Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB2; alternateBy similarity
Modified residuei106 – 1061Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB2By similarity
Modified residuei114 – 1141N6-acetyllysineBy similarity

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, Phosphoprotein

Proteomic databases

EPDiP26583.
MaxQBiP26583.
PaxDbiP26583.
PeptideAtlasiP26583.
PRIDEiP26583.
TopDownProteomicsiP26583.

PTM databases

iPTMnetiP26583.
PhosphoSiteiP26583.
SwissPalmiP26583.

Miscellaneous databases

PMAP-CutDBP26583.

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

  • RAGE receptor binding Source: UniProtKB
  • transcription factor binding Source: AgBase

Protein-protein interaction databases

BioGridi109391. 48 interactions.
IntActiP26583. 21 interactions.
MINTiMINT-240190.
STRINGi9606.ENSP00000296503.

Structurei

3D structure databases

ProteinModelPortaliP26583.
SMRiP26583. Positions 1-166.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni165 – 18016Required for chemotactic activity1 PublicationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi186 – 20924Asp/Glu-rich (acidic)Add
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the HMGB family.Curated
Contains 2 HMG box DNA-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.30.10. 2 hits.
InterProiIPR009071. HMG_box_dom.
IPR017967. HMG_boxA_CS.
IPR031075. HMGB2.
[Graphical view]
PANTHERiPTHR13711:SF217. PTHR13711:SF217. 1 hit.
PfamiPF00505. HMG_box. 1 hit.
PF09011. HMG_box_2. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 2 hits.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 2 hits.
PROSITEiPS00353. HMG_BOX_1. 1 hit.
PS50118. HMG_BOX_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti163 – 1631R → G in CAA78938 (PubMed:1475204).Curated

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.

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.
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.

3D structure databases

ProteinModelPortaliP26583.
SMRiP26583. Positions 1-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109391. 48 interactions.
IntActiP26583. 21 interactions.
MINTiMINT-240190.
STRINGi9606.ENSP00000296503.

PTM databases

iPTMnetiP26583.
PhosphoSiteiP26583.
SwissPalmiP26583.

Polymorphism and mutation databases

BioMutaiHMGB2.
DMDMi123374.

Proteomic databases

EPDiP26583.
MaxQBiP26583.
PaxDbiP26583.
PeptideAtlasiP26583.
PRIDEiP26583.
TopDownProteomicsiP26583.

Protocols and materials databases

DNASUi3148.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3148.
GeneCardsiHMGB2.
HGNCiHGNC:5000. HMGB2.
HPAiCAB037206.
HPA003506.
HPA053314.
MIMi163906. gene.
neXtProtiNX_P26583.
PharmGKBiPA35091.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-211227. Activation of DNA fragmentation factor.
SIGNORiP26583.

Miscellaneous databases

ChiTaRSiHMGB2. human.
GeneWikiiHMGB2.
GenomeRNAii3148.
PMAP-CutDBP26583.
PROiP26583.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164104.
CleanExiHS_HMGB2.
ExpressionAtlasiP26583. baseline and differential.
GenevisibleiP26583. HS.

Family and domain databases

Gene3Di1.10.30.10. 2 hits.
InterProiIPR009071. HMG_box_dom.
IPR017967. HMG_boxA_CS.
IPR031075. HMGB2.
[Graphical view]
PANTHERiPTHR13711:SF217. PTHR13711:SF217. 1 hit.
PfamiPF00505. HMG_box. 1 hit.
PF09011. HMG_box_2. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 2 hits.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 2 hits.
PROSITEiPS00353. HMG_BOX_1. 1 hit.
PS50118. HMG_BOX_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHMGB2_HUMAN
AccessioniPrimary (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: September 7, 2016
This is version 170 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.