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Protein

High mobility group protein B3

Gene

HMGB3

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. Associates with chromatin and 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 similarity). Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor (By similarity). Negatively regulates B-cell and myeloid cell differentiation. In hematopoietic stem cells may regulate the balance between self-renewal and differentiation. Involved in negative regulation of canonical Wnt signaling (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi9 – 79HMG box 1PROSITE-ProRule annotationAdd BLAST71
DNA bindingi93 – 161HMG box 2PROSITE-ProRule annotationAdd BLAST69

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000029993-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
High mobility group protein B3
Alternative name(s):
High mobility group protein 2a
Short name:
HMG-2a
High mobility group protein 4
Short name:
HMG-4
Gene namesi
Name:HMGB3
Synonyms:HMG2A, HMG4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:5004. HMGB3.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotationBy similarity
  • Chromosome Curated
  • Cytoplasm By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Microphthalmia, syndromic, 13 (MCOPS13)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS13 patients exhibit colobomatous microphthalmia with microcephaly, short stature, and psychomotor retardation.
See also OMIM:300915

Keywords - Diseasei

Microphthalmia

Organism-specific databases

DisGeNETi3149.
MalaCardsiHMGB3.
MIMi300915. phenotype.
OpenTargetsiENSG00000029993.
PharmGKBiPA35092.

Polymorphism and mutation databases

BioMutaiHMGB3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000485391 – 200High mobility group protein B3Add BLAST200

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi23 ↔ 45In disulfide HMGB3By similarity
Modified residuei23Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB3; alternateBy similarity1
Modified residuei45Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB3; alternateBy similarity1
Modified residuei104Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB3By similarity1

Post-translational modificationi

Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-104 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 HMGB3 (HMGB3C23hC45hC104h), 2- disulfide HMGB3 (HMGB3C23-C45C104h) and 3- sulfonyl HMGB3 (HMGB3C23soC45soC104so).By similarity1 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiO15347.
MaxQBiO15347.
PaxDbiO15347.
PeptideAtlasiO15347.
PRIDEiO15347.
TopDownProteomicsiO15347.

PTM databases

iPTMnetiO15347.
PhosphoSitePlusiO15347.

Expressioni

Tissue specificityi

Expressed predominantly in placenta.

Gene expression databases

BgeeiENSG00000029993.
CleanExiHS_HMGB3.
ExpressionAtlasiO15347. baseline and differential.
GenevisibleiO15347. HS.

Organism-specific databases

HPAiHPA062583.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
SDCBPO005605EBI-2214136,EBI-727004
TERF2IPQ9NYB02EBI-2214136,EBI-750109

Protein-protein interaction databases

BioGridi109392. 26 interactors.
IntActiO15347. 8 interactors.
MINTiMINT-5002211.
STRINGi9606.ENSP00000359393.

Structurei

Secondary structure

1200
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 8Combined sources3
Helixi15 – 30Combined sources16
Helixi38 – 50Combined sources13
Helixi54 – 78Combined sources25
Helixi99 – 114Combined sources16
Helixi120 – 133Combined sources14
Helixi136 – 160Combined sources25

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EQZNMR-A1-79[»]
2YQINMR-A91-164[»]
ProteinModelPortaliO15347.
SMRiO15347.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15347.

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi181 – 200Asp/Glu-rich (acidic)Add BLAST20

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.
InParanoidiO15347.
KOiK11296.
OMAiDNEKQPY.
OrthoDBiEOG091G0P81.
PhylomeDBiO15347.
TreeFamiTF105371.

Family and domain databases

Gene3Di1.10.30.10. 2 hits.
InterProiIPR009071. HMG_box_dom.
IPR017967. HMG_boxA_CS.
IPR031077. HMGB3.
[Graphical view]
PANTHERiPTHR13711:SF144. PTHR13711:SF144. 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.

O15347-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKGDPKKPK GKMSAYAFFV QTCREEHKKK NPEVPVNFAE FSKKCSERWK
60 70 80 90 100
TMSGKEKSKF DEMAKADKVR YDREMKDYGP AKGGKKKKDP NAPKRPPSGF
110 120 130 140 150
FLFCSEFRPK IKSTNPGISI GDVAKKLGEM WNNLNDSEKQ PYITKAAKLK
160 170 180 190 200
EKYEKDVADY KSKGKFDGAK GPAKVARKKV EEEDEEEEEE EEEEEEEEDE
Length:200
Mass (Da):22,980
Last modified:January 23, 2007 - v4
Checksum:i31C090FAA4D581E6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13M → T in CAA71143 (PubMed:9370291).Curated1
Sequence conflicti52M → V in CAA71143 (PubMed:9370291).Curated1
Sequence conflicti187E → Q in CAA71143 (PubMed:9370291).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04955851T → A.Corresponds to variant rs16995792dbSNPEnsembl.1
Natural variantiVAR_06416256E → Q.1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10043 mRNA. Translation: CAA71143.1.
AF003626 Genomic DNA. No translation available.
BC070482 mRNA. Translation: AAH70482.1.
CCDSiCCDS35428.1.
RefSeqiNP_001288157.1. NM_001301228.1.
NP_001288158.1. NM_001301229.1.
NP_001288160.1. NM_001301231.1.
NP_005333.2. NM_005342.3.
UniGeneiHs.19114.

Genome annotation databases

EnsembliENST00000325307; ENSP00000359393; ENSG00000029993.
ENST00000448905; ENSP00000442758; ENSG00000029993.
GeneIDi3149.
KEGGihsa:3149.
UCSCiuc004fep.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10043 mRNA. Translation: CAA71143.1.
AF003626 Genomic DNA. No translation available.
BC070482 mRNA. Translation: AAH70482.1.
CCDSiCCDS35428.1.
RefSeqiNP_001288157.1. NM_001301228.1.
NP_001288158.1. NM_001301229.1.
NP_001288160.1. NM_001301231.1.
NP_005333.2. NM_005342.3.
UniGeneiHs.19114.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EQZNMR-A1-79[»]
2YQINMR-A91-164[»]
ProteinModelPortaliO15347.
SMRiO15347.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109392. 26 interactors.
IntActiO15347. 8 interactors.
MINTiMINT-5002211.
STRINGi9606.ENSP00000359393.

PTM databases

iPTMnetiO15347.
PhosphoSitePlusiO15347.

Polymorphism and mutation databases

BioMutaiHMGB3.

Proteomic databases

EPDiO15347.
MaxQBiO15347.
PaxDbiO15347.
PeptideAtlasiO15347.
PRIDEiO15347.
TopDownProteomicsiO15347.

Protocols and materials databases

DNASUi3149.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000325307; ENSP00000359393; ENSG00000029993.
ENST00000448905; ENSP00000442758; ENSG00000029993.
GeneIDi3149.
KEGGihsa:3149.
UCSCiuc004fep.4. human.

Organism-specific databases

CTDi3149.
DisGeNETi3149.
GeneCardsiHMGB3.
HGNCiHGNC:5004. HMGB3.
HPAiHPA062583.
MalaCardsiHMGB3.
MIMi300193. gene.
300915. phenotype.
neXtProtiNX_O15347.
OpenTargetsiENSG00000029993.
PharmGKBiPA35092.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0381. Eukaryota.
COG5648. LUCA.
GeneTreeiENSGT00760000119164.
HOGENOMiHOG000197861.
HOVERGENiHBG009000.
InParanoidiO15347.
KOiK11296.
OMAiDNEKQPY.
OrthoDBiEOG091G0P81.
PhylomeDBiO15347.
TreeFamiTF105371.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000029993-MONOMER.

Miscellaneous databases

EvolutionaryTraceiO15347.
GeneWikiiHMGB3.
GenomeRNAii3149.
PROiO15347.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000029993.
CleanExiHS_HMGB3.
ExpressionAtlasiO15347. baseline and differential.
GenevisibleiO15347. HS.

Family and domain databases

Gene3Di1.10.30.10. 2 hits.
InterProiIPR009071. HMG_box_dom.
IPR017967. HMG_boxA_CS.
IPR031077. HMGB3.
[Graphical view]
PANTHERiPTHR13711:SF144. PTHR13711:SF144. 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 nameiHMGB3_HUMAN
AccessioniPrimary (citable) accession number: O15347
Secondary accession number(s): O95556, Q6NS40
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 147 of the entry and version 4 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.