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UniProtKB - Q30154 (DRB5_HUMAN)

Protein

HLA class II histocompatibility antigen, DR beta 5 chain

Gene

HLA-DRB5

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

Functioni

Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.

Caution

HLA-DRB3, HLA-DRB4 and HLA-DRB5 may represent a unique gene.Curated

GO - Molecular functioni

  • peptide antigen binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processImmunity

Enzyme and pathway databases

ReactomeiR-HSA-202424 Downstream TCR signaling
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse
R-HSA-202433 Generation of second messenger molecules
R-HSA-2132295 MHC class II antigen presentation
R-HSA-389948 PD-1 signaling
R-HSA-877300 Interferon gamma signaling
SIGNORiQ30154

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class II histocompatibility antigen, DR beta 5 chain
Alternative name(s):
DR beta-5
DR2-beta-2
Dw2
MHC class II antigen DRB5
Gene namesi
Name:HLA-DRB5Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000198502.5
HGNCiHGNC:4953 HLA-DRB5
MIMi604776 gene
neXtProtiNX_Q30154

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini30 – 227ExtracellularSequence analysisAdd BLAST198
Transmembranei228 – 248HelicalSequence analysisAdd BLAST21
Topological domaini249 – 266CytoplasmicSequence analysisAdd BLAST18

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, MHC II

Pathology & Biotechi

Organism-specific databases

DisGeNETi3127
OpenTargetsiENSG00000198502
PharmGKBiPA35076

Chemistry databases

ChEMBLiCHEMBL3988561

Polymorphism and mutation databases

BioMutaiHLA-DRB5
DMDMi74754558

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 291 PublicationAdd BLAST29
ChainiPRO_500014310630 – 266HLA class II histocompatibility antigen, DR beta 5 chainAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi44 ↔ 108
Glycosylationi48N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi146 ↔ 202

Post-translational modificationi

Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to down-regulation of MHC class II.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ30154
PeptideAtlasiQ30154
PRIDEiQ30154
ProteomicsDBi61556

PTM databases

iPTMnetiQ30154
SwissPalmiQ30154

Expressioni

Gene expression databases

BgeeiENSG00000198502 Expressed in 91 organ(s), highest expression level in lung
GenevisibleiQ30154 HS

Organism-specific databases

HPAiHPA043151

Interactioni

Subunit structurei

Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic reticulum (ER) it forms a heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system; CD74 undergoes sequential degradation by various proteases; leaving a small fragment termed CLIP on each MHC class II molecule. MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and facilitate the binding of antigenic peptides.4 Publications

Protein-protein interaction databases

BioGridi109372, 16 interactors
IntActiQ30154, 6 interactors
STRINGi9606.ENSP00000364114

Structurei

Secondary structure

1266
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ30154
SMRiQ30154
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ30154

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini126 – 214Ig-like C1-typeSequence analysisAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 124Beta-1Sequence analysisAdd BLAST95
Regioni125 – 227Beta-2Sequence analysisAdd BLAST103

Sequence similaritiesi

Belongs to the MHC class II family.Sequence analysis

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWG3 Eukaryota
ENOG410YI0S LUCA
GeneTreeiENSGT00900000140849
HOVERGENiHBG012730
InParanoidiQ30154
KOiK06752
OMAiRWFRNSQ
OrthoDBiEOG091G15IU
PhylomeDBiQ30154
TreeFamiTF336626

Family and domain databases

Gene3Di2.60.40.10, 1 hit
3.10.320.10, 1 hit
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003006 Ig/MHC_CS
IPR003597 Ig_C1-set
IPR011162 MHC_I/II-like_Ag-recog
IPR014745 MHC_II_a/b_N
IPR000353 MHC_II_b_N
PfamiView protein in Pfam
PF07654 C1-set, 1 hit
PF00969 MHC_II_beta, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD000328 MHC_II_b_N, 1 hit
SMARTiView protein in SMART
SM00407 IGc1, 1 hit
SM00921 MHC_II_beta, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS00290 IG_MHC, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q30154-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MVCLKLPGGS YMAKLTVTLM VLSSPLALAG DTRPRFLQQD KYECHFFNGT 
        60         70         80         90        100
ERVRFLHRDI YNQEEDLRFD SDVGEYRAVT ELGRPDAEYW NSQKDFLEDR 
       110        120        130        140        150
RAAVDTYCRH NYGVGESFTV QRRVEPKVTV YPARTQTLQH HNLLVCSVNG 
       160        170        180        190        200
FYPGSIEVRW FRNSQEEKAG VVSTGLIQNG DWTFQTLVML ETVPRSGEVY 
       210        220        230        240        250
TCQVEHPSVT SPLTVEWRAQ SESAQSKMLS GVGGFVLGLL FLGAGLFIYF 
       260 
KNQKGHSGLH PTGLVS
Length:266
Mass (Da):30,056
Last modified:November 1, 1996 - v1
Checksum:i0D4335BAEEA6AF22
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti139Q → E AA sequence (PubMed:6576979).Curated1

Polymorphismi

The following alleles of DRB5 are known: DRB5*01:01, DRB5*01:02, DRB5*01:03, DRB5*01:04, DRB5*01:05, DRB5*01:06, DRB5*01:07, DRB5*01:09, DRB5*01:11, DRB5*01:12 DRB5*01:13, DRB5*01:14, DRB5*02:02, DRB5*02:03, DRB5*02:04, DRB5*02:05. The sequence shown is that of DRB5*01:01.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06095114K → M. Corresponds to variant dbSNP:rs1064587Ensembl.1
Natural variantiVAR_06095214K → Q. Corresponds to variant dbSNP:rs701884Ensembl.1
Natural variantiVAR_06095314K → V in allele DRB5*02:02; requires 2 nucleotide substitutions. 1
Natural variantiVAR_05035520M → T. Corresponds to variant dbSNP:rs17211043Ensembl.1
Natural variantiVAR_03987128L → S3 Publications1
Natural variantiVAR_05035633R → Q. Corresponds to variant dbSNP:rs1141741Ensembl.1
Natural variantiVAR_06095435R → C in allele DRB5*02:02, allele DRB5*02:04 and allele DRB5*02:05. Corresponds to variant dbSNP:rs1136744Ensembl.1
Natural variantiVAR_05035741K → T. Corresponds to variant dbSNP:rs200581589Ensembl.1
Natural variantiVAR_06095557H → Q. Corresponds to variant dbSNP:rs202185589Ensembl.1
Natural variantiVAR_06095659D → G in allele DRB5*01:02, allele DRB5*01:03, allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and allele DRB5*02:05. Corresponds to variant dbSNP:rs41546317Ensembl.1
Natural variantiVAR_05035862N → H. Corresponds to variant dbSNP:rs1059576Ensembl.1
Natural variantiVAR_06095866D → N in allele DRB5*01:02, allele DRB5*01:03, allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and allele DRB5*02:05. Corresponds to variant dbSNP:rs707956Ensembl.1
Natural variantiVAR_06095966D → Y in allele DRB5*01:14. Corresponds to variant dbSNP:rs707956Ensembl.1
Natural variantiVAR_06096067L → V in allele DRB5*01:02, allele DRB5*01:03, allele DRB5*01:05, allele DRB5*01:14, allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and allele DRB5*02:05. Corresponds to variant dbSNP:rs1059580Ensembl.1
Natural variantiVAR_06096187A → E in allele DRB5*01:13. 1
Natural variantiVAR_06096289Y → S in allele DRB5*01:12. Corresponds to variant dbSNP:rs41541218Ensembl.1
Natural variantiVAR_06096496F → I in allele DRB5*01:06, allele DRB5*01:07, allele DRB5*01:11, allele DRB5*02:02 and allele DRB5*02:03. Corresponds to variant dbSNP:rs696318Ensembl.1
Natural variantiVAR_06096396F → L in allele DRB5*02:05. Corresponds to variant dbSNP:rs696318Ensembl.1
Natural variantiVAR_06096599D → E. Corresponds to variant dbSNP:rs41559913Ensembl.1
Natural variantiVAR_06096699D → G. Corresponds to variant dbSNP:rs41545413Ensembl.1
Natural variantiVAR_06096799D → H. Corresponds to variant dbSNP:rs41547217Ensembl.1
Natural variantiVAR_06096899D → N in allele DRB5*01:09. Corresponds to variant dbSNP:rs41547217Ensembl.1
Natural variantiVAR_06096999D → Q in allele DRB5*01:06, allele DRB5*01:11, allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and allele DRB5*02:05; requires 2 nucleotide substitutions. 1
Natural variantiVAR_06097099D → R in allele DRB5*01:12; requires 2 nucleotide substitutions. 1
Natural variantiVAR_060971100R → A in allele DRB5*01:06, allele DRB5*01:11, allele DRB5*02:02, allele DRB5*02:03 and allele DRB5*02:04; requires 2 nucleotide substitutions. 1
Natural variantiVAR_060972100R → G. Corresponds to variant dbSNP:rs41551116Ensembl.1
Natural variantiVAR_060973100R → T in allele DRB5*01:03. Corresponds to variant dbSNP:rs41544215Ensembl.1
Natural variantiVAR_060974103A → E in allele DRB5*01:12. Corresponds to variant dbSNP:rs1059598Ensembl.1
Natural variantiVAR_060975103A → L in allele DRB5*01:04; requires 2 nucleotide substitutions. 1
Natural variantiVAR_050359106T → N. Corresponds to variant dbSNP:rs115817940Ensembl.1
Natural variantiVAR_060976107Y → V in allele DRB5*01:12; requires 2 nucleotide substitutions. 1
Natural variantiVAR_060977114V → A in allele DRB5*01:06, allele DRB5*02:02, allele DRB5*02:04 and allele DRB5*02:05. Corresponds to variant dbSNP:rs1136778Ensembl.1
Natural variantiVAR_060978115G → V in allele DRB5*01:06, allele DRB5*02:02, allele DRB5*02:04 and allele DRB5*02:05. Corresponds to variant dbSNP:rs41556512Ensembl.1
Natural variantiVAR_039872154G → A2 PublicationsCorresponds to variant dbSNP:rs113395425Ensembl.1
Natural variantiVAR_060979164S → G in allele DRB5*02:02. Corresponds to variant dbSNP:rs1059633Ensembl.1
Natural variantiVAR_060980186T → I in allele DRB5*02:02. Corresponds to variant dbSNP:rs41559420Ensembl.1
Natural variantiVAR_060981232V → I in allele DRB5*02:02. Corresponds to variant dbSNP:rs41553512Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20429 mRNA Translation: AAA59822.1
M35159 Genomic DNA Translation: AAA59791.1
AL713966 Genomic DNA Translation: CAI18079.1
AK314834 mRNA Translation: BAG37353.1
BC009234 mRNA Translation: AAH09234.1
U31770 mRNA Translation: AAB63983.1
U59685 Genomic DNA Translation: AAB52229.1
M16954 mRNA Translation: AAA36276.1
M16955 mRNA Translation: AAA36277.1
M17377 mRNA Translation: AAA59818.1
X87210 Genomic DNA No translation available.
FN430425 Genomic DNA Translation: CAZ86696.1
Z83201 Genomic DNA Translation: CAB05668.1
AF122887 Genomic DNA Translation: AAD31766.1
AJ271159 Genomic DNA Translation: CAB71144.1
AY141137 Genomic DNA Translation: AAN28924.1
AJ427352 Genomic DNA Translation: CAD20460.1
AY457037 Genomic DNA Translation: AAR20446.2
Y09342 Genomic DNA Translation: CAA70524.1
Y13727 Genomic DNA Translation: CAA74055.1
M91001 Genomic DNA No translation available.
CCDSiCCDS4751.1
PIRiB27060
B28043
B28756
C32526
D25239
I68733
PT0169
PT0170
PT0171
RefSeqiNP_002116.2, NM_002125.3
UniGeneiHs.485130
Hs.534322
Hs.696211
Hs.736560

Genome annotation databases

EnsembliENST00000374975; ENSP00000364114; ENSG00000198502
GeneIDi3127
KEGGihsa:3127
UCSCiuc003obj.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20429 mRNA Translation: AAA59822.1
M35159 Genomic DNA Translation: AAA59791.1
AL713966 Genomic DNA Translation: CAI18079.1
AK314834 mRNA Translation: BAG37353.1
BC009234 mRNA Translation: AAH09234.1
U31770 mRNA Translation: AAB63983.1
U59685 Genomic DNA Translation: AAB52229.1
M16954 mRNA Translation: AAA36276.1
M16955 mRNA Translation: AAA36277.1
M17377 mRNA Translation: AAA59818.1
X87210 Genomic DNA No translation available.
FN430425 Genomic DNA Translation: CAZ86696.1
Z83201 Genomic DNA Translation: CAB05668.1
AF122887 Genomic DNA Translation: AAD31766.1
AJ271159 Genomic DNA Translation: CAB71144.1
AY141137 Genomic DNA Translation: AAN28924.1
AJ427352 Genomic DNA Translation: CAD20460.1
AY457037 Genomic DNA Translation: AAR20446.2
Y09342 Genomic DNA Translation: CAA70524.1
Y13727 Genomic DNA Translation: CAA74055.1
M91001 Genomic DNA No translation available.
CCDSiCCDS4751.1
PIRiB27060
B28043
B28756
C32526
D25239
I68733
PT0169
PT0170
PT0171
RefSeqiNP_002116.2, NM_002125.3
UniGeneiHs.485130
Hs.534322
Hs.696211
Hs.736560

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FV1X-ray1.90B/E30-219[»]
1H15X-ray3.10B/E30-219[»]
1HQRX-ray3.20B30-219[»]
1ZGLX-ray2.80B/E/H/K30-221[»]
ProteinModelPortaliQ30154
SMRiQ30154
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109372, 16 interactors
IntActiQ30154, 6 interactors
STRINGi9606.ENSP00000364114

Chemistry databases

ChEMBLiCHEMBL3988561

PTM databases

iPTMnetiQ30154
SwissPalmiQ30154

Polymorphism and mutation databases

BioMutaiHLA-DRB5
DMDMi74754558

Proteomic databases

PaxDbiQ30154
PeptideAtlasiQ30154
PRIDEiQ30154
ProteomicsDBi61556

Protocols and materials databases

DNASUi3127
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374975; ENSP00000364114; ENSG00000198502
GeneIDi3127
KEGGihsa:3127
UCSCiuc003obj.4 human

Organism-specific databases

CTDi3127
DisGeNETi3127
EuPathDBiHostDB:ENSG00000198502.5
GeneCardsiHLA-DRB5
HGNCiHGNC:4953 HLA-DRB5
HPAiHPA043151
MIMi604776 gene
neXtProtiNX_Q30154
OpenTargetsiENSG00000198502
PharmGKBiPA35076
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWG3 Eukaryota
ENOG410YI0S LUCA
GeneTreeiENSGT00900000140849
HOVERGENiHBG012730
InParanoidiQ30154
KOiK06752
OMAiRWFRNSQ
OrthoDBiEOG091G15IU
PhylomeDBiQ30154
TreeFamiTF336626

Enzyme and pathway databases

ReactomeiR-HSA-202424 Downstream TCR signaling
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse
R-HSA-202433 Generation of second messenger molecules
R-HSA-2132295 MHC class II antigen presentation
R-HSA-389948 PD-1 signaling
R-HSA-877300 Interferon gamma signaling
SIGNORiQ30154

Miscellaneous databases

ChiTaRSiHLA-DRB5 human
EvolutionaryTraceiQ30154
GeneWikiiHLA-DRB5
GenomeRNAii3127
PROiPR:Q30154
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198502 Expressed in 91 organ(s), highest expression level in lung
GenevisibleiQ30154 HS

Family and domain databases

Gene3Di2.60.40.10, 1 hit
3.10.320.10, 1 hit
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003006 Ig/MHC_CS
IPR003597 Ig_C1-set
IPR011162 MHC_I/II-like_Ag-recog
IPR014745 MHC_II_a/b_N
IPR000353 MHC_II_b_N
PfamiView protein in Pfam
PF07654 C1-set, 1 hit
PF00969 MHC_II_beta, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD000328 MHC_II_b_N, 1 hit
SMARTiView protein in SMART
SM00407 IGc1, 1 hit
SM00921 MHC_II_beta, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS00290 IG_MHC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDRB5_HUMAN
AccessioniPrimary (citable) accession number: Q30154
Secondary accession number(s): B2RBV6
, C7C4X3, O00157, O00283, O46700, Q29703, Q29787, Q29788, Q30126, Q30150, Q30199, Q6SJR2, Q7M2H9, Q8HWS7, Q8WLR5, Q9MY54, Q9XRX6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 163 of the entry and version 1 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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