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HLA class II histocompatibility antigen, DRB1-12 beta chain



Homo sapiens (Human)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


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.

GO - Biological processi


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.

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class II histocompatibility antigen, DRB1-12 beta chain
Alternative name(s):
MHC class II antigen DRB1*12
Short name:
Short name:
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases


Subcellular locationi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei228 – 248HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases


Polymorphism and mutation databases


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
ChainiPRO_000039183230 – 266HLA class II histocompatibility antigen, DRB1-12 beta chainAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi48N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi146 ↔ 202PROSITE-ProRule annotation

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases



Gene expression databases



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.


3D structure databases


Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Belongs to the MHC class II family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases


Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
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.


Sequence statusi: Complete.

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

Q95IE3-1 [UniParc]FASTAAdd to basket

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Mass (Da):29,878
Last modified:December 1, 2001 - v1


The following alleles of DRB1-12 are known: DRB1*12:01, DRB1*12:02, DRB1*12:03, DRB1*12:04, DRB1*12:05, DRB1*12:06, DRB1*12:07, DRB1*12:08, DRB1*12:09, DRB1*12:10, DRB1*12:11, DRB1*12:12, DRB1*12:13, DRB1*12:14, DRB1*12:15, DRB1*12:16, DRB1*12:17, DRB1*12:18 and DRB1*12:19. The sequence shown is that of DRB1*12:01.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0628185R → K in allele DRB1*12:17. 1
Natural variantiVAR_06281913A → T in allele DRB1*12:17. 1
Natural variantiVAR_06282014V → A in allele DRB1*12:17. 1
Natural variantiVAR_06282114V → I in allele DRB1*12:10. 1
Natural variantiVAR_06282254R → L in allele DRB1*12:13. 1
Natural variantiVAR_06282355L → F in allele DRB1*12:08. 1
Natural variantiVAR_06282466L → F in allele DRB1*12:05, allele DRB1*12:14 and allele DRB1*12:15. 1
Natural variantiVAR_06282567L → V in allele DRB1*12:14. 1
Natural variantiVAR_06282676F → L in allele DRB1*12:11. 1
Natural variantiVAR_06282786V → D in allele DRB1*12:04 and allele DRB1*12:09. 1
Natural variantiVAR_06282887A → E in allele DRB1*12:04. 1
Natural variantiVAR_06282988E → Q in allele DRB1*12:18. 1
Natural variantiVAR_06283089S → Y in allele DRB1*12:04 and allele DRB1*12:09. 1
Natural variantiVAR_06283196I → F in allele DRB1*12:02, allele DRB1*12:13, allele DRB1*12:15, allele DRB1*12:16, allele DRB1*12:18 and allele DRB1*12:19. 1
Natural variantiVAR_06283296I → L in allele DRB1*12:12. 1
Natural variantiVAR_06283398E → G in allele DRB1*12:07. 1
Natural variantiVAR_062834114A → V in allele DRB1*12:03, allele DRB1*12:16 and allele DRB1*12:19. 1
Natural variantiVAR_062835115V → G in allele DRB1*12:16. 1
Natural variantiVAR_062836125H → E in allele DRB1*12:17; requires 2 nucleotide substitutions. 1
Natural variantiVAR_062837169T → A in allele DRB1*12:17. 1
Natural variantiVAR_062838178H → Q in allele DRB1*12:06 and allele DRB1*12:17. 1
Natural variantiVAR_062839262R → T in allele DRB1*12:17. Corresponds to variant dbSNP:rs9269744Ensembl.1

Sequence databases

Select the link destinations:
Links Updated
AJ302075 mRNA. Translation: CAC44379.1.
AY626551 mRNA. Translation: AAV34808.1.
EU375850 mRNA. Translation: ABY78039.1.
AY663396 Genomic DNA. Translation: AAU87983.1.
AH010330 Genomic DNA. Translation: AAK07563.1.
AJ870921 Genomic DNA. Translation: CAI35044.1.
AY033428 Genomic DNA. Translation: AAK55114.1.
DQ533486 Genomic DNA. Translation: ABF74752.1.
FJ374889 Genomic DNA. Translation: ACJ09136.1.
FJ481086 Genomic DNA. Translation: ACK77491.1.
D86503 Genomic DNA. Translation: BAA13098.1.
AB112911 Genomic DNA. Translation: BAD02942.1.
AY339246 Genomic DNA. Translation: AAQ18913.1.
AY899825 Genomic DNA. Translation: AAW82078.1.
DQ250650 Genomic DNA. Translation: ABC59072.1.
DQ343834 Genomic DNA. Translation: ABC70992.1.
EF688603 Genomic DNA. Translation: ABS11697.1.
X83455 Genomic DNA. No translation available.
AY174091 Genomic DNA. Translation: AAO20088.1.
AF017439 mRNA. Translation: AAB70553.1.

Genome annotation databases

EnsembliENST00000328980; ENSP00000331343; ENSG00000206306.
ENST00000399450; ENSP00000382378; ENSG00000206240.
ENST00000412634; ENSP00000408795; ENSG00000228080.
ENST00000415796; ENSP00000412168; ENSG00000206306.
ENST00000419393; ENSP00000403458; ENSG00000228080.
ENST00000428566; ENSP00000392280; ENSG00000206240.

Keywords - Coding sequence diversityi


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.

Entry informationi

Entry namei2B1C_HUMAN
AccessioniPrimary (citable) accession number: Q95IE3
Secondary accession number(s): A7LA26
, B0LUZ6, B6VCX2, B7UDB2, O19585, Q19AF2, Q29771, Q2L9H4, Q2MZ92, Q5EER6, Q5NDB9, Q5UT58, Q5Y7G0, Q768U4, Q7YP04, Q861H8, Q95IT6, Q9BD40
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 2, 2010
Last sequence update: December 1, 2001
Last modified: July 5, 2017
This is version 112 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.


Keywords - Technical termi

Complete proteome, Reference proteome


  1. Human chromosome 6
    Human chromosome 6: 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. SIMILARITY comments
    Index of protein domains and families