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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

HLA-DRA Gene

protein-coding GIFtS: 64
GCID: GC06P032412

major histocompatibility complex, class II, DR alpha

(Previous symbol: HLA-DRA1)

Explore 60 diseases affiliated with
HLA-DRA via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Major Histocompatibility Complex, Class II, DR Alpha¹ ²		Histocompatibility Antigen HLA-DR Alpha²
HLA-DRA1¹ ² ³		HLA Class II Histocompatibility Antigen, DR Alpha Chain²
MHC Class II Antigen DRA² ³		MHC Cell Surface Glycoprotein²
MLRW²

External Ids:	HGNC: 4947¹	Entrez Gene: 3122²	Ensembl: ENSG00000204287⁷	OMIM: 142860⁵	UniProtKB: P01903³

Export aliases for HLA-DRA gene to outside databases

Previous GC identifers: GC06P032434 GC06Pd32422 GC06P032178

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for HLA-DRA:

HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an

alpha and a beta chain, both anchored in the membrane. It plays a central role in the immune system by presenting

peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B

lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons.

Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the

transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as

the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: DRA_HUMAN, P01903

Function: 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 miroenvironment has been implicated in the

regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and

efficient peptide loading

Gene Wiki entry for HLA-DRA

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000006.11 NC_018917.1 NT_007592.15 NT_113891.2 NT_167245.1 NT_167246.1 NT_167247.1 NT_167248.1

NT_167249.1

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the HLA-DRA gene promoter:
Pax-5 AML1a GCNF CUTL1 Arnt AREB6 IRF-2 GCNF-1 Pax-4a GCNF-2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: HLA-DRA promoter sequence

Search SABiosciences Chromatin IP Primers for HLA-DRA

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat HLA-DRA

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6p21.3 Ensembl cytogenetic band: 6p21.32 HGNC cytogenetic band: 6p21.3

HLA-DRA Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HLA-DRA gene location

GeneLoc information about chromosome 6 GeneLoc Exon Structure

GeneLoc location for GC06P032412: view genomic region (about GC identifiers)

Start:	32,407,619 bp from pter	End:	32,412,823 bp from pter
Size:	5,205 bases	Orientation:	plus strand

6 alternative locations:

Chr6+,ALT_REF_LOCI_6 32,365,090-32,405,881	Chr6+,ALT_REF_LOCI_5 32,397,816-32,403,026	Chr6+,ALT_REF_LOCI_3 32,382,335-32,398,583
Chr6+,ALT_REF_LOCI_4 32,369,338-32,374,549	Chr6+,ALT_REF_LOCI_2 32,355,870-32,400,225	Chr6+,ALT_REF_LOCI_7 32,343,748-32,348,958

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: DRA_HUMAN, P01903 (See protein sequence)

Recommended Name: HLA class II histocompatibility antigen, DR alpha chain precursor

Size: 254 amino acids; 28607 Da

Subunit: 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

Subcellular location: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass

type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome

membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Late endosome

membrane; Single-pass type I membrane protein. Note=The MHC class II complex transits through a number of

intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation

Sequence caution: Sequence=CAA25076.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

6/58 PDB 3D structures from and Proteopedia for HLA-DRA (see all 58):

1A6A (3D)

1AQD (3D)

1BX2 (3D)

1D5M (3D)

1D5X (3D)

1D5Z (3D)

Secondary accessions: A2BET4 Q30160 Q6IAZ1 Q861I2 Q9TP70

Explore the universe of human proteins at neXtProt for HLA-DRA: NX_P01903

Post-translational modifications:

Ubiquitinated by MARCH1 or MARCH8 at Lys-244 leading to down-regulation of MHC class II. When associated with

ubiquitination of the beta subunit of HLA-DR: HLA-DRB4 'Lys-254', the down-regulation of MHC class II may be highly

effective¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P01903

HLA-DRA Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_061984.2

ENSEMBL proteins:

ENSP00000378786 ENSP00000364121

Reactome Protein details: P01903
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate: HLA-DRA OriGene Custom Protein Services for HLA-DRA
	GenScript Custom Purified and Recombinant Proteins Services for HLA-DRA
	Novus Biologicals HLA-DRA Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Uscn

Gene Ontology (GO): 5/16 cellular component terms (GO ID links to tree view) (see all 16): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000139	Golgi membrane	TAS	--
GO:0005764	lysosome	IDA	8890155
GO:0005765	lysosomal membrane	TAS	--
GO:0005789	endoplasmic reticulum membrane	--	--
GO:0005794	Golgi apparatus	--	--

HLA-DRA for ontologies About GeneDecksing

HLA-DRA Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	R&D Systems Antibodies for HLA-DRA (HLA-DR)
	OriGene Antibodies: HLA-DRA OriGene Custom Antibody Services for HLA-DRA
	GenScript Custom Superior Antibodies Services for HLA-DRA
	Novus Biologicals HLA-DRA Antibodies
	Abcam antibodies for HLA-DRA
	Browse Antibodies at Uscn
	Search ThermoFisher Antibodies for HLA-DRA

Assay Products for HLA-DRA:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for HLA-DRA
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

HLA-DRA for domains About GeneDecksing

5/7 InterPro domains/families (see all 7):

IPR001003 MHC_II_a_N

IPR011162 MHC_I/II-like_Ag-recog

IPR013783 Ig-like_fold

IPR014745 MHC_II_a/b_N

IPR003597 Ig_C1-set

Graphical View of Domain Structure for InterPro Entry P01903

ProtoNet protein and cluster: P01903

2 Blocks protein families:

IPB001003 MHC Class II alpha chain

IPB003597 Immunoglobulin C-type

UniProtKB/Swiss-Prot: DRA_HUMAN, P01903

Similarity: Belongs to the MHC class II family

Similarity: Contains 1 Ig-like C1-type (immunoglobulin-like) domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: