P05538 (DQB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HLA class II histocompatibility antigen, DQ beta 2 chain

Alternative name(s):
HLA class II histocompatibility antigen, DX beta chain
MHC class II antigen DQB2

Gene names

Name:	HLA-DQB2
Synonyms:	HLA-DXB

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	268 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

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.
Subunit structure	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. 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 similarities	Belongs to the MHC class II family. Contains 1 Ig-like C1-type (immunoglobulin-like) domain.
Caution	This gene appears not to be expressed.
Sequence caution	The sequence CAA60790.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Immunity
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Lysosome MHC II Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome antigen processing and presentation of exogenous peptide antigen via MHC class II Traceable author statement. Source: Reactome interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	ER to Golgi transport vesicle membrane Traceable author statement. Source: Reactome Golgi membrane Traceable author statement. Source: Reactome MHC class II protein complex Non-traceable author statement Ref.6. Source: UniProtKB clathrin-coated endocytic vesicle membrane Traceable author statement. Source: Reactome endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to lumenal side of endoplasmic reticulum membrane Traceable author statement. Source: Reactome lysosomal membrane Traceable author statement. Source: Reactome trans-Golgi network membrane Traceable author statement. Source: Reactome
Molecular_function	MHC class II receptor activity Non-traceable author statement Ref.6. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P05538-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P05538-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: Missing.
     221-257: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32
	Chain	33 – 268	236	HLA class II histocompatibility antigen, DQ beta 2 chain		PRO_0000018992
Regions
	Topological domain	33 – 229	197	Extracellular Potential
	Transmembrane	230 – 250	21	Helical; Potential
	Topological domain	251 – 268	18	Cytoplasmic Potential
	Domain	128 – 216	89	Ig-like C1-type
	Region	33 – 126	94	Beta-1
	Region	127 – 229	103	Beta-2
Amino acid modifications
	Glycosylation	51	1	N-linked (GlcNAc...) Potential
	Disulfide bond	47 ↔ 110		By similarity
	Disulfide bond	148 ↔ 204		By similarity
Natural variations
	Alternative sequence	1 – 4	4	Missing in isoform 2.		VSP_045914
	Alternative sequence	221 – 257	37	Missing in isoform 2.		VSP_045915
Experimental info
	Sequence conflict	106	1	V → L in AAA52667. Ref.6
	Sequence conflict	106	1	V → L in AAA52668. Ref.6
	Sequence conflict	106	1	V → L in AAA52669. Ref.6
	Sequence conflict	106	1	V → L in AAA52670. Ref.6
	Sequence conflict	161	1	R → Q in BC031995. Ref.4
	Sequence conflict	266 – 268	3	LLH → HLL in CAA60790. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: 2746ED6CC5D44AF2	FASTA	268	30,387
	10 20 30 40 50 60 MSWKMALQIP GGFWAAAVTV MLVMLSTPVA EARDFPKDFL VQFKGMCYFT NGTERVRGVA 70 80 90 100 110 120 RYIYNREEYG RFDSDVGEFQ AVTELGRSIE DWNNYKDFLE QERAAVDKVC RHNYEAELRT 130 140 150 160 170 180 TLQRQVEPTV TISPSRTEAL NHHNLLVCSV TDFYPAQIKV RWFRNDQEET AGVVSTSLIR 190 200 210 220 230 240 NGDWTFQILV MLEITPQRGD IYTCQVEHPS LQSPITVEWR AQSESAQSKM LSGIGGFVLG 250 260 LIFLGLGLII RHRGQKGPRG PPPAGLLH
	Isoform 2 [UniParc]. Checksum: B03817F038B6371F	FASTA	227	26,031
	10 20 30 40 50 60 MALQIPGGFW AAAVTVMLVM LSTPVAEARD FPKDFLVQFK GMCYFTNGTE RVRGVARYIY 70 80 90 100 110 120 NREEYGRFDS DVGEFQAVTE LGRSIEDWNN YKDFLEQERA AVDKVCRHNY EAELRTTLQR 130 140 150 160 170 180 QVEPTVTISP SRTEALNHHN LLVCSVTDFY PAQIKVRWFR NDQEETAGVV STSLIRNGDW 190 200 210 220 TFQILVMLEI TPQRGDIYTC QVEHPSLQSP ITVEWRPRGP PPAGLLH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Class II genes of the human major histocompatibility complex. Comparisons of the DQ and DX alpha and beta genes." Jonsson A.-K., Hyldig-Nielsen J.-J., Servenius B., Larhammar D., Andersson G., Joergensen F., Peterson P.A., Rask L. J. Biol. Chem. 262:8767-8777(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Evolutionary dynamics of non-coding sequences within the class II region of the human MHC." Beck S., Abdulla S., Alderton R.P., Glynne R.J., Gut I.G., Hosking L.K., Jackson A., Kelly A., Newell W.R., Sanseau P., Radley E., Thorpe K.L., Trowsdale J. J. Mol. Biol. 255:1-13(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Squamous cell carcinoma.
[5]	"Gene organization of DC and DX subregions of the human major histocompatibility complex." Okada K., Boss J.M., Prentice H., Spies T., Mengler R., Auffray C., Lillie J.W., Grossberger D., Strominger J.L. Proc. Natl. Acad. Sci. U.S.A. 82:3410-3414(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-125.
[6]	"Remarkable sequence conservation of the HLA-DQB2 locus (DX beta) within the highly polymorphic DQ subregion of the human MHC." Berdoz J., Tiercy J.-M., Rollini P., Mach B., Gorski J. Immunogenetics 29:241-248(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-125.
[7]	"The nonpolymorphic MHC class II isotype, HLA-DQA2, is expressed on the surface of B lymphoblastoid cells." Rudy G.B., Lew A.M. J. Immunol. 158:2116-2125(1997) [PubMed] [Europe PMC] [Abstract] Cited for: LACK OF EXPRESSION.
[8]	"Absence of in vivo DNA-protein interactions in the DQA2 and DQB2 promoter regions." Indovina P., Megiorni F., Fontemaggi G., Coni P., Mora B., Mazzilli M.C. Hum. Immunol. 62:504-508(2001) [PubMed] [Europe PMC] [Abstract] Cited for: LACK OF EXPRESSION.
[9]	"Invariant chain structure and MHC class II function." Cresswell P. Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[10]	"Presentation of antigens by MHC class II molecules: getting the most out of them." Villadangos J.A. Mol. Immunol. 38:329-346(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[11]	"MHC class II molecules on the move for successful antigen presentation." Rocha N., Neefjes J. EMBO J. 27:1-5(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"Autophagy in MHC class II presentation: sampling from within." Menendez-Benito V., Neefjes J. Immunity 26:1-3(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[13]	"MHC class II transport at a glance." Berger A.C., Roche P.A. J. Cell Sci. 122:1-4(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[14]	"CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract." Beswick E.J., Reyes V.E. World J. Gastroenterol. 15:2855-2861(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M29614 Genomic DNA. No translation available. M29615 Genomic DNA. No translation available. X87344 Genomic DNA. Translation: CAA60790.1. Different initiation. AL671681 Genomic DNA. No translation available. AL672104 Genomic DNA. No translation available. AL713890 Genomic DNA. No translation available. BX296564 Genomic DNA. Translation: CAM26036.1. CR936921 Genomic DNA. Translation: CAQ07315.1. BC031995 mRNA. No translation available. M11136 Genomic DNA. No translation available. M24920 Genomic DNA. Translation: AAA52667.1. M24921 Genomic DNA. Translation: AAA52668.1. M24922 Genomic DNA. Translation: AAA52669.1. M24923 Genomic DNA. Translation: AAA52670.1.
IPI	IPI00848108.
PIR	D29312. G35058.
RefSeq	NP_001185787.1. NM_001198858.1.
UniGene	Hs.731563.
3D structure databases
ProteinModelPortal	P05538.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000409159.
Polymorphism databases
DMDM	122271.
Proteomic databases
PaxDb	P05538.
PRIDE	P05538.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000399661; ENSP00000382569; ENSG00000196610. ENST00000411527; ENSP00000390431; ENSG00000232629. ENST00000426733; ENSP00000393969; ENSG00000226165. ENST00000430849; ENSP00000389067; ENSG00000228813. ENST00000432486; ENSP00000410132; ENSG00000228254. ENST00000438757; ENSP00000408884; ENSG00000224305. ENST00000456529; ENSP00000399594; ENSG00000230675. ENST00000457432; ENSP00000396502; ENSG00000229493.
GeneID	3120.
Organism-specific databases
CTD	3120.
GeneCards	GC06M032728.
H-InvDB	HIX0165918. HIX0166089. HIX0166694. HIX0167203.
HGNC	HGNC:4945. HLA-DQB2.
neXtProt	NX_P05538.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG68200.
OrthoDB	EOG461454.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P05538.
Genevestigator	P05538.
GermOnline	ENSG00000204275. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit. 3.10.320.10. 1 hit.
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. [Graphical view]
Pfam	PF07654. C1-set. 1 hit. PF00969. MHC_II_beta. 1 hit. [Graphical view]
ProDom	PD000328. MHC_II_b_N. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00407. IGc1. 1 hit. SM00921. MHC_II_beta. 1 hit. [Graphical view]
SUPFAM	SSF54452. MHC_I/II-like_Ag-recog. 1 hit.
PROSITE	PS50835. IG_LIKE. 1 hit. PS00290. IG_MHC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3120.
NextBio	12384.

Entry information

Entry name

DQB2_HUMAN

Accession

Primary (citable) accession number: P05538
Secondary accession number(s): A6NIA5 , Q29826, Q29870, Q29871, Q29872, Q29873, Q5SR06

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.