Q29974 (2B1G_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HLA class II histocompatibility antigen, DRB1-16 beta chain

Alternative name(s):
MHC class II antigen DRB1*16
Short name=DR-16
Short name=DR16

Gene names

Name:

HLA-DRB1

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	266 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein 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. 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. Ref.19
Post-translational modification	Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHC class II Probable. Ref.19
Polymorphism	The following alleles of DRB1-16 are known: DRB1*16:01; DRB1*16:02; DRB1*16:03; DRB1*16:04; DRB1*16:05; DRB1*16:07; DRB1*16:08; DRB1*16:09; DRB1*16:10; DRB1*16:11 and DRB1*16:12. The sequence shown is that of DRB1*16:02.
Sequence similarities	Belongs to the MHC class II family. Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Immunity
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Lysosome MHC II Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Isopeptide bond Ubl conjugation
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 T-helper 1 type immune response Inferred from sequence or structural similarity. Source: UniProtKB antigen processing and presentation of exogenous peptide antigen via MHC class II Traceable author statement. Source: Reactome detection of bacterium Inferred from sequence or structural similarity. Source: UniProtKB humoral immune response mediated by circulating immunoglobulin Inferred from sequence or structural similarity. Source: UniProtKB immunoglobulin production involved in immunoglobulin mediated immune response Inferred from sequence or structural similarity. Source: UniProtKB inflammatory response to antigenic stimulus Inferred from sequence or structural similarity. Source: UniProtKB interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome negative regulation of T cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of interferon-gamma production Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from sequence or structural similarity. Source: UniProtKB protein tetramerization Inferred from sequence or structural similarity. Source: UniProtKB regulation of interleukin-10 secretion Inferred from sequence or structural similarity. Source: UniProtKB regulation of interleukin-4 production Inferred from sequence or structural similarity. Source: UniProtKB
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 Inferred from electronic annotation. Source: UniProtKB-KW clathrin-coated endocytic vesicle membrane Traceable author statement. Source: Reactome external side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to lumenal side of endoplasmic reticulum membrane Traceable author statement. Source: Reactome late endosome membrane Inferred from direct assay Ref.19. Source: UniProtKB lysosomal membrane Inferred from direct assay Ref.19. Source: UniProtKB trans-Golgi network membrane Traceable author statement. Source: Reactome
Molecular_function	MHC class II receptor activity Non-traceable author statement Ref.2. Source: UniProtKB peptide antigen binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Chain	30 – 266	237	HLA class II histocompatibility antigen, DRB1-16 beta chain		PRO_0000391833
Regions
	Transmembrane	228 – 248	21	Helical; Potential
	Domain	126 – 214	89	Ig-like C1-type
Amino acid modifications
	Glycosylation	48	1	N-linked (GlcNAc...) Potential
	Disulfide bond	146 ↔ 202		By similarity
	Cross-link	254		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Natural variant	42	1	R → K in allele DRB1*16:12.		VAR_062840
	Natural variant	43	1	E → K in allele DRB1*16:11.		VAR_062841
	Natural variant	56	1	L → P in allele DRB1*16:07.		VAR_062842
	Natural variant	66	1	S → N in allele DRB1*16:08.		VAR_062843
	Natural variant	76	1	Y → F in allele DRB1*16:09 and allele DRB1*16:10.		VAR_062844
	Natural variant	96	1	F → I in allele DRB1*16:05 and allele DRB1*16:07.		VAR_062845
	Natural variant	96	1	F → L in allele DRB1*16:02, allele DRB1*16:10, allele DRB1*16:11 and allele DRB1*16:12.		VAR_062846
	Natural variant	101	1	R → A in allele DRB1*16:03; requires 2 nucleotide substitutions.		VAR_062847
	Natural variant	103	1	A → L in allele DRB1*16:04; requires 2 nucleotide substitutions.		VAR_062848
	Natural variant	262	1	T → R. Corresponds to variant rs9269744 [ dbSNP | Ensembl ].		VAR_062849

Sequences

	Sequence		Length	Mass (Da)
	Q29974 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 871CC341692ECA4D	FASTA	266	30,030
	10 20 30 40 50 60 MVCLKLPGGS CMTALTVTLM VLSSPLALAG DTRPRFLWQP KRECHFFNGT ERVRFLDRYF 70 80 90 100 110 120 YNQEESVRFD SDVGEYRAVT ELGRPDAEYW NSQKDFLEDR RAAVDTYCRH NYGVGESFTV 130 140 150 160 170 180 QRRVQPKVTV YPSKTQPLQH HNLLVCSVSG FYPGSIEVRW FLNGQEEKAG MVSTGLIQNG 190 200 210 220 230 240 DWTFQTLVML ETVPRSGEVY TCQVEHPSVT SPLTVEWRAR SESAQSKMLS GVGGFVLGLL 250 260 FLGAGLFIYF RNQKGHSGLQ PTGFLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and sequencing reveals that the electrophoretically constant DR beta 2 molecules, as well as the variable DR beta 1 molecules, from HLA-DR2 subtypes have different amino acid sequences including a hypervariable region for a functionally important epitope." Wu S.K., Yabe T., Madden M., Saunders T.L., Bach F.H. J. Immunol. 138:2953-2959(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*16:01).
[2]	"Molecular studies of a rare DR2/LD-5a/DQw3 HLA class II haplotype. Multiple genetic mechanisms in the generation of polymorphic HLA class II genes." Liu C.P., Bach F.H., Wu S.K. J. Immunol. 140:3631-3639(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*16:02).
[3]	"A novel HLA-DRB1-DR2 allele associated with HLA mistyping." Rosenlicht J.W., Hartung K., Deicher H., Frey J. Immunogenetics 37:479-479(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*16:03). Tissue: Blood.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DRB1*16:01). Tissue: Small intestine.
[5]	"HLA-DR2 subtypes form an additional supertypic family of DR beta alleles." Lee B.S.M., Rust N.A., McMichael A.J., McDevitt H.O. Proc. Natl. Acad. Sci. U.S.A. 84:4591-4595(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-266 (ALLELE DRB1*16:01).
[6]	"The nature of diversity of HLA-DRB1 exon 3." Horn P.A., Albis-Camps M., Verboom M., Bunce M., Yousaf K., Williams S., Blasczyk R. Tissue Antigens 70:335-337(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-216 (ALLELE DRB1*16:04). Tissue: Peripheral blood.
[7]	"HLA-DRB1*1608: a new HLA-DRB1*16 allele with a short DRB1*03 sequence." Reviron D., Dormoy A., Andre M., Froelich N., Roudier J., Tongio M.M., Mercier P. Immunogenetics 46:444-445(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*16:08).
[8]	"A novel HLA allele, DRB1*1609, identified in the Chinese Han population*." Miao K.R., Pan Q.Q., Xue M., Zhou X.Y., Fei X.M., Tang Y.H., Xu R., Zhang J.W., Zhao X., Osowski L., Shi W.X., Xu A.L., Wang C.Y., Kukuruga D. Tissue Antigens 66:248-250(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*16:09).
[9]	"A novel HLA-DRB1 allele, DRB*1611, is identified in two Taiwanese individuals." Chu C.-C., Lee H.-L., Lin M. Tissue Antigens 74:175-176(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*16:11).
[10]	"Novel HLA-DRB1 allele." Gedil M.A., Steiner N.K., Hurley C.K. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*16:05).
[11]	"Identification a novel HLA-DRB1*16 allele by sequence based typing in Chinese." Yan L., Zhu F., He J. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*16:10).
[12]	"Novel HLA class II allele." Lazaro A.M., Xiao Y., Hurley C.K. Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB1*16:12).
[13]	"Two DR2-associated novel alleles arose from the silent mutation of codon 72: DRB1*16012, DRB5*01012." Lin Y.S., Tang T.F., Ng J., Hartzman R., Hurley C.K. Tissue Antigens 54:405-408(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-119 (ALLELE DRB1*16:01). Tissue: Blood.
[14]	Brautbar C., Israel S., Safirman C., Smith A.G. Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 39-120 (ALLELE DRB1*16:07).
[15]	"Invariant chain structure and MHC class II function." Cresswell P. Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation." De Gassart A., Camosseto V., Thibodeau J., Ceppi M., Catalan N., Pierre P., Gatti E. Proc. Natl. Acad. Sci. U.S.A. 105:3491-3496(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY MARCH1, SUBCELLULAR LOCATION.
[20]	"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.
[21]	"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	M28583 mRNA. Translation: AAA59680.1. M20504 mRNA. Translation: AAA59827.1. L02545 mRNA. Translation: AAA59777.1. AK291987 mRNA. Translation: BAF84676.1. M16959 mRNA. Translation: AAA36281.1. AM110006 Genomic DNA. Translation: CAJ33613.1. Z72424 Genomic DNA. No translation available. AY912074 Genomic DNA. Translation: AAY17287.1. DQ837166 Genomic DNA. Translation: ABH05946.1. AY428805 Genomic DNA. Translation: AAR07616.1. DQ192647 Genomic DNA. Translation: ABA39176.1. EU029801 Genomic DNA. Translation: ABU86860.1. U59686 Genomic DNA. Translation: AAB52230.1. U26659 Genomic DNA. Translation: AAD09441.1.
IPI	IPI00955414.
PIR	B27618. D25239. F27060. I54509.
RefSeq	NP_002115.2. NM_002124.3.
UniGene	Hs.485130. Hs.534322. Hs.696211. Hs.716081. Hs.723344. Hs.736560.
3D structure databases
HSSP	HSSP built from PDB template 1JWU based on UniProtKB P01903.
ProteinModelPortal	Q29974.
SMR	Q29974. Positions 32-222.
ModBase	Search...
Polymorphism databases
DMDM	74762149.
Proteomic databases
PRIDE	Q29974.
Protocols and materials databases
DNASU	3123.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360004; ENSP00000353099; ENSG00000196126.
GeneID	3123.
KEGG	hsa:3123.
Organism-specific databases
CTD	3123.
GeneCards	GC06M032546.
HGNC	HGNC:4948. HLA-DRB1.
HPA	CAB015400. CAB034021.
MIM	142857. gene.
neXtProt	NX_Q29974.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG012730.
KO	K06752.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q29974.
Bgee	Q29974.
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
ChiTaRS	HLA-DRB1. human.
GenomeRNAi	3123.
NextBio	12394.
SOURCE	Search...

Entry information

Entry name

2B1G_HUMAN

Accession

Primary (citable) accession number: Q29974
Secondary accession number(s): A7X5J4 , O98212, Q0PGR5, Q29792, Q30120, Q30159, Q30200, Q3HUP9, Q3KTM1, Q3LA84, Q6T865, Q95383

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 2, 2010
Last sequence update:	November 1, 1996
Last modified:	April 3, 2013
This is version 102 of the entry and version 1 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.