DRB4_HUMAN
ID DRB4_HUMAN Reviewed; 266 AA.
AC P13762; B0S863; O78042; P79664; Q29889; Q30163; Q6TLK6; Q860N4; Q861F3;
AC Q8WLT9; Q9BS54;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 2.
DT 25-MAY-2022, entry version 157.
DE RecName: Full=HLA class II histocompatibility antigen, DR beta 4 chain;
DE AltName: Full=MHC class II antigen DRB4;
DE Flags: Precursor;
GN Name=HLA-DRB4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB4*01:01).
RX PubMed=3110774; DOI=10.1073/pnas.84.14.4929;
RA Young J.A.T., Wilkinson D., Bodmer W.F., Trowsdale J.;
RT "Sequence and evolution of HLA-DR7- and -DRw53-associated beta-chain
RT genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:4929-4933(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB4*01:03).
RX PubMed=11972878; DOI=10.1034/j.1399-0039.2002.590108.x;
RA De Pablo R., Solis R., Balas A., Vilches C.;
RT "Specific amplification of the HLA-DRB4 gene from c-DNA. Complete coding
RT sequence of the HLA alleles DRB4*0103101 and DRB4*01033.";
RL Tissue Antigens 59:44-46(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB4*01:03).
RA Song C.-H., Lee J.-K., Koh I., Lee J.-Y., Lim Y.-H., Kang J., Cha Y.-Y.,
RA Yun H.-S., Lee E.-J., Kwack K.;
RT "Human leukocyte antigen DRB4*01030101 allele.";
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB4*01:03).
RA Wallace L.T., Rudersdorf R., Watkins D.I.;
RT "The MHC class II alleles of Homo sapiens.";
RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DRB4*01:03).
RC TISSUE=Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE DRB4*01:03).
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DRB4*01:03).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-266 (ALLELE DRB4*01:03).
RX PubMed=3467350; DOI=10.1073/pnas.84.1.209;
RA Curtsinger J.M., Hilden J.M., Cairns J.S., Bach F.H.;
RT "Evolutionary and genetic implications of sequence variation in two
RT nonallelic HLA-DR beta-chain cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:209-213(1987).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-266 (ALLELE DRB4*01:03).
RX PubMed=3036826; DOI=10.1016/s0021-9258(18)47480-7;
RA Andersson G., Larhammar D., Widmark E., Servenius B., Peterson P.A.,
RA Rask L.;
RT "Class II genes of the human major histocompatibility complex. Organization
RT and evolutionary relationship of the DR beta genes.";
RL J. Biol. Chem. 262:8748-8758(1987).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-217 (ALLELE DRB4*01:02).
RA Greville W.D.;
RT "HLA-DRB4 exon 2 and exon 3 variation.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-214 (ALLELE DRB4*01:06).
RA Chapman G., Hogbin J.-P., Greville W.D.;
RT "Novel HLA-DRB4 allele identified by sequencing based typing.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB4*01:04).
RA Kashiwase K.;
RT "HLA-DRB4*01V1(DRB4*0104) DNA Sequence.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 37-116 (ALLELE DRB4*01:05).
RX PubMed=9234493; DOI=10.1111/j.1399-0039.1997.tb02819.x;
RA Voorter C., Emonds M.P., van den Berg-Loonen E.;
RT "Identification of a new DRB4 allele (DRB4*0105) by sequence-based
RT typing.";
RL Tissue Antigens 49:662-664(1997).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 58-120 (ALLELE DRB4*01:07).
RA Mele L., Binello S., Balza G., Mazzola G., Garino E.;
RT "DRB4* genomic sequence: a new allele.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP REVIEW.
RX PubMed=8598037; DOI=10.1016/s0092-8674(00)81025-9;
RA Cresswell P.;
RT "Invariant chain structure and MHC class II function.";
RL Cell 84:505-507(1996).
RN [16]
RP REVIEW.
RX PubMed=11684289; DOI=10.1016/s0161-5890(01)00069-4;
RA Villadangos J.A.;
RT "Presentation of antigens by MHC class II molecules: getting the most out
RT of them.";
RL Mol. Immunol. 38:329-346(2001).
RN [17]
RP REVIEW.
RX PubMed=17241953; DOI=10.1016/j.immuni.2007.01.005;
RA Menendez-Benito V., Neefjes J.;
RT "Autophagy in MHC class II presentation: sampling from within.";
RL Immunity 26:1-3(2007).
RN [18]
RP REVIEW.
RX PubMed=18046453; DOI=10.1038/sj.emboj.7601945;
RA Rocha N., Neefjes J.;
RT "MHC class II molecules on the move for successful antigen presentation.";
RL EMBO J. 27:1-5(2008).
RN [19]
RP UBIQUITINATION BY MARCH1, AND SUBCELLULAR LOCATION.
RX PubMed=18305173; DOI=10.1073/pnas.0708874105;
RA De Gassart A., Camosseto V., Thibodeau J., Ceppi M., Catalan N., Pierre P.,
RA Gatti E.;
RT "MHC class II stabilization at the surface of human dendritic cells is the
RT result of maturation-dependent MARCH I down-regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3491-3496(2008).
RN [20]
RP UBIQUITINATION AT LYS-254 BY MARCH1 AND MARCH8, MUTAGENESIS OF LYS-254;
RP LEU-264 AND LEU-265, AND SUBCELLULAR LOCATION.
RX PubMed=19117940; DOI=10.1074/jbc.m805736200;
RA Lapaque N., Jahnke M., Trowsdale J., Kelly A.P.;
RT "The HLA-DRalpha chain is modified by polyubiquitination.";
RL J. Biol. Chem. 284:7007-7016(2009).
RN [21]
RP REVIEW.
RX PubMed=19092054; DOI=10.1242/jcs.035089;
RA Berger A.C., Roche P.A.;
RT "MHC class II transport at a glance.";
RL J. Cell Sci. 122:1-4(2009).
RN [22]
RP REVIEW.
RX PubMed=19533806; DOI=10.3748/wjg.15.2855;
RA Beswick E.J., Reyes V.E.;
RT "CD74 in antigen presentation, inflammation, and cancers of the
RT gastrointestinal tract.";
RL World J. Gastroenterol. 15:2855-2861(2009).
CC -!- FUNCTION: Binds peptides derived from antigens that access the
CC endocytic route of antigen presenting cells (APC) and presents them on
CC the cell surface for recognition by the CD4 T-cells. The peptide
CC binding cleft accommodates peptides of 10-30 residues. The peptides
CC presented by MHC class II molecules are generated mostly by degradation
CC of proteins that access the endocytic route, where they are processed
CC by lysosomal proteases and other hydrolases. Exogenous antigens that
CC have been endocytosed by the APC are thus readily available for
CC presentation via MHC II molecules, and for this reason this antigen
CC presentation pathway is usually referred to as exogenous. As membrane
CC proteins on their way to degradation in lysosomes as part of their
CC normal turn-over are also contained in the endosomal/lysosomal
CC compartments, exogenous antigens must compete with those derived from
CC endogenous components. Autophagy is also a source of endogenous
CC peptides, autophagosomes constitutively fuse with MHC class II loading
CC compartments. In addition to APCs, other cells of the gastrointestinal
CC tract, such as epithelial cells, express MHC class II molecules and
CC CD74 and act as APCs, which is an unusual trait of the GI tract. To
CC produce a MHC class II molecule that presents an antigen, three MHC
CC class II molecules (heterodimers of an alpha and a beta chain)
CC associate with a CD74 trimer in the ER to form a heterononamer. Soon
CC after the entry of this complex into the endosomal/lysosomal system
CC where antigen processing occurs, CD74 undergoes a sequential
CC degradation by various proteases, including CTSS and CTSL, leaving a
CC small fragment termed CLIP (class-II-associated invariant chain
CC peptide). The removal of CLIP is facilitated by HLA-DM via direct
CC binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM
CC stabilizes MHC class II molecules until primary high affinity antigenic
CC peptides are bound. The MHC II molecule bound to a peptide is then
CC transported to the cell membrane surface. In B-cells, the interaction
CC between HLA-DM and MHC class II molecules is regulated by HLA-DO.
CC Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal
CC microenvironment has been implicated in the regulation of antigen
CC loading into MHC II molecules, increased acidification produces
CC increased proteolysis and efficient peptide loading.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit; also referred as
CC MHC class II molecule. In the endoplasmic reticulum (ER) it forms a
CC heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also
CC known as invariant chain or HLA class II histocompatibility antigen
CC gamma chain). In the endosomal/lysosomal system; CD74 undergoes
CC sequential degradation by various proteases; leaving a small fragment
CC termed CLIP on each MHC class II molecule. MHC class II molecule
CC interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP
CC and facilitate the binding of antigenic peptides.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Endoplasmic reticulum membrane; Single-pass type I membrane
CC protein. Golgi apparatus, trans-Golgi network membrane; Single-pass
CC type I membrane protein. Endosome membrane; Single-pass type I membrane
CC protein. Lysosome membrane; Single-pass type I membrane protein. Late
CC endosome membrane; Single-pass type I membrane protein. Note=The MHC
CC class II complex transits through a number of intracellular
CC compartments in the endocytic pathway until it reaches the cell
CC membrane for antigen presentation.
CC -!- PTM: Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting
CC into the endosome system and down-regulation of MHC class II. When
CC associated with ubiquitination of the alpha subunit of HLA-DR: HLA-DRA
CC 'Lys-244', the down-regulation of MHC class II may be highly effective.
CC {ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:19117940}.
CC -!- POLYMORPHISM: The following alleles of DRB4 are known: DRB4*01:01,
CC DRB4*01:02, DRB4*01:03, DRB4*01:04, DRB4*01:05, DRB4*01:06 and
CC DRB4*01:07. The sequence shown is that of DRB4*01:03.
CC -!- SIMILARITY: Belongs to the MHC class II family. {ECO:0000305}.
CC -!- CAUTION: HLA-DRB3, HLA-DRB4 and HLA-DRB5 may represent a unique gene.
CC {ECO:0000305}.
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DR EMBL; M16942; AAA36296.1; -; mRNA.
DR EMBL; AF361548; AAM00252.1; -; mRNA.
DR EMBL; AF361549; AAM00253.1; -; mRNA.
DR EMBL; DQ284431; ABC66198.1; -; mRNA.
DR EMBL; GQ891550; ACX50637.1; -; mRNA.
DR EMBL; AK292151; BAF84840.1; -; mRNA.
DR EMBL; BX571807; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX120007; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX927235; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR788250; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005312; AAH05312.1; -; mRNA.
DR EMBL; M15178; AAA35995.1; -; mRNA.
DR EMBL; M20555; AAA59830.1; -; Genomic_DNA.
DR EMBL; AH012539; AAO43051.1; -; Genomic_DNA.
DR EMBL; AH011268; AAL48256.1; -; Genomic_DNA.
DR EMBL; AB107960; BAC75547.1; -; Genomic_DNA.
DR EMBL; Y09313; CAA70497.1; -; Genomic_DNA.
DR EMBL; AY394720; AAQ96922.1; -; Genomic_DNA.
DR PIR; B28031; B28031.
DR PIR; I59092; I59092.
DR PIR; PT0168; PT0168.
DR RefSeq; NP_068818.4; NM_021983.4.
DR RefSeq; XP_016885779.1; XM_017030290.1.
DR AlphaFoldDB; P13762; -.
DR SMR; P13762; -.
DR BioGRID; 109371; 10.
DR IntAct; P13762; 1.
DR ChEMBL; CHEMBL3988561; -.
DR DrugBank; DB05121; 1D09C3.
DR DrugBank; DB11294; Coccidioides immitis spherule.
DR GlyGen; P13762; 1 site.
DR iPTMnet; P13762; -.
DR PhosphoSitePlus; P13762; -.
DR BioMuta; HLA-DRB4; -.
DR DMDM; 281371554; -.
DR jPOST; P13762; -.
DR MassIVE; P13762; -.
DR PeptideAtlas; P13762; -.
DR PRIDE; P13762; -.
DR ProteomicsDB; 52984; -.
DR DNASU; 3126; -.
DR Ensembl; ENST00000411565.2; ENSP00000410857.2; ENSG00000227357.2.
DR Ensembl; ENST00000457451.6; ENSP00000412031.2; ENSG00000231021.9.
DR GeneID; 3126; -.
DR KEGG; hsa:3126; -.
DR CTD; 3126; -.
DR DisGeNET; 3126; -.
DR GeneCards; HLA-DRB4; -.
DR HGNC; HGNC:4952; HLA-DRB4.
DR neXtProt; NX_P13762; -.
DR OpenTargets; ENSG00000227357; -.
DR PharmGKB; PA35075; -.
DR InParanoid; P13762; -.
DR OrthoDB; 1249505at2759; -.
DR PhylomeDB; P13762; -.
DR PathwayCommons; P13762; -.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-HSA-202430; Translocation of ZAP-70 to Immunological synapse.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-389948; PD-1 signaling.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; P13762; -.
DR SIGNOR; P13762; -.
DR BioGRID-ORCS; 3126; 0 hits in 1 CRISPR screen.
DR GeneWiki; HLA-DRB4; -.
DR GenomeRNAi; 3126; -.
DR Pharos; P13762; Tdark.
DR PRO; PR:P13762; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P13762; protein.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0042613; C:MHC class II protein complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0030658; C:transport vesicle membrane; TAS:Reactome.
DR GO; GO:0023026; F:MHC class II protein complex binding; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IBA:GO_Central.
DR GO; GO:0002503; P:peptide antigen assembly with MHC class II protein complex; IBA:GO_Central.
DR GO; GO:0050870; P:positive regulation of T cell activation; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.10.320.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR InterPro; IPR014745; MHC_II_a/b_N.
DR InterPro; IPR000353; MHC_II_b_N.
DR Pfam; PF07654; C1-set; 1.
DR Pfam; PF00969; MHC_II_beta; 1.
DR SMART; SM00407; IGc1; 1.
DR SMART; SM00921; MHC_II_beta; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF54452; SSF54452; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00290; IG_MHC; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Endosome; Glycoprotein; Golgi apparatus; Immunity; Isopeptide bond;
KW Lysosome; Membrane; MHC II; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..29
FT CHAIN 30..266
FT /note="HLA class II histocompatibility antigen, DR beta 4
FT chain"
FT /id="PRO_0000018991"
FT TOPO_DOM 30..227
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 126..216
FT /note="Ig-like C1-type"
FT REGION 30..124
FT /note="Beta-1"
FT REGION 125..227
FT /note="Beta-2"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 146..202
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CROSSLNK 254
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:19117940"
FT VARIANT 105
FT /note="D -> G (in allele DRB4*01:02)"
FT /id="VAR_060778"
FT VARIANT 106
FT /note="T -> N (in allele DRB4*01:04)"
FT /id="VAR_060779"
FT VARIANT 110
FT /note="Y -> H (in allele DRB4*01:05)"
FT /id="VAR_060780"
FT VARIANT 113
FT /note="G -> R (in allele DRB4*01:07)"
FT /id="VAR_060781"
FT VARIANT 141
FT /note="H -> Y (in allele DRB4*01:06)"
FT /id="VAR_060782"
FT VARIANT 164
FT /note="G -> S (in allele DRB4*01:01 and allele DRB4*01:06)"
FT /id="VAR_060783"
FT MUTAGEN 254
FT /note="K->R: Almost no change in down-regulation of MHC
FT class II. No ubiquitination and complete loss of down-
FT regulation of MHC class II; when associated with 'R-244' of
FT HLA-DRA."
FT /evidence="ECO:0000269|PubMed:19117940"
FT MUTAGEN 264
FT /note="L->A: Almost no change in down-regulation of MHC
FT class II; when associated with A-265."
FT /evidence="ECO:0000269|PubMed:19117940"
FT MUTAGEN 265
FT /note="L->A: Almost no change in down-regulation of MHC
FT class II; when associated with A-264."
FT /evidence="ECO:0000269|PubMed:19117940"
SQ SEQUENCE 266 AA; 29941 MW; 96FF5FE572403FAE CRC64;
MVCLKLPGGS CMAALTVTLT VLSSPLALAG DTQPRFLEQA KCECHFLNGT ERVWNLIRYI
YNQEEYARYN SDLGEYQAVT ELGRPDAEYW NSQKDLLERR RAEVDTYCRY NYGVVESFTV
QRRVQPKVTV YPSKTQPLQH HNLLVCSVNG FYPGSIEVRW FRNGQEEKAG VVSTGLIQNG
DWTFQTLVML ETVPRSGEVY TCQVEHPSMM SPLTVQWSAR SESAQSKMLS GVGGFVLGLL
FLGTGLFIYF RNQKGHSGLQ PTGLLS
