DRB5_HUMAN
ID DRB5_HUMAN Reviewed; 266 AA.
AC Q30154; B2RBV6; C7C4X3; O00157; O00283; O46700; Q29703; Q29787; Q29788;
AC Q30126; Q30150; Q30199; Q6SJR2; Q7M2H9; Q8HWS7; Q8WLR5; Q9MY54; Q9XRX6;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=HLA class II histocompatibility antigen, DR beta 5 chain;
DE AltName: Full=DR beta-5;
DE AltName: Full=DR2-beta-2;
DE AltName: Full=Dw2;
DE AltName: Full=MHC class II antigen DRB5;
DE Flags: Precursor;
GN Name=HLA-DRB5 {ECO:0000312|EMBL:CAI18079.1};
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] {ECO:0000305, ECO:0000312|PIR:D25239}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS SER-28 AND ALA-154.
RX PubMed=3099214; DOI=10.1038/324676a0;
RA Wu S., Saunders T.L., Bach F.H.;
RT "Polymorphism of human Ia antigens generated by reciprocal intergenic
RT exchange between two DR beta loci.";
RL Nature 324:676-679(1986).
RN [2] {ECO:0000305, ECO:0000312|PIR:C32526}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-28.
RX PubMed=3571980;
RA Wu S.K., Yabe T., Madden M., Saunders T.L., Bach F.H.;
RT "cDNA cloning and sequencing reveals that the electrophoretically constant
RT DR beta 2 molecules, as well as the variable DR beta 1 molecules, from HLA-
RT DR2 subtypes have different amino acid sequences including a hypervariable
RT region for a functionally important epitope.";
RL J. Immunol. 138:2953-2959(1987).
RN [3] {ECO:0000312|EMBL:AAA59822.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB5*01:01).
RX PubMed=3259543; DOI=10.1007/bf00364432;
RA Lock C.B., So A.K., Welsh K.I., Parkes J.D., Trowsdale J.;
RT "MHC class II sequences of an HLA-DR2 narcoleptic.";
RL Immunogenetics 27:449-455(1988).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAA59791.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-28.
RX PubMed=2001975; DOI=10.1016/0198-8859(91)90069-l;
RA Demopulos J.T., Hodge T.W., Wooten V., Acton R.T.;
RT "A novel DRB1 allele in DR2-positive American blacks.";
RL Hum. Immunol. 30:41-44(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DRB5*01:01).
RC TISSUE=Stomach;
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] {ECO:0000305, ECO:0000312|EMBL:CAI18079.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE DRB5*01:01).
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] {ECO:0000305, ECO:0000312|EMBL:AAH09234.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DRB5*01:01).
RC TISSUE=B-cell {ECO:0000312|EMBL:AAH09234.1};
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 28-140 (ALLELE DRB5*01:04), AND NUCLEOTIDE
RP SEQUENCE [GENOMIC DNA] OF 35-119 (ALLELE DRB5*02:04).
RC TISSUE=Blood;
RX PubMed=9162096; DOI=10.1007/s002510050248;
RA Robbins F., Hurley C.K., Tang T., Yao H., Lin Y.S., Wade J., Goeken N.,
RA Hartzman R.J.;
RT "Diversity associated with the second expressed HLA-DRB locus in the human
RT population.";
RL Immunogenetics 46:104-110(1997).
RN [9] {ECO:0000312|EMBL:AAA36276.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 30-266 (ALLELES DRB5*01:01 AND DRB5*01:02).
RX PubMed=2885840; DOI=10.1073/pnas.84.13.4591;
RA Lee B.S.M., Rust N.A., McMichael A.J., McDevitt H.O.;
RT "HLA-DR2 subtypes form an additional supertypic family of DR beta
RT alleles.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:4591-4595(1987).
RN [10] {ECO:0000305, ECO:0000312|EMBL:AAA59818.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 30-266, AND VARIANT ALA-154.
RX PubMed=3476943; DOI=10.1073/pnas.84.17.6234;
RA Bell J.I., Denney D. Jr., Foster L., Belt T.K., Todd J.A., McDevitt H.O.;
RT "Allelic variation in the DR subregion of the human major
RT histocompatibility complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6234-6238(1987).
RN [11] {ECO:0000312|PIR:B28756}
RP PROTEIN SEQUENCE OF 30-148 AND 158-178.
RX PubMed=6576979; DOI=10.1515/bchm2.1983.364.1.749;
RA Goetz H., Kratzin H., Thinnes F.P., Yang C.-Y., Kruse T., Pauly E.,
RA Koelbel S., Egert G., Wernet P., Hilschmann N.;
RT "Primary structure of human class II histocompatibility antigens 3rd
RT communication. Amino acid sequence comparison between DR and DC subclass
RT antigens derived from a lymphoblastoid B cell line homozygous at the HLA
RT loci (HLA-A3,3; B7,7; Dw2,2; DR2,2: MT1,1; Dc1,1: MB1,1).";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:749-755(1983).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 34-122 (ALLELE DRB5*01:05).
RX PubMed=8773325; DOI=10.1111/j.1399-0039.1996.tb02563.x;
RA Poli F., Bianchi P., Crespiatico L., Terragna C., van den Berg-Loonen E.,
RA Sirchia G.;
RT "Characterization of a new HLA-DRB5 allele (DRB5*0105) by PCR-SSP and
RT direct sequencing.";
RL Tissue Antigens 47:338-340(1996).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-217 (ALLELE DRB5*01:14).
RC TISSUE=Blood;
RA Anholts J.D.H.;
RT "New sequences found during routine HLA typing.";
RL Submitted (JUL-2009) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB5*01:06).
RX PubMed=9226128; DOI=10.1111/j.1365-2370.1997.00267.x;
RA Kervaire B., Tiercy J.;
RT "Sequence of a new HLA-DR allele, DRB5*0106.";
RL Eur. J. Immunogenet. 24:225-228(1997).
RN [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB5*01:03).
RC TISSUE=Blood;
RA Hurley C.K.;
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [16]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB5*02:05).
RA Carter V., Day S., Dunn P.;
RT "Identification of a new DRB5*02 variant allele by PCR-SSP and SBT.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [17]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB5*01:11).
RA Greville W.D., Chapman G., Hogbin J.-P., Velickovic Z.;
RT "Novel HLA-DRB5 allele found by sequence based typing.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [18]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB5*01:12).
RX PubMed=14617041; DOI=10.1046/j.1399-0039.2003.00124.x;
RA Atkinson D.C., Jobson S.E., Dunn P.P., Briggs D.C.;
RT "Identification of a new HLA-DRB5 allele, DRB5*0112, by routine PCR-SSP.";
RL Tissue Antigens 62:554-555(2003).
RN [19]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-123 (ALLELE DRB5*01:13).
RX PubMed=16671952; DOI=10.1111/j.1399-0039.2006.00588.x;
RA Garino E., Berrino M., Bertinetto F., Caropreso P., Chidichimo R.,
RA Dametto E., Fasano M.E., Frisaldi E., Mazzola G., Tondat F., Boccadoro M.,
RA Bruno B., Amoroso A.;
RT "Identification of a new allele, HLA-DRB5*0113, through three different
RT molecular biology techniques.";
RL Tissue Antigens 67:427-429(2006).
RN [20]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-115 (ALLELE DRB5*01:07).
RX PubMed=9458128; DOI=10.1111/j.1399-0039.1997.tb02933.x;
RA Buyse I.M., Couture C., Hashemi-Tavoularis S.;
RT "Identification of novel DRB1*11 (DRB1*11013, DRB1*1129), DRB1*08
RT (DRB1*0816) and DRB5* (DRB5*0107) alleles.";
RL Tissue Antigens 50:678-681(1997).
RN [21]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-115 (ALLELE DRB5*01:09).
RX PubMed=9694360; DOI=10.1111/j.1399-0039.1998.tb03010.x;
RA Buyse I.M., Ouellet S., Hashemi-Tavoularis S.;
RT "Identification of novel DRB1*13 (DRB1*1333), DRB1*04 (DRB1*0426) and DRB5*
RT (DRB5*0109) alleles.";
RL Tissue Antigens 51:658-662(1998).
RN [22]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 36-119 (ALLELE DRB5*02:03).
RX PubMed=1471145; DOI=10.1111/j.1399-0039.1992.tb02047.x;
RA Grooms A., Dunckley H., Gao X., Serjeantson S.W.;
RT "DRB5*HK: a new HLA-DRB5 allele in Cantonese.";
RL Tissue Antigens 40:210-211(1992).
RN [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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).
RN [30]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-48.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [32] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 30-219 OF HLA-DRA/HLA-DRB5
RP HETERODIMER IN COMPLEX WITH MBP PEPTIDE, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=11080454; DOI=10.1006/jmbi.2000.4198;
RA Li Y., Li H., Martin R., Mariuzza R.A.;
RT "Structural basis for the binding of an immunodominant peptide from myelin
RT basic protein in different registers by two HLA-DR2 proteins.";
RL J. Mol. Biol. 304:177-188(2000).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 30-219 OF HLA-DRA/HLA-DRB5
RP HETERODIMER IN COMPLEX WITH MPB PEPTIDE AND STREPTOCOCCUS PYOGENES SPEC
RP PEPTIDE, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=11163233; DOI=10.1016/s1074-7613(01)00092-9;
RA Li Y., Li H., Dimasi N., McCormick J.K., Martin R., Schuck P.,
RA Schlievert P.M., Mariuzza R.A.;
RT "Crystal structure of a superantigen bound to the high-affinity, zinc-
RT dependent site on MHC class II.";
RL Immunity 14:93-104(2001).
RN [34] {ECO:0000312|PDB:1H15}
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 30-219 OF HLA-DRA/HLA-DRB5
RP HETERODIMER IN COMPLEX EPSTEIN-BARR VIRUS BALF5 PEPTIDE, SUBUNIT, AND
RP DISULFIDE BONDS.
RX PubMed=12244309; DOI=10.1038/ni835;
RA Lang H.L.E., Jacobsen H., Ikemizu S., Andersson C., Harlos K., Madsen L.,
RA Hjorth P., Sondergaard L., Svejgaard A., Wucherpfennig K., Stuart D.I.,
RA Bell J.I., Jones E.Y., Fugger L.;
RT "A functional and structural basis for TCR cross-reactivity in multiple
RT sclerosis.";
RL Nat. Immunol. 3:940-943(2002).
RN [35] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 30-221 OF HLA-DRA/HLA-DRB5
RP HETERODIMER IN COMPLEX WITH MBP PEPTIDE AND TRAC, SUBUNIT, AND DISULFIDE
RP BONDS.
RX PubMed=16079912; DOI=10.1038/sj.emboj.7600771;
RA Li Y., Huang Y., Lue J., Quandt J.A., Martin R., Mariuzza R.A.;
RT "Structure of a human autoimmune TCR bound to a myelin basic protein self-
RT peptide and a multiple sclerosis-associated MHC class II molecule.";
RL EMBO J. 24:2968-2979(2005).
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 {ECO:0000269|PubMed:11080454, ECO:0000269|PubMed:11163233,
CC ECO:0000269|PubMed:12244309, ECO:0000269|PubMed:16079912}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18305173};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:18305173,
CC ECO:0000305}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18305173}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:18305173, ECO:0000305}. Golgi apparatus, trans-
CC Golgi network membrane {ECO:0000269|PubMed:18305173}; Single-pass type
CC I membrane protein {ECO:0000269|PubMed:18305173, ECO:0000305}. Endosome
CC membrane {ECO:0000269|PubMed:18305173}; Single-pass type I membrane
CC protein {ECO:0000269|PubMed:18305173, ECO:0000305}. Lysosome membrane
CC {ECO:0000269|PubMed:18305173}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:18305173, ECO:0000305}. Late endosome membrane
CC {ECO:0000269|PubMed:18305173}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:18305173, ECO:0000305}. Note=The MHC class II
CC complex transits through a number of intracellular compartments in the
CC endocytic pathway until it reaches the cell membrane for antigen
CC presentation.
CC -!- PTM: Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to down-
CC regulation of MHC class II. {ECO:0000305|PubMed:18305173}.
CC -!- POLYMORPHISM: The following alleles of DRB5 are known: DRB5*01:01,
CC DRB5*01:02, DRB5*01:03, DRB5*01:04, DRB5*01:05, DRB5*01:06, DRB5*01:07,
CC DRB5*01:09, DRB5*01:11, DRB5*01:12 DRB5*01:13, DRB5*01:14, DRB5*02:02,
CC DRB5*02:03, DRB5*02:04, DRB5*02:05. The sequence shown is that of
CC DRB5*01:01.
CC -!- SIMILARITY: Belongs to the MHC class II family. {ECO:0000255}.
CC -!- CAUTION: HLA-DRB3, HLA-DRB4 and HLA-DRB5 may represent a unique gene.
CC {ECO:0000305}.
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DR EMBL; M20429; AAA59822.1; -; mRNA.
DR EMBL; M35159; AAA59791.1; -; Genomic_DNA.
DR EMBL; AL713966; CAI18079.1; -; Genomic_DNA.
DR EMBL; AK314834; BAG37353.1; -; mRNA.
DR EMBL; BC009234; AAH09234.1; -; mRNA.
DR EMBL; U31770; AAB63983.1; -; mRNA.
DR EMBL; U59685; AAB52229.1; -; Genomic_DNA.
DR EMBL; M16954; AAA36276.1; -; mRNA.
DR EMBL; M16955; AAA36277.1; -; mRNA.
DR EMBL; M17377; AAA59818.1; -; mRNA.
DR EMBL; X87210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FN430425; CAZ86696.1; -; Genomic_DNA.
DR EMBL; Z83201; CAB05668.1; -; Genomic_DNA.
DR EMBL; AF122887; AAD31766.1; -; Genomic_DNA.
DR EMBL; AJ271159; CAB71144.1; -; Genomic_DNA.
DR EMBL; AY141137; AAN28924.1; -; Genomic_DNA.
DR EMBL; AJ427352; CAD20460.1; -; Genomic_DNA.
DR EMBL; AY457037; AAR20446.2; -; Genomic_DNA.
DR EMBL; Y09342; CAA70524.1; -; Genomic_DNA.
DR EMBL; Y13727; CAA74055.1; -; Genomic_DNA.
DR EMBL; M91001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS4751.1; -.
DR PIR; B27060; B27060.
DR PIR; B28043; B28043.
DR PIR; B28756; B28756.
DR PIR; C32526; C32526.
DR PIR; D25239; D25239.
DR PIR; I68733; I68733.
DR PIR; PT0169; PT0169.
DR PIR; PT0170; PT0170.
DR PIR; PT0171; PT0171.
DR RefSeq; NP_002116.2; NM_002125.3.
DR PDB; 1FV1; X-ray; 1.90 A; B/E=30-219.
DR PDB; 1H15; X-ray; 3.10 A; B/E=30-219.
DR PDB; 1HQR; X-ray; 3.20 A; B=30-219.
DR PDB; 1ZGL; X-ray; 2.80 A; B/E/H/K=30-221.
DR PDBsum; 1FV1; -.
DR PDBsum; 1H15; -.
DR PDBsum; 1HQR; -.
DR PDBsum; 1ZGL; -.
DR AlphaFoldDB; Q30154; -.
DR SMR; Q30154; -.
DR BioGRID; 109372; 39.
DR IntAct; Q30154; 12.
DR MINT; Q30154; -.
DR STRING; 9606.ENSP00000364114; -.
DR ChEMBL; CHEMBL3988561; -.
DR DrugBank; DB05121; 1D09C3.
DR DrugBank; DB11294; Coccidioides immitis spherule.
DR GlyConnect; 1378; 2 N-Linked glycans (1 site).
DR GlyGen; Q30154; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q30154; -.
DR PhosphoSitePlus; Q30154; -.
DR SwissPalm; Q30154; -.
DR BioMuta; HLA-DRB5; -.
DR DMDM; 74754558; -.
DR jPOST; Q30154; -.
DR MassIVE; Q30154; -.
DR PaxDb; Q30154; -.
DR PeptideAtlas; Q30154; -.
DR PRIDE; Q30154; -.
DR ProteomicsDB; 61556; -.
DR Antibodypedia; 13708; 135 antibodies from 24 providers.
DR DNASU; 3127; -.
DR Ensembl; ENST00000374975.4; ENSP00000364114.3; ENSG00000198502.6.
DR GeneID; 3127; -.
DR KEGG; hsa:3127; -.
DR MANE-Select; ENST00000374975.4; ENSP00000364114.3; NM_002125.4; NP_002116.2.
DR UCSC; uc003obj.4; human.
DR CTD; 3127; -.
DR DisGeNET; 3127; -.
DR GeneCards; HLA-DRB5; -.
DR HGNC; HGNC:4953; HLA-DRB5.
DR HPA; ENSG00000198502; Tissue enhanced (lung, lymphoid tissue).
DR MIM; 604776; gene.
DR neXtProt; NX_Q30154; -.
DR NIAGADS; ENSG00000198502; -.
DR OpenTargets; ENSG00000198502; -.
DR PharmGKB; PA35076; -.
DR VEuPathDB; HostDB:ENSG00000198502; -.
DR eggNOG; ENOG502RYBQ; Eukaryota.
DR GeneTree; ENSGT00940000154993; -.
DR HOGENOM; CLU_047501_13_1_1; -.
DR InParanoid; Q30154; -.
DR OMA; KGRENIV; -.
DR OrthoDB; 1249505at2759; -.
DR PhylomeDB; Q30154; -.
DR TreeFam; TF336626; -.
DR PathwayCommons; Q30154; -.
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; Q30154; -.
DR SIGNOR; Q30154; -.
DR BioGRID-ORCS; 3127; 11 hits in 995 CRISPR screens.
DR ChiTaRS; HLA-DRB5; human.
DR EvolutionaryTrace; Q30154; -.
DR GeneWiki; HLA-DRB5; -.
DR GenomeRNAi; 3127; -.
DR Pharos; Q30154; Tbio.
DR PRO; PR:Q30154; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q30154; protein.
DR Bgee; ENSG00000198502; Expressed in granulocyte and 101 other tissues.
DR ExpressionAtlas; Q30154; baseline and differential.
DR Genevisible; Q30154; HS.
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:0070062; C:extracellular exosome; HDA:UniProtKB.
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; ISS:CAFA.
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:0042605; F:peptide antigen binding; ISS:CAFA.
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 3D-structure; Adaptive immunity; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein;
KW Golgi apparatus; Immunity; Lysosome; Membrane; MHC II; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..29
FT /evidence="ECO:0000269|PubMed:6576979"
FT CHAIN 30..266
FT /note="HLA class II histocompatibility antigen, DR beta 5
FT chain"
FT /id="PRO_5000143106"
FT TOPO_DOM 30..227
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..248
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 249..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 126..214
FT /note="Ig-like C1-type"
FT /evidence="ECO:0000255"
FT REGION 30..124
FT /note="Beta-1"
FT /evidence="ECO:0000255"
FT REGION 125..227
FT /note="Beta-2"
FT /evidence="ECO:0000255"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT DISULFID 44..108
FT DISULFID 146..202
FT VARIANT 14
FT /note="K -> M (in dbSNP:rs1064587)"
FT /id="VAR_060951"
FT VARIANT 14
FT /note="K -> Q (in dbSNP:rs701884)"
FT /id="VAR_060952"
FT VARIANT 14
FT /note="K -> V (in allele DRB5*02:02; requires 2 nucleotide
FT substitutions)"
FT /id="VAR_060953"
FT VARIANT 20
FT /note="M -> T (in dbSNP:rs17211043)"
FT /id="VAR_050355"
FT VARIANT 28
FT /note="L -> S"
FT /evidence="ECO:0000269|PubMed:2001975,
FT ECO:0000269|PubMed:3099214, ECO:0000269|PubMed:3571980"
FT /id="VAR_039871"
FT VARIANT 33
FT /note="R -> Q (in dbSNP:rs1141741)"
FT /id="VAR_050356"
FT VARIANT 35
FT /note="R -> C (in allele DRB5*02:02, allele DRB5*02:04 and
FT allele DRB5*02:05; dbSNP:rs1136744)"
FT /id="VAR_060954"
FT VARIANT 41
FT /note="K -> T (in dbSNP:rs200581589)"
FT /id="VAR_050357"
FT VARIANT 57
FT /note="H -> Q (in dbSNP:rs202185589)"
FT /id="VAR_060955"
FT VARIANT 59
FT /note="D -> G (in allele DRB5*01:02, allele DRB5*01:03,
FT allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and
FT allele DRB5*02:05; dbSNP:rs41546317)"
FT /id="VAR_060956"
FT VARIANT 62
FT /note="N -> H (in dbSNP:rs1059576)"
FT /id="VAR_050358"
FT VARIANT 66
FT /note="D -> N (in allele DRB5*01:02, allele DRB5*01:03,
FT allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and
FT allele DRB5*02:05; dbSNP:rs707956)"
FT /id="VAR_060958"
FT VARIANT 66
FT /note="D -> Y (in allele DRB5*01:14; dbSNP:rs707956)"
FT /id="VAR_060959"
FT VARIANT 67
FT /note="L -> V (in allele DRB5*01:02, allele DRB5*01:03,
FT allele DRB5*01:05, allele DRB5*01:14, allele DRB5*02:02,
FT allele DRB5*02:03, allele DRB5*02:04 and allele DRB5*02:05;
FT dbSNP:rs1059580)"
FT /id="VAR_060960"
FT VARIANT 87
FT /note="A -> E (in allele DRB5*01:13)"
FT /id="VAR_060961"
FT VARIANT 89
FT /note="Y -> S (in allele DRB5*01:12; dbSNP:rs41541218)"
FT /id="VAR_060962"
FT VARIANT 96
FT /note="F -> I (in allele DRB5*01:06, allele DRB5*01:07,
FT allele DRB5*01:11, allele DRB5*02:02 and allele DRB5*02:03;
FT dbSNP:rs696318)"
FT /id="VAR_060964"
FT VARIANT 96
FT /note="F -> L (in allele DRB5*02:05; dbSNP:rs696318)"
FT /id="VAR_060963"
FT VARIANT 99
FT /note="D -> E (in dbSNP:rs41559913)"
FT /id="VAR_060965"
FT VARIANT 99
FT /note="D -> G (in dbSNP:rs41545413)"
FT /id="VAR_060966"
FT VARIANT 99
FT /note="D -> H (in dbSNP:rs41547217)"
FT /id="VAR_060967"
FT VARIANT 99
FT /note="D -> N (in allele DRB5*01:09; dbSNP:rs41547217)"
FT /id="VAR_060968"
FT VARIANT 99
FT /note="D -> Q (in allele DRB5*01:06, allele DRB5*01:11,
FT allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and
FT allele DRB5*02:05; requires 2 nucleotide substitutions)"
FT /id="VAR_060969"
FT VARIANT 99
FT /note="D -> R (in allele DRB5*01:12; requires 2 nucleotide
FT substitutions)"
FT /id="VAR_060970"
FT VARIANT 100
FT /note="R -> A (in allele DRB5*01:06, allele DRB5*01:11,
FT allele DRB5*02:02, allele DRB5*02:03 and allele DRB5*02:04;
FT requires 2 nucleotide substitutions)"
FT /id="VAR_060971"
FT VARIANT 100
FT /note="R -> G (in dbSNP:rs41551116)"
FT /id="VAR_060972"
FT VARIANT 100
FT /note="R -> T (in allele DRB5*01:03; dbSNP:rs41544215)"
FT /id="VAR_060973"
FT VARIANT 103
FT /note="A -> E (in allele DRB5*01:12; dbSNP:rs1059598)"
FT /id="VAR_060974"
FT VARIANT 103
FT /note="A -> L (in allele DRB5*01:04; requires 2 nucleotide
FT substitutions)"
FT /id="VAR_060975"
FT VARIANT 106
FT /note="T -> N (in dbSNP:rs115817940)"
FT /id="VAR_050359"
FT VARIANT 107
FT /note="Y -> V (in allele DRB5*01:12; requires 2 nucleotide
FT substitutions)"
FT /id="VAR_060976"
FT VARIANT 114
FT /note="V -> A (in allele DRB5*01:06, allele DRB5*02:02,
FT allele DRB5*02:04 and allele DRB5*02:05; dbSNP:rs1136778)"
FT /id="VAR_060977"
FT VARIANT 115
FT /note="G -> V (in allele DRB5*01:06, allele DRB5*02:02,
FT allele DRB5*02:04 and allele DRB5*02:05; dbSNP:rs41556512)"
FT /id="VAR_060978"
FT VARIANT 154
FT /note="G -> A (in dbSNP:rs113395425)"
FT /evidence="ECO:0000269|PubMed:3099214,
FT ECO:0000269|PubMed:3476943"
FT /id="VAR_039872"
FT VARIANT 164
FT /note="S -> G (in allele DRB5*02:02; dbSNP:rs1059633)"
FT /id="VAR_060979"
FT VARIANT 186
FT /note="T -> I (in allele DRB5*02:02; dbSNP:rs41559420)"
FT /id="VAR_060980"
FT VARIANT 232
FT /note="V -> I (in allele DRB5*02:02; dbSNP:rs41553512)"
FT /id="VAR_060981"
FT CONFLICT 139
FT /note="Q -> E (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 36..47
FT /evidence="ECO:0007829|PDB:1FV1"
FT TURN 48..51
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 52..61
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:1FV1"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:1FV1"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:1FV1"
FT HELIX 84..91
FT /evidence="ECO:0007829|PDB:1FV1"
FT HELIX 94..101
FT /evidence="ECO:0007829|PDB:1FV1"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:1FV1"
FT HELIX 108..115
FT /evidence="ECO:0007829|PDB:1FV1"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:1FV1"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 137..154
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 157..166
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 169..173
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 184..192
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:1FV1"
FT STRAND 213..218
FT /evidence="ECO:0007829|PDB:1FV1"
SQ SEQUENCE 266 AA; 30056 MW; 0D4335BAEEA6AF22 CRC64;
MVCLKLPGGS YMAKLTVTLM VLSSPLALAG DTRPRFLQQD KYECHFFNGT ERVRFLHRDI
YNQEEDLRFD SDVGEYRAVT ELGRPDAEYW NSQKDFLEDR RAAVDTYCRH NYGVGESFTV
QRRVEPKVTV YPARTQTLQH HNLLVCSVNG FYPGSIEVRW FRNSQEEKAG VVSTGLIQNG
DWTFQTLVML ETVPRSGEVY TCQVEHPSVT SPLTVEWRAQ SESAQSKMLS GVGGFVLGLL
FLGAGLFIYF KNQKGHSGLH PTGLVS
