ID HG2A_HUMAN Reviewed; 296 AA. AC P04233; A8K7R1; B4DNE8; D3DQG3; D3DQG4; Q14597; Q29832; Q5U0J8; AC Q8SNA0; Q8WLP6; DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 3. DT 13-APR-2016, entry version 186. DE RecName: Full=HLA class II histocompatibility antigen gamma chain; DE AltName: Full=HLA-DR antigens-associated invariant chain; DE AltName: Full=Ia antigen-associated invariant chain; DE Short=Ii; DE AltName: Full=p33; DE AltName: CD_antigen=CD74; GN Name=CD74; Synonyms=DHLAG; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=6324166; DOI=10.1073/pnas.80.24.7395; RA Claesson L., Larhammar D., Rask L., Peterson P.A.; RT "cDNA clone for the human invariant gamma chain of class II RT histocompatibility antigens and its implications for the protein RT structure."; RL Proc. Natl. Acad. Sci. U.S.A. 80:7395-7399(1983). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=6586420; RA Strubin M., Mach B., Long E.O.; RT "The complete sequence of the mRNA for the HLA-DR-associated invariant RT chain reveals a polypeptide with an unusual transmembrane polarity."; RL EMBO J. 3:869-872(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM RP 2). RX PubMed=3001652; DOI=10.1093/nar/13.24.8827; RA Kudo J., Chao L.-Y., Narni F., Saunders G.F.; RT "Structure of the human gene encoding the invariant gamma-chain of RT class II histocompatibility antigens."; RL Nucleic Acids Res. 13:8827-8841(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS RP 1 AND 2). RC TISSUE=Liver; RX PubMed=3459184; DOI=10.1073/pnas.83.12.4484; RA O'Sullivan D.M., Larhammar D., Wilson M.C., Peterson P.A., RA Quaranta V.; RT "Structure of the human Ia-associated invariant (gamma)-chain gene: RT identification of 5' sequences shared with major histocompatibility RT complex class II genes."; RL Proc. Natl. Acad. Sci. U.S.A. 83:4484-4488(1986). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Heart, and 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=B-cell, and Tonsil; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP PROTEIN SEQUENCE OF 22-35; 81-94; 171-179 AND 273-288, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (JUN-2005) to UniProtKB. RN [11] RP PROTEIN SEQUENCE OF 97-120. RX PubMed=1448172; DOI=10.1038/360474a0; RA Riberdy J.M., Newcomb J.R., Surman M.J., Barbosa J.A., Cresswell P.; RT "HLA-DR molecules from an antigen-processing mutant cell line are RT associated with invariant chain peptides."; RL Nature 360:474-477(1992). RN [12] RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH ROS1. RX PubMed=12661006; DOI=10.1002/gcc.10207; RA Charest A., Lane K., McMahon K., Park J., Preisinger E., Conroy H., RA Housman D.; RT "Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma RT with an interstitial del(6)(q21q21)."; RL Genes Chromosomes Cancer 37:58-71(2003). RN [13] RP INTERACTION WITH MIF. RX PubMed=12782713; DOI=10.1084/jem.20030286; RA Leng L., Metz C.N., Fang Y., Xu J., Donnelly S., Baugh J., RA Delohery T., Chen Y., Mitchell R.A., Bucala R.; RT "MIF signal transduction initiated by binding to CD74."; RL J. Exp. Med. 197:1467-1476(2003). RN [14] 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 [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136. 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 RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [16] 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., RA Buerckstuemmer T., 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 [17] RP GLYCOSYLATION AT THR-203, STRUCTURE OF CARBOHYDRATES, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=22171320; DOI=10.1074/mcp.M111.013649; RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.; RT "Human urinary glycoproteomics; attachment site specific analysis of RT N-and O-linked glycosylations by CID and ECD."; RL Mol. Cell. Proteomics 0:0-0(2011). RN [18] RP GLYCOSYLATION AT THR-203 AND SER-281, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=23234360; DOI=10.1021/pr300963h; RA Halim A., Ruetschi U., Larson G., Nilsson J.; RT "LC-MS/MS characterization of O-glycosylation sites and glycan RT structures of human cerebrospinal fluid glycoproteins."; RL J. Proteome Res. 12:573-584(2013). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 103-117 (CLIP) IN COMPLEX RP WITH HLA-DRA/HLA-DRB1 HETERODIMER. RX PubMed=7477400; DOI=10.1038/378457a0; RA Ghosh P., Amaya M., Mellins E., Wiley D.C.; RT "The structure of an intermediate in class II MHC maturation: CLIP RT bound to HLA-DR3."; RL Nature 378:457-462(1995). RN [21] RP STRUCTURE BY NMR OF 134-208. RX PubMed=9843486; DOI=10.1093/emboj/17.23.6812; RA Jasanoff A., Wagner G., Wiley D.C.; RT "Structure of a trimeric domain of the MHC class II-associated RT chaperonin and targeting protein Ii."; RL EMBO J. 17:6812-6818(1998). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 210-274, GLYCOSYLATION AT RP ASN-256, AND DISULFIDE BONDS. RX PubMed=10022822; DOI=10.1093/emboj/18.4.793; RA Guncar G., Pungercic G., Klemencic I., Turk V., Turk D.; RT "Crystal structure of MHC class II-associated p41 Ii fragment bound to RT cathepsin L reveals the structural basis for differentiation between RT cathepsins L and S."; RL EMBO J. 18:793-803(1999). CC -!- FUNCTION: Plays a critical role in MHC class II antigen processing CC by stabilizing peptide-free class II alpha/beta heterodimers in a CC complex soon after their synthesis and directing transport of the CC complex from the endoplasmic reticulum to the endosomal/lysosomal CC system where the antigen processing and binding of antigenic CC peptides to MHC class II takes place. Serves as cell surface CC receptor for the cytokine MIF. CC -!- SUBUNIT: Homotrimer. In the endoplasmic reticulum (ER) it forms a CC heterononameric MHC II-Ii complex: 3 MHC class II molecules CC (heterodimers of an alpha and a beta subunit) bind to the CD74 CC homotrimer (also known as invariant chain or HLA class II CC histocompatibility antigen gamma chain). In the CC endosomal/lysosomal system, the CD74 component undergoes CC sequential degradation by various proteases, including CTSS and CC CTSL, leaving a small fragment termed CLIP (class-II-associated CC invariant chain peptide) attached to the MHC class II molecule CC (alpha-beta-CLIP complex). This processed complex interacts with CC HLA_DM and HLA_DO heterodimers in order to release CLIP and CC facilitate the binding of antigenic peptides to the MHC class II CC molecules. {ECO:0000269|PubMed:12782713, CC ECO:0000269|PubMed:7477400}. CC -!- INTERACTION: CC P61073:CXCR4; NbExp=4; IntAct=EBI-2622890, EBI-489411; CC P01909:HLA-DQA1; NbExp=2; IntAct=EBI-2622890, EBI-713389; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass CC type II membrane protein {ECO:0000305}. Endoplasmic reticulum CC membrane. Golgi apparatus, trans-Golgi network. Endosome. CC Lysosome. Note=Transits through a number of intracellular CC compartments in the endocytic pathway. It can either undergo CC proteolysis or reach the cell membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Long; CC IsoId=P04233-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=P04233-2; Sequence=VSP_005331; CC Name=3; CC IsoId=P04233-3; Sequence=VSP_037869, VSP_037870; CC -!- PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly CC core 8 glycans. {ECO:0000269|PubMed:10022822, CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:22171320, CC ECO:0000269|PubMed:23234360}. CC -!- DISEASE: Note=A chromosomal aberration involving CD74 is found in CC a non-small cell lung tumor. Results in the formation of a CD74- CC ROS1 chimeric protein. {ECO:0000269|PubMed:12661006}. CC -!- SIMILARITY: Contains 1 thyroglobulin type-1 domain. CC {ECO:0000255|PROSITE-ProRule:PRU00500}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA36304.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; K01144; AAA36304.1; ALT_INIT; mRNA. DR EMBL; X00497; CAA25192.1; -; mRNA. DR EMBL; X00497; CAA25193.1; -; mRNA. DR EMBL; X03339; CAA27046.1; -; Genomic_DNA. DR EMBL; X03340; CAA27047.1; -; Genomic_DNA. DR EMBL; M13560; AAA36033.1; -; Genomic_DNA. DR EMBL; M13555; AAA36033.1; JOINED; Genomic_DNA. DR EMBL; M13556; AAA36033.1; JOINED; Genomic_DNA. DR EMBL; M13558; AAA36033.1; JOINED; Genomic_DNA. DR EMBL; M13559; AAA36033.1; JOINED; Genomic_DNA. DR EMBL; BT019505; AAV38312.1; -; mRNA. DR EMBL; AK292076; BAF84765.1; -; mRNA. DR EMBL; AK297889; BAG60210.1; -; mRNA. DR EMBL; AC011372; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC011388; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW61727.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61728.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61729.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61730.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61731.1; -; Genomic_DNA. DR EMBL; BC018726; AAH18726.1; -; mRNA. DR EMBL; BC024272; AAH24272.1; -; mRNA. DR CCDS; CCDS34276.1; -. [P04233-3] DR CCDS; CCDS47308.1; -. [P04233-2] DR CCDS; CCDS47309.1; -. [P04233-1] DR PIR; A93981; HLHUG. DR RefSeq; NP_001020329.1; NM_001025158.2. [P04233-3] DR RefSeq; NP_001020330.1; NM_001025159.2. [P04233-1] DR RefSeq; NP_004346.1; NM_004355.3. [P04233-2] DR UniGene; Hs.436568; -. DR PDB; 1A6A; X-ray; 2.75 A; C=103-117. DR PDB; 1ICF; X-ray; 2.00 A; I/J=210-274. DR PDB; 1IIE; NMR; -; A/B/C=134-208. DR PDB; 1L3H; NMR; -; A=210-274. DR PDB; 1MUJ; X-ray; 2.15 A; C=97-121. DR PDB; 3PDO; X-ray; 1.95 A; C=102-120. DR PDB; 3PGC; X-ray; 2.66 A; C/F=106-120. DR PDB; 3PGD; X-ray; 2.72 A; C/F=106-120. DR PDB; 3QXA; X-ray; 2.71 A; C/F=103-117. DR PDB; 3QXD; X-ray; 2.30 A; C/F=103-117. DR PDB; 4AEN; X-ray; 2.20 A; C=106-120. DR PDB; 4AH2; X-ray; 2.36 A; B=106-120. DR PDBsum; 1A6A; -. DR PDBsum; 1ICF; -. DR PDBsum; 1IIE; -. DR PDBsum; 1L3H; -. DR PDBsum; 1MUJ; -. DR PDBsum; 3PDO; -. DR PDBsum; 3PGC; -. DR PDBsum; 3PGD; -. DR PDBsum; 3QXA; -. DR PDBsum; 3QXD; -. DR PDBsum; 4AEN; -. DR PDBsum; 4AH2; -. DR ProteinModelPortal; P04233; -. DR SMR; P04233; 134-208, 210-274. DR BioGrid; 107410; 10. DR IntAct; P04233; 62. DR MINT; MINT-1488574; -. DR STRING; 9606.ENSP00000009530; -. DR BindingDB; P04233; -. DR ChEMBL; CHEMBL4692; -. DR GuidetoPHARMACOLOGY; 2840; -. DR MEROPS; I31.002; -. DR iPTMnet; P04233; -. DR PhosphoSite; P04233; -. DR SwissPalm; P04233; -. DR UniCarbKB; P04233; -. DR BioMuta; CD74; -. DR DMDM; 20178292; -. DR EPD; P04233; -. DR MaxQB; P04233; -. DR PaxDb; P04233; -. DR PRIDE; P04233; -. DR DNASU; 972; -. DR Ensembl; ENST00000009530; ENSP00000009530; ENSG00000019582. [P04233-1] DR Ensembl; ENST00000353334; ENSP00000230685; ENSG00000019582. [P04233-2] DR Ensembl; ENST00000377795; ENSP00000367026; ENSG00000019582. [P04233-3] DR GeneID; 972; -. DR KEGG; hsa:972; -. DR UCSC; uc003lsc.4; human. [P04233-1] DR CTD; 972; -. DR GeneCards; CD74; -. DR HGNC; HGNC:1697; CD74. DR HPA; CAB002506; -. DR HPA; HPA010592; -. DR MIM; 142790; gene. DR neXtProt; NX_P04233; -. DR PharmGKB; PA26236; -. DR eggNOG; ENOG410IMYW; Eukaryota. DR eggNOG; ENOG410Z4PR; LUCA. DR GeneTree; ENSGT00390000008961; -. DR HOVERGEN; HBG004444; -. DR InParanoid; P04233; -. DR KO; K06505; -. DR OrthoDB; EOG793B8J; -. DR PhylomeDB; P04233; -. DR TreeFam; TF317779; -. DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall. DR Reactome; R-HSA-2132295; MHC class II antigen presentation. DR ChiTaRS; CD74; human. DR EvolutionaryTrace; P04233; -. DR GeneWiki; CD74; -. DR GenomeRNAi; 972; -. DR NextBio; 4068; -. DR PMAP-CutDB; P04233; -. DR PRO; PR:P04233; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; P04233; -. DR CleanEx; HS_CD74; -. DR ExpressionAtlas; P04233; baseline and differential. DR Genevisible; P04233; HS. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. 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:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; IDA: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:0016021; C:integral component of membrane; IDA:BHF-UCL. DR GO; GO:0005622; C:intracellular; TAS:UniProtKB. DR GO; GO:0005770; C:late endosome; IEA:Ensembl. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome. DR GO; GO:0035692; C:macrophage migration inhibitory factor receptor complex; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0042613; C:MHC class II protein complex; IEA:Ensembl. DR GO; GO:0005771; C:multivesicular body; IEA:Ensembl. DR GO; GO:0035693; C:NOS2-CD74 complex; IEA:Ensembl. 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:0005773; C:vacuole; IDA:BHF-UCL. DR GO; GO:0001540; F:beta-amyloid binding; IPI:BHF-UCL. DR GO; GO:0019955; F:cytokine binding; IPI:UniProtKB. DR GO; GO:0004896; F:cytokine receptor activity; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; TAS:UniProtKB. DR GO; GO:0035718; F:macrophage migration inhibitory factor binding; IPI:BHF-UCL. DR GO; GO:0042289; F:MHC class II protein binding; NAS:UniProtKB. DR GO; GO:0042658; F:MHC class II protein binding, via antigen binding groove; IDA:UniProtKB. DR GO; GO:0023026; F:MHC class II protein complex binding; IDA:UniProtKB. DR GO; GO:0044183; F:protein binding involved in protein folding; IDA:UniProtKB. DR GO; GO:0000187; P:activation of MAPK activity; IEA:Ensembl. DR GO; GO:0019883; P:antigen processing and presentation of endogenous antigen; NAS:UniProtKB. DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0008283; P:cell proliferation; IDA:UniProtKB. DR GO; GO:0051085; P:chaperone mediated protein folding requiring cofactor; IEA:Ensembl. DR GO; GO:0006952; P:defense response; IEA:Ensembl. DR GO; GO:0016064; P:immunoglobulin mediated immune response; ISS:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0035691; P:macrophage migration inhibitory factor signaling pathway; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL. DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:BHF-UCL. DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; IEA:Ensembl. DR GO; GO:0002792; P:negative regulation of peptide secretion; IDA:BHF-UCL. DR GO; GO:0045581; P:negative regulation of T cell differentiation; IEA:Ensembl. DR GO; GO:0045060; P:negative thymic T cell selection; IEA:Ensembl. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:BHF-UCL. DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISS:BHF-UCL. DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IMP:BHF-UCL. DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL. DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISS:BHF-UCL. DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISS:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL. DR GO; GO:0045582; P:positive regulation of T cell differentiation; IEA:Ensembl. DR GO; GO:0002830; P:positive regulation of type 2 immune response; IEA:Ensembl. DR GO; GO:0045059; P:positive thymic T cell selection; IEA:Ensembl. DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB. DR GO; GO:0006461; P:protein complex assembly; ISS:UniProtKB. DR GO; GO:0043030; P:regulation of macrophage activation; NAS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB. DR GO; GO:0045058; P:T cell selection; NAS:UniProtKB. DR Gene3D; 1.10.870.10; -; 1. DR Gene3D; 4.10.800.10; -; 1. DR InterPro; IPR015386; MHC_II-assoc_invar/CLIP_MHC-bd. DR InterPro; IPR022339; MHC_II-assoc_invar_chain. DR InterPro; IPR011988; MHC_II-assoc_invariant_trimer. DR InterPro; IPR000716; Thyroglobulin_1. DR Pfam; PF09307; MHC2-interact; 1. DR Pfam; PF08831; MHCassoc_trimer; 1. DR Pfam; PF00086; Thyroglobulin_1; 1. DR PIRSF; PIRSF001992; CD74_antigen; 1. DR PRINTS; PR01990; CD74ANTIGEN. DR SMART; SM00211; TY; 1. DR SUPFAM; SSF48305; SSF48305; 1. DR SUPFAM; SSF57610; SSF57610; 1. DR PROSITE; PS00484; THYROGLOBULIN_1_1; 1. DR PROSITE; PS51162; THYROGLOBULIN_1_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane; KW Chaperone; Complete proteome; Direct protein sequencing; KW Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; KW Golgi apparatus; Immunity; Lysosome; Membrane; Phosphoprotein; KW Proteoglycan; Reference proteome; Signal-anchor; Transmembrane; KW Transmembrane helix. FT CHAIN 1 296 HLA class II histocompatibility antigen FT gamma chain. FT /FTId=PRO_0000067954. FT TOPO_DOM 1 46 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 47 72 Helical; Signal-anchor for type II FT membrane protein. {ECO:0000255}. FT TOPO_DOM 73 296 Extracellular. {ECO:0000255}. FT DOMAIN 210 271 Thyroglobulin type-1. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT REGION 103 117 CLIP. FT SITE 208 209 Breakpoint for translocation to form a FT CD74-ROS1 fusion protein. FT MOD_RES 25 25 Phosphoserine. FT {ECO:0000250|UniProtKB:P04441}. FT CARBOHYD 130 130 N-linked (GlcNAc...). FT CARBOHYD 136 136 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:19159218}. FT CARBOHYD 203 203 O-linked (GalNAc...). FT {ECO:0000269|PubMed:22171320, FT ECO:0000269|PubMed:23234360}. FT CARBOHYD 256 256 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:10022822}. FT CARBOHYD 281 281 O-linked (GalNAc...). FT {ECO:0000269|PubMed:23234360}. FT DISULFID 213 232 {ECO:0000255|PROSITE-ProRule:PRU00500, FT ECO:0000269|PubMed:10022822}. FT DISULFID 243 250 {ECO:0000255|PROSITE-ProRule:PRU00500, FT ECO:0000269|PubMed:10022822}. FT DISULFID 252 271 {ECO:0000255|PROSITE-ProRule:PRU00500, FT ECO:0000269|PubMed:10022822}. FT VAR_SEQ 148 160 NADPLKVYPPLKG -> SHWNWRTRLLGWV (in FT isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_037869. FT VAR_SEQ 161 296 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_037870. FT VAR_SEQ 209 272 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:6324166, FT ECO:0000303|PubMed:6586420, FT ECO:0000303|Ref.5}. FT /FTId=VSP_005331. FT CONFLICT 167 167 R -> T (in Ref. 3; CAA27047). FT {ECO:0000305}. FT HELIX 139 149 {ECO:0000244|PDB:1IIE}. FT HELIX 162 172 {ECO:0000244|PDB:1IIE}. FT HELIX 175 194 {ECO:0000244|PDB:1IIE}. FT HELIX 212 217 {ECO:0000244|PDB:1ICF}. FT STRAND 236 238 {ECO:0000244|PDB:1L3H}. FT STRAND 240 244 {ECO:0000244|PDB:1ICF}. FT TURN 245 248 {ECO:0000244|PDB:1ICF}. FT STRAND 249 253 {ECO:0000244|PDB:1ICF}. FT STRAND 265 267 {ECO:0000244|PDB:1ICF}. SQ SEQUENCE 296 AA; 33516 MW; 27A13F252D5FB91D CRC64; MHRRRSRSCR EDQKPVMDDQ RDLISNNEQL PMLGRRPGAP ESKCSRGALY TGFSILVTLL LAGQATTAYF LYQQQGRLDK LTVTSQNLQL ENLRMKLPKP PKPVSKMRMA TPLLMQALPM GALPQGPMQN ATKYGNMTED HVMHLLQNAD PLKVYPPLKG SFPENLRHLK NTMETIDWKV FESWMHHWLL FEMSRHSLEQ KPTDAPPKVL TKCQEEVSHI PAVHPGSFRP KCDENGNYLP LQCYGSIGYC WCVFPNGTEV PNTRSRGHHN CSESLELEDP SSGLGVTKQD LGPVPM //