ID HG2A_HUMAN Reviewed; 296 AA. AC P04233; A8K7R1; B4DNE8; Q14597; Q29832; Q5U0J8; Q8SNA0; Q8WLP6; DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 3. DT 24-NOV-2009, entry version 120. 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 MEDLINE=84170234; 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 MEDLINE=84207945; 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 MEDLINE=86093681; 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 MEDLINE=86233451; 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 MASS RP 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 MEDLINE=93078879; 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 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 [13] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136, AND MASS RP SPECTROMETRY. 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 [14] RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 103-117. RX MEDLINE=96085023; 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 [15] RP STRUCTURE BY NMR OF 134-208. RX MEDLINE=99059718; 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). 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 compartments where CC peptide loading of class II takes place. Serves as cell surface CC receptor for the cytokine MIF. CC -!- SUBUNIT: Nonamer composed of three alpha/beta/gamma heterotrimers. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane CC protein (Potential). 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 -!- SIMILARITY: Contains 1 thyroglobulin type-1 domain. 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; EAW61731.1; -; Genomic_DNA. DR EMBL; BC018726; AAH18726.1; -; mRNA. DR EMBL; BC024272; AAH24272.1; -; mRNA. DR IPI; IPI00022933; -. DR IPI; IPI00217775; -. DR IPI; IPI00607573; -. DR PIR; A93981; HLHUG. DR RefSeq; NP_001020329.1; -. DR RefSeq; NP_001020330.1; -. DR RefSeq; NP_004346.1; -. 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=97-122. DR PDBsum; 1A6A; -. DR PDBsum; 1ICF; -. DR PDBsum; 1IIE; -. DR PDBsum; 1L3H; -. DR PDBsum; 1MUJ; -. DR STRING; P04233; -. DR PhosphoSite; P04233; -. DR PRIDE; P04233; -. DR Ensembl; ENST00000009530; ENSP00000009530; ENSG00000019582; Homo sapiens. DR GeneID; 972; -. DR UCSC; uc003lsc.1; human. DR UCSC; uc003lsd.1; human. DR CTD; 972; -. DR GeneCards; GC05M149753; -. DR H-InvDB; HIX0005314; -. DR HGNC; HGNC:1697; CD74. DR HPA; CAB002506; -. DR HPA; HPA010592; -. DR MIM; 142790; gene. DR PharmGKB; PA26236; -. DR HOGENOM; P04233; -. DR HOVERGEN; P04233; -. DR OMA; GTEVPNT; -. DR NextBio; 4068; -. DR PMAP-CutDB; P04233; -. DR ArrayExpress; P04233; -. DR Bgee; P04233; -. DR CleanEx; HS_CD74; -. DR Genevestigator; P04233; -. DR GermOnline; ENSG00000019582; Homo sapiens. DR GO; GO:0016021; C:integral to membrane; TAS:ProtInc. DR GO; GO:0019955; F:cytokine binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; TAS:UniProtKB. DR GO; GO:0042289; F:MHC class II protein binding; NAS:UniProtKB. DR GO; GO:0019883; P:antigen processing and presentation of endo...; NAS:UniProtKB. DR GO; GO:0008283; P:cell proliferation; IDA:UniProtKB. DR GO; GO:0016064; P:immunoglobulin mediated immune response; ISS:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptosis; IDA:UniProtKB. 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 InterPro; IPR016333; HLA_II_histocompat_Ag_gsu. DR InterPro; IPR015386; MHC_II-assoc_invar/CLIP_MHC-bd. DR InterPro; IPR011988; MHC_II-assoc_invariant_trimer. DR InterPro; IPR000716; Thyroglobulin_1. DR Gene3D; G3DSA:1.10.870.10; MHCII_invariant; 1. DR Gene3D; G3DSA:4.10.800.10; Thyroglobulin_1; 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 SMART; SM00211; TY; 1. DR PROSITE; PS00484; THYROGLOBULIN_1_1; 1. DR PROSITE; PS51162; THYROGLOBULIN_1_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chaperone; Complete proteome; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Immune response; Membrane; Phosphoprotein; Proteoglycan; KW Signal-anchor; Transmembrane. FT CHAIN 1 296 HLA class II histocompatibility antigen FT gamma chain. FT /FTId=PRO_0000067954. FT TOPO_DOM 1 46 Cytoplasmic (Potential). FT TRANSMEM 47 72 Signal-anchor for type II membrane FT protein (Potential). FT TOPO_DOM 73 296 Extracellular (Potential). FT DOMAIN 210 271 Thyroglobulin type-1. FT REGION 103 117 CLIP. FT MOD_RES 25 25 Phosphoserine (By similarity). FT CARBOHYD 130 130 N-linked (GlcNAc...). FT CARBOHYD 136 136 N-linked (GlcNAc...). FT CARBOHYD 282 282 O-linked (Xyl...) (glycosaminoglycan) FT (Potential). FT DISULFID 213 232 By similarity. FT DISULFID 243 250 By similarity. FT DISULFID 252 271 By similarity. FT VAR_SEQ 148 160 NADPLKVYPPLKG -> SHWNWRTRLLGWV (in FT isoform 3). FT /FTId=VSP_037869. FT VAR_SEQ 161 296 Missing (in isoform 3). FT /FTId=VSP_037870. FT VAR_SEQ 209 272 Missing (in isoform 2). FT /FTId=VSP_005331. FT CONFLICT 167 167 R -> T (in Ref. 3; CAA27047). FT HELIX 139 149 FT HELIX 162 172 FT HELIX 175 194 FT HELIX 212 217 FT STRAND 240 244 FT TURN 245 248 FT STRAND 249 253 FT STRAND 265 267 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 //