HG2A_RAT
ID HG2A_RAT Reviewed; 280 AA.
AC P10247;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=H-2 class II histocompatibility antigen gamma chain {ECO:0000305};
DE AltName: Full=Ia antigen-associated invariant chain;
DE Short=Ii;
DE AltName: Full=MHC class II-associated invariant chain;
DE AltName: CD_antigen=CD74;
DE Contains:
DE RecName: Full=Class-II-associated invariant chain peptide {ECO:0000250|UniProtKB:P04233};
DE Short=CLIP {ECO:0000250|UniProtKB:P04233};
GN Name=Cd74 {ECO:0000312|RGD:2313};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=PVG X DA; TISSUE=Spleen;
RX PubMed=2499873; DOI=10.1093/nar/17.10.3983;
RA McKnight A.J., Mason D.W., Barclay A.N.;
RT "Sequence of a rat MHC class II-associated invariant chain cDNA clone
RT containing a 64 amino acid thyroglobulin-like domain.";
RL Nucleic Acids Res. 17:3983-3984(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-192 AND 257-280.
RC STRAIN=Lewis;
RX PubMed=3264906; DOI=10.1093/nar/16.24.11822;
RA Henkes W., Syha J., Reske K.;
RT "Nucleotide sequence of rat invariant gamma chain cDNA clone pLR gamma
RT 34.3.";
RL Nucleic Acids Res. 16:11822-11822(1988).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Plays a critical role in MHC class II antigen processing by
CC stabilizing peptide-free class II alpha/beta heterodimers in a complex
CC soon after their synthesis and directing transport of the complex from
CC the endoplasmic reticulum to compartments where peptide loading of
CC class II takes place. Enhance also the stimulation of T-cell responses
CC through interaction with CD44. {ECO:0000250|UniProtKB:P04441}.
CC -!- FUNCTION: [Class-II-associated invariant chain peptide]: Binds to the
CC peptide-binding site of MHC class II alpha/beta heterodimers forming an
CC alpha-beta-CLIP complex, thereby preventing the loading of antigenic
CC peptides to the MHC class II complex until its release by HLA-DM in the
CC endosome. {ECO:0000250|UniProtKB:P04233}.
CC -!- FUNCTION: [Isoform Long]: Stabilizes the conformation of mature CTSL by
CC binding to its active site and serving as a chaperone to help maintain
CC a pool of mature enzyme in endocytic compartments and extracellular
CC space of antigen-presenting cells (APCs).
CC {ECO:0000250|UniProtKB:P04441}.
CC -!- SUBUNIT: Nonamer composed of three alpha/beta/gamma heterotrimers.
CC Interacts with CD44; this complex is essential for the MIF-induced
CC signaling cascade that results in B cell survival. {ECO:0000250,
CC ECO:0000250|UniProtKB:P04441}.
CC -!- SUBUNIT: [Isoform Long]: Interacts with the mature form of CTSL; the
CC complex survive in neutral pH environment.
CC {ECO:0000250|UniProtKB:P04441}.
CC -!- SUBCELLULAR LOCATION: [Isoform Long]: Late endosome
CC {ECO:0000250|UniProtKB:P04441}. Lysosome
CC {ECO:0000250|UniProtKB:P04441}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P04233};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:P04233}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P04233}. Golgi
CC apparatus, trans-Golgi network {ECO:0000250|UniProtKB:P04233}. Endosome
CC {ECO:0000250|UniProtKB:P04233}. Lysosome
CC {ECO:0000250|UniProtKB:P04233}. Note=Transits through a number of
CC intracellular compartments in the endocytic pathway. It can either
CC undergo proteolysis or reach the cell membrane.
CC {ECO:0000250|UniProtKB:P04233}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P10247-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P10247-2; Sequence=VSP_005333;
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DR EMBL; X14254; CAA32468.1; -; mRNA.
DR EMBL; X13044; CAA31450.1; -; mRNA.
DR PIR; S04362; S04362.
DR RefSeq; NP_037201.1; NM_013069.2. [P10247-2]
DR RefSeq; XP_006254823.1; XM_006254761.3. [P10247-1]
DR AlphaFoldDB; P10247; -.
DR SMR; P10247; -.
DR STRING; 10116.ENSRNOP00000025354; -.
DR MEROPS; I31.002; -.
DR GlyGen; P10247; 3 sites.
DR iPTMnet; P10247; -.
DR PhosphoSitePlus; P10247; -.
DR PaxDb; P10247; -.
DR Ensembl; ENSRNOT00000025344; ENSRNOP00000025342; ENSRNOG00000018735. [P10247-1]
DR GeneID; 25599; -.
DR KEGG; rno:25599; -.
DR UCSC; RGD:2313; rat. [P10247-1]
DR CTD; 972; -.
DR RGD; 2313; Cd74.
DR eggNOG; KOG1214; Eukaryota.
DR GeneTree; ENSGT00390000008961; -.
DR HOGENOM; CLU_086066_1_0_1; -.
DR InParanoid; P10247; -.
DR OMA; GTFRPQC; -.
DR OrthoDB; 1190626at2759; -.
DR PhylomeDB; P10247; -.
DR TreeFam; TF317779; -.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR PRO; PR:P10247; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000018735; Expressed in spleen and 20 other tissues.
DR ExpressionAtlas; P10247; baseline and differential.
DR Genevisible; P10247; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0035692; C:macrophage migration inhibitory factor receptor complex; ISS:BHF-UCL.
DR GO; GO:0042613; C:MHC class II protein complex; ISO:RGD.
DR GO; GO:0005771; C:multivesicular body; ISO:RGD.
DR GO; GO:0035693; C:NOS2-CD74 complex; ISS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0005773; C:vacuole; ISO:RGD.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:RGD.
DR GO; GO:0042609; F:CD4 receptor binding; ISO:RGD.
DR GO; GO:0019955; F:cytokine binding; ISO:RGD.
DR GO; GO:0004896; F:cytokine receptor activity; ISS:BHF-UCL.
DR GO; GO:0035718; F:macrophage migration inhibitory factor binding; ISO:RGD.
DR GO; GO:0042289; F:MHC class II protein binding; ISO:RGD.
DR GO; GO:0042658; F:MHC class II protein binding, via antigen binding groove; ISO:RGD.
DR GO; GO:0023026; F:MHC class II protein complex binding; ISO:RGD.
DR GO; GO:0050998; F:nitric-oxide synthase binding; ISS:BHF-UCL.
DR GO; GO:0044183; F:protein folding chaperone; ISO:RGD.
DR GO; GO:0019882; P:antigen processing and presentation; ISO:RGD.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; IDA:RGD.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; ISO:RGD.
DR GO; GO:0006952; P:defense response; ISO:RGD.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; ISO:RGD.
DR GO; GO:0006886; P:intracellular protein transport; ISO:RGD.
DR GO; GO:0035691; P:macrophage migration inhibitory factor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISS:BHF-UCL.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:BHF-UCL.
DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:0002792; P:negative regulation of peptide secretion; ISO:RGD.
DR GO; GO:0045581; P:negative regulation of T cell differentiation; ISO:RGD.
DR GO; GO:0045060; P:negative thymic T cell selection; ISO:RGD.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISO:RGD.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISS:BHF-UCL.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; ISS:BHF-UCL.
DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; ISS:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:BHF-UCL.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; ISO:RGD.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISS:BHF-UCL.
DR GO; GO:2000448; P:positive regulation of macrophage migration inhibitory factor signaling pathway; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:RGD.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; ISO:RGD.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISS:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0002830; P:positive regulation of type 2 immune response; ISO:RGD.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:RGD.
DR GO; GO:0045059; P:positive thymic T cell selection; ISO:RGD.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0070206; P:protein trimerization; IEA:InterPro.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:RGD.
DR GO; GO:0034341; P:response to interferon-gamma; ISO:RGD.
DR GO; GO:0002286; P:T cell activation involved in immune response; IBA:GO_Central.
DR CDD; cd00191; TY; 1.
DR Gene3D; 1.10.870.10; -; 1.
DR Gene3D; 4.10.800.10; -; 1.
DR InterPro; IPR043530; CD74_antigen.
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; IPR036613; MHCII_invariant_trimer_sf.
DR InterPro; IPR000716; Thyroglobulin_1.
DR InterPro; IPR036857; Thyroglobulin_1_sf.
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 Adaptive immunity; Alternative splicing; Cell membrane; Chaperone;
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..280
FT /note="H-2 class II histocompatibility antigen gamma chain"
FT /id="PRO_0000067956"
FT PEPTIDE 81..104
FT /note="Class-II-associated invariant chain peptide"
FT /evidence="ECO:0000250|UniProtKB:P04233"
FT /id="PRO_0000448888"
FT TOPO_DOM 1..30
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 31..56
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..280
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 194..255
FT /note="Thyroglobulin type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT REGION 246..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000250"
FT DISULFID 197..216
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT DISULFID 227..234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT DISULFID 236..255
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT VAR_SEQ 193..256
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_005333"
SQ SEQUENCE 280 AA; 31642 MW; D935D169A98B5732 CRC64;
MDDQRDLISN HEQLPILGQR ARAPESNCNR GVLYTSVSVL VALLLAGQAT TAYFLYQQQG
RLDKLTVTSQ NLQLENLRMK LPKSAKPVSP MRMATPLLMR PLSMDNMLQA PVKNVTKYGN
MTQDHVMHLL TKSGPVNYPQ LKGSFPENLK HLKNSMNGLD WKVFESWMKQ WLLFEMSKNS
LEEKQPTQTP PKVLTKCQEE VSHIPDVHPG AFRPKCDENG NYMPLQCHGS TGYCWCVFPN
GTEVPHTKSR GRHNCSEPLD MEDPSSGLGV TKQDMGQMFL
