P04441 (HG2A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
H-2 class II histocompatibility antigen gamma chain

Alternative name(s):
Ia antigen-associated invariant chain
Short name=Ii
MHC class II-associated invariant chain
CD_antigen=CD74

Gene names

Name:	Cd74
Synonyms:	Ii

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	279 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place.
Subunit structure	Nonamer composed of three alpha/beta/gamma heterotrimers By similarity.
Subcellular location	Membrane; Single-pass type II membrane protein Potential.
Sequence similarities	Contains 1 thyroglobulin type-1 domain.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Chaperone
PTM	Disulfide bond Glycoprotein Phosphoprotein Proteoglycan
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPK activity Inferred from electronic annotation. Source: Compara antigen processing and presentation of exogenous peptide antigen via MHC class II Inferred from mutant phenotype PubMed 7679955PubMed 8598040. Source: MGI cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB chaperone mediated protein folding requiring cofactor Inferred from direct assay PubMed 7985028. Source: MGI defense response Inferred from mutant phenotype PubMed 8098731PubMed 8294875. Source: MGI immunoglobulin mediated immune response Inferred from mutant phenotype PubMed 7679955. Source: MGI intracellular protein transport Inferred from direct assay PubMed 11754812PubMed 15294975. Source: MGI macrophage migration inhibitory factor signaling pathway Inferred from direct assay PubMed 19413900. Source: BHF-UCL negative regulation of DNA damage response, signal transduction by p53 class mediator Inferred from mutant phenotype PubMed 17045821. Source: BHF-UCL negative regulation of T cell differentiation Inferred from mutant phenotype PubMed 7679955. Source: MGI negative regulation of mature B cell apoptotic process Inferred from mutant phenotype PubMed 18056708. Source: BHF-UCL negative regulation of peptide secretion Inferred from electronic annotation. Source: Compara negative thymic T cell selection Inferred from mutant phenotype PubMed 7679955. Source: MGI positive regulation of B cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype PubMed 12782713. Source: BHF-UCL positive regulation of T cell differentiation Inferred from mutant phenotype PubMed 7679955PubMed 8598040PubMed 9432982. Source: MGI positive regulation of adaptive immune response Non-traceable author statement PubMed 18056708. Source: BHF-UCL positive regulation of chemokine (C-X-C motif) ligand 2 production Inferred from direct assay PubMed 19413900. Source: BHF-UCL positive regulation of cytokine-mediated signaling pathway Inferred from mutant phenotype PubMed 12782713. Source: BHF-UCL positive regulation of dendritic cell antigen processing and presentation Inferred from direct assay PubMed 18003616. Source: BHF-UCL positive regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of innate immune response Inferred by curator PubMed 19413900. Source: BHF-UCL positive regulation of macrophage cytokine production Inferred from direct assay PubMed 19413900. Source: BHF-UCL positive regulation of neutrophil chemotaxis Inferred from direct assay PubMed 19413900. Source: BHF-UCL positive regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype PubMed 17045821. Source: BHF-UCL positive regulation of type 2 immune response Inferred from mutant phenotype PubMed 11823488. Source: BHF-UCL positive thymic T cell selection Inferred from mutant phenotype PubMed 7679955PubMed 8598040PubMed 9432982. Source: MGI prostaglandin biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB protein complex assembly Inferred from direct assay PubMed 7985028. Source: MGI
Cellular_component	Golgi apparatus Inferred from direct assay PubMed 11854359. Source: MGI NOS2-CD74 complex Inferred from direct assay PubMed 18003616. Source: BHF-UCL endoplasmic reticulum Inferred from direct assay PubMed 11854359. Source: MGI external side of plasma membrane Inferred from direct assay PubMed 15322158PubMed 19723499PubMed 7679955. Source: MGI integral to plasma membrane Traceable author statement PubMed 7679955. Source: MGI lysosome Inferred from direct assay PubMed 11854359PubMed 15294975. Source: MGI macrophage migration inhibitory factor receptor complex Inferred from direct assay PubMed 12782713PubMed 18056708. Source: BHF-UCL multivesicular body Inferred from direct assay PubMed 11854359. Source: MGI
Molecular_function	beta-amyloid binding Inferred from electronic annotation. Source: Compara cytokine binding Inferred from sequence or structural similarity. Source: UniProtKB cytokine receptor activity Inferred from mutant phenotype PubMed 12782713. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P04441-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P04441-2)

The sequence of this isoform differs from the canonical sequence as follows:
     192-255: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 279	279	H-2 class II histocompatibility antigen gamma chain		PRO_0000067955
Regions
	Topological domain	1 – 29	29	Cytoplasmic Potential
	Transmembrane	30 – 55	26	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	56 – 279	224	Extracellular Potential
	Domain	193 – 254	62	Thyroglobulin type-1
Amino acid modifications
	Modified residue	9	1	Phosphoserine Ref.8 Ref.9
	Glycosylation	113	1	N-linked (GlcNAc...) Potential
	Glycosylation	119	1	N-linked (GlcNAc...) Potential
	Glycosylation	265	1	O-linked (Xyl...) (chondroitin sulfate) Ref.7
	Disulfide bond	196 ↔ 215		By similarity
	Disulfide bond	226 ↔ 233		By similarity
	Disulfide bond	235 ↔ 254		By similarity
Natural variations
	Alternative sequence	192 – 255	64	Missing in isoform Short.		VSP_005332
Experimental info
	Mutagenesis	265	1	S → A: No addition of glycosaminoglycan; no affect the synthesis of protein. Ref.7
	Sequence conflict	10	1	N → M Ref.2
	Sequence conflict	113	1	N → Q Ref.2
	Sequence conflict	229 – 231	3	STG → RHC in CAB37297. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified November 1, 1991. Version 3. Checksum: 300A85014F170792	FASTA	279	31,557
	10 20 30 40 50 60 MDDQRDLISN HEQLPILGNR PREPERCSRG ALYTGVSVLV ALLLAGQATT AYFLYQQQGR 70 80 90 100 110 120 LDKLTITSQN LQLESLRMKL PKSAKPVSQM RMATPLLMRP MSMDNMLLGP VKNVTKYGNM 130 140 150 160 170 180 TQDHVMHLLT RSGPLEYPQL KGTFPENLKH LKNSMDGVNW KIFESWMKQW LLFEMSKNSL 190 200 210 220 230 240 EEKKPTEAPP KVLTKCQEEV SHIPAVYPGA FRPKCDENGN YLPLQCHGST GYCWCVFPNG 250 260 270 TEVPHTKSRG RHNCSEPLDM EDLSSGLGVT RQELGQVTL
	Isoform Short [UniParc]. Checksum: 090928B6B0F4200C	FASTA	215	24,454
	10 20 30 40 50 60 MDDQRDLISN HEQLPILGNR PREPERCSRG ALYTGVSVLV ALLLAGQATT AYFLYQQQGR 70 80 90 100 110 120 LDKLTITSQN LQLESLRMKL PKSAKPVSQM RMATPLLMRP MSMDNMLLGP VKNVTKYGNM 130 140 150 160 170 180 TQDHVMHLLT RSGPLEYPQL KGTFPENLKH LKNSMDGVNW KIFESWMKQW LLFEMSKNSL 190 200 210 EEKKPTEAPP KEPLDMEDLS SGLGVTRQEL GQVTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of the gene for the murine Ia antigen-associated invariant chains (Ii). An alternatively spliced exon encodes a cysteine-rich domain highly homologous to a repetitive sequence of thyroglobulin." Koch N., Lauer W., Habicht J., Dobberstein B. EMBO J. 6:1677-1683(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM LONG), ALTERNATIVE SPLICING. Strain: AKR.
[2]	"Complete sequence of the murine invariant chain (Ii) gene." Zhu L., Jones P.P. Nucleic Acids Res. 17:447-448(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: AKR. Tissue: Liver.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Mammary gland.
[4]	"Nucleotide sequences of the murine Ia-associated invariant chain (Ii) and I-E (H-2S, Beta) chain expressible cDNA clones." Stone J., Perry R., Todd J.A., McDevitt H.O. Submitted (MAR-1988) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-58. Tissue: Spleen.
[5]	"The IFN-gamma response of the murine invariant chain gene is mediated by a complex enhancer that includes several MHC class II consensus elements." Eades A.-M., Litfin M., Rahmsdorf H.J. J. Immunol. 144:4399-4409(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-25.
[6]	"Structure of the murine Ia-associated invariant (Ii) chain as deduced from a cDNA clone." Singer P.A., Lauer W., Dembic Z., Mayer W.E., Lipp J., Koch N., Hammerling G., Klein J., Dobberstein B. EMBO J. 3:873-877(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 47-279 (ISOFORM SHORT).
[7]	"Identification of the glycosaminoglycan-attachment site of mouse invariant-chain proteoglycan core protein by site-directed mutagenesis." Miller J., Hatch J.A., Simonis S., Cullen S.E. Proc. Natl. Acad. Sci. U.S.A. 85:1359-1363(1988) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT SER-265, MUTAGENESIS OF SER-265.
[8]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, MASS SPECTROMETRY. Tissue: Melanoma.
[9]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X05428 Genomic DNA. Translation: CAA29010.1. X05429 Genomic DNA. Translation: CAA29012.2. X05430 Genomic DNA. Translation: CAB37297.1. X13414 Genomic DNA. No translation available. BC003476 mRNA. Translation: AAH03476.1. X07129 mRNA. Translation: CAA30141.1. M35872 Genomic DNA. Translation: AAA37897.1. X00496 mRNA. Translation: CAA25191.1.
IPI	IPI00115892. IPI00223264.
PIR	HLHMSG. B27866.
RefSeq	NP_001036070.1. NM_001042605.1.
UniGene	Mm.439737.
3D structure databases
ProteinModelPortal	P04441.
SMR	P04441. Positions 117-191, 193-256.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1488725.
STRING	10090.ENSMUSP00000095171.
Protein family/group databases
MEROPS	I31.002.
PTM databases
PhosphoSite	P04441.
Proteomic databases
PaxDb	P04441.
PRIDE	P04441.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000050487; ENSMUSP00000057836; ENSMUSG00000024610. ENSMUST00000097563; ENSMUSP00000095171; ENSMUSG00000024610. ENSMUST00000167610; ENSMUSP00000126688; ENSMUSG00000024610.
GeneID	16149.
KEGG	mmu:16149.
UCSC	uc008faz.1. mouse.
Organism-specific databases
CTD	972.
MGI	MGI:96534. Cd74.
Phylogenomic databases
eggNOG	NOG248215.
HOGENOM	HOG000013145.
HOVERGEN	HBG004444.
InParanoid	P04441.
KO	K06505.
OMA	GTEVPNT.
OrthoDB	EOG4WQ13R.
Gene expression databases
ArrayExpress	P04441.
Bgee	P04441.
Genevestigator	P04441.
GermOnline	ENSMUSG00000024610. Mus musculus.
Family and domain databases
Gene3D	1.10.870.10. 1 hit. 4.10.800.10. 1 hit.
InterPro	IPR015386. MHC_II-assoc_invar/CLIP_MHC-bd. IPR022339. MHC_II-assoc_invar_chain. IPR011988. MHC_II-assoc_invariant_trimer. IPR000716. Thyroglobulin_1. [Graphical view]
PANTHER	PTHR14093. PTHR14093. 1 hit.
Pfam	PF09307. MHC2-interact. 1 hit. PF08831. MHCassoc_trimer. 1 hit. PF00086. Thyroglobulin_1. 1 hit. [Graphical view]
PIRSF	PIRSF001992. CD74_antigen. 1 hit.
PRINTS	PR01990. CD74ANTIGEN.
SMART	SM00211. TY. 1 hit. [Graphical view]
SUPFAM	SSF48305. MHC_II-assoc_invariant_trimer. 1 hit. SSF57610. Thyroglobulin_1. 1 hit.
PROSITE	PS00484. THYROGLOBULIN_1_1. 1 hit. PS51162. THYROGLOBULIN_1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CD74. mouse.
NextBio	288935.
SOURCE	Search...

Entry information

Entry name

HG2A_MOUSE

Accession

Primary (citable) accession number: P04441
Secondary accession number(s): O19452

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	November 1, 1991
Last modified:	May 29, 2013
This is version 133 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program