PROW: CD74

PROW and IWHLDA present the GUIDE on:
CD74
Author: Peter Moeller
Reviewer: Norbert Koch
[GUIDE BAR]

ALTERNATE NAMES FOR CD74

Class II-specific chaperone
Ii
Invariant chain

MAJOR LINKS FOR CD74

NCBI LocusLink Record: 972
Mendelian Inheritance in Man (OMIM): 142790
SwissProt annotated protein record: P04233

FUNCTION BIOCHEMICAL ACTIVITY OF CD74 - No information

CELLULAR FUNCTION OF CD74

Intracellular sorting of MHC class II molecules

DISEASE RELEVANCE OF CD74 AND FUNCTION OF CD74 IN INTACT ANIMAL

Not known for humans
Ii knockout mice are deficient in processing of antigen

STRUCTURE MOLECULAR FAMILY FOR CD74

MOLECULAR STRUCTURE OF CD74

Type II integral transmembrane molecule
Ii 33 has a cytoplasmic domain of 30 amino acids (aa), a 26 aa transmembrane region, and a 160 aa luminal/extracellular region
Ii35 contains an ER retention signal and a sorting signal close to the N-terminus*
A stretch formed by residues 81-104 is the class II binding site and is called class II associated invariant chain peptide (CLIP)
Residues 91-99 of CLIP occupy the groove of class II heterodimers during intracellular transport. A stretch formed by residues 163 to 183 is the site where newly formed Ii trimerizes*

MOLECULAR MASS OF CD74

CELL TYPE	MW UNREDUCED	MW REDUCED	Comment
Various	33 kDa, 35 kDa, (41kDa)		Isoforms

POST-TRANSCRIPTIONAL MODIFICATION OF CD74

Ii gene contains 9 exons
Ii33 is encoded by 8 exons
Ii41 arises via alternative splicing from 9 exons
Exon 6b encodes a sequence of 64 aa inserted close to the C-terminus
By alternative usage of two in-phase initiation codons, the two isoforms Ii33 and Ii41 can be elongated by 16 N-terminal aa*

POST-TRANSLATIONAL MODIFICATION OF CD74

Proteoglycan: During Golgi passage, Ii polypeptides can be N- and O-glycosylated; a proteoglycan form of Ii can arise though chondroitin sulfate linkage to serin-201
In addition, minor subfractions of Ii are palmitylated, sulfated, or phosphorylated

MOLECULAR INTERACTIONS PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD74

MOLECULE	COMMENT
NFkB	The promoter region of the Ii gene has two NFkb binding sites*

Expression of Ii and MHC class II polypeptides are co-regulated and expression is induced by interferon-g, IL4, and by TNF alpha*

SUBSTRATES FOR CD74 - Not known

ENZYMES WHICH MODIFY CD74

MOLECULE	COMMENT
Cathepsin S	Within the MHC class II loading compartment*; then HLA-DM removes CLIP

LIGANDS FOR CD74 AND MOLECULES ASSOCIATED WITH CD74

MOLECULE	COMMENT
HLA-DR heterodimers	cf 11
CD44	Single observation not yet been confirmed by other lab

EXPRESSION MAIN CELLULAR EXPRESSION OF CD74

B-cells
Activated T-cells
Macrophages
Activated endothelial and epithelial cells

AUTHOR'S ADDITIONAL INSIGHTS ON CD74 - No information

REAGENTS CD74-SPECIFIC MABS NEWLY ASSIGNED AT SIXTH INTERNATIONAL WORKSHOP

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
SN10 (B064)	Ben K Seon, Buffalo, NY

SELECTION OF OTHER CD74-SPECIFIC REFERENCE MAB

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
BY2 (CD74.1)	Karen Pulford, Oxford, UK
BU-45 (CD74.2)	Deborah L Hardie, Birmingham, UK
BU-43 (CD74.6)	Deborah L Hardie, Birmingham, UK
M-B741 (CD74)	Peter Rieber, Dresden, FRG

SELECTED REFERENCES ON CD74

REVIEWS

1. Cresswell P Assembly, transport, and function of MHC class II molecules. Annu Rev Immunol 1994 12:259 PubMed

PRIMARY CITATIONS

2. Bakke O,Dobberstein B MHC class II-associated invariant chain contains a sorting signal for endosomal compartments. Cell 1990 63:707 PubMed

3. Freisewinkel IM,Schenck K,Koch N The segment of invariant chain that is critical for association with major histocompatibility complex class II molecules contains the sequence of a peptide eluted from class II polypeptides. Proc Natl Acad Sci U S A 1993 90:9703 PubMed

4. Ghosh P,Amaya M,Mellins E,Wiley DC The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3. Nature 1995 378:457 PubMed

5. Koch N,Moldenhauer G,Hofmann WJ,Moller P Rapid intracellular pathway gives rise to cell surface expression of the MHC class II-associated invariant chain (CD74). J Immunol 1991 147:2643 PubMed

6. Lotteau V,Teyton L,Peleraux A,Nilsson T,Karlsson L,Schmid SL,Quaranta V,Peterson PA Intracellular transport of class II MHC molecules directed by invariant chain. Nature 1990 348:600 PubMed

7. Roche PA,Cresswell P Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding. Nature 1990 345:615 PubMed

8. Stockinger B,Pessara U,Lin RH,Habicht J,Grez M,Koch N A role of Ia-associated invariant chains in antigen processing and presentation. Cell 1989 56:683 PubMed

9. Strubin M,Long EO,Mach B Two forms of the Ia antigen-associated invariant chain result from alternative initiations at two in-phase AUGs. Cell 1986 47:619 PubMed

10. Viville S,Neefjes J,Lotteau V,Dierich A,Lemeur M,Ploegh H,Benoist C,Mathis D Mice lacking the MHC class II-associated invariant chain. Cell 1993 72:635 PubMed

11. Wraight CJ,van Endert P,Moller P,Lipp J,Ling NR,MacLennan IC,Koch N,Moldenhauer G Human major histocompatibility complex class II invariant chain is expressed on the cell surface. J Biol Chem 1990 265:5787 PubMed

WWW RESOURCES

* indicates ammended by reviewer, ** indicates added by reviewer

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99 mpr@mail.nih.gov