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FLASH GENE

Symbol

CD74

contributors: mct/ - updated : 22-06-2016

HGNC name	CD74 molecule, major histocompatibility complex, class II invariant chain
HGNC id	1697

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	5q32      Physical location : 149.781.200 - 149.792.332
Synonym name	CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)
	cell differentiation antigen CD74, identified by monoclonal antibodies LN2, BU-43, BU-45, chain Ii
	HLA-DR-gamma
	MHC HLA-DR gamma chain
	gamma chain of class II antigens
Synonym symbol(s)	DHLAG, HLADG, Ia-GAMMA, p33, li, HLA-DR-gamma, CLIP

DNA

TYPE	functioning gene
STRUCTURE	11.13 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

Promoter (CAAT box) (TATA box)

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001025159 9 splicing 1519 NP_001020330 - 296 - 2014 25304249 variant 1, containing exon 1b (shorter than 1a), exon 9b (shorter than 9a) isoform a NM_004355 8 splicing 1327 NP_004346 - 232 - 2014 25304249 variant 2, containing exon 1b (shorter than 1a), exon 9b (shorter than 9a) lacking exon 7 isoform b NM_001025158 6 splicing 1155 NP_001020329 - 160 - 2014 25304249 variant 3, containing exon 1a (longer than 1b), exon 9a (longer than 9b) lacking exons 5, 6 & 7 isoform c

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen       highly   thymus       highly Cardiovascular heart       highly Digestive intestine large intestine colon   highly Homo sapiens Endocrine pancreas       highly Hearing/Equilibrium ear       highly Mus musculus Nervous brain       highly Respiratory lung       highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Epithelial secretory glandular endocrine   Lymphoid         Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Digestive epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a thyroglobulin type-I domain

conjugated

GlycoP

mono polymer

heteromer , trimer , polymer

HOMOLOGY

interspecies	homolog to C.elegans T04H1.5
	homolog to rattus Cd74 (75.92 pc)
	homolog to murine Cd74 (75.26 pc)

Homologene

FAMILY

CATEGORY

chaperone/stress , antigen

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,lysosome
text	type II membrane protein

basic FUNCTION	playing 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
	directing transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place
	forms functional complexes with CXCR4 that mediate MIF-specific signaling
	is a survival receptor on colon epithelial cells
	MIF and CD74 play roles in CCL2-induced macrophage adhesion and migration, and they indicate that MIF and CD74 mediate this effect via both common and independent mechanisms
	MIF and its receptor, CD74, are involved in regulating the migration of human mesenchymal stem cells (MSCs
	presence of CD74 on statoacoustic ganglion (SAG) neurons supports the existence of a signaling pathway by which MIF influences SAG survival and outgrowth
	mediates targeting of the MHCII complex to endosomal compartments, where CD74 undergoes degradation allowing MHCII to acquire peptides

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

a component

nonamer composed of three alpha/beta/gamma heterotrimers

INTERACTION

DNA

RNA

small molecule

protein	interacting with CXCR4 and MIF (CD74 forms functional complexes with CXCR4 that mediate MIF-specific signaling)
	MIF inhibits the migration of cartilage end plate-derived stem cells by reacting with CD74
	MIF promotes the migration of B cells through a ZAP70-dependent pathway mediated by cooperative engagement of CXCR4 and CD74
	role of SPPL2A in CD74 proteolysis is conserved in human B cells, providing support for modulation of SPPL2A activity as a therapeutic concept
	transcription factor MEF2A and PLAGL1 mediate MIF-induced SLC2A4 expression through CD74-dependent AMPK activation in cardiomyocytes
	SPPL2A-mediated processing of CD74 N-terminal fragment (NTF) is indispensable to maintain appropriate levels of tonic BCR signaling to promote B cell maturation
	MIF mediates its actions through a cell surface class II major histocompatibility chaperone, CD74 and co-receptors such as CD44, CXCR2, CXCR4 or CXCR7

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   overexpressed in ulcerative colitis low expressed in gastric cancer constitutional     --low   leads to altered macrophage activation towards a pro-inflammatory signature and a disturbed crosstalk with trophoblasts tumoral     --over   CD74, MIF and TLR4 were found to be expressed in gastric cancer and increased significantly in the advanced stage, and were also associated with lymph node metastasis

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS