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FLASH GENE

Symbol

SCG5

contributors: mct/npt - updated : 26-08-2014

HGNC name	secretogranin V (7B2 protein)
HGNC id	10816

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001144757 6 - 1244 NP_001138229 - 212 - 2007 17334394 NM_003020 6 - 1241 NP_003011 - 211 - 2007 17334394

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 Endocrine neuroendocrine         Homo sapiens   pancreas       highly Homo sapiens Nervous brain       highly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

C-terminal peptide that can inhibit PC2 and may contribute to keep the enzyme transiently inactive (Mbikay 2001)

HOMOLOGY

interspecies	homolog to rattus Sgne1
	ortholog to murine Sgne1
	homolog to Xenopus Xl.1105
	homolog to zebrafish Dr.12487
	homolog to C.elegans R07E3.7

Homologene

FAMILY

granin family of proteins

CATEGORY

chaperone/stress , regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,granule
text	neuroendocrine and endocrine secretory granules

basic FUNCTION	acting as a enzyme activator
	acting as a specific chaperone for proprotein convertase-2 (PC2)
	acidic protein residing in the secretory granules of neuroendocrine cells (Mbikay 2001)
	regulator/activator of the prohormone convertase 2 which is involved in the processing of numerous neuropeptides, including insulin, glucagon and pro-opiomelanocortin
	role for SCG5 in the modulation of body weight
	PCSK2 requires interaction with the neuroendocrine protein SCG5 for the production of an activatable zymogen
	can also act as a postfolding chaperone to block the aggregation of a number of other proteins, for example, SNCA
	is a natively disordered protein whose function as an antiaggregant chaperone is likely facilitated by its lack of appreciable secondary structure and tendency to form oligomers
	is a novel anti-aggregation secretory chaperone associated with neurodegenerative disease
	likely playing a role in the etiology of aggregate formation in neurodegenerative disease
	neuronal SCG5 could function to block neurodegenerative disease-related protein aggregation
	SCG5 and PCSK1N may perform a chaperone role as secretory anti-aggregants in normal islet cell function and in type 2 diabetes

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

neuropeptide signaling pathway

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	GTP

protein	required for the production of active prohormone convertase 2 (PCSK2), an enzyme involved in the synthesis of peptide hormones, such as glucagon and POMC
	is a prohormone convertase 2 (PCSK2)-binding protein
	it is possible that SCG5 acts via similar molecular mechanisms to decrease APP protein oligomerization, fibrillation, and cytotoxicity

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   silenced gene in medulloblastomas (Waha 2007) constitutional     --over   in brain tissues of AD patients, and in the cerebrospinal fluid of amyotrophic lateral sclerosis patients tumoral     --low   silenced by DNA methylation in astrocytic gliomas

Susceptibility

to glucoise intolerance in obesity to colorectal cancer (CRC)

Variant & Polymorphism SNP	SNP -1,701A>G did not associate with risk of T2D but tends to associate with incidence of type 2 diabetes (may worsen glucose intolerance and insulin resistance, especially in the background of severe and early onset obesity) (Bouatia-Naji 2007)
	SNPs near SCG5 were strongly associated with increased CRC risk (Jaeger 2008)

Candidate gene	good marker of several neuroendocrine cell dysfunctions (Mbikay 2001)
Marker
Therapy target

ANIMAL & CELL MODELS