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FLASH GENE

Symbol

ISCU

contributors: mct/npt - updated : 26-01-2013

HGNC name	iron-sulfur cluster scaffold homolog (E. coli)
HGNC id	29882

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	6.87 kb     6 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_014301 6 splicing 1189 NP_055116 15.1 142 - 2006 16527810 also called variant 1 or ISCU1 found in the cytosol and nucleus have a role similar to that of its mitochondrial counterpart in Fe& 8722;S cluster formation in the cytosol (PMID: 20481466) NM_213595 5 splicing 1093 NP_998760 17.9 167 - 2006 16527810 also called variant 2 or ISCU2 found in the mitochondrion

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart         Homo sapiens Adult Endocrine neuroendocrine pituitary     highly   parathyroid       highly Hearing/Equilibrium ear       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac     Homo sapiens Adult

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	the first beta-strand of ISCU provides potentially the binding interface for the ISCU-HSCB interaction
	conserved 99LPPVK103 motif

mono polymer

monomer

HOMOLOGY

interspecies

homolog to E;Coli Iscu

Homologene

FAMILY

nifU family

CATEGORY

enzyme , storage

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	involved in respiratory chain biogenesis
	functional cysteine desulfurase that can collaborate with cytosolic ISCU to promote de novo iron-sulfur cluster formation
	being important in iron homeostasis and, among other functions, essential for aconitase activity
	are thought to assemble Fe/S clusters for mitochondrial aconitase and for lipoate synthase, the enzyme producing lipoate for pyruvate dehydrogenase complex (PDC)
	ISCU and FXN stimulate NFS1 and LYRM4 cysteine desulfurase activity
	play an important role in cellular iron homeostasis
	ISCU assembled [Fe-S] clusters appear to be preferentially channeled to aconitase and complex II
	scaffold protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis and transfer

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

complex SDU and SDUF comprised of NFS1, LYRM4, and ISCU and NFS1, LYRM4, ISCU, and FXN, respectively (SDUF is capable of synthesizing Fe/S cluster)

INTERACTION

DNA

RNA

small molecule

protein	interaction with extra-mitochondrial frataxin
	interaction between ISCU and HSCB is critical for successful assembly of iron-sulfur clusters
	ISCU (iron-sulfur cluster scaffold homolog) and COX10 (cytochrome c oxidase assembly protein), two important factors of the mitochondria electron transport chain and the tricarboxylic acid cycle have been identified as potential targets of MIR210
	interaction with NFU1 (NFU1 could function as an alternate scaffold to ISCU for assembly of [Fe-S] proteins, thus providing parallel pathways)
	defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1
	HSCB interacts with multiple proteins involved in ISC biogenesis including the ISCU ISC biogenesis complex and the HSPA9 ISC chaperone
	modulation of the degradation of ISCU by the PIM1 protease is a regulatory mechanism serving to rapidly help balance the cell need for critical iron-requiring processes under changing environmental conditions
	NFS1 alone could catalyze Fe-S cluster assembly on ISCU and that the addition of LYRM4 increased the Fe-S cluster assembly rate
	ISCU suppressor mimics the frataxin effects on NFS1, explaining the bypassing activity
	FXN accelerates persulfide formation on NFS1 and favors a helix-to-coil interconversion on ISCU that facilitates the transfer of sulfur from NFS1 to ISCU as an initial step in Fe-S cluster biosynthesis
	PTBP1 acts as a dominant repressor of ISCU mis-splicing

cell & other

REGULATION

repressed by

iron deprivation

ASSOCIATED DISORDERS

corresponding disease(s)

MPEI1

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

complete loss of Iscu in mice results in early embryonic death