AiPD: Autoinhibited Protein Database

Q9H1K1

Gene name	ISCU (NIFUN)
Protein name	Iron-sulfur cluster assembly enzyme ISCU, mitochondrial
Names	NifU-like N-terminal domain-containing protein, NifU-like protein
Species	Homo sapiens (Human)
KEGG Pathway	hsa:23479
EC number
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

1-53 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

1-53 (Predicted disordered autoinhibitory region)

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

No accessory elements

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell Systems, 2, 89-100

Autoinhibited structure

Activated structure

10 structures for Q9H1K1

Entry ID	Method	Resolution	Chain	Position	Source
5KZ5	EM	1430 A	a/b/c/d/e/f/g/h/i/j/k/l	50-167	PDB
5WKP	X-ray	315 A	D/H	38-167	PDB
5WLW	X-ray	332 A	D/H	38-167	PDB
6NZU	EM	320 A	D/H	34-157	PDB
6UXE	X-ray	157 A	D	35-167	PDB
6W1D	X-ray	179 A	D	35-167	PDB
6WI2	X-ray	195 A	D	35-167	PDB
6WIH	X-ray	190 A	D	35-167	PDB
7RTK	X-ray	250 A	D	35-167	PDB
AF-Q9H1K1-F1	Predicted				AlphaFoldDB

171 variants for Q9H1K1

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV002492903 CA320619 rs558084375 RCV000585143	4	A>P	Hereditary myopathy with lactic acidosis due to ISCU deficiency [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV000676518 RCV001730706 rs10778648 CA6768684	7	F>C	Hereditary myopathy with lactic acidosis due to ISCU deficiency [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP
CA243319973 RCV002493118 rs67681514 RCV000676517	7	F>G	Hereditary myopathy with lactic acidosis due to ISCU deficiency [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA6768681 RCV000947483 rs10778647 RCV001730741	7	F>V	Hereditary myopathy with lactic acidosis due to ISCU deficiency [ClinVar]	Yes	ClinGen ClinVar 1000Genomes TOPMed dbSNP gnomAD
VAR_060728 RCV000676519 CA6768701 RCV001730707 rs2287555	12	A>V	Hereditary myopathy with lactic acidosis due to ISCU deficiency [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA251603 RCV000000819 rs267607190	50	G>E	Hereditary myopathy with lactic acidosis due to ISCU deficiency [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA386427963 rs770958308	2	A>E		No	ClinGen ExAC TOPMed gnomAD
rs749513691 CA6768668	2	A>T		No	ClinGen ExAC gnomAD
CA6768669 rs770958308	2	A>V		No	ClinGen ExAC TOPMed gnomAD
rs918807914 CA243319871	3	A>V		No	ClinGen TOPMed gnomAD
CA6768672 rs768035762	4	A>D		No	ClinGen ExAC TOPMed gnomAD
rs768035762 CA6768671	4	A>G		No	ClinGen ExAC TOPMed gnomAD
CA386427982 rs558084375	4	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs587780954 CA6768674	5	G>A		No	ClinGen ExAC TOPMed gnomAD
CA243319892 rs587780954	5	G>E		No	ClinGen ExAC TOPMed gnomAD
rs761089629 CA6768673	5	G>R		No	ClinGen ExAC gnomAD
rs764795692 CA6768679	6	A>G		No	ClinGen ExAC TOPMed gnomAD
rs1565873350 CA386427997	6	A>P		No	ClinGen Ensembl
CA16043786 RCV000416263 rs764795692	6	A>V		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA6768682 rs10778647	7	F>L		No	ClinGen 1000Genomes TOPMed gnomAD
CA386428011 rs10778648	7	F>S		No	ClinGen 1000Genomes ExAC TOPMed
CA386428009 rs10778648	7	F>Y		No	ClinGen 1000Genomes ExAC TOPMed
CA6768686 rs11548233	8	R>C		No	ClinGen ExAC TOPMed gnomAD
CA386428018 rs1222524283	8	R>H		No	ClinGen gnomAD
CA243320016 rs11548233	8	R>S		No	ClinGen ExAC TOPMed gnomAD
rs780992137 CA386428024	9	L>P		No	ClinGen ExAC TOPMed gnomAD
rs780992137 CA6768690	9	L>R		No	ClinGen ExAC TOPMed gnomAD
CA6768689 rs561720120	9	L>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6768692 rs779041657	10	R>G		No	ClinGen ExAC TOPMed
CA6768694 rs745953998	10	R>K		No	ClinGen ExAC gnomAD
CA6768693 rs745953998	10	R>M		No	ClinGen ExAC gnomAD
CA386428032 CA6768695 rs776009693	10	R>S		No	ClinGen ExAC gnomAD
rs745953998 CA386428030	10	R>T		No	ClinGen ExAC gnomAD
CA6768698 rs550874413	11	R>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs550874413 CA6768699	11	R>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6768697 rs550874413	11	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs761091987 CA6768696	11	R>W		No	ClinGen ExAC TOPMed
CA6768702 rs2287555	12	A>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6768700 rs764955289	12	A>S		No	ClinGen ExAC TOPMed gnomAD
CA386428039 rs764955289	12	A>T		No	ClinGen ExAC TOPMed gnomAD
CA386428054 rs751470117	13	A>G		No	ClinGen ExAC TOPMed gnomAD
rs1300314086 CA386428049	13	A>S		No	ClinGen gnomAD
rs1300314086 CA386428050	13	A>T		No	ClinGen gnomAD
CA6768704 rs751470117	13	A>V		No	ClinGen ExAC TOPMed gnomAD
rs750191026 CA243320113	14	S>*		No	ClinGen ExAC TOPMed gnomAD
rs750191026 CA6768706	14	S>L		No	ClinGen ExAC TOPMed gnomAD
rs750191026 CA386428061	14	S>W		No	ClinGen ExAC TOPMed gnomAD
rs1296224565 CA386428071	15	A>D		No	ClinGen gnomAD
rs752455827 CA6768707	15	A>T		No	ClinGen ExAC TOPMed gnomAD
CA386428074 rs779184027	16	L>V		No	ClinGen ExAC TOPMed gnomAD
rs746092474 CA386428079	17	L>V		No	ClinGen ExAC gnomAD
RCV000422277 CA6768711 rs142514490 RCV002058901	18	L>M		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA386428657 rs1445161770	19	R>W		No	ClinGen TOPMed gnomAD
CA386428672 rs1418863152	20	S>G		No	ClinGen gnomAD
rs1426998960 CA386428677	20	S>I		No	ClinGen gnomAD
CA386428681 rs1426998960	20	S>N		No	ClinGen gnomAD
CA386428682 rs555621394 CA386428684	20	S>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1256750610 CA386428689	21	P>S		No	ClinGen Ensembl
CA386428700 rs1465868970	22	R>G		No	ClinGen TOPMed gnomAD
CA386428698 rs1465868970	22	R>S		No	ClinGen TOPMed gnomAD
CA243320139 rs1031043758	24	P>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
CA386428731 rs1202838988	24	P>S		No	ClinGen TOPMed
rs958064468 CA243320140	25	A>P		No	ClinGen Ensembl
CA6768716 rs770293635	27	E>D		No	ClinGen ExAC gnomAD
CA6768715 rs567636479	27	E>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA386428810 rs1215764545	29	S>*		No	ClinGen TOPMed gnomAD
rs1215764545 CA386428814	29	S>L		No	ClinGen TOPMed gnomAD
rs1215764545 CA386428812	29	S>W		No	ClinGen TOPMed gnomAD
CA6768717 rs772851870	30	A>P		No	ClinGen ExAC TOPMed gnomAD
CA6768718 rs762541090 RCV000994968	30	A>V		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs376643383 CA6768719	31	P>L		No	ClinGen ExAC gnomAD
CA386428834 rs1461747642	31	P>S		No	ClinGen gnomAD
RCV000198748 rs863224044 CA323278	34	L>F		No	ClinGen ClinVar Ensembl dbSNP
rs1355496890 CA386428878	34	L>P		No	ClinGen TOPMed
CA386428889 rs1484948688	35	Y>C		No	ClinGen gnomAD
CA386428890 rs1484948688	35	Y>F		No	ClinGen gnomAD
CA386428918 rs1188300447	36	H>Q		No	ClinGen gnomAD
CA6768720 rs537876845	37	K>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA386429451 rs1592790142	39	V>A		No	ClinGen Ensembl
rs1470808236 CA386429460	40	V>L		No	ClinGen gnomAD
rs189816350 CA6768775	46	P>S		No	ClinGen 1000Genomes ExAC gnomAD
rs1592790169 CA386429625	47	R>S		No	ClinGen Ensembl
CA6768778 rs371513074	49	V>M	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD
rs267607190 CA386429676	50	G>A		No	ClinGen ExAC gnomAD
rs199905986 CA243321472	50	G>W		No	ClinGen 1000Genomes gnomAD
CA386429695 rs1283093465	51	S>F		No	ClinGen gnomAD
COSM415638 CA386429699 rs1592790222	52	L>I	urinary_tract [Cosmic]	No	ClinGen cosmic curated Ensembl
CA243321486 rs560744899	52	L>P		No	ClinGen 1000Genomes gnomAD
CA6768779 rs745476091	53	D>E		No	ClinGen ExAC gnomAD
rs1454456783 CA386429744	54	K>R		No	ClinGen TOPMed
rs771692306 CA6768780	55	T>R		No	ClinGen ExAC gnomAD
CA243321525 rs987303197	57	K>E		No	ClinGen TOPMed
CA243321530 rs1018837648	58	N>I		No	ClinGen TOPMed
rs1202910510 CA386429831	59	V>I		No	ClinGen gnomAD
rs746499171 CA6768782	60	G>E		No	ClinGen ExAC gnomAD
CA6768783 rs768274666	62	G>*		No	ClinGen ExAC TOPMed gnomAD
CA386429963 rs1323474561	62	G>E		No	ClinGen gnomAD
COSM1127583 CA386429975 rs1592790363	63	L>M	prostate [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1198278882 CA386429989	64	V>M		No	ClinGen gnomAD
TCGA novel	66	A>G	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA386430131 rs1424424933	70	G>S		No	ClinGen TOPMed
COSM299680 CA243321569 rs914914914	72	V>I	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA TOPMed gnomAD
CA386431362 rs1361221215	77	I>V		No	ClinGen gnomAD
CA386431375 rs1323766038	78	Q>E		No	ClinGen gnomAD
TCGA novel	80	D>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
COSM1648871 rs991905634 COSM546233 CA243322276	81	E>K	lung Variant assessed as Somatic; impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated NCI-TCGA TOPMed
TCGA novel	83	G>W	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs765732785 CA6768817	86	V>L		No	ClinGen ExAC gnomAD
CA386431516 rs1238719521	89	R>K		No	ClinGen gnomAD
CA386431529 rs1592791551	90	F>V		No	ClinGen Ensembl
TCGA novel	93	F>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1460815080 CA386431578	93	F>S		No	ClinGen gnomAD
rs1592791562 CA386431616	96	G>V		No	ClinGen Ensembl
CA243322286 rs11548230	98	A>T		No	ClinGen TOPMed
rs1565875385 CA386431638	98	A>V		No	ClinGen Ensembl
CA386431660 rs1378676771	100	A>V		No	ClinGen TOPMed
rs766774170 CA6768820	102	S>G		No	ClinGen ExAC TOPMed gnomAD
rs1417640251 CA386431690	103	S>A		No	ClinGen TOPMed
rs886636562 CA243322311	103	S>L		No	ClinGen Ensembl
CA6768822 rs754633460	104	L>F		No	ClinGen ExAC gnomAD
rs145206633 CA243322332	105	A>G		No	ClinGen ESP TOPMed gnomAD
CA6768823 rs780745695	106	T>A		No	ClinGen ExAC gnomAD
TCGA novel	107	E>G	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA386431789 rs1565875446	110	K>E		No	ClinGen Ensembl
CA6768826 rs777792833	112	K>N		No	ClinGen ExAC gnomAD
CA6768825 rs755742014	112	K>R		No	ClinGen ExAC gnomAD
rs749241265 CA6768828	113	T>K		No	ClinGen ExAC TOPMed gnomAD
CA386431831 rs749241265	113	T>M		No	ClinGen ExAC TOPMed gnomAD
CA386431970 rs1323736473	114	V>L		No	ClinGen gnomAD
rs1261703827 CA386432068	121	K>N		No	ClinGen TOPMed
CA386432095 rs1264112340	123	T>I		No	ClinGen gnomAD
CA6768844 rs758914155	125	I>N		No	ClinGen ExAC gnomAD
CA243323536 rs758914155	125	I>T		No	ClinGen ExAC gnomAD
CA6768846 rs752409460	126	A>S		No	ClinGen ExAC gnomAD
CA6768847 rs752409460	126	A>T		No	ClinGen ExAC gnomAD
rs749189743 CA6768849	128	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs757239278 CA6768850	128	E>V		No	ClinGen ExAC TOPMed gnomAD
CA386432175 rs1298441714	129	L>P		No	ClinGen gnomAD
rs778757470 CA6768851	132	P>L		No	ClinGen ExAC gnomAD
TCGA novel	132	P>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs745674081 CA386432238	134	V>L		No	ClinGen ExAC TOPMed gnomAD
rs745674081 CA6768852	134	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1368276054 CA386432273	136	L>P		No	ClinGen gnomAD
CA243323591 rs926473212	137	H>L		No	ClinGen TOPMed
rs1565876473 CA386432341	139	S>F		No	ClinGen Ensembl
CA243323599 rs757195824	140	M>V		No	ClinGen Ensembl
rs763835364	141	L>=	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	NCI-TCGA
rs1434646948 CA386433743	141	L>P		No	ClinGen gnomAD
CA386433763 rs1469697807	144	D>G		No	ClinGen TOPMed gnomAD
rs1363097548 CA386433759	144	D>N		No	ClinGen gnomAD
CA386433768 rs1156929296	145	A>S		No	ClinGen gnomAD
rs1409881370 CA386433772	145	A>V		No	ClinGen gnomAD
CA386433774 rs369278453	146	I>F		No	ClinGen ESP ExAC TOPMed gnomAD
rs1420515354 CA386433777	146	I>S		No	ClinGen gnomAD
rs369278453 CA6768887	146	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA243324590 rs941426062	148	A>P		No	ClinGen TOPMed gnomAD
rs941426062 CA386433788	148	A>S		No	ClinGen TOPMed gnomAD
rs941426062 CA386433787	148	A>T		No	ClinGen TOPMed gnomAD
rs750338671 CA386433792	149	A>S		No	ClinGen ExAC TOPMed gnomAD
CA6768889 rs750338671	149	A>T		No	ClinGen ExAC TOPMed gnomAD
CA386433815 rs1314573372	153	Y>N		No	ClinGen gnomAD
rs113036584 RCV000676523 CA6768892	159	P>A		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA386433863 rs1244830983	159	P>H		No	ClinGen gnomAD
TCGA novel	159	P>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA6768893 rs113036584	159	P>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1565877384 CA386433871	160	K>R		No	ClinGen Ensembl
rs200756181 CA6768894	162	G>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA386433891 rs1230261024	163	E>G		No	ClinGen TOPMed gnomAD
rs1210147654 CA386433905	165	E>G		No	ClinGen gnomAD
CA386433901 rs1489347558	165	E>K		No	ClinGen gnomAD
CA386433915 rs1426924887	166	K>N		No	ClinGen TOPMed

1 associated diseases with Q9H1K1

[MIM: 255125]: Myopathy with exercise intolerance Swedish type (MEIS)

Autosomal recessive metabolic disease characterized by lifelong severe exercise intolerance, in which minor exertion causes fatigue of active muscles, shortness of breath, and cardiac palpitations in association with lactic acidosis. The biochemical phenotype is characterized by a deficiency in mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism. {ECO:0000269|PubMed:18304497}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

Autosomal recessive metabolic disease characterized by lifelong severe exercise intolerance, in which minor exertion causes fatigue of active muscles, shortness of breath, and cardiac palpitations in association with lactic acidosis. The biochemical phenotype is characterized by a deficiency in mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism. {ECO:0000269|PubMed:18304497}. Note=The disease is caused by variants affecting the gene represented in this entry.

1 regional properties for Q9H1K1

Type	Name	Position	InterPro Accession
domain	NIF system FeS cluster assembly, NifU, N-terminal	13 - 165	IPR002871

Functions

		Description
EC Number
Subcellular Localization	[Isoform 1]: Mitochondrion ;
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

6 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
iron-sulfur cluster assembly complex	A protein complex capable of assembling an iron-sulfur (Fe-S) cluster.
mitochondrial matrix	The gel-like material, with considerable fine structure, that lies in the matrix space, or lumen, of a mitochondrion. It contains the enzymes of the tricarboxylic acid cycle and, in some organisms, the enzymes concerned with fatty acid oxidation.
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

4 GO annotations of molecular function

Name	Definition
2 iron, 2 sulfur cluster binding	Binding to a 2 iron, 2 sulfur (2Fe-2S) cluster; this cluster consists of two iron atoms, with two inorganic sulfur atoms found between the irons and acting as bridging ligands.
ferrous iron binding	Binding to a ferrous iron ion, Fe(II).
iron ion binding	Binding to an iron (Fe) ion.
molecular adaptor activity	The binding activity of a molecule that brings together two or more molecules through a selective, non-covalent, often stoichiometric interaction, permitting those molecules to function in a coordinated way.

8 GO annotations of biological process

Name	Definition
[2Fe-2S] cluster assembly	The incorporation of two iron atoms and two sulfur atoms into an iron-sulfur cluster.
[4Fe-4S] cluster assembly	The incorporation of four iron atoms and four sulfur atoms into an iron-sulfur cluster.
cellular iron ion homeostasis	Any process involved in the maintenance of an internal steady state of iron ions at the level of a cell.
iron ion homeostasis	Any process involved in the maintenance of an internal steady state of iron ions within an organism or cell.
iron-sulfur cluster assembly	The incorporation of iron and exogenous sulfur into a metallo-sulfur cluster.
negative regulation of iron ion import across plasma membrane	Any process that stops, prevents or reduces the frequency, rate or extent of iron ions import across plasma membrane.
positive regulation of aconitate hydratase activity	Any process that activates or increases the frequency, rate or extent of aconitate hydratase activity.
positive regulation of mitochondrial electron transport, NADH to ubiquinone	Any process that activates or increases the frequency, rate or extent of mitochondrial electron transport, NADH to ubiquinone.

1 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q9D7P6	Iscu	Iron-sulfur cluster assembly enzyme ISCU, mitochondrial	Mus musculus (Mouse)	PR

10	20	30	40	50	60
MAAAGAFRLR	RAASALLLRS	PRLPARELSA	PARLYHKKVV	DHYENPRNVG	SLDKTSKNVG
70	80	90	100	110	120
TGLVGAPACG	DVMKLQIQVD	EKGKIVDARF	KTFGCGSAIA	SSSLATEWVK	GKTVEEALTI
130	140	150	160
KNTDIAKELC	LPPVKLHCSM	LAEDAIKAAL	ADYKLKQEPK	KGEAEKK