AiPD: Autoinhibited Protein Database

Q86U28

Gene name	ISCA2 (HBLD1)
Protein name	Iron-sulfur cluster assembly 2 homolog, mitochondrial
Names	HESB-like domain-containing protein 1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:122961
EC number
Protein Class

Descriptions

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

Autoinhibitory domains (AIDs)

1-70 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

1-70 (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

1 structures for Q86U28

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q86U28-F1	Predicted				AlphaFoldDB

132 variants for Q86U28

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
VAR_073794 RCV000162184 rs730882246 RCV000170534 RCV000255374 RCV000310400 CA249967	77	G>S	Multiple mitochondrial dysfunctions syndrome 4 Global developmental delay Variant assessed as Somatic; impact. Fatal multiple mitochondrial dysfunctions syndrome MMDS4 [ClinVar, NCI-TCGA, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl NCI-TCGA dbSNP
RCV000627031 CA7268351 RCV002529803 rs767352340	112	S>G	Multiple mitochondrial dysfunctions syndrome 4 [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV001090125 CA390380156 rs1595231072 RCV000790919	119	A>T	Multiple mitochondrial dysfunctions syndrome 4 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV001333707 CA7268357 rs201908228 RCV001865789	121	V>L	Multiple mitochondrial dysfunctions syndrome 4 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs777458795 CA7268242	2	A>D		No	ClinGen ExAC TOPMed gnomAD
rs1214092510 CA390377229	4	A>D		No	ClinGen gnomAD
CA390377223 rs1214092510	4	A>V		No	ClinGen gnomAD
rs1339989244 CA390377247	5	W>*		No	ClinGen TOPMed gnomAD
rs1215329371 CA390377242	5	W>R		No	ClinGen TOPMed
rs1207122929 CA390377269 CA390377266	6	G>R		No	ClinGen TOPMed gnomAD
rs950263114	7	S>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs780853372 CA7268245	7	S>W		No	ClinGen ExAC TOPMed gnomAD
rs1248063555 CA390377316	8	S>F		No	ClinGen gnomAD
CA263573430 rs1044687761	9	L>Q		No	ClinGen TOPMed gnomAD
TCGA novel	10	T>A	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs919184603 CA263573433	10	T>M		No	ClinGen gnomAD
CA390377334 rs1387724988	10	T>S		No	ClinGen gnomAD
rs745738187 CA7268246	11	A>V		No	ClinGen ExAC gnomAD
CA263573450 rs1005573226	12	A>G		No	ClinGen TOPMed
CA263573439 rs868097207	12	A>T		No	ClinGen Ensembl
rs1350706747 CA390377397	14	Q>*		No	ClinGen gnomAD
CA390377408 rs1443774530	14	Q>L		No	ClinGen TOPMed
CA263573453 rs868238817	16	A>V		No	ClinGen TOPMed
CA390377474 rs1367435389	19	P>L		No	ClinGen gnomAD
rs769838954 CA7268248	19	P>S		No	ClinGen ExAC TOPMed gnomAD
rs749090744 CA7268250	20	W>*		No	ClinGen ExAC gnomAD
rs372853525 CA7268251	21	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1226430569 CA390377519	22	R>G		No	ClinGen gnomAD
rs571679292 CA390377534 CA7268253	22	R>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1451835980 CA390377548	23	G>D		No	ClinGen gnomAD
CA390377560 rs1245744358	24	R>T		No	ClinGen gnomAD
CA390377553 rs1207642936	24	R>W		No	ClinGen gnomAD
CA7268264 rs371830968	28	A>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1336080975 CA390377816	35	R>L		No	ClinGen gnomAD
rs1408962132 CA390377859	38	A>T		No	ClinGen gnomAD
rs779995225 CA7268266	39	S>*		No	ClinGen ExAC TOPMed gnomAD
CA390377895 rs1351959603	40	S>F		No	ClinGen TOPMed gnomAD
CA390377913 rs1254968232	41	S>F		No	ClinGen gnomAD
CA390377902 rs1179386242	41	S>P		No	ClinGen TOPMed
rs749217402 CA390377922	42	S>I		No	ClinGen ExAC TOPMed gnomAD
rs749217402 CA7268267	42	S>N		No	ClinGen ExAC TOPMed gnomAD
CA390377944 rs201157942	44	E>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
RCV000430078 RCV000941746 rs201157942 CA7268269	44	E>Q		No	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs1291648725 CA390377953	44	E>V		No	ClinGen Ensembl
rs1180501609 CA390377981	45	A>G		No	ClinGen gnomAD
CA390377961 rs1482990844	45	A>T		No	ClinGen TOPMed gnomAD
CA390377984 rs1254350754	46	G>S		No	ClinGen gnomAD
rs747996482 CA7268270	47	E>*		No	ClinGen ExAC TOPMed gnomAD
rs1376056160 CA390378024	48	G>A		No	ClinGen gnomAD
CA390378030 rs1174291178	49	Q>*		No	ClinGen gnomAD
CA390378033 rs1376030154	49	Q>L		No	ClinGen TOPMed gnomAD
rs17853112 CA263573538	51	R>C		No	ClinGen gnomAD
rs760723089 CA7268273	52	L>F		No	ClinGen ExAC gnomAD
rs1303434815 CA390378141	55	S>N		No	ClinGen gnomAD
rs770936590 CA7268275	55	S>R		No	ClinGen ExAC gnomAD
rs549025538 CA7268276	57	V>I		No	ClinGen 1000Genomes ExAC gnomAD
rs941559644 CA263573551	58	Q>*		No	ClinGen TOPMed gnomAD
TCGA novel	58	Q>=	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA390378190 rs1265500137	58	Q>H		No	ClinGen gnomAD
CA7268277 rs759964533	58	Q>R		No	ClinGen ExAC gnomAD
CA7268304 rs145780483	59	R>K		No	ClinGen ESP ExAC gnomAD
TCGA novel	60	L>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1566606963 CA390378342	64	T>S		No	ClinGen Ensembl
rs1486157182 CA390378369	65	E>D		No	ClinGen gnomAD
rs1242716128 CA390378346	65	E>K		No	ClinGen TOPMed gnomAD
CA263573652 rs761507807	66	G>E		No	ClinGen Ensembl
CA390378480 rs1032889672	69	F>L		No	ClinGen TOPMed gnomAD
CA390378506 rs1165249976	71	R>K		No	ClinGen gnomAD
CA263573661 rs955740935	71	R>S		No	ClinGen TOPMed
CA7268306 rs752655836	73	Q>*		No	ClinGen ExAC gnomAD
rs934278588 CA263573667	77	G>D		No	ClinGen Ensembl
rs1345262361 CA390378647	78	G>R		No	ClinGen gnomAD
CA390378679 rs1455107217	79	C>Y		No	ClinGen TOPMed
CA7268309 rs200054853	80	S>F		No	ClinGen ExAC TOPMed gnomAD
CA263573671 rs201006924	82	F>S		No	ClinGen 1000Genomes
CA7268311 rs148923908	85	K>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs148923908 CA7268312	85	K>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1464591028 CA390378870	86	F>Y		No	ClinGen TOPMed
rs1555346491 CA7268315	89	D>G		No	ClinGen Ensembl
CA390378951 rs1566607048	90	T>A		No	ClinGen Ensembl
CA390378990 rs1595230589	91	V>G		No	ClinGen Ensembl
CA390379006 rs1595230594	92	I>T		No	ClinGen Ensembl
rs749819188 CA7268319	94	P>S		No	ClinGen ExAC gnomAD
CA7268321 rs774568931	95	D>G		No	ClinGen ExAC gnomAD
CA390379043 rs1254141943	95	D>H		No	ClinGen gnomAD
CA390379042 rs1254141943	95	D>N		No	ClinGen gnomAD
CA263573694 rs1024075514	97	R>K		No	ClinGen TOPMed gnomAD
CA390379082 rs1024075514	97	R>T		No	ClinGen TOPMed gnomAD
rs759191528 CA7268344	99	F>Y		No	ClinGen ExAC gnomAD
CA7268345 rs764668481	100	E>*		No	ClinGen ExAC gnomAD
rs1463264518 CA390379930	102	G>D		No	ClinGen TOPMed
CA7268346 rs774966429	102	G>S		No	ClinGen ExAC gnomAD
CA390379945 rs1217568018	104	A>T		No	ClinGen TOPMed gnomAD
rs191915715 CA7268347	105	R>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1339923795 CA390380009	108	V>A		No	ClinGen TOPMed gnomAD
CA7268349 rs763903016	108	V>I		No	ClinGen ExAC TOPMed gnomAD
CA7268348 rs763903016	108	V>L		No	ClinGen ExAC TOPMed gnomAD
CA7268350 rs756950086	111	D>N		No	ClinGen ExAC gnomAD
CA390380098 rs1254399904	114	A>V		No	ClinGen TOPMed gnomAD
rs143682573 CA390380112	115	F>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs780495589 CA7268354	116	V>M		No	ClinGen ExAC gnomAD
rs912516391 CA263573942	119	A>V		No	ClinGen TOPMed
CA263573947 rs200091735	120	Q>K		No	ClinGen 1000Genomes
rs1387181239 CA390380199	122	D>V		No	ClinGen TOPMed
rs748723689 CA7268358	123	F>V		No	ClinGen ExAC gnomAD
rs1246024069 CA390380240	125	Q>*		No	ClinGen TOPMed gnomAD
rs1566607386 CA390380244	125	Q>R		No	ClinGen Ensembl
CA390380262 rs1167339418	126	E>V		No	ClinGen gnomAD
CA7268359 rs772256953	127	L>Q		No	ClinGen ExAC gnomAD
rs778212097 CA7268360	128	I>F		No	ClinGen ExAC TOPMed gnomAD
rs778212097 CA263573956	128	I>L		No	ClinGen ExAC TOPMed gnomAD
CA390380283 rs1195251020	128	I>T		No	ClinGen TOPMed
rs1362959396 CA390380290	129	R>*		No	ClinGen gnomAD
CA390380292 rs1432725522	129	R>Q		No	ClinGen gnomAD
TCGA novel	130	S>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA390380304 rs1447373822	130	S>N		No	ClinGen TOPMed
rs769431371 CA7268362	131	S>*		No	ClinGen ExAC gnomAD
rs1226306501 CA390380329	132	F>V		No	ClinGen gnomAD
rs762424386 CA7268364	133	Q>*		No	ClinGen ExAC gnomAD
rs1033568969 CA263573977	137	N>D		No	ClinGen Ensembl
rs768231972 CA7268365	137	N>S		No	ClinGen ExAC gnomAD
CA390380435 rs1194517263	140	A>T		No	ClinGen gnomAD
CA7268367 rs375133115	141	Q>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA7268368 rs375133115	141	Q>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA7268369 rs375133115	141	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA7268370 rs760591235	143	G>D		No	ClinGen ExAC gnomAD
rs1456856512 CA390380526	146	C>F		No	ClinGen gnomAD
CA7268372 rs754136287	147	G>R		No	ClinGen ExAC gnomAD
rs754136287 CA390380532	147	G>W		No	ClinGen ExAC gnomAD
TCGA novel	149	S>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1318866650 CA390380560	151	S>C		No	ClinGen gnomAD
rs779056370 CA7268374	155	L>R		No	ClinGen ExAC TOPMed gnomAD

1 associated diseases with Q86U28

[MIM: 616370]: Multiple mitochondrial dysfunctions syndrome 4 (MMDS4)

A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. {ECO:0000269|PubMed:25539947}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. {ECO:0000269|PubMed:25539947}. Note=The disease is caused by variants affecting the gene represented in this entry.

2 regional properties for Q86U28

Type	Name	Position	InterPro Accession
domain	FeS cluster biogenesis	49 - 147	IPR000361
conserved_site	FeS cluster insertion, C-terminal, conserved site	133 - 150	IPR017870

Functions

		Description
EC Number
Subcellular Localization	Mitochondrion
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

2 GO annotations of cellular component

Name	Definition
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.

3 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.
4 iron, 4 sulfur cluster binding	Binding to a 4 iron, 4 sulfur (4Fe-4S) cluster; this cluster consists of four iron atoms, with the inorganic sulfur atoms found between the irons and acting as bridging ligands.
iron ion binding	Binding to an iron (Fe) ion.

2 GO annotations of biological process

Name	Definition
iron-sulfur cluster assembly	The incorporation of iron and exogenous sulfur into a metallo-sulfur cluster.
protein maturation by [4Fe-4S] cluster transfer	The transfer of an assembled 4Fe-4S] cluster from a scaffold protein to an acceptor protein that contributes to the attainment of the full functional capacity of a protein.

2 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q8GW20	At5g03900	Uncharacterized protein At5g03900, chloroplastic	Arabidopsis thaliana (Mouse-ear cress)	PR
Q8LCY2	At5g03905	Iron-sulfur assembly protein IscA-like 2, mitochondrial	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MAAAWGSSLT	AATQRAVTPW	PRGRLLTASL	GPQARREASS	SSPEAGEGQI	RLTDSCVQRL
70	80	90	100	110	120
LEITEGSEFL	RLQVEGGGCS	GFQYKFSLDT	VINPDDRVFE	QGGARVVVDS	DSLAFVKGAQ
130	140	150
VDFSQELIRS	SFQVLNNPQA	QQGCSCGSSF	SIKL