ISCA1_HUMAN
ID ISCA1_HUMAN Reviewed; 129 AA.
AC Q9BUE6; B3KP34; B4DJI5; Q8ND75; Q9BZR2;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Iron-sulfur cluster assembly 1 homolog, mitochondrial;
DE AltName: Full=HESB-like domain-containing protein 2;
DE AltName: Full=Iron-sulfur assembly protein IscA;
DE Short=hIscA;
DE Flags: Precursor;
GN Name=ISCA1; Synonyms=HBLD2; ORFNames=GK004;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=15262227; DOI=10.1016/j.bbapap.2004.05.004;
RA Cozar-Castellano I., del Valle Machargo M., Trujillo E., Arteaga M.F.,
RA Gonzalez T., Martin-Vasallo P., Avila J.;
RT "hIscA: a protein implicated in the biogenesis of iron-sulfur clusters.";
RL Biochim. Biophys. Acta 1700:179-188(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver cancer;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22323289; DOI=10.1091/mbc.e11-09-0772;
RA Sheftel A.D., Wilbrecht C., Stehling O., Niggemeyer B., Elsasser H.P.,
RA Muhlenhoff U., Lill R.;
RT "The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for
RT [4Fe-4S] protein maturation.";
RL Mol. Biol. Cell 23:1157-1166(2012).
RN [9]
RP INTERACTION WITH CRY2.
RX PubMed=26569474; DOI=10.1038/nmat4484;
RA Qin S., Yin H., Yang C., Dou Y., Liu Z., Zhang P., Yu H., Huang Y.,
RA Feng J., Hao J., Hao J., Deng L., Yan X., Dong X., Zhao Z., Jiang T.,
RA Wang H.W., Luo S.J., Xie C.;
RT "A magnetic protein biocompass.";
RL Nat. Mater. 15:217-226(2016).
RN [10]
RP VARIANT MMDS5 LYS-87.
RX PubMed=28356563; DOI=10.1038/jhg.2017.35;
RA Shukla A., Hebbar M., Srivastava A., Kadavigere R., Upadhyai P., Kanthi A.,
RA Brandau O., Bielas S., Girisha K.M.;
RT "Homozygous p.(Glu87Lys) variant in ISCA1 is associated with a multiple
RT mitochondrial dysfunctions syndrome.";
RL J. Hum. Genet. 62:723-727(2017).
CC -!- FUNCTION: Involved in the maturation of mitochondrial 4Fe-4S proteins
CC functioning late in the iron-sulfur cluster assembly pathway. Probably
CC involved in the binding of an intermediate of Fe/S cluster assembly.
CC {ECO:0000269|PubMed:15262227, ECO:0000269|PubMed:22323289}.
CC -!- SUBUNIT: Interacts with CRY2, but not with CRY1 (in vitro).
CC {ECO:0000269|PubMed:26569474}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:15262227,
CC ECO:0000269|PubMed:22323289}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BUE6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BUE6-2; Sequence=VSP_057035;
CC -!- TISSUE SPECIFICITY: Detected in cerebellum, kidney and heart.
CC {ECO:0000269|PubMed:15262227}.
CC -!- DISEASE: Multiple mitochondrial dysfunctions syndrome 5 (MMDS5)
CC [MIM:617613]: An autosomal recessive, severe disorder characterized by
CC early onset neurological deterioration, seizures, cerebral and
CC cerebellar leukodystrophy, dysmyelination, cortical migrational
CC abnormalities, lactic acidosis and early demise.
CC {ECO:0000269|PubMed:28356563}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the HesB/IscA family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG59854.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAD39021.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY015642; AAG40950.1; -; mRNA.
DR EMBL; AF284752; AAG59854.1; ALT_INIT; mRNA.
DR EMBL; AK055643; BAG51546.1; -; mRNA.
DR EMBL; AK296093; BAG58847.1; -; mRNA.
DR EMBL; AL834356; CAD39021.1; ALT_INIT; mRNA.
DR EMBL; AL137849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471089; EAW62713.1; -; Genomic_DNA.
DR EMBL; BC002675; AAH02675.1; -; mRNA.
DR EMBL; BC071621; AAH71621.1; -; mRNA.
DR CCDS; CCDS35056.1; -. [Q9BUE6-1]
DR RefSeq; NP_112202.2; NM_030940.3. [Q9BUE6-1]
DR AlphaFoldDB; Q9BUE6; -.
DR SMR; Q9BUE6; -.
DR BioGRID; 123569; 127.
DR IntAct; Q9BUE6; 31.
DR MINT; Q9BUE6; -.
DR STRING; 9606.ENSP00000365159; -.
DR iPTMnet; Q9BUE6; -.
DR PhosphoSitePlus; Q9BUE6; -.
DR BioMuta; ISCA1; -.
DR DMDM; 74761270; -.
DR EPD; Q9BUE6; -.
DR jPOST; Q9BUE6; -.
DR MassIVE; Q9BUE6; -.
DR MaxQB; Q9BUE6; -.
DR PaxDb; Q9BUE6; -.
DR PeptideAtlas; Q9BUE6; -.
DR PRIDE; Q9BUE6; -.
DR ProteomicsDB; 79080; -. [Q9BUE6-1]
DR Antibodypedia; 27810; 66 antibodies from 16 providers.
DR DNASU; 81689; -.
DR Ensembl; ENST00000375991.9; ENSP00000365159.4; ENSG00000135070.15. [Q9BUE6-1]
DR GeneID; 81689; -.
DR KEGG; hsa:81689; -.
DR MANE-Select; ENST00000375991.9; ENSP00000365159.4; NM_030940.4; NP_112202.2.
DR UCSC; uc004aop.4; human. [Q9BUE6-1]
DR CTD; 81689; -.
DR DisGeNET; 81689; -.
DR GeneCards; ISCA1; -.
DR GeneReviews; ISCA1; -.
DR HGNC; HGNC:28660; ISCA1.
DR HPA; ENSG00000135070; Low tissue specificity.
DR MalaCards; ISCA1; -.
DR MIM; 611006; gene.
DR MIM; 617613; phenotype.
DR neXtProt; NX_Q9BUE6; -.
DR OpenTargets; ENSG00000135070; -.
DR Orphanet; 569274; Multiple mitochondrial dysfunctions syndrome type 5.
DR PharmGKB; PA162392301; -.
DR VEuPathDB; HostDB:ENSG00000135070; -.
DR eggNOG; KOG1120; Eukaryota.
DR GeneTree; ENSGT00490000043385; -.
DR HOGENOM; CLU_069054_4_0_1; -.
DR InParanoid; Q9BUE6; -.
DR OMA; YQLYFDE; -.
DR OrthoDB; 1578799at2759; -.
DR PhylomeDB; Q9BUE6; -.
DR TreeFam; TF314956; -.
DR PathwayCommons; Q9BUE6; -.
DR Reactome; R-HSA-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR SignaLink; Q9BUE6; -.
DR BioGRID-ORCS; 81689; 225 hits in 1045 CRISPR screens.
DR ChiTaRS; ISCA1; human.
DR GeneWiki; ISCA1; -.
DR GenomeRNAi; 81689; -.
DR Pharos; Q9BUE6; Tbio.
DR PRO; PR:Q9BUE6; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9BUE6; protein.
DR Bgee; ENSG00000135070; Expressed in endothelial cell and 204 other tissues.
DR ExpressionAtlas; Q9BUE6; baseline and differential.
DR Genevisible; Q9BUE6; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IBA:GO_Central.
DR GO; GO:0097428; P:protein maturation by iron-sulfur cluster transfer; IBA:GO_Central.
DR Gene3D; 2.60.300.12; -; 1.
DR InterPro; IPR000361; FeS_biogenesis.
DR InterPro; IPR016092; FeS_cluster_insertion.
DR InterPro; IPR017870; FeS_cluster_insertion_CS.
DR InterPro; IPR035903; HesB-like_dom_sf.
DR Pfam; PF01521; Fe-S_biosyn; 1.
DR SUPFAM; SSF89360; SSF89360; 1.
DR TIGRFAMs; TIGR00049; TIGR00049; 1.
DR PROSITE; PS01152; HESB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Iron; Iron-sulfur; Metal-binding;
KW Mitochondrion; Reference proteome; Transit peptide.
FT TRANSIT 1..12
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 13..129
FT /note="Iron-sulfur cluster assembly 1 homolog,
FT mitochondrial"
FT /id="PRO_0000042734"
FT BINDING 57
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0AAC8"
FT BINDING 121
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0AAC8"
FT BINDING 123
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0AAC8"
FT VAR_SEQ 1
FT /note="M -> MVAAGGGARTEGAVRRSLWRQCARRVHGEKLRRPTFGPRHRGAGTAK
FT M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057035"
FT VARIANT 87
FT /note="E -> K (in MMDS5; unknown pathological significance;
FT dbSNP:rs776679653)"
FT /evidence="ECO:0000269|PubMed:28356563"
FT /id="VAR_079296"
SQ SEQUENCE 129 AA; 14179 MW; 2CA45D7821A62C43 CRC64;
MSASLVRATV RAVSKRKLQP TRAALTLTPS AVNKIKQLLK DKPEHVGVKV GVRTRGCNGL
SYTLEYTKTK GDSDEEVIQD GVRVFIEKKA QLTLLGTEMD YVEDKLSSEF VFNNPNIKGT
CGCGESFNI
