ISCA2_HUMAN
ID ISCA2_HUMAN Reviewed; 154 AA.
AC Q86U28; A6NFF1; A8K3W3; G3V291; Q8IYZ0; Q96BB2;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Iron-sulfur cluster assembly 2 homolog, mitochondrial;
DE AltName: Full=HESB-like domain-containing protein 1;
DE Flags: Precursor;
GN Name=ISCA2; Synonyms=HBLD1;
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 [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood, and Brain;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP INVOLVEMENT IN MMDS4, AND VARIANT MMDS4 SER-77.
RX PubMed=25539947; DOI=10.1136/jmedgenet-2014-102592;
RA Al-Hassnan Z.N., Al-Dosary M., Alfadhel M., Faqeih E.A., Alsagob M.,
RA Kenana R., Almass R., Al-Harazi O.S., Al-Hindi H., Malibari O.I.,
RA Almutari F.B., Tulbah S., Alhadeq F., Al-Sheddi T., Alamro R., AlAsmari A.,
RA Almuntashri M., Alshaalan H., Al-Mohanna F.A., Colak D., Kaya N.;
RT "ISCA2 mutation causes infantile neurodegenerative mitochondrial
RT disorder.";
RL J. Med. Genet. 52:186-194(2015).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Involved in the maturation of mitochondrial 4Fe-4S proteins
CC functioning late in the iron-sulfur cluster assembly pathway. May be
CC involved in the binding of an intermediate of Fe/S cluster assembly.
CC {ECO:0000269|PubMed:22323289}.
CC -!- INTERACTION:
CC Q86U28; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-10258659, EBI-11954519;
CC Q86U28; P28329-3: CHAT; NbExp=3; IntAct=EBI-10258659, EBI-25837549;
CC Q86U28; G5E9A7: DMWD; NbExp=3; IntAct=EBI-10258659, EBI-10976677;
CC Q86U28; P60228: EIF3E; NbExp=3; IntAct=EBI-10258659, EBI-347740;
CC Q86U28; Q9H5Z6-2: FAM124B; NbExp=3; IntAct=EBI-10258659, EBI-11986315;
CC Q86U28; P22607: FGFR3; NbExp=3; IntAct=EBI-10258659, EBI-348399;
CC Q86U28; P55040: GEM; NbExp=3; IntAct=EBI-10258659, EBI-744104;
CC Q86U28; P28799: GRN; NbExp=3; IntAct=EBI-10258659, EBI-747754;
CC Q86U28; P06396: GSN; NbExp=3; IntAct=EBI-10258659, EBI-351506;
CC Q86U28; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-10258659, EBI-11978177;
CC Q86U28; Q5T440: IBA57; NbExp=4; IntAct=EBI-10258659, EBI-10714899;
CC Q86U28; O60333-2: KIF1B; NbExp=3; IntAct=EBI-10258659, EBI-10975473;
CC Q86U28; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-10258659, EBI-741158;
CC Q86U28; D3DTS7: PMP22; NbExp=3; IntAct=EBI-10258659, EBI-25882629;
CC Q86U28; Q9H4P4: RNF41; NbExp=6; IntAct=EBI-10258659, EBI-2130266;
CC Q86U28; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-10258659, EBI-5235340;
CC Q86U28; P51687: SUOX; NbExp=3; IntAct=EBI-10258659, EBI-3921347;
CC Q86U28; P02766: TTR; NbExp=3; IntAct=EBI-10258659, EBI-711909;
CC Q86U28; O76024: WFS1; NbExp=3; IntAct=EBI-10258659, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:22323289}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86U28-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86U28-2; Sequence=VSP_055691, VSP_055692;
CC -!- DISEASE: Multiple mitochondrial dysfunctions syndrome 4 (MMDS4)
CC [MIM:616370]: A severe disorder of systemic energy metabolism,
CC resulting in weakness, respiratory failure, lack of neurologic
CC development, lactic acidosis, hyperglycinemia and early death.
CC {ECO:0000269|PubMed:25539947}. 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=CAD62580.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BX248252; CAD62580.1; ALT_INIT; mRNA.
DR EMBL; AK290728; BAF83417.1; -; mRNA.
DR EMBL; AC005479; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81180.1; -; Genomic_DNA.
DR EMBL; BC015771; AAH15771.2; -; mRNA.
DR EMBL; BC032893; AAH32893.1; -; mRNA.
DR CCDS; CCDS32122.1; -. [Q86U28-1]
DR CCDS; CCDS61504.1; -. [Q86U28-2]
DR RefSeq; NP_001258936.1; NM_001272007.1. [Q86U28-2]
DR RefSeq; NP_919255.2; NM_194279.3. [Q86U28-1]
DR AlphaFoldDB; Q86U28; -.
DR SASBDB; Q86U28; -.
DR SMR; Q86U28; -.
DR BioGRID; 125808; 89.
DR IntAct; Q86U28; 22.
DR STRING; 9606.ENSP00000452007; -.
DR iPTMnet; Q86U28; -.
DR PhosphoSitePlus; Q86U28; -.
DR BioMuta; ISCA2; -.
DR DMDM; 125950361; -.
DR EPD; Q86U28; -.
DR jPOST; Q86U28; -.
DR MassIVE; Q86U28; -.
DR MaxQB; Q86U28; -.
DR PaxDb; Q86U28; -.
DR PeptideAtlas; Q86U28; -.
DR PRIDE; Q86U28; -.
DR ProteomicsDB; 32564; -.
DR ProteomicsDB; 69761; -. [Q86U28-1]
DR Antibodypedia; 25630; 159 antibodies from 23 providers.
DR DNASU; 122961; -.
DR Ensembl; ENST00000554924.1; ENSP00000450523.1; ENSG00000165898.14. [Q86U28-2]
DR Ensembl; ENST00000556816.6; ENSP00000452007.1; ENSG00000165898.14. [Q86U28-1]
DR GeneID; 122961; -.
DR KEGG; hsa:122961; -.
DR MANE-Select; ENST00000556816.6; ENSP00000452007.1; NM_194279.4; NP_919255.2.
DR UCSC; uc001xpz.4; human. [Q86U28-1]
DR CTD; 122961; -.
DR DisGeNET; 122961; -.
DR GeneCards; ISCA2; -.
DR GeneReviews; ISCA2; -.
DR HGNC; HGNC:19857; ISCA2.
DR HPA; ENSG00000165898; Low tissue specificity.
DR MalaCards; ISCA2; -.
DR MIM; 615317; gene.
DR MIM; 616370; phenotype.
DR neXtProt; NX_Q86U28; -.
DR OpenTargets; ENSG00000165898; -.
DR Orphanet; 457406; Multiple mitochondrial dysfunctions syndrome type 4.
DR PharmGKB; PA162392315; -.
DR VEuPathDB; HostDB:ENSG00000165898; -.
DR eggNOG; KOG1119; Eukaryota.
DR GeneTree; ENSGT00390000005700; -.
DR HOGENOM; CLU_069054_1_4_1; -.
DR InParanoid; Q86U28; -.
DR OMA; SLDYCTG; -.
DR OrthoDB; 1360948at2759; -.
DR PhylomeDB; Q86U28; -.
DR TreeFam; TF314519; -.
DR PathwayCommons; Q86U28; -.
DR Reactome; R-HSA-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR SignaLink; Q86U28; -.
DR BioGRID-ORCS; 122961; 496 hits in 1091 CRISPR screens.
DR ChiTaRS; ISCA2; human.
DR GenomeRNAi; 122961; -.
DR Pharos; Q86U28; Tbio.
DR PRO; PR:Q86U28; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q86U28; protein.
DR Bgee; ENSG00000165898; Expressed in left ventricle myocardium and 184 other tissues.
DR ExpressionAtlas; Q86U28; baseline and differential.
DR Genevisible; Q86U28; HS.
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:0051539; F:4 iron, 4 sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IBA:GO_Central.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IBA:GO_Central.
DR GO; GO:0106035; P:protein maturation by [4Fe-4S] 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; Primary mitochondrial disease; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..8
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 9..154
FT /note="Iron-sulfur cluster assembly 2 homolog,
FT mitochondrial"
FT /id="PRO_0000277588"
FT REGION 29..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 79
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0AAC8"
FT BINDING 144
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0AAC8"
FT BINDING 146
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0AAC8"
FT VAR_SEQ 59..60
FT /note="RL -> GI (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_055691"
FT VAR_SEQ 61..154
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_055692"
FT VARIANT 77
FT /note="G -> S (in MMDS4; dbSNP:rs730882246)"
FT /evidence="ECO:0000269|PubMed:25539947"
FT /id="VAR_073794"
FT CONFLICT 51
FT /note="R -> C (in Ref. 5; AAH32893)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="V -> F (in Ref. 5; AAH15771)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 154 AA; 16476 MW; D6D16E4451F04625 CRC64;
MAAAWGSSLT AATQRAVTPW PRGRLLTASL GPQARREASS SSPEAGEGQI RLTDSCVQRL
LEITEGSEFL RLQVEGGGCS GFQYKFSLDT VINPDDRVFE QGGARVVVDS DSLAFVKGAQ
VDFSQELIRS SFQVLNNPQA QQGCSCGSSF SIKL
