ID HSC20_MOUSE Reviewed; 234 AA.
AC Q8K3A0; Q3V294;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2004, sequence version 2.
DT 08-NOV-2023, entry version 142.
DE RecName: Full=Iron-sulfur cluster co-chaperone protein HscB {ECO:0000305};
DE Contains:
DE RecName: Full=Iron-sulfur cluster co-chaperone protein HscB, mitochondrial;
DE Short=C-HSC20 {ECO:0000250|UniProtKB:Q8IWL3};
DE Contains:
DE RecName: Full=Iron-sulfur cluster co-chaperone protein HscB, cytoplasmic;
GN Name=Hscb {ECO:0000312|MGI:MGI:2141135}; Synonyms=Hsc20;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=32634119; DOI=10.1172/jci135479;
RA Crispin A., Guo C., Chen C., Campagna D.R., Schmidt P.J., Lichtenstein D.,
RA Cao C., Sendamarai A.K., Hildick-Smith G.J., Huston N.C., Boudreaux J.,
RA Bottomley S.S., Heeney M.M., Paw B.H., Fleming M.D., Ducamp S.;
RT "Mutations in the iron-sulfur cluster biogenesis protein HSCB cause
RT congenital sideroblastic anemia.";
RL J. Clin. Invest. 130:5245-5256(2020).
CC -!- FUNCTION: [Iron-sulfur cluster co-chaperone protein HscB,
CC mitochondrial]: Acts as a co-chaperone in iron-sulfur cluster assembly
CC in mitochondria. Required for incorporation of iron-sulfur clusters
CC into SDHB, the iron-sulfur protein subunit of succinate dehydrogenase
CC that is involved in complex II of the mitochondrial electron transport
CC chain. Recruited to SDHB by interaction with SDHAF1 which first binds
CC SDHB and then recruits the iron-sulfur transfer complex formed by
CC HSC20, HSPA9 and ISCU through direct binding to HSC20 (By similarity).
CC Plays an essential role in hematopoiesis (PubMed:32634119).
CC {ECO:0000250|UniProtKB:Q8IWL3, ECO:0000269|PubMed:32634119}.
CC -!- FUNCTION: [Iron-sulfur cluster co-chaperone protein HscB, cytoplasmic]:
CC Acts as a co-chaperone in iron-sulfur cluster assembly in the
CC cytoplasm. Also mediates complex formation between components of the
CC cytosolic iron-sulfur biogenesis pathway and the CIA targeting complex
CC composed of CIAO1, DIPK1B/FAM69B and MMS19 by binding directly to the
CC scaffold protein ISCU and to CIAO1. This facilitates iron-sulfur
CC cluster insertion into a number of cytoplasmic and nuclear proteins
CC including POLD1, ELP3, DPYD and PPAT. {ECO:0000250|UniProtKB:Q8IWL3}.
CC -!- PATHWAY: Cofactor biosynthesis; iron-sulfur cluster biosynthesis.
CC -!- SUBUNIT: [Iron-sulfur cluster co-chaperone protein HscB,
CC mitochondrial]: Interacts with ISCU and HSPA9 to form an iron-sulfur
CC transfer complex. Interacts with SDHAF1 (via the first LYR motif); the
CC interaction recruits the iron-sulfur transfer complex composed of
CC HSC20, HSPA9 and ISCU and mediates the incorporation of iron-sulfur
CC clusters into SDHB which also interacts with HSC20. Interacts with the
CC cytoplasmic form of ISCU and with CIA complex member CIAO1 (via LYR
CC motif). {ECO:0000250|UniProtKB:Q8IWL3}.
CC -!- SUBUNIT: [Iron-sulfur cluster co-chaperone protein HscB, cytoplasmic]:
CC Homodimer. Interacts with ISCU (cytoplasmic form); this interaction
CC stabilzes the (Fe-S) clusters on ISCU. Interacts with the CIA complex
CC member CIAO1 (via LYR motif). {ECO:0000250|UniProtKB:Q8IWL3}.
CC -!- SUBCELLULAR LOCATION: [Iron-sulfur cluster co-chaperone protein HscB,
CC cytoplasmic]: Cytoplasm {ECO:0000250|UniProtKB:Q8IWL3}.
CC -!- SUBCELLULAR LOCATION: [Iron-sulfur cluster co-chaperone protein HscB,
CC mitochondrial]: Mitochondrion {ECO:0000250|UniProtKB:Q8IWL3}.
CC -!- DISRUPTION PHENOTYPE: Knockout of the gene is embryonic lethal.
CC Specific loss of the gene in erythroblasts is also lethal due to
CC anemia. {ECO:0000269|PubMed:32634119}.
CC -!- SIMILARITY: Belongs to the HscB family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH27641.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK131961; BAE20904.1; -; mRNA.
DR EMBL; BC027641; AAH27641.1; ALT_INIT; mRNA.
DR CCDS; CCDS51613.1; -.
DR RefSeq; NP_705799.2; NM_153571.2.
DR AlphaFoldDB; Q8K3A0; -.
DR SMR; Q8K3A0; -.
DR BioGRID; 221552; 2.
DR STRING; 10090.ENSMUSP00000062811; -.
DR iPTMnet; Q8K3A0; -.
DR PhosphoSitePlus; Q8K3A0; -.
DR REPRODUCTION-2DPAGE; IPI00170051; -.
DR REPRODUCTION-2DPAGE; Q8K3A0; -.
DR EPD; Q8K3A0; -.
DR MaxQB; Q8K3A0; -.
DR PaxDb; 10090-ENSMUSP00000062811; -.
DR PeptideAtlas; Q8K3A0; -.
DR ProteomicsDB; 273275; -.
DR Pumba; Q8K3A0; -.
DR GeneID; 100900; -.
DR KEGG; mmu:100900; -.
DR UCSC; uc008yrv.2; mouse.
DR AGR; MGI:2141135; -.
DR CTD; 150274; -.
DR MGI; MGI:2141135; Hscb.
DR eggNOG; KOG3192; Eukaryota.
DR InParanoid; Q8K3A0; -.
DR OrthoDB; 5473494at2759; -.
DR PhylomeDB; Q8K3A0; -.
DR TreeFam; TF319992; -.
DR Reactome; R-MMU-1268020; Mitochondrial protein import.
DR Reactome; R-MMU-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR UniPathway; UPA00266; -.
DR BioGRID-ORCS; 100900; 31 hits in 78 CRISPR screens.
DR ChiTaRS; Hscb; mouse.
DR PRO; PR:Q8K3A0; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8K3A0; Protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0001671; F:ATPase activator activity; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051087; F:protein-folding chaperone binding; IEA:InterPro.
DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; IBA:GO_Central.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; ISO:MGI.
DR GO; GO:0060319; P:primitive erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0060215; P:primitive hemopoiesis; IMP:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:InterPro.
DR Gene3D; 1.10.287.110; DnaJ domain; 1.
DR Gene3D; 1.20.1280.20; HscB, C-terminal domain; 1.
DR HAMAP; MF_00682; HscB; 1.
DR InterPro; IPR004640; HscB.
DR InterPro; IPR040682; HscB_4_cys.
DR InterPro; IPR036386; HscB_C_sf.
DR InterPro; IPR009073; HscB_oligo_C.
DR InterPro; IPR036869; J_dom_sf.
DR NCBIfam; TIGR00714; hscB; 1.
DR PANTHER; PTHR14021; IRON-SULFUR CLUSTER CO-CHAPERONE PROTEIN HSCB; 1.
DR PANTHER; PTHR14021:SF15; IRON-SULFUR CLUSTER CO-CHAPERONE PROTEIN HSCB; 1.
DR Pfam; PF18256; HscB_4_cys; 1.
DR Pfam; PF07743; HSCB_C; 1.
DR SUPFAM; SSF46565; Chaperone J-domain; 1.
DR SUPFAM; SSF47144; HSC20 (HSCB), C-terminal oligomerisation domain; 1.
PE 1: Evidence at protein level;
KW Chaperone; Cytoplasm; Metal-binding; Mitochondrion; Reference proteome.
FT CHAIN 1..234
FT /note="Iron-sulfur cluster co-chaperone protein HscB,
FT cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IWL3"
FT /id="PRO_0000446243"
FT CHAIN 30..234
FT /note="Iron-sulfur cluster co-chaperone protein HscB,
FT mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000007263"
FT DOMAIN 71..143
FT /note="J"
FT BINDING 40
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q8IWL3"
FT BINDING 43
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q8IWL3"
FT BINDING 57
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q8IWL3"
FT BINDING 60
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q8IWL3"
FT CONFLICT 49
FT /note="A -> V (in Ref. 1; BAE20904)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 234 AA; 26645 MW; AA9544500EC4F59B CRC64;
MWGCGARALL GVWEVRLAGF LGRRLLGSNA AAGKSIAPQC WNCGHAREAG CGDEFFCSHC
RALQPPDPTR DYFSLMNCNR SFRVDVTKLQ HRYQQLQRLV HPDFFSQKSQ TEKHFSDKHS
TLVNDAYKTL QAPLTRGLYL LKLQGIEIPE GTDYKADSQF LVEIMEINER LADAQSEAAM
EEIEATVRAK QKEFTDNINS AFEQGDFEKA KELLTKMRYF SNIEEKIKLS KTPL
//
