ID CIAO3_HUMAN Reviewed; 476 AA. AC Q9H6Q4; A1L385; B3KTJ3; Q53GC6; Q96S10; Q9H6J8; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 27-MAR-2024, entry version 168. DE RecName: Full=Cytosolic iron-sulfur assembly component 3 {ECO:0000305}; DE AltName: Full=Cytosolic Fe-S cluster assembly factor NARFL; DE AltName: Full=Iron-only hydrogenase-like protein 1 {ECO:0000303|PubMed:16956324}; DE Short=IOP1 {ECO:0000303|PubMed:16956324}; DE AltName: Full=Nuclear prelamin A recognition factor-like protein; DE AltName: Full=Protein related to Narf; GN Name=CIAO3 {ECO:0000312|HGNC:HGNC:14179}; GN Synonyms=NARFL {ECO:0000312|HGNC:HGNC:14179}, PRN; 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). RA Barton R.M., Worman H.J.; RT "A comparison of Narf, HPRN and Nar1p in human and yeast cells."; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain; 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 MRNA] (ISOFORM 1). RC TISSUE=Small intestine; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11157797; DOI=10.1093/hmg/10.4.339; RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.; RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of RT the short arm of human chromosome 16."; RL Hum. Mol. Genet. 10:339-352(2001). RN [5] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=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 [8] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=16956324; DOI=10.1042/bj20060635; RA Huang J., Song D., Flores A., Zhao Q., Mooney S.M., Shaw L.M., Lee F.S.; RT "IOP1, a novel hydrogenase-like protein that modulates hypoxia-inducible RT factor-1alpha activity."; RL Biochem. J. 401:341-352(2007). RN [9] RP FUNCTION. RX PubMed=18270200; DOI=10.1074/jbc.m708077200; RA Song D., Lee F.S.; RT "A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis."; RL J. Biol. Chem. 283:9231-9238(2008). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] 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 [12] RP IDENTIFICATION IN THE CIA COMPLEX. RX PubMed=22678362; DOI=10.1126/science.1219723; RA Stehling O., Vashisht A.A., Mascarenhas J., Jonsson Z.O., Sharma T., RA Netz D.J., Pierik A.J., Wohlschlegel J.A., Lill R.; RT "MMS19 assembles iron-sulfur proteins required for DNA metabolism and RT genomic integrity."; RL Science 337:195-199(2012). RN [13] RP IDENTIFICATION IN THE CIA COMPLEX. RX PubMed=22678361; DOI=10.1126/science.1219664; RA Gari K., Leon Ortiz A.M., Borel V., Flynn H., Skehel J.M., Boulton S.J.; RT "MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism."; RL Science 337:243-245(2012). RN [14] RP IDENTIFICATION IN THE CIA COMPLEX, AND INTERACTION WITH CIAO1 AND MMS19. RX PubMed=23585563; DOI=10.1074/jbc.m112.416602; RA Seki M., Takeda Y., Iwai K., Tanaka K.; RT "IOP1 protein is an external component of the human cytosolic iron-sulfur RT cluster assembly (CIA) machinery and functions in the MMS19 protein- RT dependent CIA pathway."; RL J. Biol. Chem. 288:16680-16689(2013). CC -!- FUNCTION: Component of the cytosolic iron-sulfur protein assembly (CIA) CC complex, a multiprotein complex that mediates the incorporation of CC iron-sulfur cluster into extramitochondrial Fe/S proteins. Seems to CC negatively regulate the level of HIF1A expression, although this effect CC could be indirect. {ECO:0000269|PubMed:16956324, CC ECO:0000269|PubMed:18270200}. CC -!- SUBUNIT: External component of the CIA complex (PubMed:22678361, CC PubMed:22678362, PubMed:23585563). In the CIA complex, interacts CC directly with CIAO1 and MMS19 (PubMed:23585563). CC {ECO:0000269|PubMed:22678361, ECO:0000269|PubMed:22678362, CC ECO:0000269|PubMed:23585563}. CC -!- INTERACTION: CC Q9H6Q4; Q96T76: MMS19; NbExp=3; IntAct=EBI-10977788, EBI-1044169; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9H6Q4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H6Q4-2; Sequence=VSP_025694; CC Name=3; CC IsoId=Q9H6Q4-3; Sequence=VSP_025695; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:16956324}. CC -!- SIMILARITY: Belongs to the NARF family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAK61251.1; Type=Erroneous gene model prediction; 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; AY129231; AAM98737.1; -; mRNA. DR EMBL; AK025641; BAB15199.1; -; mRNA. DR EMBL; AK025861; BAB15261.1; -; mRNA. DR EMBL; AK095675; BAG53105.1; -; mRNA. DR EMBL; AK223005; BAD96725.1; -; mRNA. DR EMBL; AE006464; AAK61251.1; ALT_SEQ; Genomic_DNA. DR EMBL; Z98258; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471112; EAW85723.1; -; Genomic_DNA. DR EMBL; BC030248; AAH30248.1; -; mRNA. DR EMBL; BC129940; AAI29941.1; -; mRNA. DR CCDS; CCDS10425.1; -. [Q9H6Q4-1] DR CCDS; CCDS76798.1; -. [Q9H6Q4-3] DR RefSeq; NP_001291728.1; NM_001304799.1. [Q9H6Q4-3] DR RefSeq; NP_071938.1; NM_022493.2. [Q9H6Q4-1] DR AlphaFoldDB; Q9H6Q4; -. DR SMR; Q9H6Q4; -. DR BioGRID; 122176; 35. DR ComplexPortal; CPX-2837; CIAO1-CIAO2B-CIAO3-MMS19 cytosolic iron-sulfur protein assembly complex. DR ComplexPortal; CPX-2840; CIAO1-CIAO2A-CIAO3 cytosolic iron-sulfur protein assembly complex. DR CORUM; Q9H6Q4; -. DR IntAct; Q9H6Q4; 12. DR STRING; 9606.ENSP00000251588; -. DR GlyGen; Q9H6Q4; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9H6Q4; -. DR MetOSite; Q9H6Q4; -. DR PhosphoSitePlus; Q9H6Q4; -. DR BioMuta; NARFL; -. DR DMDM; 74733617; -. DR EPD; Q9H6Q4; -. DR jPOST; Q9H6Q4; -. DR MassIVE; Q9H6Q4; -. DR MaxQB; Q9H6Q4; -. DR PaxDb; 9606-ENSP00000251588; -. DR PeptideAtlas; Q9H6Q4; -. DR ProteomicsDB; 81009; -. [Q9H6Q4-1] DR ProteomicsDB; 81010; -. [Q9H6Q4-2] DR ProteomicsDB; 81011; -. [Q9H6Q4-3] DR Pumba; Q9H6Q4; -. DR Antibodypedia; 42404; 223 antibodies from 28 providers. DR DNASU; 64428; -. DR Ensembl; ENST00000251588.7; ENSP00000251588.2; ENSG00000103245.14. [Q9H6Q4-1] DR Ensembl; ENST00000540986.5; ENSP00000444008.1; ENSG00000103245.14. [Q9H6Q4-3] DR Ensembl; ENST00000568545.5; ENSP00000457058.1; ENSG00000103245.14. [Q9H6Q4-3] DR GeneID; 64428; -. DR KEGG; hsa:64428; -. DR MANE-Select; ENST00000251588.7; ENSP00000251588.2; NM_022493.3; NP_071938.1. DR UCSC; uc002cjp.4; human. [Q9H6Q4-1] DR AGR; HGNC:14179; -. DR CTD; 64428; -. DR DisGeNET; 64428; -. DR GeneCards; CIAO3; -. DR HGNC; HGNC:14179; CIAO3. DR HPA; ENSG00000103245; Low tissue specificity. DR MIM; 611118; gene. DR neXtProt; NX_Q9H6Q4; -. DR OpenTargets; ENSG00000103245; -. DR PharmGKB; PA128394707; -. DR VEuPathDB; HostDB:ENSG00000103245; -. DR eggNOG; KOG2439; Eukaryota. DR GeneTree; ENSGT00940000153514; -. DR HOGENOM; CLU_018240_0_0_1; -. DR InParanoid; Q9H6Q4; -. DR OMA; GYLHHVL; -. DR OrthoDB; 5477067at2759; -. DR PhylomeDB; Q9H6Q4; -. DR TreeFam; TF106273; -. DR PathwayCommons; Q9H6Q4; -. DR Reactome; R-HSA-2564830; Cytosolic iron-sulfur cluster assembly. DR SignaLink; Q9H6Q4; -. DR BioGRID-ORCS; 64428; 834 hits in 1158 CRISPR screens. DR ChiTaRS; CIAO3; human. DR GenomeRNAi; 64428; -. DR Pharos; Q9H6Q4; Tbio. DR PRO; PR:Q9H6Q4; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q9H6Q4; Protein. DR Bgee; ENSG00000103245; Expressed in apex of heart and 125 other cell types or tissues. DR ExpressionAtlas; Q9H6Q4; baseline and differential. DR GO; GO:0097361; C:CIA complex; IDA:UniProtKB. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0032364; P:intracellular oxygen homeostasis; IDA:HGNC-UCL. DR GO; GO:0016226; P:iron-sulfur cluster assembly; IMP:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; IDA:HGNC-UCL. DR Gene3D; 3.40.50.1780; -; 1. DR InterPro; IPR009016; Fe_hydrogenase. DR InterPro; IPR004108; Fe_hydrogenase_lsu_C. DR InterPro; IPR003149; Fe_hydrogenase_ssu. DR PANTHER; PTHR11615:SF322; CYTOSOLIC IRON-SULFUR ASSEMBLY COMPONENT 3; 1. DR PANTHER; PTHR11615; NITRATE, FORMATE, IRON DEHYDROGENASE; 1. DR Pfam; PF02906; Fe_hyd_lg_C; 1. DR Pfam; PF02256; Fe_hyd_SSU; 1. DR SMART; SM00902; Fe_hyd_SSU; 1. DR SUPFAM; SSF53920; Fe-only hydrogenase; 1. DR Genevisible; Q9H6Q4; HS. PE 1: Evidence at protein level; KW 4Fe-4S; Acetylation; Alternative splicing; Iron; Iron-sulfur; KW Metal-binding; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:20068231" FT CHAIN 2..476 FT /note="Cytosolic iron-sulfur assembly component 3" FT /id="PRO_0000288485" FT BINDING 24 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255" FT BINDING 71 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255" FT BINDING 74 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255" FT BINDING 77 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255" FT BINDING 190 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000255" FT BINDING 246 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000255" FT BINDING 395 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000255" FT BINDING 399 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000255" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:20068231" FT VAR_SEQ 1..243 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_025694" FT VAR_SEQ 1..102 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_025695" FT VARIANT 38 FT /note="V -> M (in dbSNP:rs8045850)" FT /id="VAR_053911" FT VARIANT 444 FT /note="H -> R (in dbSNP:rs7188554)" FT /id="VAR_053912" FT CONFLICT 205 FT /note="I -> T (in Ref. 3; BAD96725)" FT /evidence="ECO:0000305" SQ SEQUENCE 476 AA; 53020 MW; 88A019DA4D7988EA CRC64; MASPFSGALQ LTDLDDFIGP SQECIKPVKV EKRAGSGVAK IRIEDDGSYF QINQDGGTRR LEKAKVSLND CLACSGCITS AETVLITQQS HEELKKVLDA NKMAAPSQQR LVVVSVSPQS RASLAARFQL NPTDTARKLT SFFKKIGVHF VFDTAFSRHF SLLESQREFV RRFRGQADCR QALPLLASAC PGWICYAEKT HGSFILPHIS TARSPQQVMG SLVKDFFAQQ QHLTPDKIYH VTVMPCYDKK LEASRPDFFN QEHQTRDVDC VLTTGEVFRL LEEEGVSLPD LEPAPLDSLC SGASAEEPTS HRGGGSGGYL EHVFRHAARE LFGIHVAEVT YKPLRNKDFQ EVTLEKEGQV LLHFAMAYGF RNIQNLVQRL KRGRCPYHYV EVMACPSGCL NGGGQLQAPD RPSRELLQHV ERLYGMVRAE APEDAPGVQE LYTHWLQGTD SECAGRLLHT QYHAVEKAST GLGIRW //