ID CIA2A_HUMAN Reviewed; 160 AA. AC Q9H5X1; A6NKS1; B2R5F8; B7Z8Z5; DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 24-JAN-2024, entry version 163. DE RecName: Full=Cytosolic iron-sulfur assembly component 2A {ECO:0000305}; DE AltName: Full=MIP18 family protein FAM96A; GN Name=CIAO2A {ECO:0000312|HGNC:HGNC:26235}; GN Synonyms=CIA2A {ECO:0000303|PubMed:23891004}, FAM96A GN {ECO:0000312|HGNC:HGNC:26235}; 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] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Trachea; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [5] 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 [6] RP FUNCTION, IDENTIFICATION IN THE CIA COMPLEX, AND INTERACTION WITH CIAO1 AND RP IREB2. RX PubMed=23891004; DOI=10.1016/j.cmet.2013.06.015; RA Stehling O., Mascarenhas J., Vashisht A.A., Sheftel A.D., Niggemeyer B., RA Roesser R., Pierik A.J., Wohlschlegel J.A., Lill R.; RT "Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and RT maturation of different subsets of cytosolic-nuclear iron-sulfur RT proteins."; RL Cell Metab. 18:187-198(2013). RN [7] RP ERRATUM OF PUBMED:23891004. RX PubMed=29320706; DOI=10.1016/j.cmet.2017.12.009; RA Stehling O., Mascarenhas J., Vashisht A.A., Sheftel A.D., Niggemeyer B., RA Roesser R., Pierik A.J., Wohlschlegel J.A., Lill R.; RT "Human CIA2A-FAM96A and CIA2B-FAM96B Integrate Iron Homeostasis and RT Maturation of Different Subsets of Cytosolic-Nuclear Iron-Sulfur RT Proteins."; RL Cell Metab. 27:263-263(2018). RN [8] RP FUNCTION, AND INTERACTION WITH APAF1. RX PubMed=25716227; DOI=10.1002/ijc.29498; RA Schwamb B., Pick R., Fernandez S.B., Voelp K., Heering J., Doetsch V., RA Boesser S., Jung J., Beinoraviciute-Kellner R., Wesely J., Zoernig I., RA Hammerschmidt M., Nowak M., Penzel R., Zatloukal K., Joos S., Rieker R.J., RA Agaimy A., Soeder S., Reid-Lombardo K.M., Kendrick M.L., Bardsley M.R., RA Hayashi Y., Asuzu D.T., Syed S.A., Ordog T., Zoernig M.; RT "FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal RT stromal tumors."; RL Int. J. Cancer 137:1318-1329(2015). RN [9] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 31-157, SUBUNIT, SUBCELLULAR RP LOCATION, ZINC-BINDING SITES, TISSUE SPECIFICITY, AND INTERACTION WITH RP CIAO1. RX PubMed=22683786; DOI=10.1107/s0907444912006592; RA Chen K.E., Richards A.A., Ariffin J.K., Ross I.L., Sweet M.J., Kellie S., RA Kobe B., Martin J.L.; RT "The mammalian DUF59 protein Fam96a forms two distinct types of domain- RT swapped dimer."; RL Acta Crystallogr. D 68:637-648(2012). 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 CC (PubMed:23891004). As a CIA complex component and in collaboration with CC CIAO1 specifically matures ACO1 and stabilizes IREB2, connecting CC cytosolic iron-sulfur protein maturation with cellular iron regulation CC (PubMed:23891004). May play a role in chromosome segregation through CC establishment of sister chromatid cohesion. May induce apoptosis in CC collaboration with APAF1 (PubMed:25716227). {ECO:0000250, CC ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:25716227}. CC -!- SUBUNIT: Monomer and homodimer (PubMed:22683786). Component of the CIA CC complex (PubMed:23891004). Interacts with CIAO1 (PubMed:23891004, CC PubMed:22683786). Interacts with IREB2 (PubMed:23891004). Interacts CC with APAF1 (PubMed:25716227). {ECO:0000269|PubMed:22683786, CC ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:25716227}. CC -!- INTERACTION: CC Q9H5X1; P02652: APOA2; NbExp=3; IntAct=EBI-752069, EBI-1171525; CC Q9H5X1; O76071: CIAO1; NbExp=17; IntAct=EBI-752069, EBI-725145; CC Q9H5X1; Q9NX76: CMTM6; NbExp=3; IntAct=EBI-752069, EBI-1054315; CC Q9H5X1; Q96BA8: CREB3L1; NbExp=5; IntAct=EBI-752069, EBI-6942903; CC Q9H5X1; Q9BUN8: DERL1; NbExp=3; IntAct=EBI-752069, EBI-398977; CC Q9H5X1; Q6ZPD8: DGAT2L6; NbExp=3; IntAct=EBI-752069, EBI-12831978; CC Q9H5X1; O00559: EBAG9; NbExp=3; IntAct=EBI-752069, EBI-8787095; CC Q9H5X1; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-752069, EBI-781551; CC Q9H5X1; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-752069, EBI-3918971; CC Q9H5X1; P48165: GJA8; NbExp=3; IntAct=EBI-752069, EBI-17458373; CC Q9H5X1; O15499: GSC2; NbExp=3; IntAct=EBI-752069, EBI-19954058; CC Q9H5X1; Q9NZI2-2: KCNIP1; NbExp=3; IntAct=EBI-752069, EBI-22452746; CC Q9H5X1; Q9H400: LIME1; NbExp=3; IntAct=EBI-752069, EBI-2830566; CC Q9H5X1; Q5EB52: MEST; NbExp=3; IntAct=EBI-752069, EBI-1050204; CC Q9H5X1; Q04941: PLP2; NbExp=3; IntAct=EBI-752069, EBI-608347; CC Q9H5X1; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-752069, EBI-11721828; CC Q9H5X1; Q96GM1: PLPPR2; NbExp=3; IntAct=EBI-752069, EBI-12955265; CC Q9H5X1; O60831: PRAF2; NbExp=3; IntAct=EBI-752069, EBI-2506064; CC Q9H5X1; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-752069, EBI-17589229; CC Q9H5X1; Q9NVD3-4: SETD4; NbExp=3; IntAct=EBI-752069, EBI-23709068; CC Q9H5X1; H3BQL7: SIN3A; NbExp=3; IntAct=EBI-752069, EBI-13384308; CC Q9H5X1; Q6PL24: TMED8; NbExp=6; IntAct=EBI-752069, EBI-11603430; CC Q9H5X1; Q9UBN6: TNFRSF10D; NbExp=3; IntAct=EBI-752069, EBI-1044859; CC Q9H5X1; Q15836: VAMP3; NbExp=3; IntAct=EBI-752069, EBI-722343; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22683786}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9H5X1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H5X1-2; Sequence=VSP_042683; CC -!- TISSUE SPECIFICITY: Substantially enriched in macrophages. CC {ECO:0000269|PubMed:22683786}. CC -!- SIMILARITY: Belongs to the MIP18 family. {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; AK026528; BAB15496.1; -; mRNA. DR EMBL; AK304202; BAH14131.1; -; mRNA. DR EMBL; AK312171; BAG35105.1; -; mRNA. DR EMBL; AC021541; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471082; EAW77661.1; -; Genomic_DNA. DR EMBL; CH471082; EAW77662.1; -; Genomic_DNA. DR EMBL; BC008865; AAH08865.1; -; mRNA. DR CCDS; CCDS10189.1; -. [Q9H5X1-1] DR CCDS; CCDS45278.1; -. [Q9H5X1-2] DR RefSeq; NP_001014812.1; NM_001014812.2. [Q9H5X1-2] DR RefSeq; NP_001276037.1; NM_001289108.1. [Q9H5X1-2] DR RefSeq; NP_115607.1; NM_032231.5. [Q9H5X1-1] DR PDB; 2M5H; NMR; -; A=28-160. DR PDB; 3UX2; X-ray; 1.80 A; A=31-157. DR PDB; 3UX3; X-ray; 1.80 A; A/B=31-157. DR PDBsum; 2M5H; -. DR PDBsum; 3UX2; -. DR PDBsum; 3UX3; -. DR AlphaFoldDB; Q9H5X1; -. DR BMRB; Q9H5X1; -. DR SMR; Q9H5X1; -. DR BioGRID; 123939; 195. DR ComplexPortal; CPX-2840; CIAO1-CIAO2A-CIAO3 cytosolic iron-sulfur protein assembly complex. DR IntAct; Q9H5X1; 25. DR MINT; Q9H5X1; -. DR STRING; 9606.ENSP00000300030; -. DR ChEMBL; CHEMBL4295943; -. DR iPTMnet; Q9H5X1; -. DR MetOSite; Q9H5X1; -. DR PhosphoSitePlus; Q9H5X1; -. DR BioMuta; FAM96A; -. DR DMDM; 20455359; -. DR EPD; Q9H5X1; -. DR jPOST; Q9H5X1; -. DR MassIVE; Q9H5X1; -. DR MaxQB; Q9H5X1; -. DR PaxDb; 9606-ENSP00000300030; -. DR PeptideAtlas; Q9H5X1; -. DR ProteomicsDB; 80937; -. [Q9H5X1-1] DR ProteomicsDB; 80938; -. [Q9H5X1-2] DR Pumba; Q9H5X1; -. DR Antibodypedia; 25761; 128 antibodies from 19 providers. DR DNASU; 84191; -. DR Ensembl; ENST00000300030.8; ENSP00000300030.3; ENSG00000166797.11. [Q9H5X1-1] DR Ensembl; ENST00000380290.7; ENSP00000369644.3; ENSG00000166797.11. [Q9H5X1-2] DR Ensembl; ENST00000557835.5; ENSP00000454079.1; ENSG00000166797.11. [Q9H5X1-2] DR GeneID; 84191; -. DR KEGG; hsa:84191; -. DR MANE-Select; ENST00000300030.8; ENSP00000300030.3; NM_032231.7; NP_115607.1. DR UCSC; uc002amt.3; human. [Q9H5X1-1] DR AGR; HGNC:26235; -. DR CTD; 84191; -. DR DisGeNET; 84191; -. DR GeneCards; CIAO2A; -. DR HGNC; HGNC:26235; CIAO2A. DR HPA; ENSG00000166797; Tissue enhanced (liver). DR MIM; 618382; gene. DR neXtProt; NX_Q9H5X1; -. DR OpenTargets; ENSG00000166797; -. DR PharmGKB; PA142671829; -. DR VEuPathDB; HostDB:ENSG00000166797; -. DR eggNOG; KOG3381; Eukaryota. DR GeneTree; ENSGT00390000017697; -. DR HOGENOM; CLU_075876_4_0_1; -. DR InParanoid; Q9H5X1; -. DR OMA; HELGYRN; -. DR OrthoDB; 7394at2759; -. DR PhylomeDB; Q9H5X1; -. DR TreeFam; TF323934; -. DR PathwayCommons; Q9H5X1; -. DR SignaLink; Q9H5X1; -. DR BioGRID-ORCS; 84191; 113 hits in 1152 CRISPR screens. DR ChiTaRS; FAM96A; human. DR GenomeRNAi; 84191; -. DR Pharos; Q9H5X1; Tbio. DR PRO; PR:Q9H5X1; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q9H5X1; Protein. DR Bgee; ENSG00000166797; Expressed in ileal mucosa and 187 other cell types or tissues. DR ExpressionAtlas; Q9H5X1; baseline and differential. DR GO; GO:0097361; C:CIA complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW. DR GO; GO:0016226; P:iron-sulfur cluster assembly; IMP:UniProtKB. DR GO; GO:0106035; P:protein maturation by [4Fe-4S] cluster transfer; IEA:InterPro. DR GO; GO:0097428; P:protein maturation by iron-sulfur cluster transfer; IMP:UniProtKB. DR Gene3D; 6.10.250.1280; -; 1. DR Gene3D; 3.30.300.130; Fe-S cluster assembly (FSCA); 1. DR InterPro; IPR034904; FSCA_dom_sf. DR InterPro; IPR039796; MIP18. DR InterPro; IPR002744; MIP18-like. DR PANTHER; PTHR12377:SF2; CYTOSOLIC IRON-SULFUR ASSEMBLY COMPONENT 2A; 1. DR PANTHER; PTHR12377; UNCHARACTERIZED; 1. DR Pfam; PF01883; FeS_assembly_P; 1. DR SUPFAM; SSF117916; Fe-S cluster assembly (FSCA) domain-like; 1. DR Genevisible; Q9H5X1; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromosome partition; Cytoplasm; KW Metal-binding; Reference proteome; Zinc. FT CHAIN 1..160 FT /note="Cytosolic iron-sulfur assembly component 2A" FT /id="PRO_0000212689" FT BINDING 89 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="ligand shared between dimeric partners" FT BINDING 89 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="ligand shared between dimeric partners" FT BINDING 123 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="ligand shared between dimeric partners" FT BINDING 123 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="ligand shared between dimeric partners" FT BINDING 150 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="ligand shared between dimeric partners" FT BINDING 150 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="ligand shared between dimeric partners" FT BINDING 153 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="ligand shared between dimeric partners" FT BINDING 153 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="ligand shared between dimeric partners" FT VAR_SEQ 97..160 FT /note="GLCLRVKLQRCLPFKHKLEIYISEGTHSTEEDINKQINDKERVAAAMENPNL FT REIVEQCVLEPD -> VGNLHF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042683" FT HELIX 31..44 FT /evidence="ECO:0007829|PDB:3UX2" FT STRAND 50..55 FT /evidence="ECO:0007829|PDB:3UX2" FT TURN 56..60 FT /evidence="ECO:0007829|PDB:3UX2" FT HELIX 64..66 FT /evidence="ECO:0007829|PDB:3UX2" FT STRAND 67..73 FT /evidence="ECO:0007829|PDB:3UX2" FT STRAND 76..81 FT /evidence="ECO:0007829|PDB:3UX2" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:2M5H" FT HELIX 92..107 FT /evidence="ECO:0007829|PDB:3UX2" FT STRAND 112..120 FT /evidence="ECO:0007829|PDB:3UX3" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:3UX3" FT HELIX 129..134 FT /evidence="ECO:0007829|PDB:3UX2" FT HELIX 136..144 FT /evidence="ECO:0007829|PDB:3UX2" FT HELIX 146..156 FT /evidence="ECO:0007829|PDB:3UX2" SQ SEQUENCE 160 AA; 18355 MW; 8580E4E397067319 CRC64; MQRVSGLLSW TLSRVLWLSG LSEPGAARQP RIMEEKALEV YDLIRTIRDP EKPNTLEELE VVSESCVEVQ EINEEEYLVI IRFTPTVPHC SLATLIGLCL RVKLQRCLPF KHKLEIYISE GTHSTEEDIN KQINDKERVA AAMENPNLRE IVEQCVLEPD //