ID ZNG1C_HUMAN Reviewed; 395 AA. AC Q5JTY5; B4DNG9; Q6VB91; DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 15-FEB-2005, sequence version 1. DT 27-MAR-2024, entry version 129. DE RecName: Full=Zinc-regulated GTPase metalloprotein activator 1C {ECO:0000303|PubMed:35584702}; DE EC=3.6.5.- {ECO:0000250|UniProtKB:Q8VEH6}; DE AltName: Full=Cobalamin synthase W domain-containing protein 3 {ECO:0000305}; DE Short=COBW domain-containing protein 3 {ECO:0000305}; GN Name=ZNG1C {ECO:0000303|PubMed:35584702, ECO:0000312|HGNC:HGNC:18519}; GN Synonyms=CBWD3 {ECO:0000312|HGNC:HGNC:18519}; 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). RX PubMed=15233989; DOI=10.1016/j.ygeno.2004.03.001; RA Wong A., Vallender E.J., Heretis K., Ilkin Y., Lahn B.T., Lese Martin C., RA Ledbetter D.H.; RT "Diverse fates of paralogs following segmental duplication of telomeric RT genes."; RL Genomics 84:239-247(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Embryo; 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=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 [4] RP IDENTIFICATION. RX PubMed=12421752; DOI=10.1101/gr.338402; RA Fan Y., Newman T., Linardopoulou E., Trask B.J.; RT "Gene content and function of the ancestral chromosome fusion site in human RT chromosome 2q13-2q14.1 and paralogous regions."; RL Genome Res. 12:1663-1672(2002). RN [5] RP NOMENCLATURE. RX PubMed=35584702; DOI=10.1016/j.cell.2022.04.011; RA Weiss A., Murdoch C.C., Edmonds K.A., Jordan M.R., Monteith A.J., RA Perera Y.R., Rodriguez Nassif A.M., Petoletti A.M., Beavers W.N., RA Munneke M.J., Drury S.L., Krystofiak E.S., Thalluri K., Wu H., RA Kruse A.R.S., DiMarchi R.D., Caprioli R.M., Spraggins J.M., Chazin W.J., RA Giedroc D.P., Skaar E.P.; RT "Zn-regulated GTPase metalloprotein activator 1 modulates vertebrate zinc RT homeostasis."; RL Cell 185:2148-2163(2022). CC -!- FUNCTION: Zinc chaperone that directly transfers zinc cofactor to CC target metalloproteins, thereby activating them. Catalyzes zinc CC insertion into the active site of methionine aminopeptidase METAP1, CC which function to cleave the initiator methionine from polypeptides CC during or after protein translation. Mechanistically, the N-terminal CC psi-PxLVp motif binds to the C6H2-type zinc finger of inactive form of CC METAP1. After formation of the docked complex, zinc is transferred from CC the CXCC motif in the GTPase domain of ZNG1C to the zinc binding site CC in the peptidase domain of METAP1 in a process requiring GTP CC hydrolysis. GTP/GDP exchange is required for release of active METAP1. CC {ECO:0000250|UniProtKB:Q8VEH6}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; CC Evidence={ECO:0000250|UniProtKB:Q8VEH6}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000250|UniProtKB:Q8VEH6}; CC -!- INTERACTION: CC Q5JTY5; Q92870-2: APBB2; NbExp=3; IntAct=EBI-723434, EBI-21535880; CC Q5JTY5; P55212: CASP6; NbExp=3; IntAct=EBI-723434, EBI-718729; CC Q5JTY5; P50570-2: DNM2; NbExp=3; IntAct=EBI-723434, EBI-10968534; CC Q5JTY5; O00291: HIP1; NbExp=3; IntAct=EBI-723434, EBI-473886; CC Q5JTY5; P42858: HTT; NbExp=6; IntAct=EBI-723434, EBI-466029; CC Q5JTY5; P13473-2: LAMP2; NbExp=3; IntAct=EBI-723434, EBI-21591415; CC Q5JTY5; Q7Z412: PEX26; NbExp=3; IntAct=EBI-723434, EBI-752057; CC Q5JTY5; P62826: RAN; NbExp=3; IntAct=EBI-723434, EBI-286642; CC Q5JTY5; O14656-2: TOR1A; NbExp=3; IntAct=EBI-723434, EBI-25847109; CC Q5JTY5; Q96E35: ZMYND19; NbExp=3; IntAct=EBI-723434, EBI-746595; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8VEH6}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5JTY5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5JTY5-2; Sequence=VSP_055975; CC -!- SIMILARITY: Belongs to the SIMIBI class G3E GTPase family. ZNG1 CC subfamily. {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; AY344633; AAQ76870.1; -; mRNA. DR EMBL; AK297912; BAG60231.1; -; mRNA. DR EMBL; AL353608; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX284632; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS35038.2; -. [Q5JTY5-1] DR RefSeq; NP_001278750.1; NM_001291821.1. [Q5JTY5-2] DR RefSeq; NP_958861.2; NM_201453.3. [Q5JTY5-1] DR RefSeq; XP_005272807.1; XM_005272750.1. DR AlphaFoldDB; Q5JTY5; -. DR SMR; Q5JTY5; -. DR BioGRID; 128658; 12. DR BioGRID; 138650; 168. DR IntAct; Q5JTY5; 34. DR STRING; 9606.ENSP00000353295; -. DR iPTMnet; Q5JTY5; -. DR PhosphoSitePlus; Q5JTY5; -. DR BioMuta; CBWD3; -. DR DMDM; 74742238; -. DR EPD; Q5JTY5; -. DR jPOST; Q5JTY5; -. DR MassIVE; Q5JTY5; -. DR MaxQB; Q5JTY5; -. DR PaxDb; 9606-ENSP00000353295; -. DR PeptideAtlas; Q5JTY5; -. DR Pumba; Q5JTY5; -. DR Antibodypedia; 73768; 10 antibodies from 5 providers. DR DNASU; 445571; -. DR Ensembl; ENST00000360171.11; ENSP00000353295.6; ENSG00000196873.16. [Q5JTY5-1] DR GeneID; 445571; -. DR KEGG; hsa:445571; -. DR MANE-Select; ENST00000360171.11; ENSP00000353295.6; NM_201453.4; NP_958861.2. DR UCSC; uc004agi.6; human. [Q5JTY5-1] DR AGR; HGNC:18519; -. DR AGR; HGNC:24584; -. DR CTD; 445571; -. DR GeneCards; ZNG1C; -. DR HGNC; HGNC:18519; ZNG1C. DR HPA; ENSG00000196873; Low tissue specificity. DR MIM; 611080; gene. DR neXtProt; NX_Q5JTY5; -. DR OpenTargets; ENSG00000147996; -. DR OpenTargets; ENSG00000196873; -. DR PharmGKB; PA134863724; -. DR VEuPathDB; HostDB:ENSG00000196873; -. DR eggNOG; KOG2743; Eukaryota. DR GeneTree; ENSGT00640000091523; -. DR InParanoid; Q5JTY5; -. DR OMA; HSQGFET; -. DR OrthoDB; 1010489at2759; -. DR PhylomeDB; Q5JTY5; -. DR TreeFam; TF332679; -. DR PathwayCommons; Q5JTY5; -. DR SignaLink; Q5JTY5; -. DR BioGRID-ORCS; 220869; 265 hits in 671 CRISPR screens. DR BioGRID-ORCS; 445571; 656 hits in 985 CRISPR screens. DR ChiTaRS; CBWD3; human. DR Pharos; Q5JTY5; Tdark. DR PRO; PR:Q5JTY5; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q5JTY5; Protein. DR Bgee; ENSG00000196873; Expressed in calcaneal tendon and 98 other cell types or tissues. DR ExpressionAtlas; Q5JTY5; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR CDD; cd03112; CobW-like; 1. DR Gene3D; 3.30.1220.10; CobW-like, C-terminal domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR036627; CobW-likC_sf. DR InterPro; IPR011629; CobW-like_C. DR InterPro; IPR003495; CobW/HypB/UreG_dom. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR13748:SF31; COBW DOMAIN-CONTAINING PROTEIN 1-RELATED; 1. DR PANTHER; PTHR13748; COBW-RELATED; 1. DR Pfam; PF02492; cobW; 1. DR Pfam; PF07683; CobW_C; 1. DR SMART; SM00833; CobW_C; 1. DR SUPFAM; SSF90002; Hypothetical protein YjiA, C-terminal domain; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR Genevisible; Q5JTY5; HS. PE 1: Evidence at protein level; KW Alternative splicing; Chaperone; GTP-binding; Hydrolase; Metal-binding; KW Nucleotide-binding; Nucleus; Reference proteome; Zinc. FT CHAIN 1..395 FT /note="Zinc-regulated GTPase metalloprotein activator 1C" FT /id="PRO_0000317238" FT DOMAIN 274..377 FT /note="CobW C-terminal" FT REGION 1..22 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 17..24 FT /note="psi-PxLVp motif" FT /evidence="ECO:0000250|UniProtKB:Q8VEH6" FT MOTIF 107..110 FT /note="CXCC motif" FT /evidence="ECO:0000255" FT BINDING 49..56 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255" FT BINDING 107 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q8VEH6" FT BINDING 109 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q8VEH6" FT BINDING 110..114 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255" FT BINDING 110 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q8VEH6" FT BINDING 203..206 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255" FT VAR_SEQ 145..164 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055975" FT CONFLICT 132 FT /note="D -> Y (in Ref. 1; AAQ76870)" FT /evidence="ECO:0000305" SQ SEQUENCE 395 AA; 44038 MW; 52EE727920F143DE CRC64; MLPAVGSVDE EEDPAEEDCP ELVPIETTQS EEEEKSGLGA KIPVTIITGY LGAGKTTLLN YILTEQHSKR VAVILNESGE GSALEKSLAV SQGGELYEEW LELRNGCLCC SVKDNGLRAI ENLMQKKGKF DDILLETTGL ADPGAVASMF WVDAELGSDI YLDGIITIVD SKYGLKHLTE EKPDGLINEA TRQVALADII LINKTDLVPE EDVKKLRTTI RSINGLGQIL ETQRSRVDLS NVLDLHAFDS LSGISLQKKL QHVPGTQPHL DQSIVTITFE VPGNAKEEHL NMFIQNLLWE KNVRNKDNHC MEVIRLKGLV SIKDKSQQVI VQGVHELYDL EETPVSWKDD TERTNRLVLI GRNLDKDILK QLFIATVTET EKQWTTHFKE DQVCT //