ID GET3_HUMAN Reviewed; 348 AA. AC O43681; A6NHP8; A8K740; Q53FC6; Q92849; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 10-JUN-2026, entry version 216. DE RecName: Full=ATPase GET3 {ECO:0000255|HAMAP-Rule:MF_03112}; DE EC=3.6.4.- {ECO:0000269|PubMed:9712828}; DE AltName: Full=Arsenical pump-driving ATPase {ECO:0000255|HAMAP-Rule:MF_03112}; DE AltName: Full=Arsenite-stimulated ATPase {ECO:0000255|HAMAP-Rule:MF_03112, ECO:0000303|PubMed:9712828}; DE AltName: Full=Guided entry of tail-anchored proteins factor 3, ATPase {ECO:0000255|HAMAP-Rule:MF_03112}; DE AltName: Full=Transmembrane domain recognition complex 40 kDa ATPase subunit {ECO:0000303|PubMed:17382883}; DE AltName: Full=hARSA-I; DE AltName: Full=hASNA-I {ECO:0000303|PubMed:9712828}; GN Name=GET3 {ECO:0000255|HAMAP-Rule:MF_03112, GN ECO:0000312|HGNC:HGNC:752}; GN Synonyms=ARSA {ECO:0000312|HGNC:HGNC:752}, ASNA1 GN {ECO:0000255|HAMAP-Rule:MF_03112}, TRC40 {ECO:0000303|PubMed:17382883, GN ECO:0000312|HGNC:HGNC:752}; 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]. RA Hu G.; RT "Human homolog of bacterial and mouse arsenite translocating ATPase gene, RT ArsA."; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Salivary gland; 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]. RC TISSUE=Cerebellum; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-332. RG NIEHS SNPs program; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 18-348. RX PubMed=8884272; DOI=10.1006/geno.1996.0494; RA Kurdi-Haidar B., Aebi S., Heath D., Enns R.E., Naredi P., Hom D.K., RA Howell S.B.; RT "Isolation of the ATP-binding human homolog of the arsA component of the RT bacterial arsenite transporter."; RL Genomics 36:486-491(1996). RN [9] RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=9712828; DOI=10.1074/jbc.273.35.22173; RA Kurdi-Haidar B., Heath D., Aebi S., Howell S.B.; RT "Biochemical characterization of the human arsenite-stimulated ATPase RT (hASNA-I)."; RL J. Biol. Chem. 273:22173-22176(1998). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=9736449; RX DOI=10.1002/(sici)1097-4644(19981001)71:1<1::aid-jcb1>3.3.co;2-r; RA Kurdi-Haidar B., Hom D.K., Flittner D.E., Heath D., Fink L., Naredi P., RA Howell S.B.; RT "Dual cytoplasmic and nuclear distribution of the novel arsenite-stimulated RT human ATPase (hASNA-I)."; RL J. Cell. Biochem. 71:1-10(1998). RN [11] RP TISSUE SPECIFICITY. RX PubMed=9774623; DOI=10.1177/002215549804601104; RA Kurdi-Haidar B., Heath D., Naredi P., Varki N., Howell S.B.; RT "Immunohistochemical analysis of the distribution of the human ATPase RT (hASNA-I) in normal tissues and its overexpression in breast adenomas and RT carcinomas."; RL J. Histochem. Cytochem. 46:1243-1248(1998). RN [12] RP FUNCTION, IDENTIFICATION IN THE TRC COMPLEX, MUTAGENESIS OF GLY-46, RP SUBCELLULAR LOCATION, AND INTERACTION WITH SEC61B. RX PubMed=17382883; DOI=10.1016/j.cell.2007.01.036; RA Stefanovic S., Hegde R.S.; RT "Identification of a targeting factor for posttranslational membrane RT protein insertion into the ER."; RL Cell 128:1147-1159(2007). RN [13] RP FUNCTION, AND INTERACTION WITH SERP1 AND SEC61B. RX PubMed=18477612; DOI=10.1242/jcs.020321; RA Favaloro V., Spasic M., Schwappach B., Dobberstein B.; RT "Distinct targeting pathways for the membrane insertion of tail-anchored RT (TA) proteins."; RL J. Cell Sci. 121:1832-1840(2008). RN [14] 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]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [15] 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 [16] RP INTERACTION WITH GET1, AND SUBCELLULAR LOCATION. RX PubMed=21444755; DOI=10.1242/jcs.084277; RA Vilardi F., Lorenz H., Dobberstein B.; RT "WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored RT proteins into the ER membrane."; RL J. Cell Sci. 124:1301-1307(2011). RN [17] RP FUNCTION, IDENTIFICATION IN GET COMPLEX, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=23041287; DOI=10.1016/j.molcel.2012.08.028; RA Yamamoto Y., Sakisaka T.; RT "Molecular machinery for insertion of tail-anchored membrane proteins into RT the endoplasmic reticulum membrane in mammalian cells."; RL Mol. Cell 48:387-397(2012). RN [18] 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 [19] RP INTERACTION WITH CAMLG AND GET1. RX PubMed=24392163; DOI=10.1371/journal.pone.0085033; RA Vilardi F., Stephan M., Clancy A., Janshoff A., Schwappach B.; RT "WRB and CAML are necessary and sufficient to mediate tail-anchored protein RT targeting to the ER membrane."; RL PLoS ONE 9:e85033-e85033(2014). RN [20] RP FUNCTION, AND MUTAGENESIS OF LYS-86. RX PubMed=25535373; DOI=10.1073/pnas.1402745112; RA Mock J.Y., Chartron J.W., Zaslaver M., Xu Y., Ye Y., Clemons W.M. Jr.; RT "Bag6 complex contains a minimal tail-anchor-targeting module and a mock RT BAG domain."; RL Proc. Natl. Acad. Sci. U.S.A. 112:106-111(2015). RN [21] RP INVOLVEMENT IN CMD2H, VARIANTS CMD2H ALA-163; TRP-289 AND 305-GLN--GLN-348 RP DEL, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=31461301; DOI=10.1161/circgen.119.002507; RA Verhagen J.M.A., van den Born M., van der Linde H.C., Nikkels P.G.J., RA Verdijk R.M., Kivlen M.H., van Unen L.M.A., Baas A.F., Ter Heide H., RA van Osch-Gevers L., Hoogeveen-Westerveld M., Herkert J.C., RA Bertoli-Avella A.M., van Slegtenhorst M.A., Wessels M.W., Verheijen F.W., RA Hassel D., Hofstra R.M.W., Hegde R.S., van Hasselt P.M., van Ham T.J., RA van de Laar I.M.B.H.; RT "Biallelic variants in ASNA1, encoding a cytosolic targeting factor of RT tail-anchored proteins, cause rapidly progressive pediatric RT cardiomyopathy."; RL Circ. Genom. Precis. Med. 12:397-406(2019). RN [22] RP INTERACTION WITH GET4. RX PubMed=34887561; DOI=10.1038/s41594-021-00690-7; RA Keszei A.F.A., Yip M.C.J., Hsieh T.C., Shao S.; RT "Structural insights into metazoan pretargeting GET complexes."; RL Nat. Struct. Mol. Biol. 28:1029-1037(2021). RN [23] RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) OF THE GET COMPLEX. RX PubMed=32910895; DOI=10.1016/j.molcel.2020.08.012; RA McDowell M.A., Heimes M., Fiorentino F., Mehmood S., Farkas A., RA Coy-Vergara J., Wu D., Bolla J.R., Schmid V., Heinze R., Wild K., RA Flemming D., Pfeffer S., Schwappach B., Robinson C.V., Sinning I.; RT "Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET RT Insertase Complex."; RL Mol. Cell 80:72-86(2020). RN [24] {ECO:0007744|PDB:8CQZ, ECO:0007744|PDB:8CR1, ECO:0007744|PDB:8CR2} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH GET1 AND GET2. RX PubMed=37963916; DOI=10.1038/s41467-023-42867-2; RA McDowell M.A., Heimes M., Enkavi G., Farkas A., Saar D., Wild K., RA Schwappach B., Vattulainen I., Sinning I.; RT "The GET insertase exhibits conformational plasticity and induces membrane RT thinning."; RL Nat. Commun. 14:7355-7355(2023). CC -!- FUNCTION: ATPase required for the post-translational delivery of tail- CC anchored (TA) proteins to the endoplasmic reticulum (PubMed:17382883). CC Recognizes and selectively binds the transmembrane domain of TA CC proteins in the cytosol. This complex then targets to the endoplasmic CC reticulum by membrane-bound receptors GET1/WRB and CAMLG/GET2, where CC the tail-anchored protein is released for insertion. This process is CC regulated by ATP binding and hydrolysis. ATP binding drives the CC homodimer towards the closed dimer state, facilitating recognition of CC newly synthesized TA membrane proteins. ATP hydrolysis is required for CC insertion. Subsequently, the homodimer reverts towards the open dimer CC state, lowering its affinity for the GET1-CAMLG receptor, and returning CC it to the cytosol to initiate a new round of targeting. May be involved CC in insulin signaling. {ECO:0000255|HAMAP-Rule:MF_03112, CC ECO:0000269|PubMed:17382883, ECO:0000269|PubMed:18477612, CC ECO:0000269|PubMed:23041287, ECO:0000269|PubMed:25535373, CC ECO:0000269|PubMed:31461301}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + phosphate + H(+); Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:9712828}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.22 mM for ATP {ECO:0000269|PubMed:9712828}; CC Vmax=16.6 nmol/min/mg enzyme for ATP {ECO:0000269|PubMed:9712828}; CC -!- SUBUNIT: Homodimer (PubMed:9712828). Component of the Golgi to ER CC traffic (GET) complex, which is composed of GET1/WRB, CAMLG/GET2 and CC GET3/TRC40 (PubMed:21444755, PubMed:23041287, PubMed:24392163, CC PubMed:32910895, PubMed:37963916). Within the complex, CAMLG and GET1 CC form a heterotetramer which is stabilized by phosphatidylinositol CC binding and which binds to the GET3 homodimer (PubMed:32910895). CC Interacts with CAMLG (via N-terminus) (By similarity). GET3 shows a CC higher affinity for CAMLG than for GET1 (PubMed:24392163). Interacts CC with SERP1 and SEC61B (PubMed:17382883, PubMed:18477612). Interacts CC with GET4 (PubMed:34887561). {ECO:0000250|UniProtKB:G3V9T7, CC ECO:0000255|HAMAP-Rule:MF_03112, ECO:0000269|PubMed:17382883, CC ECO:0000269|PubMed:18477612, ECO:0000269|PubMed:21444755, CC ECO:0000269|PubMed:23041287, ECO:0000269|PubMed:24392163, CC ECO:0000269|PubMed:32910895, ECO:0000269|PubMed:34887561, CC ECO:0000269|PubMed:37963916, ECO:0000269|PubMed:9712828}. CC -!- INTERACTION: CC O43681; O95994: AGR2; NbExp=7; IntAct=EBI-2515857, EBI-712648; CC O43681; Q12797: ASPH; NbExp=3; IntAct=EBI-2515857, EBI-2967294; CC O43681; Q12797-6: ASPH; NbExp=3; IntAct=EBI-2515857, EBI-12092171; CC O43681; P49069: CAMLG; NbExp=8; IntAct=EBI-2515857, EBI-1748958; CC O43681; Q8TEY5: CREB3L4; NbExp=3; IntAct=EBI-2515857, EBI-3925424; CC O43681; O95196-2: CSPG5; NbExp=3; IntAct=EBI-2515857, EBI-18400097; CC O43681; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-2515857, EBI-742054; CC O43681; Q7Z589-5: EMSY; NbExp=3; IntAct=EBI-2515857, EBI-11989522; CC O43681; Q96GL9: FAM163A; NbExp=3; IntAct=EBI-2515857, EBI-11793142; CC O43681; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-2515857, EBI-18304435; CC O43681; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-2515857, EBI-3918971; CC O43681; Q7L5D6: GET4; NbExp=7; IntAct=EBI-2515857, EBI-711823; CC O43681; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-2515857, EBI-712073; CC O43681; Q96SL4: GPX7; NbExp=6; IntAct=EBI-2515857, EBI-749411; CC O43681; Q8TED1: GPX8; NbExp=3; IntAct=EBI-2515857, EBI-11721746; CC O43681; Q9Y5L2: HILPDA; NbExp=3; IntAct=EBI-2515857, EBI-8803836; CC O43681; P24592: IGFBP6; NbExp=3; IntAct=EBI-2515857, EBI-947015; CC O43681; Q8WWG9: KCNE4; NbExp=3; IntAct=EBI-2515857, EBI-11750916; CC O43681; Q9UJ90: KCNE5; NbExp=3; IntAct=EBI-2515857, EBI-11981259; CC O43681; O15165-2: LDLRAD4; NbExp=3; IntAct=EBI-2515857, EBI-13302279; CC O43681; Q15084: PDIA6; NbExp=3; IntAct=EBI-2515857, EBI-1043087; CC O43681; O75381: PEX14; NbExp=3; IntAct=EBI-2515857, EBI-594898; CC O43681; O00264: PGRMC1; NbExp=3; IntAct=EBI-2515857, EBI-1045534; CC O43681; O15173: PGRMC2; NbExp=3; IntAct=EBI-2515857, EBI-1050125; CC O43681; Q04118: PRB3; NbExp=3; IntAct=EBI-2515857, EBI-13360404; CC O43681; Q16378: PRR4; NbExp=3; IntAct=EBI-2515857, EBI-738624; CC O43681; Q15293: RCN1; NbExp=5; IntAct=EBI-2515857, EBI-948278; CC O43681; Q6ZWK4: RHEX; NbExp=3; IntAct=EBI-2515857, EBI-18304046; CC O43681; Q96E16: SMIM19; NbExp=3; IntAct=EBI-2515857, EBI-17657124; CC O43681; P10451: SPP1; NbExp=3; IntAct=EBI-2515857, EBI-723648; CC O43681; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-2515857, EBI-17280858; CC O43681; Q5VXT5-2: SYPL2; NbExp=3; IntAct=EBI-2515857, EBI-18196631; CC O43681; Q6P9G4: TMEM154; NbExp=3; IntAct=EBI-2515857, EBI-13329239; CC O43681; Q9NW97: TMEM51; NbExp=3; IntAct=EBI-2515857, EBI-726044; CC O43681; Q9H3N1: TMX1; NbExp=3; IntAct=EBI-2515857, EBI-1051115; CC O43681; Q2TAL6: VWC2; NbExp=3; IntAct=EBI-2515857, EBI-11957238; CC O43681; Q8IUB2: WFDC3; NbExp=3; IntAct=EBI-2515857, EBI-7963932; CC O43681; Q56975: yscD; Xeno; NbExp=2; IntAct=EBI-2515857, EBI-6413916; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17382883, CC ECO:0000269|PubMed:21444755, ECO:0000269|PubMed:9736449}. Endoplasmic CC reticulum {ECO:0000269|PubMed:17382883, ECO:0000269|PubMed:21444755, CC ECO:0000269|PubMed:31461301}. Nucleus, nucleolus CC {ECO:0000269|PubMed:21444755, ECO:0000269|PubMed:9736449}. CC -!- TISSUE SPECIFICITY: Expressed in the epithelial cells of the liver, CC kidney, and stomach wall, in the adrenal medulla, in the islet cells of CC the pancreas, in the red pulp of the spleen, and in cardiac and CC skeletal muscle. {ECO:0000269|PubMed:9774623}. CC -!- DISEASE: Cardiomyopathy, dilated, 2H (CMD2H) [MIM:620203]: A form of CC dilated cardiomyopathy, a disorder characterized by ventricular CC dilation and impaired systolic function, resulting in congestive heart CC failure and arrhythmia. Patients are at risk of premature death. CMD2H CC is an autosomal recessive form characterized by rapid progression and CC death in early infancy. {ECO:0000269|PubMed:31461301}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the arsA ATPase family. {ECO:0000255|HAMAP- CC Rule:MF_03112}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC50731.1; Type=Frameshift; 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; AF047469; AAC03551.1; -; mRNA. DR EMBL; AK291855; BAF84544.1; -; mRNA. DR EMBL; AK223363; BAD97083.1; -; mRNA. DR EMBL; AY304483; AAP45050.1; -; Genomic_DNA. DR EMBL; AC018761; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471106; EAW84303.1; -; Genomic_DNA. DR EMBL; BC002651; AAH02651.1; -; mRNA. DR EMBL; U60276; AAC50731.1; ALT_FRAME; mRNA. DR CCDS; CCDS32920.1; -. DR RefSeq; NP_001358417.1; NM_001371488.1. DR RefSeq; NP_001358418.1; NM_001371489.1. DR RefSeq; NP_004308.2; NM_004317.4. DR PDB; 6SO5; EM; 4.20 A; A/B=1-348. DR PDB; 8CQZ; X-ray; 2.80 A; A=1-348. DR PDB; 8CR1; EM; 3.20 A; A/B=1-348. DR PDB; 8CR2; EM; 4.20 A; A/B=1-348. DR PDBsum; 6SO5; -. DR PDBsum; 8CQZ; -. DR PDBsum; 8CR1; -. DR PDBsum; 8CR2; -. DR AlphaFoldDB; O43681; -. DR EMDB; EMD-10266; -. DR EMDB; EMD-16801; -. DR EMDB; EMD-16802; -. DR SMR; O43681; -. DR BioGRID; 106931; 134. DR ComplexPortal; CPX-6464; GET complex. DR FunCoup; O43681; 2853. DR IntAct; O43681; 73. DR MINT; O43681; -. DR STRING; 9606.ENSP00000466379; -. DR ChEMBL; CHEMBL6066311; -. DR DrugBank; DB00171; ATP. DR TCDB; 3.A.19.1.1; the guided entry of tail anchored protein (get) family. DR CarbonylDB; O43681; -. DR GlyGen; O43681; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O43681; -. DR MetOSite; O43681; -. DR PhosphoSitePlus; O43681; -. DR SwissPalm; O43681; -. DR BioMuta; ASNA1; -. DR OGP; O43681; -. DR jPOST; O43681; -. DR MassIVE; O43681; -. DR PaxDb; 9606-ENSP00000466379; -. DR PeptideAtlas; O43681; -. DR ProteomicsDB; 49111; -. DR Pumba; O43681; -. DR Antibodypedia; 26148; 362 antibodies from 36 providers. DR DNASU; 439; -. DR Ensembl; ENST00000357332.8; ENSP00000349887.3; ENSG00000198356.13. DR Ensembl; ENST00000591090.5; ENSP00000466379.1; ENSG00000198356.13. DR GeneID; 439; -. DR KEGG; hsa:439; -. DR MANE-Select; ENST00000357332.8; ENSP00000349887.3; NM_004317.4; NP_004308.2. DR UCSC; uc002muv.3; human. DR AGR; HGNC:752; -. DR ClinPGx; PA25051; -. DR CTD; 439; -. DR DisGeNET; 439; -. DR GeneCards; GET3; -. DR HGNC; HGNC:752; GET3. DR HPA; ENSG00000198356; Low tissue specificity. DR MalaCards; GET3; -. DR MIM; 601913; gene. DR MIM; 620203; phenotype. DR OpenTargets; ENSG00000198356; -. DR Orphanet; 154; Familial isolated dilated cardiomyopathy. DR VEuPathDB; HostDB:ENSG00000198356; -. DR eggNOG; KOG2825; Eukaryota. DR GeneTree; ENSGT00390000003817; -. DR InParanoid; O43681; -. DR OMA; MDAPYEF; -. DR OrthoDB; 1770at2759; -. DR PAN-GO; O43681; 3 GO annotations based on evolutionary models. DR PhylomeDB; O43681; -. DR BRENDA; 7.3.2.7; 2681. DR PathwayCommons; O43681; -. DR Reactome; R-HSA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane. DR SABIO-RK; O43681; -. DR SignaLink; O43681; -. DR Agora; ENSG00000198356; -. DR BioGRID-ORCS; 439; 563 hits in 1170 CRISPR screens. DR ChiTaRS; ASNA1; human. DR GeneWiki; ASNA1; -. DR GenomeRNAi; 439; -. DR Pharos; O43681; Tbio. DR PRO; PR:O43681; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O43681; protein. DR Bgee; ENSG00000198356; Expressed in monocyte and 205 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProt. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0043529; C:GET complex; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0140597; F:protein carrier chaperone; IDA:UniProt. DR GO; GO:0045048; P:protein insertion into ER membrane; NAS:ComplexPortal. DR GO; GO:0071816; P:tail-anchored membrane protein insertion into ER membrane; IDA:UniProtKB. DR CDD; cd02035; ArsA; 1. DR FunFam; 3.40.50.300:FF:000235; ATPase ASNA1; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR HAMAP; MF_03112; Asna1_Get3; 1. DR InterPro; IPR025723; ArsA/GET3_ATPase-like. DR InterPro; IPR016300; ATPase_ArsA/GET3. DR InterPro; IPR027542; ATPase_ArsA/GET3_euk. DR InterPro; IPR027417; P-loop_NTPase. DR NCBIfam; TIGR00345; GET3_arsA_TRC40; 1. DR PANTHER; PTHR10803; ARSENICAL PUMP-DRIVING ATPASE ARSENITE-TRANSLOCATING ATPASE; 1. DR PANTHER; PTHR10803:SF3; ATPASE GET3; 1. DR Pfam; PF02374; ArsA_ATPase; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cardiomyopathy; Cytoplasm; KW Disease variant; Endoplasmic reticulum; Hydrolase; Metal-binding; KW Nucleotide-binding; Nucleus; Proteomics identification; Reference proteome; KW Transport; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..348 FT /note="ATPase GET3" FT /id="PRO_0000152253" FT ACT_SITE 74 FT /evidence="ECO:0000255|HAMAP-Rule:MF_03112" FT BINDING 45 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5, ECO:0000255|HAMAP- FT Rule:MF_03112" FT BINDING 46 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5, ECO:0000255|HAMAP- FT Rule:MF_03112" FT BINDING 49 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5, ECO:0000255|HAMAP- FT Rule:MF_03112" FT BINDING 50 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5, ECO:0000255|HAMAP- FT Rule:MF_03112" FT BINDING 51 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5, ECO:0000255|HAMAP- FT Rule:MF_03112" FT BINDING 52 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5, ECO:0000255|HAMAP- FT Rule:MF_03112" FT BINDING 251 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5, ECO:0000255|HAMAP- FT Rule:MF_03112" FT BINDING 278 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5, ECO:0000255|HAMAP- FT Rule:MF_03112" FT BINDING 289 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03112, FT ECO:0000269|PubMed:32910895, ECO:0000269|PubMed:37963916, FT ECO:0007744|PDB:6SO5, ECO:0007744|PDB:8CR1, FT ECO:0007744|PDB:8CR2" FT BINDING 292 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03112, FT ECO:0000269|PubMed:32910895, ECO:0000269|PubMed:37963916, FT ECO:0007744|PDB:6SO5, ECO:0007744|PDB:8CR1, FT ECO:0007744|PDB:8CR2" FT BINDING 319 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5" FT BINDING 321 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:Q6IQE5" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT VARIANT 163 FT /note="V -> A (in CMD2H; contrary to the wild type, the FT mutant is unable to rescue cardiac failure in zebrafish FT lacking GET3; results in decreased function in FT tail-anchored membrane protein insertion into ER membrane; FT has no effect on thermal stability)" FT /evidence="ECO:0000269|PubMed:31461301" FT /id="VAR_088104" FT VARIANT 289 FT /note="C -> W (in CMD2H; when associated in cis with FT 305-Q--Q-348 del)" FT /evidence="ECO:0000269|PubMed:31461301" FT /id="VAR_088105" FT VARIANT 305..348 FT /note="Missing (in CMD2H; when associated in cis with FT variant W-289)" FT /evidence="ECO:0000269|PubMed:31461301" FT /id="VAR_088106" FT VARIANT 332 FT /note="N -> S (in dbSNP:rs8177499)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018844" FT MUTAGEN 46 FT /note="G->R: Abolishes ATPase activity, dominantly inhibits FT the TA protein insertion pathway." FT /evidence="ECO:0000269|PubMed:17382883" FT MUTAGEN 86 FT /note="K->D: Reduces TA protein insertion pathway." FT /evidence="ECO:0000269|PubMed:25535373" FT CONFLICT 113..114 FT /note="EL -> DV (in Ref. 8; AAC50731)" FT /evidence="ECO:0000305" FT CONFLICT 205 FT /note="C -> F (in Ref. 1; AAC03551)" FT /evidence="ECO:0000305" FT CONFLICT 303 FT /note="L -> P (in Ref. 3; BAD97083)" FT /evidence="ECO:0000305" FT TURN 13..15 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 19..25 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 26..28 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 29..33 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 39..45 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 48..64 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 68..72 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 78..82 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 98..104 FT /evidence="ECO:0007829|PDB:8CQZ" FT TURN 107..110 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 116..121 FT /evidence="ECO:0007829|PDB:8CR1" FT HELIX 123..137 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 140..158 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 161..166 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 172..177 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 179..185 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 187..209 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 213..216 FT /evidence="ECO:0007829|PDB:8CQZ" FT TURN 220..224 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 225..236 FT /evidence="ECO:0007829|PDB:8CQZ" FT TURN 239..241 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 242..248 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 252..267 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 272..280 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 285..287 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 290..309 FT /evidence="ECO:0007829|PDB:8CQZ" FT TURN 310..312 FT /evidence="ECO:0007829|PDB:8CQZ" FT STRAND 313..319 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 320..322 FT /evidence="ECO:0007829|PDB:8CR1" FT HELIX 328..337 FT /evidence="ECO:0007829|PDB:8CQZ" FT HELIX 341..344 FT /evidence="ECO:0007829|PDB:8CQZ" SQ SEQUENCE 348 AA; 38793 MW; DA52C4ACC35C7A36 CRC64; MAAGVAGWGV EAEEFEDAPD VEPLEPTLSN IIEQRSLKWI FVGGKGGVGK TTCSCSLAVQ LSKGRESVLI ISTDPAHNIS DAFDQKFSKV PTKVKGYDNL FAMEIDPSLG VAELPDEFFE EDNMLSMGKK MMQEAMSAFP GIDEAMSYAE VMRLVKGMNF SVVVFDTAPT GHTLRLLNFP TIVERGLGRL MQIKNQISPF ISQMCNMLGL GDMNADQLAS KLEETLPVIR SVSEQFKDPE QTTFICVCIA EFLSLYETER LIQELAKCKI DTHNIIVNQL VFPDPEKPCK MCEARHKIQA KYLDQMEDLY EDFHIVKLPL LPHEVRGADK VNTFSALLLE PYKPPSAQ //