ID ASSY_HUMAN Reviewed; 412 AA. AC P00966; Q6LDL2; Q86UZ0; Q96GT4; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 03-APR-2002, sequence version 2. DT 29-MAY-2024, entry version 242. DE RecName: Full=Argininosuccinate synthase {ECO:0000305}; DE EC=6.3.4.5 {ECO:0000269|PubMed:18473344, ECO:0000269|PubMed:27287393, ECO:0000269|PubMed:8792870}; DE AltName: Full=Citrulline--aspartate ligase; GN Name=ASS1 {ECO:0000312|HGNC:HGNC:758}; GN Synonyms=ASS {ECO:0000312|HGNC:HGNC:758}; 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]. RX PubMed=6194510; DOI=10.1093/nar/11.18.6505; RA Bock H.-G.O., Su T.-S., O'Brien W.E., Beaudet A.L.; RT "Sequence for human argininosuccinate synthetase cDNA."; RL Nucleic Acids Res. 11:6505-6512(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6321498; DOI=10.1016/s0021-9258(17)43275-3; RA Freytag S.O., Bock H.-G.O., Beaudet A.L., O'Brien W.E.; RT "Molecular structures of human argininosuccinate synthetase pseudogenes. RT Evolutionary and mechanistic implications."; RL J. Biol. Chem. 259:3160-3166(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CTLN1 LEU-108; ARG-179; RP VAL-362 AND ARG-390. RX PubMed=11941481; DOI=10.1007/s00439-002-0686-6; RA Haeberle J., Pauli S., Linnebank M., Kleijer W.J., Bakker H.D., RA Wanders R.J.A., Harms E., Koch H.G.; RT "Structure of the human argininosuccinate synthetase gene and an improved RT system for molecular diagnostics in patients with classical and mild RT citrullinemia."; RL Hum. Genet. 110:327-333(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Small intestine; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney, and Muscle; 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 [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24. RX PubMed=3027451; DOI=10.1007/bf01819307; RA Jinno Y., Nomiyama H., Matuo S., Shimada K., Matsuda I., Saheki T.; RT "Structure of the 5' end region of the human argininosuccinate synthetase RT gene."; RL J. Inherit. Metab. Dis. 8:157-159(1985). RN [7] RP PROTEIN SEQUENCE OF 148-161. RX PubMed=2788888; RA Isashiki Y., Noda T., Kobayashi K., Sase M., Saheki T., Titani K.; RT "Identification of essential arginine residue(s) for Mg-ATP binding of RT human argininosuccinate synthetase."; RL Protein Seq. Data Anal. 2:283-287(1989). RN [8] RP PROTEIN SEQUENCE OF 200-209. RC TISSUE=Colon carcinoma; RX PubMed=9150948; DOI=10.1002/elps.1150180344; RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.; RT "A two-dimensional gel database of human colon carcinoma proteins."; RL Electrophoresis 18:605-613(1997). RN [9] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=1708740; DOI=10.1016/0378-1119(91)90125-u; RA Surh L.C., Beaudet A.L., O'Brien W.E.; RT "Molecular characterization of the murine argininosuccinate synthetase RT locus."; RL Gene 99:181-189(1991). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180 AND THR-219, AND RP IDENTIFICATION BY MASS SPECTROMETRY [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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-219, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-113 AND THR-219, AND 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 [14] RP ACETYLATION AT LYS-165 AND LYS-176, MUTAGENESIS OF LYS-165 AND LYS-176, RP INTERACTION WITH CLOCK, AND SUBCELLULAR LOCATION. RX PubMed=28985504; DOI=10.1016/j.molcel.2017.09.008; RA Lin R., Mo Y., Zha H., Qu Z., Xie P., Zhu Z.J., Xu Y., Xiong Y., Guan K.L.; RT "CLOCK acetylates ASS1 to drive circadian rhythm of ureagenesis."; RL Mol. Cell 68:198-209(2017). RN [15] RP CHARACTERIZATION OF VARIANTS CLNT1 VAL-192; ARG-280; CYS-272 AND TRP-304, RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=8792870; DOI=10.1159/000474998; RA Shaheen N., Kobayashi K., Terazono H., Fukushige T., Horiuchi M., RA Saheki T.; RT "Characterization of human wild-type and mutant argininosuccinate RT synthetase proteins expressed in bacterial cells."; RL Enzyme Protein 48:251-264(1994). RN [16] RP INTERACTION WITH NMRAL1. RX PubMed=17496144; DOI=10.1073/pnas.0700480104; RA Zheng X., Dai X., Zhao Y., Chen Q., Lu F., Yao D., Yu Q., Liu X., Zhang C., RA Gu X., Luo M.; RT "Restructuring of the dinucleotide-binding fold in an NADP(H) sensor RT protein."; RL Proc. Natl. Acad. Sci. U.S.A. 104:8809-8814(2007). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH CITRULLINE AND RP ASPARTATE, AND SUBUNIT. RX PubMed=18323623; DOI=10.1107/s0907444907067455; RA Karlberg T., Collins R., van den Berg S., Flores A., Hammarstrom M., RA Hogbom M., Holmberg Schiavone L., Uppenberg J.; RT "Structure of human argininosuccinate synthetase."; RL Acta Crystallogr. D 64:279-286(2008). RN [18] RP INVOLVEMENT IN CTLN1, AND VARIANTS CTLN1 SER-14; HIS-157; ASN-180; TRP-304; RP SER-324; TRP-363 AND ARG-390. RX PubMed=2358466; DOI=10.1016/s0021-9258(19)38601-6; RA Kobayashi K., Jackson M.J., Tick D.B., O'Brien W.E., Beaudet A.L.; RT "Heterogeneity of mutations in argininosuccinate synthetase causing human RT citrullinemia."; RL J. Biol. Chem. 265:11361-11367(1990). RN [19] RP VARIANTS CTLN1 LEU-18 AND CYS-86. RX PubMed=1943692; RA Kobayashi K., Rosenbloom C., Beaudet A.L., O'Brien W.E.; RT "Additional mutations in argininosuccinate synthetase causing RT citrullinemia."; RL Mol. Biol. Med. 8:95-100(1991). RN [20] RP VARIANTS CTLN1 THR-118; VAL-192; CYS-272; ARG-280; TRP-304 AND LEU-363. RX PubMed=7977368; RA Kobayashi K., Shaheen N., Terazono H., Saheki T.; RT "Mutations in argininosuccinate synthetase mRNA of Japanese patients, RT causing classical citrullinemia."; RL Am. J. Hum. Genet. 55:1103-1112(1994). RN [21] RP VARIANTS CTLN1 ALA-69; LEU-108; ASP-117; ILE-119; GLN-270 AND ARG-390. RX PubMed=11708871; DOI=10.1006/mgme.2001.3221; RA Vilaseca M.A., Kobayashi K., Briones P., Lambruschini N., Campistol J., RA Tabata A., Alomar A., Rodes M., Lluch M., Saheki T.; RT "Phenotype and genotype heterogeneity in Mediterranean citrullinemia."; RL Mol. Genet. Metab. 74:396-398(2001). RN [22] RP VARIANTS CTLN1 ARG-19; HIS-86; SER-95; SER-96; ASP-117; SER-117; CYS-157; RP ARG-179; LYS-191; HIS-265; MET-269; CYS-272; LYS-283; TRP-304; GLN-310; RP SER-324; VAL-362; GLN-363; TRP-363; ILE-389 AND ARG-390. RX PubMed=12815590; DOI=10.1002/humu.10230; RA Gao H.-Z., Kobayashi K., Tabata A., Tsuge H., Iijima M., Yasuda T., RA Kalkanoglu H.S., Dursun A., Tokatli A., Coskun T., Trefz F.K., Skladal D., RA Mandel H., Seidel J., Kodama S., Shirane S., Ichida T., Makino S., RA Yoshino M., Kang J.-H., Mizuguchi M., Barshop B.A., Fuchinoue S., RA Seneca S., Zeesman S., Knerr I., Rodes M., Wasant P., Yoshida I., RA De Meirleir L., Abdul-Jalil M., Begum L., Horiuchi M., Katunuma N., RA Nakagawa S., Saheki T.; RT "Identification of 16 novel mutations in the argininosuccinate synthetase RT gene and genotype-phenotype correlation in 38 classical citrullinemia RT patients."; RL Hum. Mutat. 22:24-34(2003). RN [23] RP VARIANTS CTLN1 SER-14; LEU-40; GLN-127; ARG-179; ASP-190; GLU-202; MET-263; RP MET-269; SER-324; GLY-345 AND VAL-362. RX PubMed=14680976; DOI=10.1016/j.ymgme.2003.08.002; RA Haeberle J., Pauli S., Schmidt E., Schulze-Eilfing B., Berning C., RA Koch H.G.; RT "Mild citrullinemia in Caucasians is an allelic variant of RT argininosuccinate synthetase deficiency (citrullinemia type 1)."; RL Mol. Genet. Metab. 80:302-306(2003). RN [24] RP VARIANT CTLN1 ARG-310. RX PubMed=15863597; DOI=10.1097/01.aog.0000157769.90230.24; RA Enns G.M., O'Brien W.E., Kobayashi K., Shinzawa H., Pellegrino J.E.; RT "Postpartum 'psychosis' in mild argininosuccinate synthetase deficiency."; RL Obstet. Gynecol. 105:1244-1246(2005). RN [25] RP VARIANTS CTLN1 ASN-124; HIS-157; GLN-270; GLN-279; LYS-283; SER-324; RP GLY-363 AND ARG-390. RX PubMed=16475226; DOI=10.1002/pd.1390; RA Kleijer W.J., Garritsen V.H., van der Sterre M.L., Berning C., Haeberle J., RA Huijmans J.G.M.; RT "Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: RT evidence for a transmission ratio distortion in citrullinemia."; RL Prenat. Diagn. 26:242-247(2006). RN [26] RP VARIANTS CTLN1 CYS-265 AND VAL-302, CHARACTERIZATION OF VARIANTS CTLN1 RP THR-118; ARG-179; VAL-263; CYS-265; VAL-302; SER-324; VAL-362 AND ARG-390, RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=18473344; DOI=10.1002/humu.20784; RA Berning C., Bieger I., Pauli S., Vermeulen T., Vogl T., Rummel T., RA Hoehne W., Koch H.G., Rolinski B., Gempel K., Haeberle J.; RT "Investigation of citrullinemia type I variants by in vitro expression RT studies."; RL Hum. Mutat. 29:1222-1227(2008). RN [27] RP VARIANTS CTLN1 PRO-79; HIS-96; GLN-127; TRP-127; PRO-160; GLN-191; PRO-206; RP CYS-265; THR-277; ILE-284; SER-291; GLY-296; VAL-324; PHE-341; ARG-347 AND RP ASP-359. RX PubMed=19006241; DOI=10.1002/humu.20847; RA Engel K., Hoehne W., Haeberle J.; RT "Mutations and polymorphisms in the human argininosuccinate synthetase RT (ASS1) gene."; RL Hum. Mutat. 30:300-307(2009). RN [28] RP VARIANTS CTLN1 LYS-283 AND ARG-337. RX PubMed=23611581; DOI=10.1016/j.braindev.2013.03.005; RA Wu T.F., Liu Y.P., Li X.Y., Wang Q., Song J.Q., Yang Y.L.; RT "Prenatal diagnosis of citrullinemia type 1: a Chinese family with a novel RT mutation of the ASS1 gene."; RL Brain Dev. 36:264-267(2014). RN [29] RP VARIANTS CTLN1 PRO-91; CYS-157; ILE-180; LYS-283 AND ARG-390, AND VARIANT RP LEU-127. RX PubMed=24889030; DOI=10.1016/j.ymgme.2014.05.004; RA Miller M.J., Soler-Alfonso C.R., Grund J.E., Fang P., Sun Q., Elsea S.H., RA Sutton V.R.; RT "Improved standards for prenatal diagnosis of citrullinemia."; RL Mol. Genet. Metab. 112:205-209(2014). RN [30] RP VARIANTS CTLN1 GLY-141 AND CYS-265. RX PubMed=25179242; DOI=10.1016/j.cca.2014.08.028; RA Kimani J.K., Wei T., Chol K., Li Y., Yu P., Ye S., Huang X., Qi M.; RT "Functional analysis of novel splicing and missense mutations identified in RT the ASS1 gene in classical citrullinemia patients."; RL Clin. Chim. Acta 438:323-329(2015). RN [31] RP VARIANTS CTLN1 PRO-91; LEU-96; SER-117; THR-118; ILE-119; ASN-124; CYS-157; RP HIS-157; CYS-272; HIS-272 AND LEU-272, CHARACTERIZATION OF VARIANTS CTLN1 RP PRO-91; SER-95; HIS-96; LEU-96; SER-96; SER-117; THR-118; ILE-119; ASN-124; RP GLN-127; TRP-127; CYS-157; HIS-157; ASN-180; ILE-180; GLN-191; GLN-270; RP CYS-272; HIS-272 AND LEU-272, CHARACTERIZATION OF VARIANT LEU-127, RP CATALYTIC ACTIVITY, PATHWAY, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=27287393; DOI=10.1136/jmedgenet-2016-103937; RA Diez-Fernandez C., Wellauer O., Gemperle C., Ruefenacht V., Fingerhut R., RA Haeberle J.; RT "Kinetic mutations in argininosuccinate synthetase deficiency: RT characterisation and in vitro correction by substrate supplementation."; RL J. Med. Genet. 53:710-719(2016). RN [32] RP VARIANTS CTLN1 27-GLN--LYS-412 DEL; ILE-64; PRO-79; 97-CYS--LYS-412 DEL; RP CYS-100; HIS-100; ASP-111; CYS-117; 138-GLN--LYS-412 DEL; SER-157; PRO-160; RP 163-TYR--LYS-412 DEL; PRO-164; LYS-184; ASP-190; PRO-206; ARG-230; ILE-237; RP PRO-258; VAL-258; CYS-265; 275-GLY--LYS-412 DEL; THR-277; 279-ARG--LYS-412 RP DEL; ILE-284; PRO-290; SER-291; GLY-296; ASP-299; VAL-302; GLY-306; RP CYS-307; 311-GLN--LYS-412 DEL; MET-321; SER-324; VAL-324; HIS-335; PHE-341; RP 344-ARG--LYS-412 DEL; ARG-347; VAL-356; 357-GLN--LYS-412 DEL; ASP-359; RP 380-GLN--LYS-412 DEL AND PRO-389. RX PubMed=28111830; DOI=10.1002/humu.23184; RA Diez-Fernandez C., Ruefenacht V., Haeberle J.; RT "Mutations in the human argininosuccinate synthetase (ASS1) gene, impact on RT patients, common changes, and structural considerations."; RL Hum. Mutat. 38:471-484(2017). CC -!- FUNCTION: One of the enzymes of the urea cycle, the metabolic pathway CC transforming neurotoxic amonia produced by protein catabolism into CC inocuous urea in the liver of ureotelic animals. Catalyzes the CC formation of arginosuccinate from aspartate, citrulline and ATP and CC together with ASL it is responsible for the biosynthesis of arginine in CC most body tissues. {ECO:0000305|PubMed:18473344, CC ECO:0000305|PubMed:27287393, ECO:0000305|PubMed:8792870}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-aspartate + L-citrulline = 2-(N(omega)-L- CC arginino)succinate + AMP + diphosphate + H(+); Xref=Rhea:RHEA:10932, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29991, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57472, ChEBI:CHEBI:57743, CC ChEBI:CHEBI:456215; EC=6.3.4.5; CC Evidence={ECO:0000269|PubMed:18473344, ECO:0000269|PubMed:27287393, CC ECO:0000269|PubMed:8792870}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=112 uM for citrulline (at pH 7.0 and 37 degrees Celsius) CC {ECO:0000269|PubMed:18473344}; CC KM=68 uM for aspartate (at pH 7.0 and 37 degrees Celsius) CC {ECO:0000269|PubMed:18473344}; CC Vmax=143 nmol/min/mg enzyme toward citrulline (at pH 7.0 and 37 CC degrees Celsius) {ECO:0000269|PubMed:18473344}; CC Vmax=116 nmol/min/mg enzyme toward aspartate (at pH 7.0 and 37 CC degrees) {ECO:0000269|PubMed:18473344}; CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine CC from L-ornithine and carbamoyl phosphate: step 2/3. CC {ECO:0000305|PubMed:18473344, ECO:0000305|PubMed:27287393, CC ECO:0000305|PubMed:8792870}. CC -!- PATHWAY: Nitrogen metabolism; urea cycle; (N(omega)-L- CC arginino)succinate from L-aspartate and L-citrulline: step 1/1. CC {ECO:0000305|PubMed:18473344, ECO:0000305|PubMed:27287393, CC ECO:0000305|PubMed:8792870}. CC -!- SUBUNIT: Homotetramer (PubMed:18323623). Interacts with NMRAL1 CC (PubMed:17496144). Interacts with CLOCK; in a circadian manner CC (PubMed:28985504). Forms tissue-specific complexes with ASL, SLC7A1, CC HSP90AA1 and nitric oxide synthase NOS1, NOS2 or NOS3; the complex CC regulates cell-autonomous L-arginine synthesis and citrulline recycling CC while channeling extracellular L-arginine to nitric oxide synthesis CC pathway. {ECO:0000250|UniProtKB:P16460, ECO:0000269|PubMed:17496144, CC ECO:0000269|PubMed:18323623, ECO:0000269|PubMed:28985504}. CC -!- INTERACTION: CC P00966; P10398: ARAF; NbExp=4; IntAct=EBI-536842, EBI-365961; CC P00966; P00966: ASS1; NbExp=3; IntAct=EBI-536842, EBI-536842; CC P00966; Q9HBL8: NMRAL1; NbExp=3; IntAct=EBI-536842, EBI-2862643; CC P00966; Q9NVM4: PRMT7; NbExp=9; IntAct=EBI-536842, EBI-3215577; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:28985504, CC ECO:0000305|PubMed:27287393}. CC -!- TISSUE SPECIFICITY: Expressed in adult liver. CC {ECO:0000269|PubMed:1708740}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal liver and kidney. CC {ECO:0000269|PubMed:1708740}. CC -!- PTM: Acetylated by CLOCK in a circadian manner which negatively CC regulates its enzyme activity. Deacetylated by histone deacetylases. CC {ECO:0000269|PubMed:28985504}. CC -!- DISEASE: Citrullinemia 1 (CTLN1) [MIM:215700]: The classic form of CC citrullinemia, an autosomal recessive disease characterized primarily CC by elevated serum and urine citrulline levels. Ammonia intoxication is CC another manifestation. It is a disorder of the urea cycle, usually CC manifesting in the first few days of life. Affected infants appear CC normal at birth, but as ammonia builds up in the body they present CC symptoms such as lethargy, poor feeding, vomiting, seizures and loss of CC consciousness. Less commonly, a milder form can develop later in CC childhood or adulthood. {ECO:0000269|PubMed:11708871, CC ECO:0000269|PubMed:11941481, ECO:0000269|PubMed:12815590, CC ECO:0000269|PubMed:14680976, ECO:0000269|PubMed:15863597, CC ECO:0000269|PubMed:16475226, ECO:0000269|PubMed:18473344, CC ECO:0000269|PubMed:19006241, ECO:0000269|PubMed:1943692, CC ECO:0000269|PubMed:2358466, ECO:0000269|PubMed:23611581, CC ECO:0000269|PubMed:24889030, ECO:0000269|PubMed:25179242, CC ECO:0000269|PubMed:27287393, ECO:0000269|PubMed:28111830, CC ECO:0000269|PubMed:7977368}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the argininosuccinate synthase family. Type 1 CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Argininosuccinate synthetase 1 (ASS1); Note=Leiden CC Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/ASS1"; 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; X01630; CAA25771.1; -; mRNA. DR EMBL; L00084; AAA51783.1; -; Genomic_DNA. DR EMBL; L00079; AAA51783.1; JOINED; Genomic_DNA. DR EMBL; L00080; AAA51783.1; JOINED; Genomic_DNA. DR EMBL; L00081; AAA51783.1; JOINED; Genomic_DNA. DR EMBL; L00082; AAA51783.1; JOINED; Genomic_DNA. DR EMBL; L00083; AAA51783.1; JOINED; Genomic_DNA. DR EMBL; AY034076; AAK67487.1; -; Genomic_DNA. DR EMBL; AK027126; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC009243; AAH09243.1; -; mRNA. DR EMBL; BC021676; AAH21676.1; -; mRNA. DR EMBL; M34903; AAA51782.1; -; Genomic_DNA. DR CCDS; CCDS6933.1; -. DR PIR; A01195; AJHURS. DR RefSeq; NP_000041.2; NM_000050.4. DR RefSeq; NP_446464.1; NM_054012.3. DR RefSeq; XP_005272257.1; XM_005272200.3. DR PDB; 2NZ2; X-ray; 2.40 A; A=1-412. DR PDBsum; 2NZ2; -. DR AlphaFoldDB; P00966; -. DR SMR; P00966; -. DR BioGRID; 106937; 192. DR DIP; DIP-34055N; -. DR IntAct; P00966; 35. DR MINT; P00966; -. DR STRING; 9606.ENSP00000361471; -. DR DrugBank; DB00125; Arginine. DR DrugBank; DB00128; Aspartic acid. DR DrugBank; DB00171; ATP. DR DrugBank; DB00155; Citrulline. DR DrugCentral; P00966; -. DR GlyGen; P00966; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P00966; -. DR MetOSite; P00966; -. DR PhosphoSitePlus; P00966; -. DR BioMuta; ASS1; -. DR DMDM; 20141195; -. DR CPTAC; CPTAC-169; -. DR CPTAC; CPTAC-170; -. DR EPD; P00966; -. DR jPOST; P00966; -. DR MassIVE; P00966; -. DR PaxDb; 9606-ENSP00000361471; -. DR PeptideAtlas; P00966; -. DR ProteomicsDB; 51293; -. DR Pumba; P00966; -. DR Antibodypedia; 4531; 596 antibodies from 38 providers. DR DNASU; 445; -. DR Ensembl; ENST00000352480.10; ENSP00000253004.6; ENSG00000130707.18. DR Ensembl; ENST00000372393.7; ENSP00000361469.2; ENSG00000130707.18. DR Ensembl; ENST00000372394.5; ENSP00000361471.1; ENSG00000130707.18. DR GeneID; 445; -. DR KEGG; hsa:445; -. DR MANE-Select; ENST00000352480.10; ENSP00000253004.6; NM_054012.4; NP_446464.1. DR AGR; HGNC:758; -. DR CTD; 445; -. DR DisGeNET; 445; -. DR GeneCards; ASS1; -. DR GeneReviews; ASS1; -. DR HGNC; HGNC:758; ASS1. DR HPA; ENSG00000130707; Group enriched (kidney, liver). DR MalaCards; ASS1; -. DR MIM; 215700; phenotype. DR MIM; 603470; gene. DR neXtProt; NX_P00966; -. DR OpenTargets; ENSG00000130707; -. DR Orphanet; 247546; Acute neonatal citrullinemia type I. DR Orphanet; 247573; Late-onset citrullinemia type I. DR PharmGKB; PA162376926; -. DR VEuPathDB; HostDB:ENSG00000130707; -. DR eggNOG; KOG1706; Eukaryota. DR GeneTree; ENSGT00390000004524; -. DR HOGENOM; CLU_032784_4_2_1; -. DR InParanoid; P00966; -. DR OMA; ACGAFHI; -. DR OrthoDB; 350199at2759; -. DR PhylomeDB; P00966; -. DR TreeFam; TF300736; -. DR BioCyc; MetaCyc:HS05425-MONOMER; -. DR BRENDA; 6.3.4.5; 2681. DR PathwayCommons; P00966; -. DR Reactome; R-HSA-70635; Urea cycle. DR SABIO-RK; P00966; -. DR SignaLink; P00966; -. DR UniPathway; UPA00068; UER00113. DR UniPathway; UPA00158; UER00272. DR BioGRID-ORCS; 445; 27 hits in 1124 CRISPR screens. DR ChiTaRS; ASS1; human. DR EvolutionaryTrace; P00966; -. DR GeneWiki; Argininosuccinate_synthetase_1; -. DR GenomeRNAi; 445; -. DR Pharos; P00966; Tbio. DR PRO; PR:P00966; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P00966; Protein. DR Bgee; ENSG00000130707; Expressed in right lobe of liver and 207 other cell types or tissues. DR ExpressionAtlas; P00966; baseline and differential. DR GO; GO:0070852; C:cell body fiber; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0043204; C:perikaryon; IEA:Ensembl. DR GO; GO:0016597; F:amino acid binding; IMP:BHF-UCL. DR GO; GO:0004055; F:argininosuccinate synthase activity; IMP:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0015643; F:toxic substance binding; IEA:Ensembl. DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl. DR GO; GO:0006526; P:arginine biosynthetic process; IMP:UniProtKB. DR GO; GO:0000053; P:argininosuccinate metabolic process; IMP:BHF-UCL. DR GO; GO:0006531; P:aspartate metabolic process; IMP:BHF-UCL. DR GO; GO:0071418; P:cellular response to amine stimulus; IEA:Ensembl. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl. DR GO; GO:0071242; P:cellular response to ammonium ion; IEA:Ensembl. DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEA:Ensembl. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; IMP:BHF-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0071400; P:cellular response to oleic acid; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl. DR GO; GO:0007623; P:circadian rhythm; IDA:UniProtKB. DR GO; GO:0000052; P:citrulline metabolic process; IMP:BHF-UCL. DR GO; GO:0060539; P:diaphragm development; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0001889; P:liver development; IEA:Ensembl. DR GO; GO:0007494; P:midgut development; IEA:Ensembl. DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; IMP:BHF-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0060416; P:response to growth hormone; IEA:Ensembl. DR GO; GO:0010046; P:response to mycotoxin; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl. DR GO; GO:0000050; P:urea cycle; IMP:UniProtKB. DR CDD; cd01999; Argininosuccinate_Synthase; 1. DR Gene3D; 3.90.1260.10; Argininosuccinate synthetase, chain A, domain 2; 1. DR Gene3D; 3.40.50.620; HUPs; 1. DR Gene3D; 1.20.5.470; Single helix bin; 1. DR HAMAP; MF_00005; Arg_succ_synth_type1; 1. DR InterPro; IPR048268; Arginosuc_syn_C. DR InterPro; IPR048267; Arginosuc_syn_N. DR InterPro; IPR001518; Arginosuc_synth. DR InterPro; IPR018223; Arginosuc_synth_CS. DR InterPro; IPR023434; Arginosuc_synth_type_1_subfam. DR InterPro; IPR024074; AS_cat/multimer_dom_body. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR NCBIfam; TIGR00032; argG; 1. DR PANTHER; PTHR11587; ARGININOSUCCINATE SYNTHASE; 1. DR PANTHER; PTHR11587:SF5; ARGININOSUCCINATE SYNTHASE; 1. DR Pfam; PF20979; Arginosuc_syn_C; 1. DR Pfam; PF00764; Arginosuc_synth; 1. DR SUPFAM; SSF52402; Adenine nucleotide alpha hydrolases-like; 1. DR SUPFAM; SSF69864; Argininosuccinate synthetase, C-terminal domain; 1. DR PROSITE; PS00564; ARGININOSUCCIN_SYN_1; 1. DR PROSITE; PS00565; ARGININOSUCCIN_SYN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Amino-acid biosynthesis; Arginine biosynthesis; KW ATP-binding; Cytoplasm; Direct protein sequencing; Disease variant; Ligase; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Urea cycle. FT CHAIN 1..412 FT /note="Argininosuccinate synthase" FT /id="PRO_0000148554" FT BINDING 10..18 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 36 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 87 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 92 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 115..123 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 119 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 123 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 123 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 124 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 127 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 180 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 189 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 270 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000269|PubMed:18323623" FT BINDING 282 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000269|PubMed:18323623" FT MOD_RES 87 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P09034" FT MOD_RES 112 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P16460" FT MOD_RES 113 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 165 FT /note="N6-acetyllysine; by CLOCK" FT /evidence="ECO:0000269|PubMed:28985504" FT MOD_RES 176 FT /note="N6-acetyllysine; by CLOCK" FT /evidence="ECO:0000269|PubMed:28985504" FT MOD_RES 180 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 219 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT VARIANT 14 FT /note="G -> S (in CTLN1; dbSNP:rs121908636)" FT /evidence="ECO:0000269|PubMed:14680976, FT ECO:0000269|PubMed:2358466" FT /id="VAR_000681" FT VARIANT 18 FT /note="S -> L (in CTLN1; dbSNP:rs121908643)" FT /evidence="ECO:0000269|PubMed:1943692" FT /id="VAR_000682" FT VARIANT 19 FT /note="C -> R (in CTLN1)" FT /evidence="ECO:0000269|PubMed:12815590" FT /id="VAR_015891" FT VARIANT 27..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078387" FT VARIANT 40 FT /note="Q -> L (in CTLN1)" FT /evidence="ECO:0000269|PubMed:14680976" FT /id="VAR_058337" FT VARIANT 64 FT /note="V -> I (in CTLN1; uncertain significance; FT dbSNP:rs556297791)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078388" FT VARIANT 69 FT /note="V -> A (in CTLN1; dbSNP:rs771594651)" FT /evidence="ECO:0000269|PubMed:11708871" FT /id="VAR_016013" FT VARIANT 79 FT /note="S -> P (in CTLN1)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058338" FT VARIANT 86 FT /note="R -> C (in CTLN1; dbSNP:rs121908644)" FT /evidence="ECO:0000269|PubMed:1943692" FT /id="VAR_000683" FT VARIANT 86 FT /note="R -> H (in CTLN1; dbSNP:rs575001023)" FT /evidence="ECO:0000269|PubMed:12815590" FT /id="VAR_015892" FT VARIANT 91 FT /note="T -> P (in CTLN1; decreased affinity for aspartate; FT decreased affinity for citrulline; decreased FT argininosuccinate synthase activity; dbSNP:rs769018733)" FT /evidence="ECO:0000269|PubMed:24889030, FT ECO:0000269|PubMed:27287393" FT /id="VAR_078389" FT VARIANT 95 FT /note="R -> S (in CTLN1; increased thermal stability; loss FT of argininosuccinate synthase activity)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:27287393" FT /id="VAR_015893" FT VARIANT 96 FT /note="P -> H (in CTLN1; decreased affinity for aspartate; FT decreased affinity for citrulline; decreased FT argininosuccinate synthase activity)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:27287393" FT /id="VAR_058339" FT VARIANT 96 FT /note="P -> L (in CTLN1; decreased thermal stability; FT decreased affinity for aspartate; decreased affinity for FT citrulline; loss of argininosuccinate synthase activity)" FT /evidence="ECO:0000269|PubMed:27287393" FT /id="VAR_078390" FT VARIANT 96 FT /note="P -> S (in CTLN1; no effect on thermal stability; FT decreased argininosuccinate synthase activity)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:27287393" FT /id="VAR_015894" FT VARIANT 97..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078391" FT VARIANT 100 FT /note="R -> C (in CTLN1; dbSNP:rs370695114)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078392" FT VARIANT 100 FT /note="R -> H (in CTLN1; dbSNP:rs138279074)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078393" FT VARIANT 108 FT /note="R -> L (in CTLN1; dbSNP:rs35269064)" FT /evidence="ECO:0000269|PubMed:11708871, FT ECO:0000269|PubMed:11941481" FT /id="VAR_016014" FT VARIANT 111 FT /note="A -> D (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078394" FT VARIANT 117 FT /note="G -> C (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078395" FT VARIANT 117 FT /note="G -> D (in CTLN1)" FT /evidence="ECO:0000269|PubMed:11708871, FT ECO:0000269|PubMed:12815590" FT /id="VAR_015896" FT VARIANT 117 FT /note="G -> S (in CTLN1; decreased thermal stability; loss FT of argininosuccinate synthase activity; dbSNP:rs770944877)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:27287393" FT /id="VAR_015895" FT VARIANT 118 FT /note="A -> T (in CTLN1; decreased thermal stability; FT decreased affinity for aspartate; decreased affinity for FT citrulline; decreased argininosuccinate synthase activity; FT dbSNP:rs775305020)" FT /evidence="ECO:0000269|PubMed:18473344, FT ECO:0000269|PubMed:27287393, ECO:0000269|PubMed:7977368" FT /id="VAR_000684" FT VARIANT 119 FT /note="T -> I (in CTLN1; decreased thermal stability; loss FT of argininosuccinate synthase activity)" FT /evidence="ECO:0000269|PubMed:11708871, FT ECO:0000269|PubMed:27287393" FT /id="VAR_016015" FT VARIANT 124 FT /note="D -> N (in CTLN1; loss of argininosuccinate synthase FT activity; dbSNP:rs936192871)" FT /evidence="ECO:0000269|PubMed:16475226, FT ECO:0000269|PubMed:27287393" FT /id="VAR_058340" FT VARIANT 127 FT /note="R -> L (increased thermal stability; loss of FT argininosuccinate synthase activity; dbSNP:rs201623252)" FT /evidence="ECO:0000269|PubMed:24889030, FT ECO:0000269|PubMed:27287393" FT /id="VAR_078396" FT VARIANT 127 FT /note="R -> Q (in CTLN1; increased thermal stability; loss FT of argininosuccinate synthase activity; dbSNP:rs201623252)" FT /evidence="ECO:0000269|PubMed:14680976, FT ECO:0000269|PubMed:19006241, ECO:0000269|PubMed:27287393" FT /id="VAR_058341" FT VARIANT 127 FT /note="R -> W (in CTLN1; severe clinical course; loss of FT argininosuccinate synthase activity; dbSNP:rs771794639)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:27287393" FT /id="VAR_058342" FT VARIANT 138..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078397" FT VARIANT 141 FT /note="V -> G (in CTLN1; dbSNP:rs1184442048)" FT /evidence="ECO:0000269|PubMed:25179242" FT /id="VAR_072792" FT VARIANT 157 FT /note="R -> C (in CTLN1; decreased thermal stability; loss FT of argininosuccinate synthase activity; dbSNP:rs770585183)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:24889030, ECO:0000269|PubMed:27287393" FT /id="VAR_015897" FT VARIANT 157 FT /note="R -> H (in CTLN1; loss of argininosuccinate synthase FT activity; dbSNP:rs121908637)" FT /evidence="ECO:0000269|PubMed:16475226, FT ECO:0000269|PubMed:2358466, ECO:0000269|PubMed:27287393" FT /id="VAR_000685" FT VARIANT 157 FT /note="R -> S (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078398" FT VARIANT 160 FT /note="L -> P (in CTLN1; dbSNP:rs969835605)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058343" FT VARIANT 163..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078399" FT VARIANT 164 FT /note="A -> P (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078400" FT VARIANT 179 FT /note="W -> R (in CTLN1; mild; decreased affinity for FT aspartate; decreased affinity for citrulline; decreased FT argininosuccinate synthase activity; dbSNP:rs121908646)" FT /evidence="ECO:0000269|PubMed:11941481, FT ECO:0000269|PubMed:12815590, ECO:0000269|PubMed:14680976, FT ECO:0000269|PubMed:18473344" FT /id="VAR_015898" FT VARIANT 180 FT /note="S -> I (in CTLN1; increased thermal stability; loss FT of argininosuccinate synthase activity; dbSNP:rs121908638)" FT /evidence="ECO:0000269|PubMed:24889030, FT ECO:0000269|PubMed:27287393" FT /id="VAR_078401" FT VARIANT 180 FT /note="S -> N (in CTLN1; decreased thermal stability; FT decreased affinity for aspartate; decreased affinity for FT citrulline; decreased argininosuccinate synthase activity; FT dbSNP:rs121908638)" FT /evidence="ECO:0000269|PubMed:2358466, FT ECO:0000269|PubMed:27287393" FT /id="VAR_000686" FT VARIANT 184 FT /note="N -> K (in CTLN1; dbSNP:rs368192467)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078402" FT VARIANT 190 FT /note="Y -> D (in CTLN1)" FT /evidence="ECO:0000269|PubMed:14680976, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058344" FT VARIANT 191 FT /note="E -> K (in CTLN1; dbSNP:rs777828000)" FT /evidence="ECO:0000269|PubMed:12815590" FT /id="VAR_015899" FT VARIANT 191 FT /note="E -> Q (in CTLN1; loss of argininosuccinate synthase FT activity)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:27287393" FT /id="VAR_058345" FT VARIANT 192 FT /note="A -> V (in CTLN1; decreased protein abundance)" FT /evidence="ECO:0000269|PubMed:7977368, FT ECO:0000269|PubMed:8792870" FT /id="VAR_000687" FT VARIANT 202 FT /note="A -> E (in CTLN1; dbSNP:rs376371866)" FT /evidence="ECO:0000269|PubMed:14680976" FT /id="VAR_058346" FT VARIANT 206 FT /note="L -> P (in CTLN1)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058347" FT VARIANT 230 FT /note="G -> R (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078403" FT VARIANT 237 FT /note="N -> I (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078404" FT VARIANT 258 FT /note="A -> P (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078405" FT VARIANT 258 FT /note="A -> V (in CTLN1; dbSNP:rs753078725)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078406" FT VARIANT 263 FT /note="V -> M (in CTLN1; mild clinical course; no effect on FT affinity for aspartate; no effect on affinity for FT citrulline; decreased argininosuccinate synthase activity; FT dbSNP:rs192838388)" FT /evidence="ECO:0000269|PubMed:14680976, FT ECO:0000269|PubMed:18473344" FT /id="VAR_058348" FT VARIANT 265 FT /note="R -> C (in CTLN1; severe clinical course; loss of FT argininosuccinate synthase activity; dbSNP:rs148918985)" FT /evidence="ECO:0000269|PubMed:18473344, FT ECO:0000269|PubMed:19006241, ECO:0000269|PubMed:25179242, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058349" FT VARIANT 265 FT /note="R -> H (in CTLN1; dbSNP:rs398123131)" FT /evidence="ECO:0000269|PubMed:12815590" FT /id="VAR_015900" FT VARIANT 269 FT /note="V -> M (in CTLN1; dbSNP:rs370595480)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:14680976" FT /id="VAR_015901" FT VARIANT 270 FT /note="E -> Q (in CTLN1; loss of argininosuccinate synthase FT activity; dbSNP:rs775163147)" FT /evidence="ECO:0000269|PubMed:11708871, FT ECO:0000269|PubMed:16475226, ECO:0000269|PubMed:27287393" FT /id="VAR_016007" FT VARIANT 272 FT /note="R -> C (in CTLN1; increased thermal stability; FT decreased affinity for aspartate; decreased affinity for FT citrulline; decreased argininosuccinate synthase activity; FT dbSNP:rs762387914)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:27287393, ECO:0000269|PubMed:7977368, FT ECO:0000269|PubMed:8792870" FT /id="VAR_000688" FT VARIANT 272 FT /note="R -> H (in CTLN1; increased thermal stability; FT decreased affinity for aspartate; decreased affinity for FT citrulline; decreased argininosuccinate synthase activity; FT dbSNP:rs768215008)" FT /evidence="ECO:0000269|PubMed:27287393" FT /id="VAR_078407" FT VARIANT 272 FT /note="R -> L (in CTLN1; increased thermal stability; FT decreased affinity for aspartate; decreased affinity for FT citrulline; decreased argininosuccinate synthase activity; FT dbSNP:rs768215008)" FT /evidence="ECO:0000269|PubMed:27287393" FT /id="VAR_078408" FT VARIANT 275..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078409" FT VARIANT 277 FT /note="K -> T (in CTLN1)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058350" FT VARIANT 279..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078410" FT VARIANT 279 FT /note="R -> Q (in CTLN1; dbSNP:rs371265106)" FT /evidence="ECO:0000269|PubMed:16475226" FT /id="VAR_016008" FT VARIANT 280 FT /note="G -> R (in CTLN1; loss of argininosuccinate synthase FT activity)" FT /evidence="ECO:0000269|PubMed:7977368, FT ECO:0000269|PubMed:8792870" FT /id="VAR_000689" FT VARIANT 283 FT /note="E -> K (in CTLN1; dbSNP:rs765338121)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:16475226, ECO:0000269|PubMed:23611581, FT ECO:0000269|PubMed:24889030" FT /id="VAR_015902" FT VARIANT 284 FT /note="T -> I (in CTLN1; mild clinical course; FT dbSNP:rs886039853)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058351" FT VARIANT 290 FT /note="L -> P (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078411" FT VARIANT 291 FT /note="Y -> S (in CTLN1)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058352" FT VARIANT 296 FT /note="D -> G (in CTLN1)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058353" FT VARIANT 299 FT /note="A -> D (in CTLN1; dbSNP:rs768394647)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078412" FT VARIANT 302 FT /note="M -> V (in CTLN1; no effect on affinity for FT aspartate; no effect on affinity for citrulline; decreased FT argininosuccinate synthase activity)" FT /evidence="ECO:0000269|PubMed:18473344, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058354" FT VARIANT 304 FT /note="R -> W (in CTLN1; decreased protein abundance; FT dbSNP:rs121908642)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:2358466, ECO:0000269|PubMed:7977368" FT /id="VAR_000690" FT VARIANT 306 FT /note="V -> G (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078413" FT VARIANT 307 FT /note="R -> C (in CTLN1; dbSNP:rs183276875)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_058355" FT VARIANT 310 FT /note="K -> Q (in CTLN1; dbSNP:rs121908648)" FT /evidence="ECO:0000269|PubMed:12815590" FT /id="VAR_016009" FT VARIANT 310 FT /note="K -> R (in CTLN1; dbSNP:rs199751308)" FT /evidence="ECO:0000269|PubMed:15863597" FT /id="VAR_015903" FT VARIANT 311..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078414" FT VARIANT 321 FT /note="V -> M (in CTLN1; dbSNP:rs727503813)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078415" FT VARIANT 324 FT /note="G -> S (in CTLN1; loss of argininosuccinate synthase FT activity; dbSNP:rs121908639)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:14680976, ECO:0000269|PubMed:16475226, FT ECO:0000269|PubMed:18473344, ECO:0000269|PubMed:2358466, FT ECO:0000269|PubMed:28111830" FT /id="VAR_000691" FT VARIANT 324 FT /note="G -> V (in CTLN1)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058356" FT VARIANT 335 FT /note="R -> H (in CTLN1; dbSNP:rs555388438)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078416" FT VARIANT 337 FT /note="C -> R (in CTLN1)" FT /evidence="ECO:0000269|PubMed:23611581" FT /id="VAR_078417" FT VARIANT 341 FT /note="S -> F (in CTLN1)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058357" FT VARIANT 344..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078418" FT VARIANT 345 FT /note="V -> G (in CTLN1)" FT /evidence="ECO:0000269|PubMed:14680976" FT /id="VAR_058358" FT VARIANT 347 FT /note="G -> R (in CTLN1; severe clinical course)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058359" FT VARIANT 356 FT /note="G -> V (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078419" FT VARIANT 357..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078420" FT VARIANT 359 FT /note="Y -> D (in CTLN1; mild clinical course)" FT /evidence="ECO:0000269|PubMed:19006241, FT ECO:0000269|PubMed:28111830" FT /id="VAR_058360" FT VARIANT 362 FT /note="G -> V (in CTLN1; mild; no effect on affinity for FT aspartate; no effect on affinity for citrulline; decreased FT argininosuccinate synthase activity; dbSNP:rs121908647)" FT /evidence="ECO:0000269|PubMed:11941481, FT ECO:0000269|PubMed:12815590, ECO:0000269|PubMed:14680976, FT ECO:0000269|PubMed:18473344" FT /id="VAR_015904" FT VARIANT 363 FT /note="R -> G (in CTLN1)" FT /evidence="ECO:0000269|PubMed:16475226" FT /id="VAR_016010" FT VARIANT 363 FT /note="R -> L (in CTLN1)" FT /evidence="ECO:0000269|PubMed:7977368" FT /id="VAR_000692" FT VARIANT 363 FT /note="R -> Q (in CTLN1; dbSNP:rs771937610)" FT /evidence="ECO:0000269|PubMed:12815590" FT /id="VAR_016011" FT VARIANT 363 FT /note="R -> W (in CTLN1; dbSNP:rs121908640)" FT /evidence="ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:2358466" FT /id="VAR_000693" FT VARIANT 380..412 FT /note="Missing (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078421" FT VARIANT 389 FT /note="T -> I (in CTLN1; dbSNP:rs1474017319)" FT /evidence="ECO:0000269|PubMed:12815590" FT /id="VAR_016012" FT VARIANT 389 FT /note="T -> P (in CTLN1)" FT /evidence="ECO:0000269|PubMed:28111830" FT /id="VAR_078422" FT VARIANT 390 FT /note="G -> R (in CTLN1; loss of argininosuccinate synthase FT activity; dbSNP:rs121908641)" FT /evidence="ECO:0000269|PubMed:11708871, FT ECO:0000269|PubMed:11941481, ECO:0000269|PubMed:12815590, FT ECO:0000269|PubMed:16475226, ECO:0000269|PubMed:18473344, FT ECO:0000269|PubMed:2358466, ECO:0000269|PubMed:24889030" FT /id="VAR_000694" FT MUTAGEN 165 FT /note="K->Q,R: Significant loss of acetylation but no FT decrease in enzyme activity; when associated with Q-176 or FT R-176." FT /evidence="ECO:0000269|PubMed:28985504" FT MUTAGEN 176 FT /note="K->Q,R: Significant loss of acetylation but no FT decrease in enzyme activity; when associated with Q-165 or FT R-165." FT /evidence="ECO:0000269|PubMed:28985504" FT CONFLICT 325..327 FT /note="FWH -> LRP (in Ref. 1; CAA25771 and 2; AAA51783)" FT /evidence="ECO:0000305" FT STRAND 5..10 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 15..26 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 29..39 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 44..54 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 57..63 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 65..71 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 73..78 FT /evidence="ECO:0007829|PDB:2NZ2" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:2NZ2" FT TURN 90..93 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 94..109 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 112..115 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 124..135 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 140..142 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 144..146 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 148..151 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 158..166 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 181..183 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 193..196 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 204..206 FT /evidence="ECO:0007829|PDB:2NZ2" FT TURN 213..215 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 221..228 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 231..237 FT /evidence="ECO:0007829|PDB:2NZ2" FT TURN 238..240 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 247..261 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 265..271 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 277..283 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 285..301 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 304..323 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 326..328 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 329..341 FT /evidence="ECO:0007829|PDB:2NZ2" FT TURN 342..344 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 347..354 FT /evidence="ECO:0007829|PDB:2NZ2" FT STRAND 357..364 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 372..375 FT /evidence="ECO:0007829|PDB:2NZ2" FT HELIX 385..404 FT /evidence="ECO:0007829|PDB:2NZ2" SQ SEQUENCE 412 AA; 46530 MW; 47CAD2373AE47E47 CRC64; MSSKGSVVLA YSGGLDTSCI LVWLKEQGYD VIAYLANIGQ KEDFEEARKK ALKLGAKKVF IEDVSREFVE EFIWPAIQSS ALYEDRYLLG TSLARPCIAR KQVEIAQREG AKYVSHGATG KGNDQVRFEL SCYSLAPQIK VIAPWRMPEF YNRFKGRNDL MEYAKQHGIP IPVTPKNPWS MDENLMHISY EAGILENPKN QAPPGLYTKT QDPAKAPNTP DILEIEFKKG VPVKVTNVKD GTTHQTSLEL FMYLNEVAGK HGVGRIDIVE NRFIGMKSRG IYETPAGTIL YHAHLDIEAF TMDREVRKIK QGLGLKFAEL VYTGFWHSPE CEFVRHCIAK SQERVEGKVQ VSVLKGQVYI LGRESPLSLY NEELVSMNVQ GDYEPTDATG FININSLRLK EYHRLQSKVT AK //