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 21-AUG-2007, entry version 92. DE Argininosuccinate synthase (EC 6.3.4.5) (Citrulline--aspartate DE ligase). GN Name=ASS1; Synonyms=ASS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=84015388; 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 MEDLINE=84135824; PubMed=6321498; RA Freytag S.O., Bock H.-G.O., Beaudet A.L., O'Brien W.E.; RT "Molecular structures of human argininosuccinate synthetase RT pseudogenes. Evolutionary and mechanistic implications."; RL J. Biol. Chem. 259:3160-3166(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CTLN1 LEU-108; RP ARG-179; VAL-362 AND ARG-390. RX MEDLINE=21938160; 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 RT improved system for molecular diagnostics in patients with classical RT and mild 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 RT project: 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; RA Jinno Y., Nomiyama H., Matuo S., Shimada K., Matsuda I., Saheki T.; RT "Structure of the 5' end region of the human argininosuccinate RT synthetase gene."; RL J. Inherit. Metab. Dis. 8:157-159(1985). RN [7] RP PROTEIN SEQUENCE OF 148-161. RX MEDLINE=89367258; 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 MEDLINE=97295306; PubMed=9150948; 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 VARIANTS CTLN1 SER-14; HIS-157; ASN-180; TRP-304; SER-324; TRP-363 AND RP ARG-390. RX MEDLINE=90293089; PubMed=2358466; RA Kobayashi K., Jackson M.J., Tick D.B., O'Brien W.E., Beaudet A.L.; RT "Heterogeneity of mutations in argininosuccinate synthetase causing RT human citrullinemia."; RL J. Biol. Chem. 265:11361-11367(1990). RN [10] RP VARIANTS CTLN1 LEU-18 AND CYS-86. RX MEDLINE=92048472; 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 [11] RP VARIANTS CTLN1 THR-118; VAL-192; CYS-272; ARG-280; TRP-304 AND RP LEU-363. RX MEDLINE=95067972; 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 [12] RP CHARACTERIZATION OF SOME CTLN1 VARIANTS. RX MEDLINE=96385010; PubMed=8792870; 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(1995). RN [13] RP VARIANTS CTLN1 ALA-69; LEU-108; ASP-117; ILE-119; GLN-270 AND ARG-390. RX MEDLINE=21566400; PubMed=11708871; DOI=10.1006/mgme.2001.3221; RA Vilaseca M.A., Kobayashi K., Briones P., Lambruschini N., RA Campistol J., Tabata A., Alomar A., Rodes M., Lluch M., Saheki T.; RT "Phenotype and genotype heterogeneity in Mediterranean RT citrullinemia."; RL Mol. Genet. Metab. 74:396-398(2001). RN [14] RP VARIANTS CTLN1 ARG-19; HIS-86; SER-95; SER-96; ASP-117; SER-117; RP CYS-157; ARG-179; LYS-191; HIS-265; MET-269; CYS-272; LYS-283; RP TRP-304; GLN-310; SER-324; VAL-362; GLN-363; TRP-363; ILE-389 AND RP ARG-390. RX MEDLINE=22699243; 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., RA Skladal D., Mandel H., Seidel J., Kodama S., Shirane S., Ichida T., RA Makino S., Yoshino M., Kang J.-H., Mizuguchi M., Barshop B.A., RA Fuchinoue S., Seneca S., Zeesman S., Knerr I., Rodes M., Wasant P., RA Yoshida I., De Meirleir L., Abdul Jalil M., Begum L., Horiuchi M., RA Katunuma N., Nakagawa S., Saheki T.; RT "Identification of 16 novel mutations in the argininosuccinate RT synthetase gene and genotype-phenotype correlation in 38 classical RT citrullinemia patients."; RL Hum. Mutat. 22:24-34(2003). CC -!- CATALYTIC ACTIVITY: ATP + L-citrulline + L-aspartate = AMP + CC diphosphate + N(omega)-(L-arginino)succinate. CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L- CC arginine from L-ornithine and carbamoyl phosphate: step 2/3. CC -!- PATHWAY: Nitrogen metabolism; urea cycle; N(omega)-(L- CC arginino)succinate from L-aspartate and L-citrulline: step 1/1. CC -!- SUBUNIT: Homotetramer. CC -!- INTERACTION: CC P10398:ARAF; NbExp=3; IntAct=EBI-536842, EBI-365961; CC -!- DISEASE: Defects in ASS1 are the cause of citrullinemia type 1 CC (CTLN1) [MIM:215700]. Citrullinemia belongs to the urea cycle CC disorders. It is an autosomal recessive disease characterized CC primarily by elevated serum and urine citrulline levels. Ammonia CC intoxication is another manifestation. CTLN1 usually manifests in CC the first few days of life. Affected infants appear normal at CC birth, but as ammonia builds up in the body they present symptoms CC such as lethargy, poor feeding, vomiting, seizures and loss of CC consciousness. Less commonly, a milder CTLN1 form can develop CC later in childhood or adulthood. CC -!- SIMILARITY: Belongs to the argininosuccinate synthase family. Type CC 1 subfamily. CC -!- WEB RESOURCE: NAME=GeneReviews; CC URL="http://www.genetests.org/query?gene=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; BC052288; AAH52288.1; ALT_INIT; mRNA. DR EMBL; M34903; AAA51782.1; -; Genomic_DNA. DR PIR; A01195; AJHURS. DR UniGene; Hs.160786; -. DR HSSP; P22767; 1KP2. DR IntAct; P00966; -. DR REPRODUCTION-2DPAGE; P00966; HUMAN. DR Ensembl; ENSG00000130707; Homo sapiens. DR KEGG; hsa:445; -. DR H-InvDB; HIX0008469; -. DR HGNC; HGNC:758; ASS1. DR HPA; CAB001953; -. DR MIM; 215700; phenotype. DR MIM; 603470; gene. DR Orphanet; 187; Citrullinemia. DR PharmGKB; PA30299; -. DR BioCyc; MetaCyc:MONOMER-11304; -. DR Reactome; REACT_13.1; Metabolism of amino acids and related nitrogen-containing molecules. DR LinkHub; P00966; -. DR ArrayExpress; P00966; -. DR GermOnline; ENSG00000130707; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0000050; P:urea cycle; TAS:ProtInc. DR InterPro; IPR001518; Arginosuc_synth. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR Gene3D; G3DSA:3.40.50.620; Rossmann-like_a/b/a_fold; 1. DR PANTHER; PTHR11587; Arginosuc_synth; 1. DR Pfam; PF00764; Arginosuc_synth; 1. DR TIGRFAMs; TIGR00032; argG; 1. DR PROSITE; PS00564; ARGININOSUCCIN_SYN_1; 1. DR PROSITE; PS00565; ARGININOSUCCIN_SYN_2; 1. PE 1: Evidence at protein level; KW Amino-acid biosynthesis; Arginine biosynthesis; ATP-binding; KW Direct protein sequencing; Disease mutation; Ligase; KW Nucleotide-binding; Urea cycle. FT CHAIN 1 412 Argininosuccinate synthase. FT /FTId=PRO_0000148554. FT NP_BIND 10 18 ATP (By similarity). FT NP_BIND 115 123 ATP (By similarity). FT BINDING 36 36 ATP; via amide nitrogen and carbonyl FT oxygen (By similarity). FT BINDING 87 87 Citrulline (By similarity). FT BINDING 92 92 Citrulline (By similarity). FT BINDING 119 119 Aspartate (By similarity). FT BINDING 123 123 Aspartate (By similarity). FT BINDING 123 123 Citrulline (By similarity). FT BINDING 124 124 Aspartate; via amide nitrogen (By FT similarity). FT BINDING 127 127 Citrulline (By similarity). FT BINDING 180 180 Citrulline (By similarity). FT BINDING 189 189 Citrulline (By similarity). FT BINDING 270 270 Citrulline (By similarity). FT BINDING 282 282 Citrulline (By similarity). FT VARIANT 14 14 G -> S (in CTLN1). FT /FTId=VAR_000681. FT VARIANT 18 18 S -> L (in CTLN1). FT /FTId=VAR_000682. FT VARIANT 19 19 C -> R (in CTLN1). FT /FTId=VAR_015891. FT VARIANT 69 69 V -> A (in CTLN1). FT /FTId=VAR_016013. FT VARIANT 86 86 R -> C (in CTLN1). FT /FTId=VAR_000683. FT VARIANT 86 86 R -> H (in CTLN1). FT /FTId=VAR_015892. FT VARIANT 95 95 R -> S (in CTLN1). FT /FTId=VAR_015893. FT VARIANT 96 96 P -> S (in CTLN1). FT /FTId=VAR_015894. FT VARIANT 108 108 R -> L (in CTLN1). FT /FTId=VAR_016014. FT VARIANT 117 117 G -> D (in CTLN1). FT /FTId=VAR_015896. FT VARIANT 117 117 G -> S (in CTLN1). FT /FTId=VAR_015895. FT VARIANT 118 118 A -> T (in CTLN1). FT /FTId=VAR_000684. FT VARIANT 119 119 T -> I (in CTLN1). FT /FTId=VAR_016015. FT VARIANT 157 157 R -> C (in CTLN1). FT /FTId=VAR_015897. FT VARIANT 157 157 R -> H (in CTLN1). FT /FTId=VAR_000685. FT VARIANT 179 179 W -> R (in CTLN1; mild). FT /FTId=VAR_015898. FT VARIANT 180 180 S -> N (in CTLN1). FT /FTId=VAR_000686. FT VARIANT 191 191 E -> K (in CTLN1). FT /FTId=VAR_015899. FT VARIANT 192 192 A -> V (in CTLN1). FT /FTId=VAR_000687. FT VARIANT 265 265 R -> H (in CTLN1). FT /FTId=VAR_015900. FT VARIANT 269 269 V -> M (in CTLN1). FT /FTId=VAR_015901. FT VARIANT 270 270 E -> Q (in CTLN1). FT /FTId=VAR_016007. FT VARIANT 272 272 R -> C (in CTLN1). FT /FTId=VAR_000688. FT VARIANT 279 279 R -> Q (in CTLN1). FT /FTId=VAR_016008. FT VARIANT 280 280 G -> R (in CTLN1). FT /FTId=VAR_000689. FT VARIANT 283 283 E -> K (in CTLN1). FT /FTId=VAR_015902. FT VARIANT 304 304 R -> W (in CTLN1). FT /FTId=VAR_000690. FT VARIANT 310 310 K -> Q (in CTLN1). FT /FTId=VAR_016009. FT VARIANT 310 310 K -> R (in CTLN1). FT /FTId=VAR_015903. FT VARIANT 324 324 G -> S (in CTLN1). FT /FTId=VAR_000691. FT VARIANT 362 362 G -> V (in CTLN1; mild). FT /FTId=VAR_015904. FT VARIANT 363 363 R -> G (in CTLN1). FT /FTId=VAR_016010. FT VARIANT 363 363 R -> L (in CTLN1). FT /FTId=VAR_000692. FT VARIANT 363 363 R -> Q (in CTLN1). FT /FTId=VAR_016011. FT VARIANT 363 363 R -> W (in CTLN1). FT /FTId=VAR_000693. FT VARIANT 389 389 T -> I (in CTLN1). FT /FTId=VAR_016012. FT VARIANT 390 390 G -> R (in CTLN1). FT /FTId=VAR_000694. FT CONFLICT 325 327 FWH -> LRP (in Ref. 1 and 2). 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 //