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-SEP-2011, entry version 137. DE RecName: Full=Argininosuccinate synthase; DE EC=6.3.4.5; DE AltName: Full=Citrulline--aspartate 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; 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 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; 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 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., RA Zhang C., 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-352, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18187866; DOI=10.2116/analsci.24.161; RA Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.; RT "Automated phosphoproteome analysis for cultured cancer cells by two- RT dimensional nanoLC-MS using a calcined titania/C18 biphasic column."; RL Anal. Sci. 24:161-166(2008). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-165, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [12] 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., RA Buerckstuemmer T., 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 [13] 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 [14] RP REVIEW ON VARIANTS. 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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). RN [21] RP VARIANTS CTLN1 SER-14; LEU-40; GLN-127; ARG-179; ASP-190; MET-263; RP MET-269; SER-324 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 [22] 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., RA Haeberle J., 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). 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. Interacts with NMRAL1. CC -!- INTERACTION: CC P10398:ARAF; NbExp=4; 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.ncbi.nlm.nih.gov/sites/GeneTests/lab/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; M34903; AAA51782.1; -; Genomic_DNA. DR IPI; IPI00020632; -. DR PIR; A01195; AJHURS. DR RefSeq; NP_000041.2; NM_000050.4. DR RefSeq; NP_446464.1; NM_054012.3. DR UniGene; Hs.160786; -. DR PDB; 2NZ2; X-ray; 2.40 A; A=1-412. DR PDBsum; 2NZ2; -. DR ProteinModelPortal; P00966; -. DR SMR; P00966; 4-407. DR IntAct; P00966; 10. DR MINT; MINT-5000467; -. DR STRING; P00966; -. DR PhosphoSite; P00966; -. DR PRIDE; P00966; -. DR Ensembl; ENST00000334909; ENSP00000361470; ENSG00000130707. DR Ensembl; ENST00000352480; ENSP00000253004; ENSG00000130707. DR Ensembl; ENST00000372393; ENSP00000361469; ENSG00000130707. DR Ensembl; ENST00000372394; ENSP00000361471; ENSG00000130707. DR GeneID; 445; -. DR KEGG; hsa:445; -. DR UCSC; uc004bzm.1; human. DR CTD; 445; -. DR GeneCards; GC09P102805; -. DR H-InvDB; HIX0008469; -. DR H-InvDB; HIX0025782; -. DR HGNC; HGNC:758; ASS1. DR HPA; HPA020896; -. DR HPA; HPA020934; -. DR MIM; 215700; phenotype. DR MIM; 603470; gene. DR neXtProt; NX_P00966; -. DR Orphanet; 247546; Acute neonatal citrullinemia type I. DR Orphanet; 247573; Adult-onset citrullinemia type I. DR PharmGKB; PA162376926; -. DR eggNOG; prNOG14130; -. DR HOGENOM; HBG335267; -. DR HOVERGEN; HBG001717; -. DR InParanoid; P00966; -. DR OMA; RANAIYE; -. DR OrthoDB; EOG45B1FK; -. DR PhylomeDB; P00966; -. DR BioCyc; MetaCyc:MONOMER-11304; -. DR Reactome; REACT_13; Metabolism of amino acids and derivatives. DR DrugBank; DB00171; Adenosine triphosphate. DR DrugBank; DB00125; L-Arginine. DR DrugBank; DB00128; L-Aspartic Acid. DR DrugBank; DB00155; L-Citrulline. DR NextBio; 1871; -. DR ArrayExpress; P00966; -. DR Bgee; P00966; -. DR CleanEx; HS_ASS1; -. DR Genevestigator; P00966; -. DR GermOnline; ENSG00000130707; Homo sapiens. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0004055; F:argininosuccinate synthase activity; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0006526; P:arginine biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0000050; P:urea cycle; TAS:Reactome. 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 Gene3D; G3DSA:3.90.1260.10; G3DSA:3.90.1260.10; 1. 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 3D-structure; Acetylation; Amino-acid biosynthesis; KW Arginine biosynthesis; ATP-binding; Complete proteome; KW Direct protein sequencing; Disease mutation; Ligase; KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; KW 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. FT BINDING 92 92 Citrulline. FT BINDING 119 119 Aspartate. FT BINDING 123 123 Aspartate. FT BINDING 123 123 Citrulline. FT BINDING 124 124 Aspartate. FT BINDING 127 127 Citrulline. FT BINDING 180 180 Citrulline. FT BINDING 189 189 Citrulline. FT BINDING 270 270 Citrulline. FT BINDING 282 282 Citrulline. FT MOD_RES 165 165 N6-acetyllysine. FT MOD_RES 352 352 Phosphoserine. 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 40 40 Q -> L (in CTLN1). FT /FTId=VAR_058337. FT VARIANT 65 65 S -> I (in dbSNP:rs2229556). FT /FTId=VAR_050427. FT VARIANT 69 69 V -> A (in CTLN1). FT /FTId=VAR_016013. FT VARIANT 79 79 S -> P (in CTLN1). FT /FTId=VAR_058338. 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 -> H (in CTLN1). FT /FTId=VAR_058339. FT VARIANT 96 96 P -> S (in CTLN1). FT /FTId=VAR_015894. FT VARIANT 108 108 R -> L (in CTLN1; dbSNP:rs35269064). 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 124 124 D -> N (in CTLN1). FT /FTId=VAR_058340. FT VARIANT 127 127 R -> Q (in CTLN1). FT /FTId=VAR_058341. FT VARIANT 127 127 R -> W (in CTLN1; severe clinical FT course). FT /FTId=VAR_058342. 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 160 160 L -> P (in CTLN1). FT /FTId=VAR_058343. 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 190 190 Y -> D (in CTLN1). FT /FTId=VAR_058344. FT VARIANT 191 191 E -> K (in CTLN1). FT /FTId=VAR_015899. FT VARIANT 191 191 E -> Q (in CTLN1). FT /FTId=VAR_058345. FT VARIANT 192 192 A -> V (in CTLN1). FT /FTId=VAR_000687. FT VARIANT 202 202 A -> E (in CTLN1). FT /FTId=VAR_058346. FT VARIANT 206 206 L -> P (in CTLN1). FT /FTId=VAR_058347. FT VARIANT 263 263 V -> M (in CTLN1; mild clinical course). FT /FTId=VAR_058348. FT VARIANT 265 265 R -> C (in CTLN1; severe clinical FT course). FT /FTId=VAR_058349. 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 277 277 K -> T (in CTLN1). FT /FTId=VAR_058350. 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 284 284 T -> I (in CTLN1; mild clinical course). FT /FTId=VAR_058351. FT VARIANT 291 291 Y -> S (in CTLN1). FT /FTId=VAR_058352. FT VARIANT 296 296 D -> G (in CTLN1). FT /FTId=VAR_058353. FT VARIANT 302 302 M -> V (in CTLN1). FT /FTId=VAR_058354. FT VARIANT 304 304 R -> W (in CTLN1). FT /FTId=VAR_000690. FT VARIANT 307 307 R -> C (in CTLN1). FT /FTId=VAR_058355. 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 324 324 G -> V (in CTLN1). FT /FTId=VAR_058356. FT VARIANT 341 341 S -> F (in CTLN1). FT /FTId=VAR_058357. FT VARIANT 345 345 V -> G (in CTLN1). FT /FTId=VAR_058358. FT VARIANT 347 347 G -> R (in CTLN1; severe clinical FT course). FT /FTId=VAR_058359. FT VARIANT 359 359 Y -> D (in CTLN1; mild clinical course). FT /FTId=VAR_058360. 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; CAA25771 and 2; FT AAA51783). FT STRAND 7 10 FT HELIX 16 26 FT STRAND 31 37 FT HELIX 44 53 FT STRAND 58 63 FT HELIX 65 71 FT HELIX 73 78 FT TURN 84 86 FT HELIX 94 108 FT STRAND 113 115 FT HELIX 124 135 FT STRAND 140 142 FT HELIX 144 146 FT HELIX 148 151 FT HELIX 158 166 FT STRAND 181 183 FT STRAND 188 190 FT TURN 213 215 FT STRAND 221 227 FT STRAND 232 238 FT HELIX 247 257 FT HELIX 289 301 FT HELIX 304 310 FT HELIX 316 322 FT HELIX 329 341 FT TURN 342 344 FT STRAND 349 353 FT STRAND 358 360 FT HELIX 372 375 FT HELIX 385 388 FT HELIX 392 404 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 //