NMNA1_HUMAN
ID NMNA1_HUMAN Reviewed; 279 AA.
AC Q9HAN9; B1AN63; Q8TAE9; Q9H247; Q9H6B6;
DT 09-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 {ECO:0000305};
DE Short=NMN/NaMN adenylyltransferase 1;
DE EC=2.7.7.1 {ECO:0000269|PubMed:17402747};
DE EC=2.7.7.18 {ECO:0000269|PubMed:17402747};
DE AltName: Full=Nicotinamide-nucleotide adenylyltransferase 1;
DE Short=NMN adenylyltransferase 1;
DE AltName: Full=Nicotinate-nucleotide adenylyltransferase 1;
DE Short=NaMN adenylyltransferase 1;
GN Name=NMNAT1 {ECO:0000312|HGNC:HGNC:17877}; Synonyms=NMNAT;
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 {ECO:0000312|EMBL:AAG33632.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 208-225 AND 262-272,
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH PARP1.
RX PubMed=11248244; DOI=10.1016/s0014-5793(01)02180-9;
RA Schweiger M., Hennig K., Lerner F., Niere M., Hirsch-Kauffmann M.,
RA Specht T., Weise C., Oei S.L., Ziegler M.;
RT "Characterization of recombinant human nicotinamide mononucleotide adenylyl
RT transferase (NMNAT), a nuclear enzyme essential for NAD synthesis.";
RL FEBS Lett. 492:95-100(2001).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 238-250 AND 262-272,
RP COFACTOR, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=11027696; DOI=10.1074/jbc.m008700200;
RA Emanuelli M., Carnevali F., Saccucci F., Pierella F., Amici A.,
RA Raffaelli N., Magni G.;
RT "Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial
RT expression, and enzymatic properties of human NMN adenylyltransferase.";
RL J. Biol. Chem. 276:406-412(2001).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11891043; DOI=10.1016/s0378-1119(02)00394-3;
RA Fernando F.S., Conforti L., Tosi S., Smith A.D., Coleman M.P.;
RT "Human homologue of a gene mutated in the slow Wallerian degeneration
RT (C57BL/Wld(s)) mouse.";
RL Gene 284:23-29(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovium;
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 GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6] {ECO:0000312|EMBL:BAB15345.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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=Eye;
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 SUBCELLULAR LOCATION.
RX PubMed=12574164; DOI=10.1074/jbc.m300073200;
RA Zhang X., Kurnasov O.V., Karthikeyan S., Grishin N.V., Osterman A.L.,
RA Zhang H.;
RT "Structural characterization of a human cytosolic NMN/NaMN
RT adenylyltransferase and implication in human NAD biosynthesis.";
RL J. Biol. Chem. 278:13503-13511(2003).
RN [9]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX PubMed=16118205; DOI=10.1074/jbc.m508660200;
RA Berger F., Lau C., Dahlmann M., Ziegler M.;
RT "Subcellular compartmentation and differential catalytic properties of the
RT three human nicotinamide mononucleotide adenylyltransferase isoforms.";
RL J. Biol. Chem. 280:36334-36341(2005).
RN [10]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, COFACTOR, AND
RP CATALYTIC ACTIVITY.
RX PubMed=17402747; DOI=10.1021/bi6023379;
RA Sorci L., Cimadamore F., Scotti S., Petrelli R., Cappellacci L.,
RA Franchetti P., Orsomando G., Magni G.;
RT "Initial-rate kinetics of human NMN-adenylyltransferases: substrate and
RT metal ion specificity, inhibition by products and multisubstrate analogues,
RT and isozyme contributions to NAD+ biosynthesis.";
RL Biochemistry 46:4912-4922(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [12]
RP SUBCELLULAR LOCATION, VARIANTS LCA9 THR-13; PHE-67; GLY-98; PHE-151;
RP TRP-207; LEU-237; LYS-257 AND ASP-273, AND CHARACTERIZATION OF VARIANTS
RP LCA9 TRP-207; LYS-257 AND ASP-273.
RX PubMed=22842230; DOI=10.1038/ng.2356;
RA Koenekoop R.K., Wang H., Majewski J., Wang X., Lopez I., Ren H., Chen Y.,
RA Li Y., Fishman G.A., Genead M., Schwartzentruber J., Solanki N.,
RA Traboulsi E.I., Cheng J., Logan C.V., McKibbin M., Hayward B.E.,
RA Parry D.A., Johnson C.A., Nageeb M., Poulter J.A., Mohamed M.D., Jafri H.,
RA Rashid Y., Taylor G.R., Keser V., Mardon G., Xu H., Inglehearn C.F., Fu Q.,
RA Toomes C., Chen R.;
RT "Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new
RT disease pathway for retinal degeneration.";
RL Nat. Genet. 44:1035-1039(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117 AND THR-119, 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 [15]
RP FUNCTION.
RX PubMed=27257257; DOI=10.1126/science.aad9335;
RA Wright R.H., Lioutas A., Le Dily F., Soronellas D., Pohl A., Bonet J.,
RA Nacht A.S., Samino S., Font-Mateu J., Vicent G.P., Wierer M., Trabado M.A.,
RA Schelhorn C., Carolis C., Macias M.J., Yanes O., Oliva B., Beato M.;
RT "ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for
RT chromatin remodeling.";
RL Science 352:1221-1225(2016).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 5-278 IN COMPLEX WITH SUBSTRATE
RP NMN.
RX PubMed=11959140; DOI=10.1016/s0014-5793(02)02556-5;
RA Werner E., Ziegler M., Lerner F., Schweiger M., Heinemann U.;
RT "Crystal structure of human nicotinamide mononucleotide adenylyltransferase
RT in complex with NMN.";
RL FEBS Lett. 516:239-244(2002).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=11751893; DOI=10.1074/jbc.m111589200;
RA Garavaglia S., D'Angelo I., Emanuelli M., Carnevali F., Pierella F.,
RA Magni G., Rizzi M.;
RT "Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD
RT homeostasis.";
RL J. Biol. Chem. 277:8524-8530(2002).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH PRODUCTS NAD AND
RP NAAD.
RX PubMed=11788603; DOI=10.1074/jbc.m111469200;
RA Zhou T., Kurnasov O., Tomchick D.R., Binns D.D., Grishin N.V.,
RA Marquez V.E., Osterman A.L., Zhang H.;
RT "Structure of human nicotinamide/nicotinic acid mononucleotide
RT adenylyltransferase. Basis for the dual substrate specificity and
RT activation of the oncolytic agent tiazofurin.";
RL J. Biol. Chem. 277:13148-13154(2002).
RN [19]
RP INVOLVEMENT IN SHILCA.
RX PubMed=32533184; DOI=10.1093/hmg/ddaa112;
RG TUDP (Telethon Undiagnosed Disease Program);
RA Bedoni N., Quinodoz M., Pinelli M., Cappuccio G., Torella A., Nigro V.,
RA Testa F., Simonelli F., Corton M., Lualdi S., Lanza F., Morana G.,
RA Ayuso C., Di Rocco M., Filocamo M., Banfi S., Brunetti-Pierri N.,
RA Superti-Furga A., Rivolta C.;
RT "An Alu-mediated duplication in NMNAT1, involved in NAD biosynthesis,
RT causes a novel syndrome, SHILCA, affecting multiple tissues and organs.";
RL Hum. Mol. Genet. 29:2250-2260(2020).
RN [20]
RP VARIANTS LCA9 THR-35; GLY-98; PHE-151; VAL-153; LYS-257 AND ASP-273.
RX PubMed=22842231; DOI=10.1038/ng.2370;
RA Chiang P.W., Wang J., Chen Y., Fu Q., Zhong J., Chen Y., Yi X., Wu R.,
RA Gan H., Shi Y., Chen Y., Barnett C., Wheaton D., Day M., Sutherland J.,
RA Heon E., Weleber R.G., Gabriel L.A., Cong P., Chuang K., Ye S.,
RA Sallum J.M., Qi M.;
RT "Exome sequencing identifies NMNAT1 mutations as a cause of Leber
RT congenital amaurosis.";
RL Nat. Genet. 44:972-974(2012).
RN [21]
RP VARIANTS LCA9 THR-13; VAL-69; PRO-147; PRO-153; GLY-173; MET-178; CYS-181;
RP TRP-207; ASN-217; CYS-237; SER-239 AND PRO-251.
RX PubMed=22842229; DOI=10.1038/ng.2357;
RA Perrault I., Hanein S., Zanlonghi X., Serre V., Nicouleau M.,
RA Defoort-Delhemmes S., Delphin N., Fares-Taie L., Gerber S., Xerri O.,
RA Edelson C., Goldenberg A., Duncombe A., Le Meur G., Hamel C., Silva E.,
RA Nitschke P., Calvas P., Munnich A., Roche O., Dollfus H., Kaplan J.,
RA Rozet J.M.;
RT "Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset
RT severe macular and optic atrophy.";
RL Nat. Genet. 44:975-977(2012).
RN [22]
RP VARIANTS LCA9 MET-9; THR-13; ASN-20; GLY-33; VAL-54; TRP-66; VAL-69;
RP HIS-72; GLY-98; ARG-156; MET-184; CYS-237 AND LYS-257, AND CHARACTERIZATION
RP OF VARIANTS LCA9 MET-9; TRP-66 AND CYS-237.
RX PubMed=22842227; DOI=10.1038/ng.2361;
RA Falk M.J., Zhang Q., Nakamaru-Ogiso E., Kannabiran C., Fonseca-Kelly Z.,
RA Chakarova C., Audo I., Mackay D.S., Zeitz C., Borman A.D., Staniszewska M.,
RA Shukla R., Palavalli L., Mohand-Said S., Waseem N.H., Jalali S.,
RA Perin J.C., Place E., Ostrovsky J., Xiao R., Bhattacharya S.S.,
RA Consugar M., Webster A.R., Sahel J.A., Moore A.T., Berson E.L., Liu Q.,
RA Gai X., Pierce E.A.;
RT "NMNAT1 mutations cause Leber congenital amaurosis.";
RL Nat. Genet. 44:1040-1045(2012).
CC -!- FUNCTION: Catalyzes the formation of NAD(+) from nicotinamide
CC mononucleotide (NMN) and ATP (PubMed:17402747). Can also use the
CC deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with
CC the same efficiency (PubMed:17402747). Can use triazofurin
CC monophosphate (TrMP) as substrate (PubMed:17402747). Also catalyzes the
CC reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+)
CC (PubMed:17402747). For the pyrophosphorolytic activity, prefers NAD(+)
CC and NaAD as substrates and degrades NADH, nicotinic acid adenine
CC dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide
CC (NGD) less effectively (PubMed:17402747). Involved in the synthesis of
CC ATP in the nucleus, together with PARP1, PARG and NUDT5
CC (PubMed:27257257). Nuclear ATP generation is required for extensive
CC chromatin remodeling events that are energy-consuming
CC (PubMed:27257257). Fails to cleave phosphorylated dinucleotides
CC NADP(+), NADPH and NaADP(+) (PubMed:17402747). Protects against axonal
CC degeneration following mechanical or toxic insults (By similarity).
CC {ECO:0000250|UniProtKB:Q9EPA7, ECO:0000269|PubMed:17402747,
CC ECO:0000269|PubMed:27257257}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-nicotinamide D-ribonucleotide + H(+) = diphosphate
CC + NAD(+); Xref=Rhea:RHEA:21360, ChEBI:CHEBI:14649, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57540; EC=2.7.7.1;
CC Evidence={ECO:0000269|PubMed:11027696, ECO:0000269|PubMed:17402747};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21361;
CC Evidence={ECO:0000305|PubMed:17402747};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21362;
CC Evidence={ECO:0000305|PubMed:17402747};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H(+) + nicotinate beta-D-ribonucleotide = deamido-NAD(+)
CC + diphosphate; Xref=Rhea:RHEA:22860, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57502,
CC ChEBI:CHEBI:58437; EC=2.7.7.18;
CC Evidence={ECO:0000269|PubMed:17402747};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22861;
CC Evidence={ECO:0000305|PubMed:17402747};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22862;
CC Evidence={ECO:0000305|PubMed:17402747};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11027696, ECO:0000269|PubMed:17402747};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11027696, ECO:0000269|PubMed:17402747};
CC Note=Divalent metal cations. Zn(2+) confers higher activity as compared
CC to Mg(2+). {ECO:0000269|PubMed:11027696, ECO:0000269|PubMed:17402747};
CC -!- ACTIVITY REGULATION: Activity is strongly inhibited by galotannin.
CC Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-
CC tetraphosphate (Nap4AD). {ECO:0000269|PubMed:17402747}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=34 uM for beta-nicotinamide D-ribonucleotide
CC {ECO:0000269|PubMed:16118205, ECO:0000269|PubMed:17402747};
CC KM=40 uM for ATP {ECO:0000269|PubMed:16118205,
CC ECO:0000269|PubMed:17402747};
CC KM=937 uM for PPi {ECO:0000269|PubMed:16118205,
CC ECO:0000269|PubMed:17402747};
CC KM=59 uM for NAD(+) {ECO:0000269|PubMed:16118205,
CC ECO:0000269|PubMed:17402747};
CC Vmax=25 umol/min/mg enzyme for NAD synthesis
CC {ECO:0000269|PubMed:16118205, ECO:0000269|PubMed:17402747};
CC Vmax=60.5 umol/min/ug enzyme for NAD(+) cleavage
CC {ECO:0000269|PubMed:16118205, ECO:0000269|PubMed:17402747};
CC Vmax=8.5 umol/min/ug enzyme for NADH cleavage
CC {ECO:0000269|PubMed:16118205, ECO:0000269|PubMed:17402747};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC nicotinamide D-ribonucleotide: step 1/1. {ECO:0000305|PubMed:17402747}.
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; deamido-NAD(+)
CC from nicotinate D-ribonucleotide: step 1/1.
CC {ECO:0000305|PubMed:17402747}.
CC -!- SUBUNIT: Homohexamer. Interacts with ADPRT/PARP1.
CC {ECO:0000269|PubMed:11248244, ECO:0000269|PubMed:11751893}.
CC -!- INTERACTION:
CC Q9HAN9; A0A0S2Z5G4: BANP; NbExp=3; IntAct=EBI-3917542, EBI-16429704;
CC Q9HAN9; B4DE54: BANP; NbExp=4; IntAct=EBI-3917542, EBI-16429313;
CC Q9HAN9; Q8N9N5-2: BANP; NbExp=7; IntAct=EBI-3917542, EBI-11524452;
CC Q9HAN9; P24863: CCNC; NbExp=4; IntAct=EBI-3917542, EBI-395261;
CC Q9HAN9; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-3917542, EBI-739467;
CC Q9HAN9; P52294: KPNA1; NbExp=3; IntAct=EBI-3917542, EBI-358383;
CC Q9HAN9; P52292: KPNA2; NbExp=8; IntAct=EBI-3917542, EBI-349938;
CC Q9HAN9; O00505: KPNA3; NbExp=3; IntAct=EBI-3917542, EBI-358297;
CC Q9HAN9; O60684: KPNA6; NbExp=3; IntAct=EBI-3917542, EBI-359923;
CC Q9HAN9; Q8NCF5-2: NFATC2IP; NbExp=3; IntAct=EBI-3917542, EBI-12305293;
CC Q9HAN9; Q9HAN9: NMNAT1; NbExp=9; IntAct=EBI-3917542, EBI-3917542;
CC Q9HAN9; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-3917542, EBI-79165;
CC Q9HAN9; P78317: RNF4; NbExp=3; IntAct=EBI-3917542, EBI-2340927;
CC Q9HAN9; Q96EB6: SIRT1; NbExp=3; IntAct=EBI-3917542, EBI-1802965;
CC Q9HAN9; P48775: TDO2; NbExp=4; IntAct=EBI-3917542, EBI-743494;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11248244,
CC ECO:0000269|PubMed:12574164, ECO:0000269|PubMed:16118205,
CC ECO:0000269|PubMed:22842230}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in skeletal
CC muscle, heart and kidney. Also expressed in the liver pancreas and
CC placenta. Widely expressed throughout the brain.
CC {ECO:0000269|PubMed:11027696, ECO:0000269|PubMed:11891043}.
CC -!- DISEASE: Leber congenital amaurosis 9 (LCA9) [MIM:608553]: A severe
CC dystrophy of the retina, typically becoming evident in the first years
CC of life. Visual function is usually poor and often accompanied by
CC nystagmus, sluggish or near-absent pupillary responses, photophobia,
CC high hyperopia and keratoconus. {ECO:0000269|PubMed:22842227,
CC ECO:0000269|PubMed:22842229, ECO:0000269|PubMed:22842230,
CC ECO:0000269|PubMed:22842231}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Spondyloepiphyseal dysplasia, sensorineural hearing loss,
CC impaired intellectual development, and Leber congenital amaurosis
CC (SHILCA) [MIM:619260]: An autosomal recessive disorder characterized by
CC early-onset retinal degeneration, sensorineural hearing loss, short
CC stature due to spondyloepiphyseal dysplasia, and motor and intellectual
CC delay. Brain imaging shows abnormalities including delayed myelination,
CC leukoencephalopathy, and cerebellar hypoplasia.
CC {ECO:0000269|PubMed:32533184}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase family.
CC {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; AF314163; AAG33632.1; -; mRNA.
DR EMBL; AF312734; AAG33629.1; -; mRNA.
DR EMBL; AF459819; AAL76934.1; -; mRNA.
DR EMBL; AF459823; AAL76935.1; -; Genomic_DNA.
DR EMBL; AF459820; AAL76935.1; JOINED; Genomic_DNA.
DR EMBL; AF459821; AAL76935.1; JOINED; Genomic_DNA.
DR EMBL; AF459822; AAL76935.1; JOINED; Genomic_DNA.
DR EMBL; AK026065; BAB15345.1; -; mRNA.
DR EMBL; AK315640; BAG38007.1; -; mRNA.
DR EMBL; AL603962; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71635.1; -; Genomic_DNA.
DR EMBL; BC014943; AAH14943.1; -; mRNA.
DR CCDS; CCDS108.1; -.
DR RefSeq; NP_001284707.1; NM_001297778.1.
DR RefSeq; NP_073624.2; NM_022787.3.
DR RefSeq; XP_016857596.1; XM_017002107.1.
DR PDB; 1GZU; X-ray; 2.90 A; A/B/C=2-279.
DR PDB; 1KKU; X-ray; 2.50 A; A=1-279.
DR PDB; 1KQN; X-ray; 2.20 A; A/B/C/D/E/F=1-279.
DR PDB; 1KQO; X-ray; 2.50 A; A/B/C/D/E/F=1-279.
DR PDB; 1KR2; X-ray; 2.30 A; A/B/C/D/E/F=1-279.
DR PDBsum; 1GZU; -.
DR PDBsum; 1KKU; -.
DR PDBsum; 1KQN; -.
DR PDBsum; 1KQO; -.
DR PDBsum; 1KR2; -.
DR AlphaFoldDB; Q9HAN9; -.
DR SMR; Q9HAN9; -.
DR BioGRID; 122308; 180.
DR DIP; DIP-60881N; -.
DR IntAct; Q9HAN9; 50.
DR MINT; Q9HAN9; -.
DR STRING; 9606.ENSP00000366410; -.
DR ChEMBL; CHEMBL4802016; -.
DR DrugBank; DB04099; Deamido-Nad.
DR DrugBank; DB03227; Nicotinamide Mononucleotide.
DR iPTMnet; Q9HAN9; -.
DR PhosphoSitePlus; Q9HAN9; -.
DR BioMuta; NMNAT1; -.
DR DMDM; 30580491; -.
DR EPD; Q9HAN9; -.
DR jPOST; Q9HAN9; -.
DR MassIVE; Q9HAN9; -.
DR MaxQB; Q9HAN9; -.
DR PaxDb; Q9HAN9; -.
DR PeptideAtlas; Q9HAN9; -.
DR PRIDE; Q9HAN9; -.
DR ProteomicsDB; 81410; -.
DR Antibodypedia; 27787; 265 antibodies from 31 providers.
DR DNASU; 64802; -.
DR Ensembl; ENST00000377205.6; ENSP00000366410.1; ENSG00000173614.14.
DR Ensembl; ENST00000462686.1; ENSP00000435134.1; ENSG00000173614.14.
DR GeneID; 64802; -.
DR KEGG; hsa:64802; -.
DR MANE-Select; ENST00000377205.6; ENSP00000366410.1; NM_022787.4; NP_073624.2.
DR UCSC; uc001aqp.3; human.
DR CTD; 64802; -.
DR DisGeNET; 64802; -.
DR GeneCards; NMNAT1; -.
DR HGNC; HGNC:17877; NMNAT1.
DR HPA; ENSG00000173614; Low tissue specificity.
DR MalaCards; NMNAT1; -.
DR MIM; 608553; phenotype.
DR MIM; 608700; gene.
DR MIM; 619260; phenotype.
DR neXtProt; NX_Q9HAN9; -.
DR OpenTargets; ENSG00000173614; -.
DR Orphanet; 1872; Cone rod dystrophy.
DR Orphanet; 65; Leber congenital amaurosis.
DR PharmGKB; PA31660; -.
DR VEuPathDB; HostDB:ENSG00000173614; -.
DR eggNOG; KOG3199; Eukaryota.
DR GeneTree; ENSGT00950000183179; -.
DR HOGENOM; CLU_033366_3_0_1; -.
DR InParanoid; Q9HAN9; -.
DR OMA; QPWKENI; -.
DR OrthoDB; 1308027at2759; -.
DR PhylomeDB; Q9HAN9; -.
DR TreeFam; TF315035; -.
DR BioCyc; MetaCyc:HS10701-MON; -.
DR BRENDA; 2.7.7.1; 2681.
DR BRENDA; 2.7.7.18; 2681.
DR PathwayCommons; Q9HAN9; -.
DR Reactome; R-HSA-196807; Nicotinate metabolism.
DR SABIO-RK; Q9HAN9; -.
DR SignaLink; Q9HAN9; -.
DR UniPathway; UPA00253; UER00332.
DR UniPathway; UPA00253; UER00600.
DR BioGRID-ORCS; 64802; 134 hits in 1078 CRISPR screens.
DR ChiTaRS; NMNAT1; human.
DR EvolutionaryTrace; Q9HAN9; -.
DR GeneWiki; NMNAT1; -.
DR GenomeRNAi; 64802; -.
DR Pharos; Q9HAN9; Tbio.
DR PRO; PR:Q9HAN9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9HAN9; protein.
DR Bgee; ENSG00000173614; Expressed in hindlimb stylopod muscle and 151 other tissues.
DR ExpressionAtlas; Q9HAN9; baseline and differential.
DR Genevisible; Q9HAN9; HS.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:1990966; P:ATP generation from poly-ADP-D-ribose; IDA:UniProtKB.
DR GO; GO:0009435; P:NAD biosynthetic process; IBA:GO_Central.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0009165; P:nucleotide biosynthetic process; IC:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR CDD; cd09286; NMNAT_Eukarya; 1.
DR DisProt; DP01165; -.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR004821; Cyt_trans-like.
DR InterPro; IPR005248; NadD/NMNAT.
DR InterPro; IPR045094; NMNAT_euk.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR Pfam; PF01467; CTP_transf_like; 1.
DR TIGRFAMs; TIGR00482; TIGR00482; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Deafness; Direct protein sequencing;
KW Disease variant; Dwarfism; Intellectual disability;
KW Leber congenital amaurosis; Magnesium; NAD; Nucleotide-binding;
KW Nucleotidyltransferase; Nucleus; Phosphoprotein;
KW Pyridine nucleotide biosynthesis; Reference proteome; Transferase; Zinc.
FT CHAIN 1..279
FT /note="Nicotinamide/nicotinic acid mononucleotide
FT adenylyltransferase 1"
FT /id="PRO_0000135012"
FT REGION 107..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 123..129
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 119..144
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 15..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66,
FT ECO:0000305|PubMed:11788603"
FT BINDING 24
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 55..57
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11959140"
FT BINDING 58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 92..95
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11788603,
FT ECO:0000269|PubMed:11959140"
FT BINDING 156..158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 168..169
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11788603,
FT ECO:0000269|PubMed:11959140"
FT BINDING 224..227
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 119
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 9
FT /note="V -> M (in LCA9; does not affect nuclear
FT localization; results in significantly reduced enzymatic
FT activity; dbSNP:rs387907294)"
FT /evidence="ECO:0000269|PubMed:22842227"
FT /id="VAR_068856"
FT VARIANT 13
FT /note="A -> T (in LCA9; dbSNP:rs138613460)"
FT /evidence="ECO:0000269|PubMed:22842227,
FT ECO:0000269|PubMed:22842229, ECO:0000269|PubMed:22842230"
FT /id="VAR_068857"
FT VARIANT 20
FT /note="I -> N (in LCA9; dbSNP:rs761948762)"
FT /evidence="ECO:0000269|PubMed:22842227"
FT /id="VAR_068858"
FT VARIANT 33
FT /note="D -> G (in LCA9)"
FT /evidence="ECO:0000269|PubMed:22842227"
FT /id="VAR_068859"
FT VARIANT 35
FT /note="M -> T (in LCA9)"
FT /evidence="ECO:0000269|PubMed:22842231"
FT /id="VAR_068860"
FT VARIANT 54
FT /note="A -> V (in LCA9; dbSNP:rs760965874)"
FT /evidence="ECO:0000269|PubMed:22842227"
FT /id="VAR_068861"
FT VARIANT 66
FT /note="R -> W (in LCA9; does not affect nuclear
FT localization; results in significantly reduced enzymatic
FT activity; dbSNP:rs763325435)"
FT /evidence="ECO:0000269|PubMed:22842227"
FT /id="VAR_068862"
FT VARIANT 67
FT /note="V -> F (in LCA9; dbSNP:rs756903689)"
FT /evidence="ECO:0000269|PubMed:22842230"
FT /id="VAR_068863"
FT VARIANT 69
FT /note="M -> V (in LCA9; dbSNP:rs372066126)"
FT /evidence="ECO:0000269|PubMed:22842227,
FT ECO:0000269|PubMed:22842229"
FT /id="VAR_068864"
FT VARIANT 72
FT /note="L -> H (in LCA9)"
FT /evidence="ECO:0000269|PubMed:22842227"
FT /id="VAR_068865"
FT VARIANT 98
FT /note="V -> G (in LCA9; dbSNP:rs771336246)"
FT /evidence="ECO:0000269|PubMed:22842227,
FT ECO:0000269|PubMed:22842230, ECO:0000269|PubMed:22842231"
FT /id="VAR_068866"
FT VARIANT 147
FT /note="A -> P (in LCA9)"
FT /evidence="ECO:0000269|PubMed:22842229"
FT /id="VAR_068867"
FT VARIANT 151
FT /note="V -> F (in LCA9; dbSNP:rs387907292)"
FT /evidence="ECO:0000269|PubMed:22842230,
FT ECO:0000269|PubMed:22842231"
FT /id="VAR_068868"
FT VARIANT 153
FT /note="L -> P (in LCA9)"
FT /evidence="ECO:0000269|PubMed:22842229"
FT /id="VAR_068869"
FT VARIANT 153
FT /note="L -> V (in LCA9; dbSNP:rs387907293)"
FT /evidence="ECO:0000269|PubMed:22842231"
FT /id="VAR_068870"
FT VARIANT 156
FT /note="G -> R (in LCA9; dbSNP:rs1244511644)"
FT /evidence="ECO:0000269|PubMed:22842227"
FT /id="VAR_068871"
FT VARIANT 173
FT /note="D -> G (in LCA9)"
FT /evidence="ECO:0000269|PubMed:22842229"
FT /id="VAR_068872"
FT VARIANT 178
FT /note="V -> M (in LCA9; dbSNP:rs757724544)"
FT /evidence="ECO:0000269|PubMed:22842229"
FT /id="VAR_068873"
FT VARIANT 181
FT /note="Y -> C (in LCA9; dbSNP:rs748913297)"
FT /evidence="ECO:0000269|PubMed:22842229"
FT /id="VAR_068874"
FT VARIANT 184
FT /note="I -> M (in LCA9)"
FT /evidence="ECO:0000269|PubMed:22842227"
FT /id="VAR_068875"
FT VARIANT 207
FT /note="R -> W (in LCA9; results in significantly reduced
FT enzymatic activity; dbSNP:rs142968179)"
FT /evidence="ECO:0000269|PubMed:22842229,
FT ECO:0000269|PubMed:22842230"
FT /id="VAR_068876"
FT VARIANT 217
FT /note="I -> N (in LCA9)"
FT /evidence="ECO:0000269|PubMed:22842229"
FT /id="VAR_068877"
FT VARIANT 237
FT /note="R -> C (in LCA9; does not affect nuclear
FT localization; dbSNP:rs375110174)"
FT /evidence="ECO:0000269|PubMed:22842227,
FT ECO:0000269|PubMed:22842229"
FT /id="VAR_068878"
FT VARIANT 237
FT /note="R -> L (in LCA9; dbSNP:rs368062092)"
FT /evidence="ECO:0000269|PubMed:22842230"
FT /id="VAR_068879"
FT VARIANT 239
FT /note="L -> S (in LCA9; dbSNP:rs778606847)"
FT /evidence="ECO:0000269|PubMed:22842229"
FT /id="VAR_068880"
FT VARIANT 251
FT /note="H -> P (in LCA9; dbSNP:rs1208495291)"
FT /evidence="ECO:0000269|PubMed:22842229"
FT /id="VAR_068881"
FT VARIANT 257
FT /note="E -> K (in LCA9; results in significantly reduced
FT enzymatic activity; the mutant localizes to the cytoplasm;
FT dbSNP:rs150726175)"
FT /evidence="ECO:0000269|PubMed:22842227,
FT ECO:0000269|PubMed:22842230, ECO:0000269|PubMed:22842231"
FT /id="VAR_068882"
FT VARIANT 273
FT /note="N -> D (in LCA9; results in significantly reduced
FT enzymatic activity; dbSNP:rs387907291)"
FT /evidence="ECO:0000269|PubMed:22842230,
FT ECO:0000269|PubMed:22842231"
FT /id="VAR_068883"
FT CONFLICT 20
FT /note="I -> F (in Ref. 2; AAL76934/AAL76935)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="I -> F (in Ref. 3; AAG33629)"
FT /evidence="ECO:0000305"
FT STRAND 7..15
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 22..37
FT /evidence="ECO:0007829|PDB:1KQN"
FT STRAND 39..50
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 63..73
FT /evidence="ECO:0007829|PDB:1KQN"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:1KQN"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 95..106
FT /evidence="ECO:0007829|PDB:1KQN"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 157..162
FT /evidence="ECO:0007829|PDB:1KQN"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 171..180
FT /evidence="ECO:0007829|PDB:1KQN"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 190..198
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 201..205
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:1KQN"
FT STRAND 210..214
FT /evidence="ECO:0007829|PDB:1KQN"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:1KR2"
FT HELIX 223..231
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:1KQN"
FT TURN 260..264
FT /evidence="ECO:0007829|PDB:1KQN"
FT HELIX 268..274
FT /evidence="ECO:0007829|PDB:1KQN"
SQ SEQUENCE 279 AA; 31932 MW; 740DE872CD9C22E7 CRC64;
MENSEKTEVV LLACGSFNPI TNMHLRLFEL AKDYMNGTGR YTVVKGIISP VGDAYKKKGL
IPAYHRVIMA ELATKNSKWV EVDTWESLQK EWKETLKVLR HHQEKLEASD CDHQQNSPTL
ERPGRKRKWT ETQDSSQKKS LEPKTKAVPK VKLLCGADLL ESFAVPNLWK SEDITQIVAN
YGLICVTRAG NDAQKFIYES DVLWKHRSNI HVVNEWIAND ISSTKIRRAL RRGQSIRYLV
PDLVQEYIEK HNLYSSESED RNAGVILAPL QRNTAEAKT
