MOCS1_HUMAN
ID MOCS1_HUMAN Reviewed; 636 AA.
AC Q9NZB8; B3KPT7; B4DTP1; O14940; O14941; O75710; Q5J7W0; Q5TCE1; Q5TCE2;
AC Q5TCE6; Q5TCE9; Q5TCF0; Q5TCF1; Q8N418; Q9NZB7; Q9UEM1;
DT 09-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2003, sequence version 3.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Molybdenum cofactor biosynthesis protein 1;
DE AltName: Full=Cell migration-inducing gene 11 protein;
DE AltName: Full=Molybdenum cofactor synthesis-step 1 protein A-B;
DE Includes:
DE RecName: Full=GTP 3',8-cyclase {ECO:0000305};
DE EC=4.1.99.22 {ECO:0000250|UniProtKB:P69848};
DE AltName: Full=Molybdenum cofactor biosynthesis protein A;
DE Includes:
DE RecName: Full=Cyclic pyranopterin monophosphate synthase {ECO:0000305};
DE EC=4.6.1.17 {ECO:0000269|PubMed:23627491};
DE AltName: Full=Molybdenum cofactor biosynthesis protein C;
GN Name=MOCS1; ORFNames=MIG11;
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 [GENOMIC DNA / MRNA] (ISOFORMS MOCS1A; 2 AND 8),
RP INVOLVEMENT IN MOCODA, AND TISSUE SPECIFICITY.
RX PubMed=9731530; DOI=10.1038/1706;
RA Reiss J.P., Cohen N., Dorche C., Mandel H., Mendel R.R., Stallmeyer B.,
RA Zabot M.-T., Dierks T.;
RT "Mutations in a polycistronic nuclear gene associated with molybdenum
RT cofactor deficiency.";
RL Nat. Genet. 20:51-53(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MOCS1A AND MOCS1B).
RA Larin D., Ross B.M., Gilliam T.C.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS MOCS1A AND 7).
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Colon, and Kidney;
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 [MRNA] OF 283-636 (ISOFORM 6), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 377-636 (ISOFORM MOCS1B).
RX PubMed=10917590; DOI=10.1017/s1355838200000182;
RA Gray T.A., Nicholls R.D.;
RT "Diverse splicing mechanisms fuse the evolutionarily conserved bicistronic
RT MOCS1A and MOCS1B open reading frames.";
RL RNA 6:928-936(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 386-636.
RA Kim J.W.;
RT "Identification of a human migration-inducing gene.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, AND ALTERNATIVE SPLICING (ISOFORMS MOCS1A AND MOCS1B).
RX PubMed=11891227; DOI=10.1074/jbc.m200947200;
RA Haenzelmann P., Schwarz G., Mendel R.R.;
RT "Functionality of alternative splice forms of the first enzymes involved in
RT human molybdenum cofactor biosynthesis.";
RL J. Biol. Chem. 277:18303-18312(2002).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORMS MOCS1A; 2 AND 3), AND TISSUE SPECIFICITY.
RX PubMed=12208140; DOI=10.1016/s1096-7192(02)00100-2;
RA Gross-Hardt S., Reiss J.;
RT "The bicistronic MOCS1 gene has alternative start codons on two mutually
RT exclusive exons.";
RL Mol. Genet. Metab. 76:340-343(2002).
RN [10]
RP COFACTOR, CHARACTERIZATION OF IRON-SULFUR CLUSTER-BINDING, AND MUTAGENESIS
RP OF CYS-80; CYS-84; CYS-87; CYS-312; CYS-315 AND CYS-329.
RX PubMed=15180982; DOI=10.1074/jbc.m313398200;
RA Haenzelmann P., Hernandez H.L., Menzel C., Garcia-Serres R., Huynh B.H.,
RA Johnson M.K., Mendel R.R., Schindelin H.;
RT "Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein
RT involved in human molybdenum cofactor biosynthesis.";
RL J. Biol. Chem. 279:34721-34732(2004).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-198, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
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 FUNCTION, CATALYTIC ACTIVITY OF MOCS1B, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23627491; DOI=10.1021/ja401781t;
RA Hover B.M., Loksztejn A., Ribeiro A.A., Yokoyama K.;
RT "Identification of a cyclic nucleotide as a cryptic intermediate in
RT molybdenum cofactor biosynthesis.";
RL J. Am. Chem. Soc. 135:7019-7032(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, 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 REVISION OF PTM.
RX PubMed=25697423; DOI=10.1021/ja512997j;
RA Hover B.M., Yokoyama K.;
RT "C-Terminal glycine-gated radical initiation by GTP 3',8-cyclase in the
RT molybdenum cofactor biosynthesis.";
RL J. Am. Chem. Soc. 137:3352-3359(2015).
RN [15]
RP VARIANTS MOCODA TRP-73; ASP-126; ASP-127; GLN-319 AND GLU-324.
RX PubMed=9921896; DOI=10.1007/s004390050884;
RA Reiss J.P., Christensen E., Kurlemann G., Zabot M.-T., Dorche C.;
RT "Genomic structure and mutational spectrum of the bicistronic MOCS1 gene
RT defective in molybdenum cofactor deficiency type A.";
RL Hum. Genet. 103:639-644(1998).
RN [16]
RP VARIANTS MOCODA TRP-123 AND ARG-324.
RX PubMed=12754701; DOI=10.1002/humu.10223;
RA Reiss J., Johnson J.L.;
RT "Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and
RT GEPH.";
RL Hum. Mutat. 21:569-576(2003).
RN [17]
RP VARIANTS MOCODA TRP-67; GLY-80 AND PHE-84.
RX PubMed=16021469; DOI=10.1007/s00439-005-1341-9;
RA Leimkuehler S., Charcosset M., Latour P., Dorche C., Kleppe S., Scaglia F.,
RA Szymczak I., Schupp P., Hahnewald R., Reiss J.;
RT "Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and
RT in vitro characterization of a MOCS2 mutation that abolishes the binding
RT ability of molybdopterin synthase.";
RL Hum. Genet. 117:565-570(2005).
CC -!- FUNCTION: Isoform MOCS1A and isoform MOCS1B probably form a complex
CC that catalyzes the conversion of 5'-GTP to cyclic pyranopterin
CC monophosphate (cPMP). MOCS1A catalyzes the cyclization of GTP to (8S)-
CC 3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate and MOCS1B catalyzes
CC the subsequent conversion of (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-
CC triphosphate to cPMP. {ECO:0000269|PubMed:11891227}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + GTP + S-adenosyl-L-methionine = (8S)-3',8-cyclo-7,8-
CC dihydroguanosine 5'-triphosphate + 5'-deoxyadenosine + A + H(+) + L-
CC methionine; Xref=Rhea:RHEA:49576, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17319, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:57844, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:131766; EC=4.1.99.22;
CC Evidence={ECO:0000250|UniProtKB:P69848};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate = cyclic
CC pyranopterin phosphate + diphosphate; Xref=Rhea:RHEA:49580,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:59648, ChEBI:CHEBI:131766;
CC EC=4.6.1.17; Evidence={ECO:0000269|PubMed:23627491};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:15180982};
CC Note=Binds 2 [4Fe-4S] clusters. Binds 1 [4Fe-4S] cluster coordinated
CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine and 1
CC [4Fe-4S] cluster coordinated with 3 cysteines and the GTP-derived
CC substrate. {ECO:0000269|PubMed:15180982};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.79 uM for (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate
CC {ECO:0000269|PubMed:23627491};
CC Note=kcat is 0.092 min(-1) for (8S)-3',8-cyclo-7,8-dihydroguanosine
CC 5'-triphosphate. {ECO:0000269|PubMed:23627491};
CC -!- PATHWAY: Cofactor biosynthesis; molybdopterin biosynthesis.
CC -!- SUBUNIT: Isoform MOCS1A and isoform MOCS1B probably form a
CC heterooligomer. {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=So far, the different types of MOCS1A and MOCS1B isoforms
CC have been investigated independently and several combinations might
CC be possible.;
CC Name=MOCS1B; Synonyms=MOCS1B Type-II;
CC IsoId=Q9NZB8-1; Sequence=Displayed;
CC Name=MOCS1A; Synonyms=MOCS1A Type/Iad;
CC IsoId=Q9NZB8-5; Sequence=VSP_036826, VSP_036827;
CC Name=2; Synonyms=MOCS1A Type-Ibcd;
CC IsoId=Q9NZB8-6; Sequence=VSP_036822, VSP_036826, VSP_036827;
CC Name=3; Synonyms=MOCS1A Type-Ibd;
CC IsoId=Q9NZB8-3; Sequence=VSP_036823, VSP_036826, VSP_036827;
CC Name=4;
CC IsoId=Q9NZB8-4; Sequence=VSP_036821, VSP_036824, VSP_036825;
CC Name=6; Synonyms=MOCS1B Type-III;
CC IsoId=Q9NZB8-2; Sequence=VSP_007439;
CC Name=7;
CC IsoId=Q9NZB8-7; Sequence=VSP_036821, VSP_007439;
CC Name=8;
CC IsoId=Q9NZB8-8; Sequence=VSP_036822;
CC -!- TISSUE SPECIFICITY: Isoform MOCS1A and isoform 2 are widely expressed.
CC {ECO:0000269|PubMed:12208140, ECO:0000269|PubMed:9731530}.
CC -!- DISEASE: Molybdenum cofactor deficiency, complementation group A
CC (MOCODA) [MIM:252150]: An autosomal recessive metabolic disorder
CC leading to the pleiotropic loss of molybdoenzyme activities. It is
CC clinically characterized by onset in infancy of poor feeding,
CC intractable seizures, severe psychomotor retardation, and death in
CC early childhood in most patients. {ECO:0000269|PubMed:12754701,
CC ECO:0000269|PubMed:16021469, ECO:0000269|PubMed:9731530,
CC ECO:0000269|PubMed:9921896}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The MOCS1 locus has initially been reported to produce
CC MOCS1A and MOCS1B from non-overlapping reading frames within a
CC bicistronic transcript. However, only isoform MOCS1A seems to be
CC translated from the bicistronic transcript. Isoform MOCS1B seems to be
CC translated from a monocistronic mRNA that is derived by alternative
CC splicing.
CC -!- MISCELLANEOUS: [Isoform MOCS1B]: Multidomain protein with inactive
CC MOCS1A and active MOCS1B.
CC -!- MISCELLANEOUS: [Isoform 4]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Multidomain protein with inactive MOCS1A
CC and active MOCS1B. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the MoaC family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the radical SAM
CC superfamily. MoaA family. {ECO:0000305}.
CC -!- CAUTION: The C-terminus of MOCS1A was previously believed to be
CC thiocarboxylated, but it is now known not to be the case.
CC {ECO:0000305|PubMed:25697423}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB87524.1; Type=Miscellaneous discrepancy; Note=Alternative splicing in the MOCS1A-MOCS1B joining region.; Evidence={ECO:0000305};
CC Sequence=AAS00489.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAC44526.1; Type=Miscellaneous discrepancy; Note=Alternative splicing in the MOCS1A-MOCS1B joining region.; Evidence={ECO:0000305};
CC Sequence=CAI20007.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAI20012.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAI20013.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AJ224328; CAA11897.1; -; mRNA.
DR EMBL; AJ224328; CAA11898.1; -; mRNA.
DR EMBL; AJ404969; CAC44526.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AJ293577; CAC44527.1; -; Genomic_DNA.
DR EMBL; AJ293578; CAC44527.1; JOINED; Genomic_DNA.
DR EMBL; AJ293579; CAC44527.1; JOINED; Genomic_DNA.
DR EMBL; AF034374; AAB87523.1; -; mRNA.
DR EMBL; AF034374; AAB87524.1; ALT_SEQ; mRNA.
DR EMBL; AK300300; BAG62053.1; -; mRNA.
DR EMBL; AK056740; BAG51799.1; -; mRNA.
DR EMBL; AL136089; CAI20007.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL136089; CAI20011.1; -; Genomic_DNA.
DR EMBL; AL136089; CAI20012.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL136089; CAI20013.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL136089; CAI20014.1; -; Genomic_DNA.
DR EMBL; AL136089; CAI20015.1; -; Genomic_DNA.
DR EMBL; BC036839; AAH36839.1; -; mRNA.
DR EMBL; AF214022; AAF67857.1; -; mRNA.
DR EMBL; AF214023; AAF67858.1; -; mRNA.
DR EMBL; AY423726; AAS00489.1; ALT_INIT; mRNA.
DR CCDS; CCDS43460.1; -. [Q9NZB8-5]
DR CCDS; CCDS87394.1; -. [Q9NZB8-1]
DR RefSeq; NP_001068566.1; NM_001075098.3. [Q9NZB8-5]
DR RefSeq; NP_005934.2; NM_005943.5. [Q9NZB8-6]
DR RefSeq; XP_011512934.1; XM_011514632.2.
DR RefSeq; XP_011512935.1; XM_011514633.2.
DR AlphaFoldDB; Q9NZB8; -.
DR SMR; Q9NZB8; -.
DR BioGRID; 110480; 28.
DR IntAct; Q9NZB8; 12.
DR STRING; 9606.ENSP00000362282; -.
DR iPTMnet; Q9NZB8; -.
DR PhosphoSitePlus; Q9NZB8; -.
DR BioMuta; MOCS1; -.
DR DMDM; 30913216; -.
DR EPD; Q9NZB8; -.
DR MassIVE; Q9NZB8; -.
DR MaxQB; Q9NZB8; -.
DR PaxDb; Q9NZB8; -.
DR PeptideAtlas; Q9NZB8; -.
DR PRIDE; Q9NZB8; -.
DR ProteomicsDB; 83350; -. [Q9NZB8-1]
DR ProteomicsDB; 83351; -. [Q9NZB8-2]
DR ProteomicsDB; 83352; -. [Q9NZB8-3]
DR ProteomicsDB; 83353; -. [Q9NZB8-4]
DR ProteomicsDB; 83354; -. [Q9NZB8-5]
DR ProteomicsDB; 83355; -. [Q9NZB8-6]
DR ProteomicsDB; 83356; -. [Q9NZB8-7]
DR ProteomicsDB; 83357; -. [Q9NZB8-8]
DR Antibodypedia; 51647; 194 antibodies from 21 providers.
DR DNASU; 4337; -.
DR Ensembl; ENST00000340692.10; ENSP00000344794.5; ENSG00000124615.20. [Q9NZB8-1]
DR Ensembl; ENST00000373181.8; ENSP00000362277.4; ENSG00000124615.20. [Q9NZB8-4]
DR Ensembl; ENST00000373188.6; ENSP00000362284.2; ENSG00000124615.20. [Q9NZB8-5]
DR Ensembl; ENST00000373195.7; ENSP00000362291.3; ENSG00000124615.20. [Q9NZB8-7]
DR GeneID; 4337; -.
DR KEGG; hsa:4337; -.
DR MANE-Select; ENST00000340692.10; ENSP00000344794.5; NM_001358530.2; NP_001345459.1.
DR UCSC; uc003opa.4; human. [Q9NZB8-1]
DR CTD; 4337; -.
DR DisGeNET; 4337; -.
DR GeneCards; MOCS1; -.
DR GeneReviews; MOCS1; -.
DR HGNC; HGNC:7190; MOCS1.
DR HPA; ENSG00000124615; Low tissue specificity.
DR MalaCards; MOCS1; -.
DR MIM; 252150; phenotype.
DR MIM; 603707; gene.
DR neXtProt; NX_Q9NZB8; -.
DR OpenTargets; ENSG00000124615; -.
DR Orphanet; 308386; Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A.
DR PharmGKB; PA30900; -.
DR VEuPathDB; HostDB:ENSG00000124615; -.
DR eggNOG; KOG2876; Eukaryota.
DR GeneTree; ENSGT00390000016567; -.
DR HOGENOM; CLU_009273_0_0_1; -.
DR InParanoid; Q9NZB8; -.
DR OMA; IRDAKPF; -.
DR OrthoDB; 721528at2759; -.
DR PhylomeDB; Q9NZB8; -.
DR TreeFam; TF300424; -.
DR BRENDA; 4.1.99.22; 2681.
DR BRENDA; 4.6.1.17; 2681.
DR PathwayCommons; Q9NZB8; -.
DR Reactome; R-HSA-947581; Molybdenum cofactor biosynthesis.
DR SignaLink; Q9NZB8; -.
DR UniPathway; UPA00344; -.
DR BioGRID-ORCS; 4337; 10 hits in 1080 CRISPR screens.
DR ChiTaRS; MOCS1; human.
DR GeneWiki; MOCS1; -.
DR GenomeRNAi; 4337; -.
DR Pharos; Q9NZB8; Tclin.
DR PRO; PR:Q9NZB8; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9NZB8; protein.
DR Bgee; ENSG00000124615; Expressed in apex of heart and 165 other tissues.
DR ExpressionAtlas; Q9NZB8; baseline and differential.
DR Genevisible; Q9NZB8; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0019008; C:molybdopterin synthase complex; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0061799; F:cyclic pyranopterin monophosphate synthase activity; IMP:MGI.
DR GO; GO:0061798; F:GTP 3',8'-cyclase activity; IMP:MGI.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IDA:UniProtKB.
DR GO; GO:0032324; P:molybdopterin cofactor biosynthetic process; IEA:Ensembl.
DR CDD; cd01420; MoaC_PE; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR Gene3D; 3.30.70.640; -; 1.
DR HAMAP; MF_01225_B; MoaA_B; 1.
DR HAMAP; MF_01224_B; MoaC_B; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR023045; Mo_CF_biosynth-C.
DR InterPro; IPR013483; MoaA.
DR InterPro; IPR000385; MoaA_NifB_PqqE_Fe-S-bd_CS.
DR InterPro; IPR036522; MoaC_sf.
DR InterPro; IPR010505; Mob_synth_C.
DR InterPro; IPR002820; Mopterin_CF_biosynth-C_dom.
DR InterPro; IPR007197; rSAM.
DR Pfam; PF01967; MoaC; 1.
DR Pfam; PF06463; Mob_synth_C; 1.
DR Pfam; PF04055; Radical_SAM; 1.
DR SMART; SM00729; Elp3; 1.
DR SUPFAM; SSF55040; SSF55040; 1.
DR TIGRFAMs; TIGR02666; moaA; 1.
DR TIGRFAMs; TIGR00581; moaC; 1.
DR PROSITE; PS01305; MOAA_NIFB_PQQE; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Acetylation; Alternative splicing; Disease variant; GTP-binding;
KW Iron; Iron-sulfur; Lyase; Metal-binding; Molybdenum cofactor biosynthesis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine.
FT CHAIN 1..636
FT /note="Molybdenum cofactor biosynthesis protein 1"
FT /id="PRO_0000097870"
FT DOMAIN 64..277
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 1..383
FT /note="Molybdenum cofactor biosynthesis protein A"
FT REGION 414..636
FT /note="Molybdenum cofactor biosynthesis protein C"
FT REGION 456..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 606
FT /note="For molybdenum cofactor biosynthesis protein C
FT activity"
FT /evidence="ECO:0000255"
FT BINDING 73
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 80
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305"
FT BINDING 84
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305"
FT BINDING 86
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 87
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305"
FT BINDING 123
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 215
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 249
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 312
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000305"
FT BINDING 315
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000305"
FT BINDING 317..319
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 329
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000305"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 198
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 528
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q5RKZ7"
FT VAR_SEQ 1..87
FT /note="Missing (in isoform 4 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_036821"
FT VAR_SEQ 1..41
FT /note="MAARPLSRMLRRLLRSSARSCSSGAPVTQPCPGESARAASE -> MWKSWKL
FT RTDVRVREGAGGSPCASSQPGSRGPCFLPGLSSQ (in isoform 2 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:9731530"
FT /id="VSP_036822"
FT VAR_SEQ 1..41
FT /note="MAARPLSRMLRRLLRSSARSCSSGAPVTQPCPGESARAASE -> MWKSWKL
FT RTDVR (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_036823"
FT VAR_SEQ 368..383
FT /note="Missing (in isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:10917590,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_007439"
FT VAR_SEQ 368
FT /note="G -> E (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036824"
FT VAR_SEQ 369..636
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036825"
FT VAR_SEQ 384..385
FT /note="EL -> GG (in isoform MOCS1A, isoform 2 and isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:9731530, ECO:0000303|Ref.2"
FT /id="VSP_036826"
FT VAR_SEQ 386..636
FT /note="Missing (in isoform MOCS1A, isoform 2 and isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:9731530, ECO:0000303|Ref.2"
FT /id="VSP_036827"
FT VARIANT 67
FT /note="R -> W (in MOCODA; dbSNP:rs754441164)"
FT /evidence="ECO:0000269|PubMed:16021469"
FT /id="VAR_054823"
FT VARIANT 73
FT /note="R -> W (in MOCODA; dbSNP:rs104893970)"
FT /evidence="ECO:0000269|PubMed:9921896"
FT /id="VAR_015658"
FT VARIANT 80
FT /note="C -> G (in MOCODA; dbSNP:rs151141411)"
FT /evidence="ECO:0000269|PubMed:16021469"
FT /id="VAR_054824"
FT VARIANT 84
FT /note="C -> F (in MOCODA)"
FT /evidence="ECO:0000269|PubMed:16021469"
FT /id="VAR_054825"
FT VARIANT 123
FT /note="R -> W (in MOCODA; dbSNP:rs779592342)"
FT /evidence="ECO:0000269|PubMed:12754701"
FT /id="VAR_054826"
FT VARIANT 126
FT /note="G -> D (in MOCODA; dbSNP:rs372246702)"
FT /evidence="ECO:0000269|PubMed:9921896"
FT /id="VAR_015659"
FT VARIANT 127
FT /note="G -> D (in MOCODA)"
FT /evidence="ECO:0000269|PubMed:9921896"
FT /id="VAR_015660"
FT VARIANT 319
FT /note="R -> Q (in MOCODA; dbSNP:rs104893969)"
FT /evidence="ECO:0000269|PubMed:9921896"
FT /id="VAR_015661"
FT VARIANT 324
FT /note="G -> E (in MOCODA; dbSNP:rs1187685038)"
FT /evidence="ECO:0000269|PubMed:9921896"
FT /id="VAR_015662"
FT VARIANT 324
FT /note="G -> R (in MOCODA; dbSNP:rs762253951)"
FT /evidence="ECO:0000269|PubMed:12754701"
FT /id="VAR_054827"
FT VARIANT 390
FT /note="P -> H (in dbSNP:rs11969769)"
FT /id="VAR_056131"
FT VARIANT 452
FT /note="R -> L (in dbSNP:rs11969206)"
FT /id="VAR_061346"
FT MUTAGEN 80
FT /note="C->S: Impairs precursor Z synthesis."
FT /evidence="ECO:0000269|PubMed:15180982"
FT MUTAGEN 84
FT /note="C->S: Impairs precursor Z synthesis."
FT /evidence="ECO:0000269|PubMed:15180982"
FT MUTAGEN 87
FT /note="C->S: Impairs precursor Z synthesis."
FT /evidence="ECO:0000269|PubMed:15180982"
FT MUTAGEN 312
FT /note="C->S: Impairs precursor Z synthesis."
FT /evidence="ECO:0000269|PubMed:15180982"
FT MUTAGEN 315
FT /note="C->S: Impairs precursor Z synthesis."
FT /evidence="ECO:0000269|PubMed:15180982"
FT MUTAGEN 329
FT /note="C->S: Impairs precursor Z synthesis."
FT /evidence="ECO:0000269|PubMed:15180982"
FT CONFLICT 233
FT /note="A -> V (in Ref. 3; BAG51799/BAG62053)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="L -> H (in Ref. 2; AAB87523)"
FT /evidence="ECO:0000305"
FT CONFLICT 421
FT /note="A -> G (in Ref. 3; BAG51799)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 636 AA; 70105 MW; 6774A563BAC42120 CRC64;
MAARPLSRML RRLLRSSARS CSSGAPVTQP CPGESARAAS EEVSRRRQFL REHAAPFSAF
LTDSFGRQHS YLRISLTEKC NLRCQYCMPE EGVPLTPKAN LLTTEEILTL ARLFVKEGID
KIRLTGGEPL IRPDVVDIVA QLQRLEGLRT IGVTTNGINL ARLLPQLQKA GLSAINISLD
TLVPAKFEFI VRRKGFHKVM EGIHKAIELG YNPVKVNCVV MRGLNEDELL DFAALTEGLP
LDVRFIEYMP FDGNKWNFKK MVSYKEMLDT VRQQWPELEK VPEEESSTAK AFKIPGFQGQ
ISFITSMSEH FCGTCNRLRI TADGNLKVCL FGNSEVSLRD HLRAGASEQE LLRIIGAAVG
RKKRQHAGMF SISQMKNRPM ILIELFLMFP NSPPANPSIF SWDPLHVQGL RPRMSFSSQV
ATLWKGCRVP QTPPLAQQRL GSGSFQRHYT SRADSDANSK CLSPGSWASA APSGPQLTSE
QLTHVDSEGR AAMVDVGRKP DTERVAVASA VVLLGPVAFK LVQQNQLKKG DALVVAQLAG
VQAAKVTSQL IPLCHHVALS HIQVQLELDS TRHAVKIQAS CRARGPTGVE MEALTSAAVA
ALTLYDMCKA VSRDIVLEEI KLISKTGGQR GDFHRA
