ID NRDC_HUMAN Reviewed; 1151 AA. AC O43847; A6NI41; O15241; O15242; Q5VUL0; Q96HB2; Q9NU57; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 10-OCT-2018, sequence version 3. DT 13-FEB-2019, entry version 166. DE RecName: Full=Nardilysin; DE EC=3.4.24.61; DE AltName: Full=N-arginine dibasic convertase; DE Short=NRD convertase; DE Short=NRD-C; DE AltName: Full=Nardilysin convertase {ECO:0000312|HGNC:HGNC:7995}; DE Flags: Precursor; GN Name=NRDC {ECO:0000312|HGNC:HGNC:7995}; Synonyms=NRD1; 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] (ISOFORMS 1 AND 2). RC TISSUE=Testis; RX PubMed=9581555; DOI=10.1042/bj3270773; RA Hospital V., Prat A., Joulie C., Cherif D., Day R., Cohen P.; RT "Human and rat testis express two mRNA species encoding variants of RT NRD convertase, a metalloendopeptidase of the insulinase family."; RL Biochem. J. 327:773-779(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-154 DEL. RC TISSUE=Heart; RX PubMed=9479496; DOI=10.1006/geno.1997.5078; RA Fumagalli P., Accarino M., Egeo A., Scartezzini P., Rappazzo G., RA Pizzuti A., Avvantaggiato V., Simeone A., Arrigo G., Zuffardi O., RA Ottolenghi S., Taramelli R.; RT "Human NRD convertase: a highly conserved metalloendopeptidase RT expressed at specific sites during development and in adult tissues."; RL Genomics 47:238-245(1998). RN [3] 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; 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 1-107. RX PubMed=11042131; DOI=10.1042/bj3510755; RA Winter A.G., Pierotti A.R.; RT "Gene expression of the dibasic-pair cleaving enzyme NRD convertase RT (N-arginine dibasic convertase) is differentially regulated in the GH3 RT pituitary and Mat-Lu prostate cell lines."; RL Biochem. J. 351:755-764(2000). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [10] 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-86; SER-94 AND SER-96, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [13] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Cleaves peptide substrates on the N-terminus of arginine CC residues in dibasic pairs. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of polypeptides, preferably at -Xaa-|-Arg- CC Lys-, and less commonly at -Arg-|-Arg-Xaa-, in which Xaa is not CC Arg or Lys.; EC=3.4.24.61; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250}; CC -!- INTERACTION: CC P04637:TP53; NbExp=6; IntAct=EBI-2371631, EBI-366083; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=NRD1; CC IsoId=O43847-1; Sequence=Displayed; CC Name=2; Synonyms=NRD2; CC IsoId=O43847-2; Sequence=VSP_007114; CC -!- TISSUE SPECIFICITY: Primarily in adult heart, skeletal muscle, and CC testis and at much lower levels in other tissues. CC -!- SIMILARITY: Belongs to the peptidase M16 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC39597.1; Type=Frameshift; Positions=1126; Evidence={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; X93207; CAA63694.1; -; mRNA. DR EMBL; X93209; CAA63698.1; -; mRNA. DR EMBL; U64898; AAC39597.1; ALT_FRAME; mRNA. DR EMBL; AL050343; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL589663; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX06809.1; -; Genomic_DNA. DR EMBL; BC008775; AAH08775.1; -; mRNA. DR EMBL; AJ000350; CAA04025.1; -; Genomic_DNA. DR CCDS; CCDS41335.1; -. [O43847-1] DR CCDS; CCDS559.1; -. [O43847-2] DR RefSeq; NP_001095132.1; NM_001101662.1. [O43847-1] DR RefSeq; NP_001229290.1; NM_001242361.1. DR RefSeq; NP_002516.2; NM_002525.2. [O43847-2] DR UniGene; Hs.584782; -. DR ProteinModelPortal; O43847; -. DR SMR; O43847; -. DR BioGrid; 110954; 88. DR IntAct; O43847; 31. DR MINT; O43847; -. DR STRING; 9606.ENSP00000346890; -. DR MEROPS; M16.005; -. DR iPTMnet; O43847; -. DR PhosphoSitePlus; O43847; -. DR BioMuta; NRDC; -. DR EPD; O43847; -. DR jPOST; O43847; -. DR MaxQB; O43847; -. DR PaxDb; O43847; -. DR PeptideAtlas; O43847; -. DR PRIDE; O43847; -. DR ProteomicsDB; 49200; -. DR ProteomicsDB; 49201; -. [O43847-2] DR Ensembl; ENST00000352171; ENSP00000262679; ENSG00000078618. [O43847-1] DR Ensembl; ENST00000354831; ENSP00000346890; ENSG00000078618. [O43847-2] DR GeneID; 4898; -. DR KEGG; hsa:4898; -. DR UCSC; uc001ctd.5; human. [O43847-1] DR CTD; 4898; -. DR DisGeNET; 4898; -. DR EuPathDB; HostDB:ENSG00000078618.19; -. DR GeneCards; NRDC; -. DR H-InvDB; HIX0000576; -. DR HGNC; HGNC:7995; NRDC. DR HPA; HPA053661; -. DR MIM; 602651; gene. DR neXtProt; NX_O43847; -. DR OpenTargets; ENSG00000078618; -. DR PharmGKB; PA31774; -. DR eggNOG; KOG0959; Eukaryota. DR eggNOG; COG1025; LUCA. DR GeneTree; ENSGT00940000155026; -. DR HOVERGEN; HBG006530; -. DR InParanoid; O43847; -. DR KO; K01411; -. DR OrthoDB; 1008844at2759; -. DR PhylomeDB; O43847; -. DR BRENDA; 3.4.24.61; 2681. DR SignaLink; O43847; -. DR ChiTaRS; NRDC; human. DR GeneWiki; NRD1; -. DR GenomeRNAi; 4898; -. DR PRO; PR:O43847; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000078618; Expressed in 233 organ(s), highest expression level in quadriceps femoris. DR ExpressionAtlas; O43847; baseline and differential. DR Genevisible; O43847; HS. DR GO; GO:0009986; C:cell surface; TAS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase. DR GO; GO:0048408; F:epidermal growth factor binding; TAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004222; F:metalloendopeptidase activity; NAS:UniProtKB. DR GO; GO:0016477; P:cell migration; TAS:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; TAS:UniProtKB. DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0007528; P:neuromuscular junction development; TAS:ProtInc. DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:BHF-UCL. DR GO; GO:0006508; P:proteolysis; NAS:UniProtKB. DR GO; GO:0052548; P:regulation of endopeptidase activity; IDA:BHF-UCL. DR InterPro; IPR011249; Metalloenz_LuxS/M16. DR InterPro; IPR011765; Pept_M16_N. DR InterPro; IPR001431; Pept_M16_Zn_BS. DR InterPro; IPR007863; Peptidase_M16_C. DR InterPro; IPR032632; Peptidase_M16_M. DR Pfam; PF00675; Peptidase_M16; 1. DR Pfam; PF05193; Peptidase_M16_C; 2. DR Pfam; PF16187; Peptidase_M16_M; 1. DR SUPFAM; SSF63411; SSF63411; 4. DR PROSITE; PS00143; INSULINASE; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Hydrolase; Metal-binding; KW Metalloprotease; Phosphoprotein; Polymorphism; Protease; KW Reference proteome; Signal; Zinc. FT SIGNAL 1 20 {ECO:0000255}. FT CHAIN 21 1151 Nardilysin. FT /FTId=PRO_0000026755. FT COMPBIAS 142 201 Asp/Glu-rich (highly acidic). FT COMPBIAS 144 153 Poly-Glu. FT ACT_SITE 236 236 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU10096}. FT METAL 233 233 Zinc. {ECO:0000255|PROSITE- FT ProRule:PRU10096}. FT METAL 237 237 Zinc. {ECO:0000255|PROSITE- FT ProRule:PRU10096}. FT METAL 314 314 Zinc. {ECO:0000255|PROSITE- FT ProRule:PRU10096}. FT MOD_RES 86 86 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 94 94 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 96 96 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT VAR_SEQ 210 210 Q -> QQLQSLFLLWSKLTDRLWFKSTYSKMSSTLLVETRN FT LYGVVGAESRSAPVQHLAGWQAEEQQGETDTVL (in FT isoform 2). {ECO:0000303|PubMed:9581555}. FT /FTId=VSP_007114. FT VARIANT 154 154 Missing. {ECO:0000269|PubMed:9479496}. FT /FTId=VAR_080827. FT VARIANT 832 832 Y -> S (in dbSNP:rs34957144). FT /FTId=VAR_057058. FT CONFLICT 23 24 EL -> DV (in Ref. 1; CAA63698/CAA63694). FT {ECO:0000305}. FT CONFLICT 527 527 Q -> L (in Ref. 1; CAA63698/CAA63694). FT {ECO:0000305}. FT CONFLICT 641 641 A -> G (in Ref. 2; AAC39597). FT {ECO:0000305}. FT CONFLICT 753 753 V -> A (in Ref. 1; CAA63698/CAA63694). FT {ECO:0000305}. FT CONFLICT 1087 1087 V -> A (in Ref. 2; AAC39597). FT {ECO:0000305}. FT CONFLICT 1100 1100 T -> S (in Ref. 1; CAA63698/CAA63694). FT {ECO:0000305}. FT CONFLICT 1126 1126 D -> S (in Ref. 2; AAC39597). FT {ECO:0000305}. SQ SEQUENCE 1151 AA; 131701 MW; CD03BF258AF65122 CRC64; MLRRVTVAAV CATRRKLCEA GRELAALWGI ETRGRCEDSA AARPFPILAM PGRNKAKSTC SCPDLQPNGQ DLGENSRVAR LGADESEEEG RRGSLSNAGD PEIVKSPSDP KQYRYIKLQN GLQALLISDL SNMEGKTGNT TDDEEEEEVE EEEEDDDEDS GAEIEDDDEE GFDDEDEFDD EHDDDLDTED NELEELEERA EARKKTTEKQ SAAALCVGVG SFADPDDLPG LAHFLEHMVF MGSLKYPDEN GFDAFLKKHG GSDNASTDCE RTVFQFDVQR KYFKEALDRW AQFFIHPLMI RDAIDREVEA VDSEYQLARP SDANRKEMLF GSLARPGHPM GKFFWGNAET LKHEPRKNNI DTHARLREFW MRYYSSHYMT LVVQSKETLD TLEKWVTEIF SQIPNNGLPR PNFGHLTDPF DTPAFNKLYR VVPIRKIHAL TITWALPPQQ QHYRVKPLHY ISWLVGHEGK GSILSFLRKK CWALALFGGN GETGFEQNST YSVFSISITL TDEGYEHFYE VAYTVFQYLK MLQKLGPEKR IFEEIRKIED NEFHYQEQTD PVEYVENMCE NMQLYPLQDI LTGDQLLFEY KPEVIGEALN QLVPQKANLV LLSGANEGKC DLKEKWFGTQ YSIEDIENSW AELWNSNFEL NPDLHLPAEN KYIATDFTLK AFDCPETEYP VKIVNTPQGC LWYKKDNKFK IPKAYIRFHL ISPLIQKSAA NVVLFDIFVN ILTHNLAEPA YEADVAQLEY KLVAGEHGLI IRVKGFNHKL PLLFQLIIDY LAEFNSTPAV FTMITEQLKK TYFNILIKPE TLAKDVRLLI LEYARWSMID KYQALMDGLS LESLLSFVKE FKSQLFVEGL VQGNVTSTES MDFLKYVVDK LNFKPLEQEM PVQFQVVELP SGHHLCKVKA LNKGDANSEV TVYYQSGTRS LREYTLMELL VMHMEEPCFD FLRTKQTLGY HVYPTCRNTS GILGFSVTVG TQATKYNSEV VDKKIEEFLS SFEEKIENLT EEAFNTQVTA LIKLKECEDT HLGEEVDRNW NEVVTQQYLF DRLAHEIEAL KSFSKSDLVN WFKAHRGPGS KMLSVHVVGY GKYELEEDGT PSSEDSNSSC EVMQLTYLPT SPLLADCIIP ITDIRAFTTT LNLLPYHKIV K //