O43847 (NRDC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nardilysin
EC=3.4.24.61

Alternative name(s):
N-arginine dibasic convertase
Short name=NRD convertase
Short name=NRD-C

Gene names

Name:

NRD1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1150 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs.
Catalytic activity	Hydrolysis of polypeptides, preferably at -Xaa-|-Arg-Lys-, and less commonly at -Arg-|-Arg-Xaa-, in which Xaa is not Arg or Lys.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Tissue specificity	Primarily in adult heart, skeletal muscle, and testis and at much lower levels in other tissues.
Sequence similarities	Belongs to the peptidase M16 family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell migration Traceable author statement PubMed 15544571. Source: UniProtKB cell proliferation Traceable author statement PubMed 12463163. Source: UniProtKB neuromuscular junction development Traceable author statement Ref.1. Source: ProtInc positive regulation of membrane protein ectodomain proteolysis Inferred from direct assay PubMed 18355445. Source: BHF-UCL proteolysis Non-traceable author statement Ref.2. Source: UniProtKB regulation of endopeptidase activity Inferred from direct assay PubMed 18355445. Source: BHF-UCL
Cellular_component	cell surface Traceable author statement PubMed 12463163. Source: UniProtKB cytosol Traceable author statement PubMed 12463163. Source: UniProtKB
Molecular_function	epidermal growth factor binding Traceable author statement PubMed 12463163. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43847-1)

Also known as: NRD1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O43847-2)

Also known as: NRD2;

The sequence of this isoform differs from the canonical sequence as follows:
     209-209: Q → QQLQSLFLLWSKLTDRLWFKSTYSKMSSTLLVETRNLYGVVGAESRSAPVQHLAGWQAEEQQGETDTVL

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 1150	1130	Nardilysin		PRO_0000026755
Regions
	Compositional bias	142 – 200	59	Asp/Glu-rich (highly acidic)
	Compositional bias	144 – 153	10	Poly-Glu
Sites
	Active site	235	1	Proton acceptor By similarity
	Metal binding	232	1	Zinc By similarity
	Metal binding	236	1	Zinc By similarity
	Metal binding	313	1	Zinc By similarity
Amino acid modifications
	Modified residue	86	1	Phosphoserine By similarity
	Modified residue	94	1	Phosphoserine Ref.7 Ref.8 Ref.9 Ref.11
Natural variations
	Alternative sequence	209	1	Q → QQLQSLFLLWSKLTDRLWFK STYSKMSSTLLVETRNLYGV VGAESRSAPVQHLAGWQAEE QQGETDTVL in isoform 2.		VSP_007114
	Natural variant	153	1	E → EE. Ref.2 Ref.3 Ref.4		VAR_021221
	Natural variant	831	1	Y → S. Corresponds to variant rs34957144 [ dbSNP | Ensembl ].		VAR_057058
Experimental info
	Sequence conflict	23 – 24	2	EL → DV in CAA63698. Ref.2
	Sequence conflict	23 – 24	2	EL → DV in CAA63694. Ref.2
	Sequence conflict	526	1	Q → L in CAA63698. Ref.2
	Sequence conflict	526	1	Q → L in CAA63694. Ref.2
	Sequence conflict	640	1	A → G in AAC39597. Ref.1
	Sequence conflict	752	1	V → A in CAA63698. Ref.2
	Sequence conflict	752	1	V → A in CAA63694. Ref.2
	Sequence conflict	1086	1	V → A in AAC39597. Ref.1
	Sequence conflict	1099	1	T → S in CAA63698. Ref.2
	Sequence conflict	1099	1	T → S in CAA63694. Ref.2
	Sequence conflict	1125 – 1150	26	DCIIP…HKIVK → SVSSPLLISGLSQQHSTFSP TIK Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (NRD1) [UniParc]. Last modified April 11, 2003. Version 2. Checksum: 3B46DADB898E038B	FASTA	1,150	131,572
	10 20 30 40 50 60 MLRRVTVAAV CATRRKLCEA GRELAALWGI ETRGRCEDSA AARPFPILAM PGRNKAKSTC 70 80 90 100 110 120 SCPDLQPNGQ DLGENSRVAR LGADESEEEG RRGSLSNAGD PEIVKSPSDP KQYRYIKLQN 130 140 150 160 170 180 GLQALLISDL SNMEGKTGNT TDDEEEEEVE EEEDDDEDSG AEIEDDDEEG FDDEDEFDDE 190 200 210 220 230 240 HDDDLDTEDN ELEELEERAE ARKKTTEKQS AAALCVGVGS FADPDDLPGL AHFLEHMVFM 250 260 270 280 290 300 GSLKYPDENG FDAFLKKHGG SDNASTDCER TVFQFDVQRK YFKEALDRWA QFFIHPLMIR 310 320 330 340 350 360 DAIDREVEAV DSEYQLARPS DANRKEMLFG SLARPGHPMG KFFWGNAETL KHEPRKNNID 370 380 390 400 410 420 THARLREFWM RYYSSHYMTL VVQSKETLDT LEKWVTEIFS QIPNNGLPRP NFGHLTDPFD 430 440 450 460 470 480 TPAFNKLYRV VPIRKIHALT ITWALPPQQQ HYRVKPLHYI SWLVGHEGKG SILSFLRKKC 490 500 510 520 530 540 WALALFGGNG ETGFEQNSTY SVFSISITLT DEGYEHFYEV AYTVFQYLKM LQKLGPEKRI 550 560 570 580 590 600 FEEIRKIEDN EFHYQEQTDP VEYVENMCEN MQLYPLQDIL TGDQLLFEYK PEVIGEALNQ 610 620 630 640 650 660 LVPQKANLVL LSGANEGKCD LKEKWFGTQY SIEDIENSWA ELWNSNFELN PDLHLPAENK 670 680 690 700 710 720 YIATDFTLKA FDCPETEYPV KIVNTPQGCL WYKKDNKFKI PKAYIRFHLI SPLIQKSAAN 730 740 750 760 770 780 VVLFDIFVNI LTHNLAEPAY EADVAQLEYK LVAGEHGLII RVKGFNHKLP LLFQLIIDYL 790 800 810 820 830 840 AEFNSTPAVF TMITEQLKKT YFNILIKPET LAKDVRLLIL EYARWSMIDK YQALMDGLSL 850 860 870 880 890 900 ESLLSFVKEF KSQLFVEGLV QGNVTSTESM DFLKYVVDKL NFKPLEQEMP VQFQVVELPS 910 920 930 940 950 960 GHHLCKVKAL NKGDANSEVT VYYQSGTRSL REYTLMELLV MHMEEPCFDF LRTKQTLGYH 970 980 990 1000 1010 1020 VYPTCRNTSG ILGFSVTVGT QATKYNSEVV DKKIEEFLSS FEEKIENLTE EAFNTQVTAL 1030 1040 1050 1060 1070 1080 IKLKECEDTH LGEEVDRNWN EVVTQQYLFD RLAHEIEALK SFSKSDLVNW FKAHRGPGSK 1090 1100 1110 1120 1130 1140 MLSVHVVGYG KYELEEDGTP SSEDSNSSCE VMQLTYLPTS PLLADCIIPI TDIRAFTTTL 1150 NLLPYHKIVK
	Isoform 2 (NRD2) [UniParc]. Checksum: 071971B4E83016AF	FASTA	1,218	139,284
	10 20 30 40 50 60 MLRRVTVAAV CATRRKLCEA GRELAALWGI ETRGRCEDSA AARPFPILAM PGRNKAKSTC 70 80 90 100 110 120 SCPDLQPNGQ DLGENSRVAR LGADESEEEG RRGSLSNAGD PEIVKSPSDP KQYRYIKLQN 130 140 150 160 170 180 GLQALLISDL SNMEGKTGNT TDDEEEEEVE EEEDDDEDSG AEIEDDDEEG FDDEDEFDDE 190 200 210 220 230 240 HDDDLDTEDN ELEELEERAE ARKKTTEKQQ LQSLFLLWSK LTDRLWFKST YSKMSSTLLV 250 260 270 280 290 300 ETRNLYGVVG AESRSAPVQH LAGWQAEEQQ GETDTVLSAA ALCVGVGSFA DPDDLPGLAH 310 320 330 340 350 360 FLEHMVFMGS LKYPDENGFD AFLKKHGGSD NASTDCERTV FQFDVQRKYF KEALDRWAQF 370 380 390 400 410 420 FIHPLMIRDA IDREVEAVDS EYQLARPSDA NRKEMLFGSL ARPGHPMGKF FWGNAETLKH 430 440 450 460 470 480 EPRKNNIDTH ARLREFWMRY YSSHYMTLVV QSKETLDTLE KWVTEIFSQI PNNGLPRPNF 490 500 510 520 530 540 GHLTDPFDTP AFNKLYRVVP IRKIHALTIT WALPPQQQHY RVKPLHYISW LVGHEGKGSI 550 560 570 580 590 600 LSFLRKKCWA LALFGGNGET GFEQNSTYSV FSISITLTDE GYEHFYEVAY TVFQYLKMLQ 610 620 630 640 650 660 KLGPEKRIFE EIRKIEDNEF HYQEQTDPVE YVENMCENMQ LYPLQDILTG DQLLFEYKPE 670 680 690 700 710 720 VIGEALNQLV PQKANLVLLS GANEGKCDLK EKWFGTQYSI EDIENSWAEL WNSNFELNPD 730 740 750 760 770 780 LHLPAENKYI ATDFTLKAFD CPETEYPVKI VNTPQGCLWY KKDNKFKIPK AYIRFHLISP 790 800 810 820 830 840 LIQKSAANVV LFDIFVNILT HNLAEPAYEA DVAQLEYKLV AGEHGLIIRV KGFNHKLPLL 850 860 870 880 890 900 FQLIIDYLAE FNSTPAVFTM ITEQLKKTYF NILIKPETLA KDVRLLILEY ARWSMIDKYQ 910 920 930 940 950 960 ALMDGLSLES LLSFVKEFKS QLFVEGLVQG NVTSTESMDF LKYVVDKLNF KPLEQEMPVQ 970 980 990 1000 1010 1020 FQVVELPSGH HLCKVKALNK GDANSEVTVY YQSGTRSLRE YTLMELLVMH MEEPCFDFLR 1030 1040 1050 1060 1070 1080 TKQTLGYHVY PTCRNTSGIL GFSVTVGTQA TKYNSEVVDK KIEEFLSSFE EKIENLTEEA 1090 1100 1110 1120 1130 1140 FNTQVTALIK LKECEDTHLG EEVDRNWNEV VTQQYLFDRL AHEIEALKSF SKSDLVNWFK 1150 1160 1170 1180 1190 1200 AHRGPGSKML SVHVVGYGKY ELEEDGTPSS EDSNSSCEVM QLTYLPTSPL LADCIIPITD 1210 IRAFTTTLNL LPYHKIVK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human NRD convertase: a highly conserved metalloendopeptidase expressed at specific sites during development and in adult tissues." Fumagalli P., Accarino M., Egeo A., Scartezzini P., Rappazzo G., Pizzuti A., Avvantaggiato V., Simeone A., Arrigo G., Zuffardi O., Ottolenghi S., Taramelli R. Genomics 47:238-245(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart.
[2]	"Human and rat testis express two mRNA species encoding variants of NRD convertase, a metalloendopeptidase of the insulinase family." Hospital V., Prat A., Joulie C., Cherif D., Day R., Cohen P. Biochem. J. 327:773-779(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT GLU-153 INS. Tissue: Testis.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-153 INS.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-153 INS.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[6]	"Gene expression of the dibasic-pair cleaving enzyme NRD convertase (N-arginine dibasic convertase) is differentially regulated in the GH3 pituitary and Mat-Lu prostate cell lines." Winter A.G., Pierotti A.R. Biochem. J. 351:755-764(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-107.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U64898 mRNA. Translation: AAC39597.1. X93209 mRNA. Translation: CAA63698.1. X93207 mRNA. Translation: CAA63694.1. AL589663, AL050343 Genomic DNA. Translation: CAH74100.1. AL050343, AL589663 Genomic DNA. Translation: CAI22216.1. CH471059 Genomic DNA. Translation: EAX06809.1. BC008775 mRNA. Translation: AAH08775.1. AJ000350 Genomic DNA. Translation: CAA04025.1.
IPI	IPI00478723. IPI00889668.
RefSeq	NP_001095132.1. NM_001101662.1. NP_001229290.1. NM_001242361.1. NP_002516.2. NM_002525.2.
UniGene	Hs.584782.
3D structure databases
ProteinModelPortal	O43847.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43847. 6 interactions.
STRING	9606.ENSP00000346890.
Protein family/group databases
MEROPS	M16.983.
PTM databases
PhosphoSite	O43847.
Proteomic databases
PaxDb	O43847.
PRIDE	O43847.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000352171; ENSP00000262679; ENSG00000078618.
GeneID	4898.
KEGG	hsa:4898.
UCSC	uc009vzb.3. human.
Organism-specific databases
CTD	4898.
GeneCards	GC01M052254.
H-InvDB	HIX0000576.
HGNC	HGNC:7995. NRD1.
HPA	HPA023679.
MIM	602651. gene.
neXtProt	NX_O43847.
PharmGKB	PA31774.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1025.
HOVERGEN	HBG006530.
KO	K01411.
OrthoDB	EOG4PC9R9.
Enzyme and pathway databases
BRENDA	3.4.24.61. 2681.
Gene expression databases
ArrayExpress	O43847.
Bgee	O43847.
CleanEx	HS_NRD1.
Genevestigator	O43847.
GermOnline	ENSG00000078618. Homo sapiens.
Family and domain databases
Gene3D	3.30.830.10. 5 hits.
InterPro	IPR011249. Metalloenz_LuxS/M16. IPR011237. Pept_M16_dom. IPR011765. Pept_M16_N. IPR001431. Pept_M16_Zn_BS. IPR007863. Peptidase_M16_C. [Graphical view]
Pfam	PF00675. Peptidase_M16. 1 hit. PF05193. Peptidase_M16_C. 2 hits. [Graphical view]
SUPFAM	SSF63411. Metalloenz_metal-bd. 4 hits.
PROSITE	PS00143. INSULINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NRD1. human.
GenomeRNAi	4898.
NextBio	18847.
SOURCE	Search...

Entry information

Entry name

NRDC_HUMAN

Accession

Primary (citable) accession number: O43847
Secondary accession number(s): A6NI41 , O15241, O15242, Q5VUL0, Q96HB2, Q9NU57

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	April 11, 2003
Last modified:	May 1, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.