RNPL1_HUMAN
ID RNPL1_HUMAN Reviewed; 725 AA.
AC Q9HAU8; Q5XKC3; Q6NX56; Q96AC9; Q9H033; Q9NVD0;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Aminopeptidase RNPEPL1 {ECO:0000305|PubMed:19508204};
DE EC=3.4.11.- {ECO:0000269|PubMed:19508204};
DE AltName: Full=Arginyl aminopeptidase-like 1 {ECO:0000312|HGNC:HGNC:10079};
DE AltName: Full=Methionyl aminopeptidase {ECO:0000305|PubMed:19508204};
DE EC=3.4.11.18 {ECO:0000269|PubMed:19508204};
GN Name=RNPEPL1 {ECO:0000303|PubMed:11017071, ECO:0000312|HGNC:HGNC:10079};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-725.
RC TISSUE=Pancreas, and PNS;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 99-725, AND TISSUE SPECIFICITY.
RX PubMed=11017071; DOI=10.1038/79876;
RA Horikawa Y., Oda N., Cox N.J., Li X., Orho-Melander M., Hara M.,
RA Hinokio Y., Lindner T.H., Mashima H., Schwarz P.E.H., del Bosque-Plata L.,
RA Horikawa Y., Oda Y., Yoshiuchi I., Colilla S., Polonsky K.S., Wei S.,
RA Concannon P., Iwasaki N., Schulze J., Baier L.J., Bogardus C., Groop L.,
RA Boerwinkle E., Hanis C.L., Bell G.I.;
RT "Genetic variation in the gene encoding calpain-10 is associated with type
RT 2 diabetes mellitus.";
RL Nat. Genet. 26:163-175(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 347-725.
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 MRNA] OF 473-725.
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=19508204; DOI=10.2174/092986609789071199;
RA Thompson M.W., Beasley K.A., Schmidt M.D., Seipelt R.L.;
RT "Arginyl aminopeptidase-like 1 (RNPEPL1) is an alternatively processed
RT aminopeptidase with specificity for methionine, glutamine, and citrulline
RT residues.";
RL Protein Pept. Lett. 16:1256-1266(2009).
RN [7]
RP VARIANT [LARGE SCALE ANALYSIS] MET-478.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Broad specificity aminopeptidase which preferentially
CC hydrolyzes an N-terminal methionine, citrulline or glutamine.
CC {ECO:0000269|PubMed:19508204}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of N-terminal amino acids, preferentially methionine,
CC from peptides and arylamides.; EC=3.4.11.18;
CC Evidence={ECO:0000269|PubMed:19508204};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P15144};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P15144};
CC -!- ACTIVITY REGULATION: Inhibited by calcium but not affected by chloride
CC ions. Inhibited by amastatin and to a lower extent by bestatin. Weakly
CC inhibited by puromycin. {ECO:0000269|PubMed:19508204}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.37 mM for Met-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.17 mM for Citrulline-AMC {ECO:0000269|PubMed:19508204};
CC KM=1.72 mM for Ala-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.91 mM for Arg-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.89 mM for Asn-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.41 mM for Gln-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.18 mM for His-AMC {ECO:0000269|PubMed:19508204};
CC KM=1.05 mM for Ile-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.34 mM for Leu-AMC {ECO:0000269|PubMed:19508204};
CC KM=1.72 mM for Lys-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.65 mM for Phe-AMC {ECO:0000269|PubMed:19508204};
CC KM=1.76 mM for Ser-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.12 mM for Trp-AMC {ECO:0000269|PubMed:19508204};
CC KM=0.12 mM for Tyr-AMC {ECO:0000269|PubMed:19508204};
CC pH dependence:
CC Optimum pH is 6.6-8.0. {ECO:0000269|PubMed:19508204};
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Expressed at relatively
CC higher levels in heart and skeletal muscle.
CC {ECO:0000269|PubMed:11017071, ECO:0000269|PubMed:19508204}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG22080.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH67258.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAX88943.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA91823.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC124862; AAX88943.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC017301; AAH17301.2; -; mRNA.
DR EMBL; BC067258; AAH67258.2; ALT_INIT; mRNA.
DR EMBL; BC082975; AAH82975.1; -; mRNA.
DR EMBL; AF300795; AAG22080.1; ALT_INIT; mRNA.
DR EMBL; AK001668; BAA91823.1; ALT_INIT; mRNA.
DR EMBL; AL512754; CAC21674.1; -; mRNA.
DR RefSeq; NP_060696.4; NM_018226.4.
DR AlphaFoldDB; Q9HAU8; -.
DR SMR; Q9HAU8; -.
DR BioGRID; 121399; 8.
DR IntAct; Q9HAU8; 5.
DR STRING; 9606.ENSP00000270357; -.
DR ChEMBL; CHEMBL3831223; -.
DR MEROPS; M01.022; -.
DR iPTMnet; Q9HAU8; -.
DR PhosphoSitePlus; Q9HAU8; -.
DR BioMuta; RNPEPL1; -.
DR EPD; Q9HAU8; -.
DR MassIVE; Q9HAU8; -.
DR MaxQB; Q9HAU8; -.
DR PaxDb; Q9HAU8; -.
DR PeptideAtlas; Q9HAU8; -.
DR PRIDE; Q9HAU8; -.
DR ProteomicsDB; 81443; -.
DR Antibodypedia; 34524; 85 antibodies from 15 providers.
DR DNASU; 57140; -.
DR Ensembl; ENST00000270357.10; ENSP00000270357.4; ENSG00000142327.13.
DR GeneID; 57140; -.
DR KEGG; hsa:57140; -.
DR MANE-Select; ENST00000270357.10; ENSP00000270357.4; NM_018226.6; NP_060696.4.
DR UCSC; uc061uih.1; human.
DR CTD; 57140; -.
DR DisGeNET; 57140; -.
DR GeneCards; RNPEPL1; -.
DR HGNC; HGNC:10079; RNPEPL1.
DR HPA; ENSG00000142327; Low tissue specificity.
DR MIM; 605287; gene.
DR neXtProt; NX_Q9HAU8; -.
DR OpenTargets; ENSG00000142327; -.
DR PharmGKB; PA34452; -.
DR VEuPathDB; HostDB:ENSG00000142327; -.
DR eggNOG; KOG1047; Eukaryota.
DR GeneTree; ENSGT00940000160400; -.
DR HOGENOM; CLU_014505_4_1_1; -.
DR InParanoid; Q9HAU8; -.
DR OMA; CAKPFVF; -.
DR OrthoDB; 775595at2759; -.
DR PhylomeDB; Q9HAU8; -.
DR TreeFam; TF300758; -.
DR PathwayCommons; Q9HAU8; -.
DR SignaLink; Q9HAU8; -.
DR BioGRID-ORCS; 57140; 10 hits in 253 CRISPR screens.
DR ChiTaRS; RNPEPL1; human.
DR GenomeRNAi; 57140; -.
DR Pharos; Q9HAU8; Tbio.
DR PRO; PR:Q9HAU8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HAU8; protein.
DR Bgee; ENSG00000142327; Expressed in apex of heart and 174 other tissues.
DR ExpressionAtlas; Q9HAU8; baseline and differential.
DR Genevisible; Q9HAU8; HS.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR CDD; cd09599; M1_LTA4H; 1.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 1.25.40.320; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR038502; M1_LTA-4_hydro/amino_C_sf.
DR InterPro; IPR034015; M1_LTA4H.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR015211; Peptidase_M1_C.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR InterPro; IPR033525; RNPEPL1.
DR PANTHER; PTHR45726; PTHR45726; 1.
DR PANTHER; PTHR45726:SF2; PTHR45726:SF2; 1.
DR Pfam; PF09127; Leuk-A4-hydro_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SMART; SM01263; Leuk-A4-hydro_C; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF63737; SSF63737; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Zinc.
FT CHAIN 1..725
FT /note="Aminopeptidase RNPEPL1"
FT /id="PRO_0000095094"
FT REGION 676..699
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 354
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P15144,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 326..330
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 353
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 357
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 376
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT SITE 442
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT VARIANT 478
FT /note="V -> M (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1454498603)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036046"
FT CONFLICT 609
FT /note="V -> E (in Ref. 3; AAG22080 and 4; BAA91823)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 725 AA; 80000 MW; 4D8153BD0320A0C4 CRC64;
MAAQCCCRQA PGAEAAPVRP PPEPPPALDV ASASSAQLFR LRHLQLGLEL RPEARELAGC
LVLELCALRP APRALVLDAH PALRLHSAAF RRAPAAAAET PCAFAFSAPG PGPAPPPPLP
AFPEAPGSEP ACCPLAFRVD PFTDYGSSLT VTLPPELQAH QPFQVILRYT STDAPAIWWL
DPELTYGCAK PFVFTQGHSV CNRSFFPCFD TPAVKCTYSA VVKAPSGVQV LMSATRSAYM
EEEGVFHFHM EHPVPAYLVA LVAGDLKPAD IGPRSRVWAE PCLLPTATSK LSGAVEQWLS
AAERLYGPYM WGRYDIVFLP PSFPIVAMEN PCLTFIISSI LESDEFLVID VIHEVAHSWF
GNAVTNATWE EMWLSEGLAT YAQRRITTET YGAAFTCLET AFRLDALHRQ MKLLGEDSPV
SKLQVKLEPG VNPSHLMNLF TYEKGYCFVY YLSQLCGDPQ RFDDFLRAYV EKYKFTSVVA
QDLLDSFLSF FPELKEQSVD CRAGLEFERW LNATGPPLAE PDLSQGSSLT RPVEALFQLW
TAEPLDQAAA SASAIDISKW RTFQTALFLD RLLDGSPLPQ EVVMSLSKCY SSLLDSMNAE
IRIRWLQIVV RNDYYPDLHR VRRFLESQMS RMYTIPLYED LCTGALKSFA LEVFYQTQGR
LHPNLRRAIQ QILSQGLGSS TEPASEPSTE LGKAEADTDS DAQALLLGDE APSSAISLRD
VNVSA
