PEPL1_HUMAN
ID PEPL1_HUMAN Reviewed; 523 AA.
AC Q8NDH3; A6NGZ0; B4DMW7; B7ZBN0; E9PN47; G5EA34; Q53G37; Q5W083; Q8TF28;
AC Q8WUI2; Q9H1T6; Q9HAI5;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Probable aminopeptidase NPEPL1;
DE EC=3.4.11.-;
DE AltName: Full=Aminopeptidase-like 1;
GN Name=NPEPL1; Synonyms=KIAA1974;
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 MRNA] (ISOFORMS 1; 4 AND 5), AND VARIANT
RP VAL-513.
RC TISSUE=Brain cortex, Embryo, and Heart;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-513.
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [LARGE SCALE MRNA] OF 51-523 (ISOFORM 2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11853319; DOI=10.1093/dnares/8.6.319;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXII. The
RT complete sequences of 50 new cDNA clones which code for large proteins.";
RL DNA Res. 8:319-327(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 51-523 (ISOFORM 3), AND VARIANT
RP VAL-513.
RC TISSUE=Testis;
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).
CC -!- FUNCTION: Probably catalyzes the removal of unsubstituted N-terminal
CC amino acids from various peptides.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC -!- INTERACTION:
CC Q8NDH3-4; Q12800: TFCP2; NbExp=3; IntAct=EBI-10269715, EBI-717422;
CC Q8NDH3-5; P55212: CASP6; NbExp=3; IntAct=EBI-12329915, EBI-718729;
CC Q8NDH3-5; O00291: HIP1; NbExp=3; IntAct=EBI-12329915, EBI-473886;
CC Q8NDH3-5; P13473-2: LAMP2; NbExp=3; IntAct=EBI-12329915, EBI-21591415;
CC Q8NDH3-5; Q99750: MDFI; NbExp=3; IntAct=EBI-12329915, EBI-724076;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8NDH3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NDH3-2; Sequence=VSP_007253, VSP_007254;
CC Name=3;
CC IsoId=Q8NDH3-3; Sequence=VSP_007251, VSP_007252;
CC Name=4;
CC IsoId=Q8NDH3-4; Sequence=VSP_044526;
CC Name=5;
CC IsoId=Q8NDH3-5; Sequence=VSP_044527;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:11853319}.
CC -!- SIMILARITY: Belongs to the peptidase M17 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK307771; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB13861.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 2]:
CC Sequence=CAD38816.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK021645; BAB13861.1; ALT_FRAME; mRNA.
DR EMBL; AK297667; BAG60029.1; -; mRNA.
DR EMBL; AK307771; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK223094; BAD96814.1; -; mRNA.
DR EMBL; AL139349; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75479.1; -; Genomic_DNA.
DR EMBL; BC020507; AAH20507.2; -; mRNA.
DR EMBL; AB075854; BAB85560.1; -; mRNA.
DR EMBL; AL833971; CAD38816.2; ALT_FRAME; mRNA.
DR CCDS; CCDS46621.1; -. [Q8NDH3-1]
DR CCDS; CCDS56200.1; -. [Q8NDH3-4]
DR CCDS; CCDS56201.1; -. [Q8NDH3-5]
DR RefSeq; NP_001191801.1; NM_001204872.1. [Q8NDH3-4]
DR RefSeq; NP_001191802.1; NM_001204873.1. [Q8NDH3-5]
DR RefSeq; NP_078939.3; NM_024663.3. [Q8NDH3-1]
DR AlphaFoldDB; Q8NDH3; -.
DR SMR; Q8NDH3; -.
DR BioGRID; 122832; 26.
DR IntAct; Q8NDH3; 6.
DR STRING; 9606.ENSP00000348395; -.
DR ChEMBL; CHEMBL3831223; -.
DR MEROPS; M17.006; -.
DR iPTMnet; Q8NDH3; -.
DR PhosphoSitePlus; Q8NDH3; -.
DR BioMuta; NPEPL1; -.
DR DMDM; 68847034; -.
DR EPD; Q8NDH3; -.
DR jPOST; Q8NDH3; -.
DR MassIVE; Q8NDH3; -.
DR MaxQB; Q8NDH3; -.
DR PaxDb; Q8NDH3; -.
DR PeptideAtlas; Q8NDH3; -.
DR PRIDE; Q8NDH3; -.
DR ProteomicsDB; 22305; -.
DR ProteomicsDB; 34124; -.
DR ProteomicsDB; 73027; -. [Q8NDH3-1]
DR ProteomicsDB; 73028; -. [Q8NDH3-2]
DR ProteomicsDB; 73029; -. [Q8NDH3-3]
DR Antibodypedia; 29150; 81 antibodies from 22 providers.
DR DNASU; 79716; -.
DR Ensembl; ENST00000356091.11; ENSP00000348395.6; ENSG00000215440.12. [Q8NDH3-1]
DR Ensembl; ENST00000525817.5; ENSP00000437112.1; ENSG00000215440.12. [Q8NDH3-5]
DR Ensembl; ENST00000525967.5; ENSP00000434810.1; ENSG00000215440.12. [Q8NDH3-4]
DR GeneID; 79716; -.
DR KEGG; hsa:79716; -.
DR MANE-Select; ENST00000356091.11; ENSP00000348395.6; NM_024663.4; NP_078939.3.
DR UCSC; uc010gjo.3; human. [Q8NDH3-1]
DR CTD; 79716; -.
DR DisGeNET; 79716; -.
DR GeneCards; NPEPL1; -.
DR HGNC; HGNC:16244; NPEPL1.
DR HPA; ENSG00000215440; Low tissue specificity.
DR neXtProt; NX_Q8NDH3; -.
DR OpenTargets; ENSG00000215440; -.
DR PharmGKB; PA31702; -.
DR VEuPathDB; HostDB:ENSG00000215440; -.
DR eggNOG; KOG2597; Eukaryota.
DR GeneTree; ENSGT00530000063255; -.
DR HOGENOM; CLU_013734_3_1_1; -.
DR InParanoid; Q8NDH3; -.
DR OMA; MVCEQSD; -.
DR OrthoDB; 562530at2759; -.
DR PhylomeDB; Q8NDH3; -.
DR TreeFam; TF314954; -.
DR PathwayCommons; Q8NDH3; -.
DR SignaLink; Q8NDH3; -.
DR BioGRID-ORCS; 79716; 17 hits in 1079 CRISPR screens.
DR GenomeRNAi; 79716; -.
DR Pharos; Q8NDH3; Tdark.
DR PRO; PR:Q8NDH3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8NDH3; protein.
DR Bgee; ENSG00000215440; Expressed in mucosa of stomach and 94 other tissues.
DR ExpressionAtlas; Q8NDH3; baseline and differential.
DR Genevisible; Q8NDH3; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:InterPro.
DR GO; GO:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd00433; Peptidase_M17; 1.
DR InterPro; IPR011356; Leucine_aapep/pepB.
DR InterPro; IPR041417; NPEPL1_N.
DR InterPro; IPR000819; Peptidase_M17_C.
DR PANTHER; PTHR11963; PTHR11963; 1.
DR Pfam; PF18295; Pdase_M17_N2; 1.
DR Pfam; PF00883; Peptidase_M17; 1.
DR PRINTS; PR00481; LAMNOPPTDASE.
DR PROSITE; PS00631; CYTOSOL_AP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Aminopeptidase; Hydrolase; Manganese; Metal-binding;
KW Protease; Reference proteome; Zinc.
FT CHAIN 1..523
FT /note="Probable aminopeptidase NPEPL1"
FT /id="PRO_0000165828"
FT ACT_SITE 272
FT /evidence="ECO:0000255"
FT ACT_SITE 346
FT /evidence="ECO:0000255"
FT BINDING 260
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 265
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 265
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 342
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..50
FT /note="MANVGLQFQASAGDSDPQSRPLLLLGQLHHLHRVPWSHVRGKLQPRVTEE
FT -> MELHGGNRGGYQPKALEQSGCW (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044526"
FT VAR_SEQ 1..49
FT /note="MANVGLQFQASAGDSDPQSRPLLLLGQLHHLHRVPWSHVRGKLQPRVTE ->
FT M (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044527"
FT VAR_SEQ 335..393
FT /note="TVEINNTDAEGRLVLADGVSYACKDLGADIILDMATLTGAQGIATGKYHAAV
FT LTNSAEW -> YVWPSHSFLPTVGTRDPSRPAMPAHSRHIGRALSVGVPWAAGSLLPGG
FT LGSFGSRRTSR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_007251"
FT VAR_SEQ 376..412
FT /note="GIATGKYHAAVLTNSAEWEAACVKAGRKCGDLVHPLV -> VSAPWIHPLAV
FT VPGNPTPLLTSRWGRQRVGAAVRKFS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11853319"
FT /id="VSP_007253"
FT VAR_SEQ 394..523
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_007252"
FT VAR_SEQ 413..523
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11853319"
FT /id="VSP_007254"
FT VARIANT 303
FT /note="K -> R (in dbSNP:rs8116292)"
FT /id="VAR_059756"
FT VARIANT 513
FT /note="L -> V (in dbSNP:rs6026468)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.2"
FT /id="VAR_059757"
FT CONFLICT 87
FT /note="N -> S (in Ref. 2; BAD96814)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="V -> L (in Ref. 1; AK307771)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="V -> A (in Ref. 1; BAB13861)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="R -> G (in Ref. 1; BAB13861)"
FT /evidence="ECO:0000305"
FT CONFLICT 502
FT /note="L -> P (in Ref. 1; BAG60029)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 523 AA; 55861 MW; 1B00C3422D169C0C CRC64;
MANVGLQFQA SAGDSDPQSR PLLLLGQLHH LHRVPWSHVR GKLQPRVTEE LWQAALSTLN
PNPTDSCPLY LNYATVAALP CRVSRHNSPS AAHFITRLVR TCLPPGAHRC IVMVCEQPEV
FASACALARA FPLFTHRSGA SRRLEKKTVT VEFFLVGQDN GPVEVSTLQC LANATDGVRL
AARIVDTPCN EMNTDTFLEE INKVGKELGI IPTIIRDEEL KTRGFGGIYG VGKAALHPPA
LAVLSHTPDG ATQTIAWVGK GIVYDTGGLS IKGKTTMPGM KRDCGGAAAV LGAFRAAIKQ
GFKDNLHAVF CLAENSVGPN ATRPDDIHLL YSGKTVEINN TDAEGRLVLA DGVSYACKDL
GADIILDMAT LTGAQGIATG KYHAAVLTNS AEWEAACVKA GRKCGDLVHP LVYCPELHFS
EFTSAVADMK NSVADRDNSP SSCAGLFIAS HIGFDWPGVW VHLDIAAPVH AGERATGFGV
ALLLALFGRA SEDPLLNLVS PLGCEVDVEE GDLGRDSKRR RLV
