PEPA5_MOUSE
ID PEPA5_MOUSE Reviewed; 387 AA.
AC Q9D106; Q9JKE6;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Pepsin A-5 {ECO:0000312|MGI:MGI:1915935};
DE EC=3.4.23.1 {ECO:0000269|PubMed:11566730};
DE AltName: Full=Pepsin F {ECO:0000303|PubMed:11566730};
DE Flags: Precursor;
GN Name=Pga5 {ECO:0000312|MGI:MGI:1915935};
GN Synonyms=Pepf {ECO:0000303|PubMed:11566730};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAF61241.1};
RN [1] {ECO:0000312|EMBL:AAF61241.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11566730; DOI=10.1095/biolreprod65.4.1092;
RA Chen X., Rosenfeld C.S., Roberts R.M., Green J.A.;
RT "An aspartic proteinase expressed in the yolk sac and neonatal stomach of
RT the mouse.";
RL Biol. Reprod. 65:1092-1101(2001).
RN [2] {ECO:0000312|EMBL:BAB23174.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB23174.1};
RC TISSUE=Oviduct {ECO:0000312|EMBL:BAC35604.1}, and
RC Stomach {ECO:0000312|EMBL:BAE40737.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4] {ECO:0000312|EMBL:AAI19524.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Colon, Kidney, and Stomach {ECO:0000312|EMBL:AAI19524.1};
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).
CC -!- FUNCTION: Shows particularly broad specificity; although bonds
CC involving phenylalanine and leucine are preferred, many others are also
CC cleaved to some extent (By similarity). May play a role as a
CC specialized neonatal digestive enzyme (Probable).
CC {ECO:0000250|UniProtKB:Q9N2D4, ECO:0000305|PubMed:11566730}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage: hydrophobic, preferably aromatic,
CC residues in P1 and P1' positions. Cleaves 1-Phe-|-Val-2, 4-Gln-|-His-
CC 5, 13-Glu-|-Ala-14, 14-Ala-|-Leu-15, 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-
CC 17, 23-Gly-|-Phe-24, 24-Phe-|-Phe-25 and 25-Phe-|-Tyr-26 bonds in the
CC B chain of insulin.; EC=3.4.23.1;
CC Evidence={ECO:0000269|PubMed:11566730};
CC -!- ACTIVITY REGULATION: Inhibited by pepstatin A.
CC {ECO:0000269|PubMed:11566730}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in glandular chief cells of the neonatal
CC stomach. Expressed in yolk sacs of the placenta (at protein level).
CC {ECO:0000269|PubMed:11566730}.
CC -!- DEVELOPMENTAL STAGE: In neonatal stomach, highly expressed for the
CC first two weeks after birth, with rapidly decreasing expression after
CC 17.5 days. In placenta, detected from 11.5 dpc until term.
CC {ECO:0000269|PubMed:11566730}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01103}.
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DR EMBL; AF240776; AAF61241.1; -; mRNA.
DR EMBL; AK004109; BAB23174.1; -; mRNA.
DR EMBL; AK053965; BAC35604.1; -; mRNA.
DR EMBL; AK168924; BAE40737.1; -; mRNA.
DR EMBL; AC132247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC119523; AAI19524.1; -; mRNA.
DR CCDS; CCDS29584.1; -.
DR RefSeq; NP_067428.2; NM_021453.4.
DR AlphaFoldDB; Q9D106; -.
DR SMR; Q9D106; -.
DR STRING; 10090.ENSMUSP00000025647; -.
DR MEROPS; A01.051; -.
DR PhosphoSitePlus; Q9D106; -.
DR PaxDb; Q9D106; -.
DR PRIDE; Q9D106; -.
DR ProteomicsDB; 287914; -.
DR DNASU; 58803; -.
DR Ensembl; ENSMUST00000025647; ENSMUSP00000025647; ENSMUSG00000024738.
DR GeneID; 58803; -.
DR KEGG; mmu:58803; -.
DR UCSC; uc008gqp.2; mouse.
DR CTD; 5222; -.
DR MGI; MGI:1915935; Pga5.
DR VEuPathDB; HostDB:ENSMUSG00000024738; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000153747; -.
DR HOGENOM; CLU_013253_3_0_1; -.
DR InParanoid; Q9D106; -.
DR OMA; YEPMRNY; -.
DR OrthoDB; 1619495at2759; -.
DR PhylomeDB; Q9D106; -.
DR TreeFam; TF314990; -.
DR BioGRID-ORCS; 58803; 3 hits in 72 CRISPR screens.
DR PRO; PR:Q9D106; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9D106; protein.
DR Bgee; ENSMUSG00000024738; Expressed in epithelium of stomach and 47 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:MGI.
DR GO; GO:0019538; P:protein metabolic process; TAS:MGI.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR012848; Aspartic_peptidase_N.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF07966; A1_Propeptide; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW Aspartyl protease; Disulfide bond; Hydrolase; Protease; Reference proteome;
KW Secreted; Signal; Zymogen.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT PROPEP 16..62
FT /note="Activation peptide"
FT /evidence="ECO:0000250|UniProtKB:P0DJD9"
FT /id="PRO_0000436776"
FT CHAIN 63..387
FT /note="Pepsin A-5"
FT /evidence="ECO:0000305"
FT /id="PRO_0000436777"
FT DOMAIN 74..384
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 92
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 275
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT DISULFID 105..110
FT /evidence="ECO:0000250|UniProtKB:P0DJD9"
FT DISULFID 266..270
FT /evidence="ECO:0000250|UniProtKB:P0DJD9"
FT DISULFID 309..343
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CONFLICT 176
FT /note="V -> G (in Ref. 1; AAF61241)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 387 AA; 42824 MW; 177E12140ED5A0F7 CRC64;
MKWLWVLGLV ALSECLVKIP LMKIKSMREN LRESQVLKDY LEKYPRSRAH VLLEQRRNPA
VTYEPMRNYL DLVYIGIISI GTPPQEFRVV LDTGSSVLWV PSIYCSSPAC AHHKAFNPLR
SSTFLVSGRP VNVAYGSGEM SGFLAYDTVR IGDLTVVAQA FGLSLEEPGI FMEYAVFDGI
LGLGYPNLGL QGITPVFDNL WLQGLIPQNL FAFYLSSKDE KGSMLMLGGV DPSYYHGELH
WVPVSKPSYW QLAVDSISMN GEVIACDGGC QGIMDTGTSL LTGPRSSIVN IQNLIGAKAS
GDGEYFLKCD TINTLPDIVF TIGSVTYPVP ASAYIRKDRS HNCRSNFEEG MDDPSDPEMW
VLGDVFLRLY FTVFDRANNR IGLAPAA
