HRG7_CAEEL
ID HRG7_CAEEL Reviewed; 428 AA.
AC Q18020; E0AHB8;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Aspartic protease 10;
DE EC=3.4.23.- {ECO:0000250|UniProtKB:Q9N9H4};
DE AltName: Full=Heme transporter hrg-7 {ECO:0000305};
DE AltName: Full=Heme-responsive gene 7 protein {ECO:0000312|WormBase:C15C8.3a};
DE Flags: Precursor;
GN Name=hrg-7 {ECO:0000303|PubMed:28581477, ECO:0000312|WormBase:C15C8.3a};
GN Synonyms=asp-10 {ECO:0000312|WormBase:C15C8.3a};
GN ORFNames=C15C8.3 {ECO:0000312|WormBase:C15C8.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, PROTEOLYTIC
RP CLEAVAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=28581477; DOI=10.1038/ncb3539;
RA Sinclair J., Pinter K., Samuel T., Beardsley S., Yuan X., Zhang J.,
RA Meng K., Yun S., Krause M., Hamza I.;
RT "Inter-organ signalling by HRG-7 promotes systemic haem homeostasis.";
RL Nat. Cell Biol. 19:799-807(2017).
CC -!- FUNCTION: Aspartic protease which plays a role in heme homeostasis and
CC mediates inter-organ signaling between the intestine and extra-
CC intestinal tissues when cellular heme levels are low.
CC {ECO:0000269|PubMed:28581477}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28581477}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:C15C8.3a};
CC IsoId=Q18020-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C15C8.3b};
CC IsoId=Q18020-2; Sequence=VSP_060542;
CC -!- TISSUE SPECIFICITY: Synthesized in the intestine (PubMed:28581477).
CC When secreted in low heme conditions, localizes to neurons near the
CC anterior and posterior regions of the body and in coelomocytes
CC (PubMed:28581477). {ECO:0000269|PubMed:28581477}.
CC -!- INDUCTION: By heme deficiency. {ECO:0000269|PubMed:28581477}.
CC -!- PTM: Proteolytically cleaved. {ECO:0000305|PubMed:28581477}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in larvae results in
CC defective heme accumulation in the intestine under low heme conditions
CC (PubMed:28581477). Double RNAi-mediated knockdown with hrg-4 or mrp-5
CC in larvae results in defective heme sensing (PubMed:28581477).
CC {ECO:0000269|PubMed:28581477}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01103}.
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DR EMBL; BX284605; CAA99777.1; -; Genomic_DNA.
DR EMBL; BX284605; CBW44360.1; -; Genomic_DNA.
DR PIR; T19309; T19309.
DR RefSeq; NP_001256448.1; NM_001269519.1. [Q18020-1]
DR RefSeq; NP_001256449.1; NM_001269520.1. [Q18020-2]
DR AlphaFoldDB; Q18020; -.
DR SMR; Q18020; -.
DR IntAct; Q18020; 1.
DR STRING; 6239.C15C8.3a; -.
DR MEROPS; A01.A76; -.
DR EPD; Q18020; -.
DR PaxDb; Q18020; -.
DR PeptideAtlas; Q18020; -.
DR EnsemblMetazoa; C15C8.3a.1; C15C8.3a.1; WBGene00007605. [Q18020-1]
DR EnsemblMetazoa; C15C8.3b.1; C15C8.3b.1; WBGene00007605. [Q18020-2]
DR GeneID; 182635; -.
DR KEGG; cel:CELE_C15C8.3; -.
DR UCSC; C15C8.3; c. elegans. [Q18020-1]
DR CTD; 182635; -.
DR WormBase; C15C8.3a; CE05287; WBGene00007605; hrg-7. [Q18020-1]
DR WormBase; C15C8.3b; CE45278; WBGene00007605; hrg-7. [Q18020-2]
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_3_4_1; -.
DR InParanoid; Q18020; -.
DR OMA; FYPAWML; -.
DR OrthoDB; 753343at2759; -.
DR PhylomeDB; Q18020; -.
DR Reactome; R-CEL-2132295; MHC class II antigen presentation.
DR Reactome; R-CEL-5683826; Surfactant metabolism.
DR PRO; PR:Q18020; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00007605; Expressed in larva and 3 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008219; P:cell death; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd05471; pepsin_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR034164; Pepsin-like_dom.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Aspartyl protease; Disulfide bond; Glycoprotein;
KW Hydrolase; Protease; Reference proteome; Secreted; Signal; Zymogen.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..?
FT /evidence="ECO:0000305|PubMed:28581477"
FT /id="PRO_0000449290"
FT CHAIN ?..428
FT /note="Aspartic protease 10"
FT /id="PRO_5004186738"
FT DOMAIN 72..425
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 90
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 318
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 353..385
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT VAR_SEQ 1..239
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060542"
SQ SEQUENCE 428 AA; 45993 MW; 2E1378E9F59CD14E CRC64;
MKTFIALLAL LTVVSAEVHQ FNIGYRPNMR QRMNAKGKLA EYEKERNELL SKKSLQLASS
SSPVIDYEDM AYMVQISLGS PAQNFVLFID SGSSNLWVPD ITCAGGKDAT CGSYCKSTPY
DACLTFCQEE CCTKTVEGVK VLSTTDACQS KHRFNSSLSS SYVTNGQKFD MTYNTGEVKG
FFGVDTFCFT NTSVCATGQV FGQATTIGEA FAKQPEDGII GLGWPALAVN QQTPPLFNLM
NQGKLDQPYF VVYLANIGPT SQINGGAFTV GGLDTTHCSS NVDWVPLSTQ TFWQFKLGGV
SSGSYSQAPN SGWQAAADTA ASFIGAPKSV VTSLAKAVGA TYVPLTGAFF MDCDAVVPDI
VFTINGKTYN MPSTSFVVSA GPGPCMFAFY ELTAGGFYPA WMLGPPFMRA YCHVHDMKSG
RLGLAKVL
