APRV1_HUMAN
ID APRV1_HUMAN Reviewed; 343 AA.
AC Q53RT3; Q8N5P2; Q96LT3; Q96N43;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Retroviral-like aspartic protease 1 {ECO:0000305};
DE EC=3.4.23.-;
DE AltName: Full=Skin-specific retroviral-like aspartic protease;
DE Short=SASPase;
DE Short=Skin aspartic protease;
DE AltName: Full=TPA-inducible aspartic proteinase-like protein;
DE Short=TAPS;
DE Flags: Precursor;
GN Name=ASPRV1 {ECO:0000312|HGNC:HGNC:26321};
GN Synonyms=SASP {ECO:0000303|PubMed:16098038};
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, TISSUE SPECIFICITY,
RP AUTOCATALYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-212.
RC TISSUE=Epidermis {ECO:0000269|PubMed:16098038};
RX PubMed=16098038; DOI=10.1111/j.0022-202x.2005.23816.x;
RA Bernard D., Mehul B., Thomas-Collignon A., Delattre C., Donovan M.,
RA Schmidt R.;
RT "Identification and characterization of a novel retroviral-like aspartic
RT protease specifically expressed in human epidermis.";
RL J. Invest. Dermatol. 125:278-287(2005).
RN [2] {ECO:0000312|EMBL:BAB71067.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-49.
RC TISSUE=Cerebellum {ECO:0000312|EMBL:BAB71587.1}, and
RC Teratocarcinoma {ECO:0000312|EMBL:BAB71067.1};
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 [3] {ECO:0000312|EMBL:AAY24017.1}
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 [4] {ECO:0000312|EMBL:AAH94000.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-49.
RC TISSUE=Skin;
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 [5] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=16565508; DOI=10.2353/ajpath.2006.050871;
RA Rhiemeier V., Breitenbach U., Richter K.H., Gebhardt C., Vogt I.,
RA Hartenstein B., Fuerstenberger G., Mauch C., Hess J., Angel P.;
RT "A novel aspartic proteinase-like gene expressed in stratified epithelia
RT and squamous cell carcinoma of the skin.";
RL Am. J. Pathol. 168:1354-1364(2006).
RN [6]
RP FUNCTION, INVOLVEMENT IN ADLI, VARIANTS ADLI GLU-199; PRO-311 AND THR-314,
RP AND CHARACTERIZATION OF VARIANTS ADLI GLU-199; PRO-311 AND THR-314.
RX PubMed=32516568; DOI=10.1016/j.ajhg.2020.05.013;
RA Boyden L.M., Zhou J., Hu R., Zaki T., Loring E., Scott J., Traupe H.,
RA Paller A.S., Lifton R.P., Choate K.A.;
RT "Mutations in ASPRV1 cause dominantly inherited ichthyosis.";
RL Am. J. Hum. Genet. 107:158-163(2020).
CC -!- FUNCTION: Protease responsible for filaggrin processing, essential for
CC the maintenance of a proper epidermis organization.
CC {ECO:0000269|PubMed:32516568}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q09PK2, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=Q53RT3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q53RT3-2; Sequence=VSP_061434;
CC -!- TISSUE SPECIFICITY: Expressed primarily in the granular layer of the
CC epidermis and inner root sheath of hair follicles. In psoriatic skin,
CC expressed throughout the stratum corneum. In ulcerated skin, expressed
CC in the stratum granulosum of intact epidermis but almost absent from
CC ulcerated regions. Expressed in differentiated areas of squamous cell
CC carcinomas but not in undifferentiated tumors.
CC {ECO:0000269|PubMed:16098038, ECO:0000269|PubMed:16565508}.
CC -!- PTM: Undergoes autocleavage which is necessary for activation of the
CC protein. {ECO:0000269|PubMed:16098038}.
CC -!- DISEASE: Ichthyosis, lamellar, autosomal dominant (ADLI) [MIM:146750]:
CC An autosomal dominant form of ichthyosis, a disorder of keratinization
CC with abnormal differentiation and desquamation of the epidermis,
CC resulting in abnormal skin scaling. ADLI is characterized by onset at
CC birth or within the first months of life, skin scaling on the entire
CC body with relative sparing of face, anterior chest, and abdomen, and
CC palmoplantar keratoderma. Patients may manifest mild erythema and
CC moderate pruritus. {ECO:0000269|PubMed:32516568}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-85 is the initiator.
CC {ECO:0000305}.
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DR EMBL; AK055994; BAB71067.1; -; mRNA.
DR EMBL; AK057813; BAB71587.1; -; mRNA.
DR EMBL; AC079811; AAY24017.1; -; Genomic_DNA.
DR EMBL; BC031997; AAH31997.2; -; mRNA.
DR EMBL; BC094002; AAH94002.1; -; mRNA.
DR EMBL; BC094000; AAH94000.1; -; mRNA.
DR CCDS; CCDS1897.1; -. [Q53RT3-2]
DR RefSeq; NP_690005.2; NM_152792.2.
DR AlphaFoldDB; Q53RT3; -.
DR SMR; Q53RT3; -.
DR BioGRID; 127385; 48.
DR IntAct; Q53RT3; 11.
DR STRING; 9606.ENSP00000315383; -.
DR MEROPS; A28.004; -.
DR GlyGen; Q53RT3; 1 site.
DR iPTMnet; Q53RT3; -.
DR PhosphoSitePlus; Q53RT3; -.
DR BioMuta; ASPRV1; -.
DR DMDM; 74726595; -.
DR EPD; Q53RT3; -.
DR MassIVE; Q53RT3; -.
DR PaxDb; Q53RT3; -.
DR PeptideAtlas; Q53RT3; -.
DR PRIDE; Q53RT3; -.
DR ProteomicsDB; 62526; -.
DR Antibodypedia; 31062; 79 antibodies from 23 providers.
DR DNASU; 151516; -.
DR Ensembl; ENST00000320256.6; ENSP00000315383.5; ENSG00000244617.3. [Q53RT3-2]
DR GeneID; 151516; -.
DR KEGG; hsa:151516; -.
DR MANE-Select; ENST00000320256.6; ENSP00000315383.5; NM_152792.4; NP_690005.3. [Q53RT3-2]
DR UCSC; uc002sfz.6; human. [Q53RT3-1]
DR CTD; 151516; -.
DR DisGeNET; 151516; -.
DR GeneCards; ASPRV1; -.
DR HGNC; HGNC:26321; ASPRV1.
DR HPA; ENSG00000244617; Tissue enriched (skin).
DR MalaCards; ASPRV1; -.
DR MIM; 146750; phenotype.
DR MIM; 611765; gene.
DR neXtProt; NX_Q53RT3; -.
DR OpenTargets; ENSG00000244617; -.
DR PharmGKB; PA162376919; -.
DR VEuPathDB; HostDB:ENSG00000244617; -.
DR eggNOG; ENOG502SQVT; Eukaryota.
DR GeneTree; ENSGT00390000017260; -.
DR HOGENOM; CLU_846072_0_0_1; -.
DR InParanoid; Q53RT3; -.
DR OMA; PTLLCGF; -.
DR OrthoDB; 1105506at2759; -.
DR PhylomeDB; Q53RT3; -.
DR TreeFam; TF337956; -.
DR PathwayCommons; Q53RT3; -.
DR SignaLink; Q53RT3; -.
DR BioGRID-ORCS; 151516; 12 hits in 1071 CRISPR screens.
DR GenomeRNAi; 151516; -.
DR Pharos; Q53RT3; Tbio.
DR PRO; PR:Q53RT3; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q53RT3; protein.
DR Bgee; ENSG00000244617; Expressed in upper arm skin and 126 other tissues.
DR Genevisible; Q53RT3; HS.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0043588; P:skin development; ISS:UniProtKB.
DR Gene3D; 2.40.70.10; -; 1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR033539; Asprv1.
DR InterPro; IPR001995; Peptidase_A2_cat.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR37006; PTHR37006; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS50175; ASP_PROT_RETROV; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Aspartyl protease; Autocatalytic cleavage;
KW Direct protein sequencing; Disease variant; Glycoprotein; Hydrolase;
KW Ichthyosis; Membrane; Protease; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT PROPEP 1..190
FT /evidence="ECO:0000269|PubMed:16098038"
FT /id="PRO_0000271170"
FT CHAIN 191..326
FT /note="Retroviral-like aspartic protease 1"
FT /evidence="ECO:0000269|PubMed:16098038"
FT /id="PRO_0000271171"
FT PROPEP 327..343
FT /evidence="ECO:0000269|PubMed:16098038"
FT /id="PRO_0000271172"
FT TOPO_DOM 1..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..343
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 207..288
FT /note="Peptidase A2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT ACT_SITE 212
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..84
FT /note="Missing (in isoform 2)"
FT /id="VSP_061434"
FT VARIANT 49
FT /note="T -> A (in dbSNP:rs3796097)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_051508"
FT VARIANT 199
FT /note="K -> E (in ADLI; impairs filaggrin cleavage)"
FT /evidence="ECO:0000269|PubMed:32516568"
FT /id="VAR_084554"
FT VARIANT 311
FT /note="R -> P (in ADLI; impairs filaggrin cleavage)"
FT /evidence="ECO:0000269|PubMed:32516568"
FT /id="VAR_084555"
FT VARIANT 314
FT /note="P -> T (in ADLI; impairs filaggrin cleavage)"
FT /evidence="ECO:0000269|PubMed:32516568"
FT /id="VAR_084556"
FT MUTAGEN 212
FT /note="D->A,E: Abolishes production of active form of
FT enzyme."
FT /evidence="ECO:0000269|PubMed:16098038"
FT CONFLICT 31
FT /note="Q -> R (in Ref. 2; BAB71587)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 343 AA; 36991 MW; 439BAC407F5EBCCB CRC64;
MGSPGASLGI KKALQSEQAT ALPASAPAVS QPTAPAPSCL PKAGQVIPTL LREAPFSSVI
APTLLCGFLF LAWVAAEVPE ESSRMAGSGA RSEEGRRQHA FVPEPFDGAN VVPNLWLHSF
EVINDLNHWD HITKLRFLKE SLRGEALGVY NRLSPQDQGD YGTVKEALLK AFGVPGAAPS
HLPKEIVFAN SMGKGYYLKG KIGKVPVRFL VDSGAQVSVV HPNLWEEVTD GDLDTLQPFE
NVVKVANGAE MKILGVWDTA VSLGKLKLKA QFLVANASAE EAIIGTDVLQ DHNAILDFEH
RTCTLKGKKF RLLPVGGSLE DEFDLELIEE DPSSEEGRQE LSH
