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 24-JAN-2024, entry version 129. 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 Teratocarcinoma RC {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; CCDS1897.2; -. [Q53RT3-2] DR RefSeq; NP_690005.2; NM_152792.2. [Q53RT3-2] DR AlphaFoldDB; Q53RT3; -. DR SMR; Q53RT3; -. DR BioGRID; 127385; 50. DR IntAct; Q53RT3; 11. DR STRING; 9606.ENSP00000315383; -. DR MEROPS; A28.004; -. DR GlyCosmos; Q53RT3; 1 site, No reported glycans. 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; 9606-ENSP00000315383; -. DR PeptideAtlas; Q53RT3; -. DR ProteomicsDB; 62526; -. DR Pumba; Q53RT3; -. DR Antibodypedia; 31062; 82 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 AGR; HGNC:26321; -. 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 Orphanet; 313; Lamellar ichthyosis. 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; DQGDYGT; -. DR PhylomeDB; Q53RT3; -. DR TreeFam; TF337956; -. DR PathwayCommons; Q53RT3; -. DR SignaLink; Q53RT3; -. DR BioGRID-ORCS; 151516; 13 hits in 1149 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 127 other cell types or tissues. DR GO; GO:0016020; C: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 CDD; cd00303; retropepsin_like; 1. DR Gene3D; 2.40.70.10; Acid Proteases; 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; RETROVIRAL-LIKE ASPARTIC PROTEASE 1; 1. DR PANTHER; PTHR37006:SF1; RETROVIRAL-LIKE ASPARTIC PROTEASE 1; 1. DR Pfam; PF13975; gag-asp_proteas; 1. DR SUPFAM; SSF50630; Acid proteases; 1. DR PROSITE; PS50175; ASP_PROT_RETROV; 1. DR PROSITE; PS00141; ASP_PROTEASE; 1. DR Genevisible; Q53RT3; HS. 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 //