PRS56_HUMAN
ID PRS56_HUMAN Reviewed; 603 AA.
AC P0CW18;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Serine protease 56;
DE EC=3.4.21.-;
DE Flags: Precursor;
GN Name=PRSS56;
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 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-174.
RX PubMed=15146197; DOI=10.1038/nbt971;
RA Brandenberger R., Wei H., Zhang S., Lei S., Murage J., Fisk G.J., Li Y.,
RA Xu C., Fang R., Guegler K., Rao M.S., Mandalam R., Lebkowski J.,
RA Stanton L.W.;
RT "Transcriptome characterization elucidates signaling networks that control
RT human ES cell growth and differentiation.";
RL Nat. Biotechnol. 22:707-716(2004).
RN [3]
RP FUNCTION, INVOLVEMENT IN MCOP6, VARIANTS MCOP6 GLY-176 AND SER-309, AND
RP TISSUE SPECIFICITY.
RX PubMed=21397065; DOI=10.1016/j.ajhg.2011.02.006;
RA Gal A., Rau I., El Matri L., Kreienkamp H.J., Fehr S., Baklouti K.,
RA Chouchane I., Li Y., Rehbein M., Fuchs J., Fledelius H.C., Vilhelmsen K.,
RA Schorderet D.F., Munier F.L., Ostergaard E., Thompson D.A., Rosenberg T.;
RT "Autosomal-recessive posterior microphthalmos is caused by mutations in
RT PRSS56, a gene encoding a trypsin-like serine protease.";
RL Am. J. Hum. Genet. 88:382-390(2011).
RN [4]
RP VARIANTS MCOP6 ARG-237; PHE-302; ARG-320 AND ARG-395.
RX PubMed=21850159;
RA Orr A., Dube M.P., Zenteno J.C., Jiang H., Asselin G., Evans S.C.,
RA Caqueret A., Lakosha H., Letourneau L., Marcadier J., Matsuoka M.,
RA Macgillivray C., Nightingale M., Papillon-Cavanagh S., Perry S.,
RA Provost S., Ludman M., Guernsey D.L., Samuels M.E.;
RT "Mutations in a novel serine protease PRSS56 in families with
RT nanophthalmos.";
RL Mol. Vis. 17:1850-1861(2011).
RN [5]
RP VARIANT MCOP6 ALA-599.
RX PubMed=21532570; DOI=10.1038/ng.813;
RA Nair K.S., Hmani-Aifa M., Ali Z., Kearney A.L., Ben Salem S.,
RA Macalinao D.G., Cosma I.M., Bouassida W., Hakim B., Benzina Z., Soto I.,
RA Soderkvist P., Howell G.R., Smith R.S., Ayadi H., John S.W.;
RT "Alteration of the serine protease PRSS56 causes angle-closure glaucoma in
RT mice and posterior microphthalmia in humans and mice.";
RL Nat. Genet. 43:579-584(2011).
CC -!- FUNCTION: Serine protease required during eye development.
CC {ECO:0000269|PubMed:21397065}.
CC -!- TISSUE SPECIFICITY: Expressed neural retina, cornea, sclera and optic
CC nerve. {ECO:0000269|PubMed:21397065}.
CC -!- DISEASE: Microphthalmia, isolated, 6 (MCOP6) [MIM:613517]: A
CC developmental ocular disorder characterized by small malformed eyes.
CC Clinical features are extreme hyperopia due to short axial length with
CC essentially normal anterior segment, steep corneal curvatures, shallow
CC anterior chamber, thick lenses, and thickened scleral wall. Palpebral
CC fissures appear narrow because of relatively deep-set eyes, visual
CC acuity is mildly to moderately reduced, and anisometropic or strabismic
CC amblyopia is common. The fundus of the eye shows crowded optical disks,
CC tortuous vessels, and an abnormal foveal avascular zone.
CC {ECO:0000269|PubMed:21397065, ECO:0000269|PubMed:21532570,
CC ECO:0000269|PubMed:21850159}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AC092165; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CN280933; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS74669.1; -.
DR RefSeq; NP_001182058.1; NM_001195129.1.
DR AlphaFoldDB; P0CW18; -.
DR SMR; P0CW18; -.
DR BioGRID; 571766; 14.
DR IntAct; P0CW18; 4.
DR STRING; 9606.ENSP00000479745; -.
DR MEROPS; S01.514; -.
DR GlyGen; P0CW18; 1 site.
DR PhosphoSitePlus; P0CW18; -.
DR BioMuta; PRSS56; -.
DR DMDM; 332319805; -.
DR MassIVE; P0CW18; -.
DR MaxQB; P0CW18; -.
DR PeptideAtlas; P0CW18; -.
DR PRIDE; P0CW18; -.
DR ProteomicsDB; 52517; -.
DR Antibodypedia; 71253; 57 antibodies from 11 providers.
DR DNASU; 646960; -.
DR Ensembl; ENST00000617714.2; ENSP00000479745.1; ENSG00000237412.7.
DR GeneID; 646960; -.
DR KEGG; hsa:646960; -.
DR MANE-Select; ENST00000617714.2; ENSP00000479745.1; NM_001195129.2; NP_001182058.1.
DR UCSC; uc021vyh.2; human.
DR CTD; 646960; -.
DR DisGeNET; 646960; -.
DR GeneCards; PRSS56; -.
DR HGNC; HGNC:39433; PRSS56.
DR HPA; ENSG00000237412; Group enriched (brain, retina, skeletal muscle).
DR MalaCards; PRSS56; -.
DR MIM; 613517; phenotype.
DR MIM; 613858; gene.
DR neXtProt; NX_P0CW18; -.
DR OpenTargets; ENSG00000237412; -.
DR Orphanet; 35612; Nanophthalmos.
DR VEuPathDB; HostDB:ENSG00000237412; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000157183; -.
DR HOGENOM; CLU_034171_0_0_1; -.
DR InParanoid; P0CW18; -.
DR OMA; VVMEIQH; -.
DR OrthoDB; 1314811at2759; -.
DR PathwayCommons; P0CW18; -.
DR SignaLink; P0CW18; -.
DR BioGRID-ORCS; 646960; 11 hits in 310 CRISPR screens.
DR GenomeRNAi; 646960; -.
DR Pharos; P0CW18; Tbio.
DR PRO; PR:P0CW18; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P0CW18; protein.
DR Bgee; ENSG00000237412; Expressed in hindlimb stylopod muscle and 34 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IBA:GO_Central.
DR GO; GO:0043010; P:camera-type eye development; IMP:UniProtKB.
DR GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Microphthalmia;
KW Protease; Reference proteome; Serine protease; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..603
FT /note="Serine protease 56"
FT /id="PRO_0000408091"
FT DOMAIN 105..337
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 64..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 573..603
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 145
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 191
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 286
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 130..146
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 225..292
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 256..271
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 282..313
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VARIANT 176
FT /note="R -> G (in MCOP6; dbSNP:rs387907096)"
FT /evidence="ECO:0000269|PubMed:21397065"
FT /id="VAR_065076"
FT VARIANT 237
FT /note="G -> R (in MCOP6; dbSNP:rs730882160)"
FT /evidence="ECO:0000269|PubMed:21850159"
FT /id="VAR_069226"
FT VARIANT 302
FT /note="V -> F (in MCOP6; dbSNP:rs74703359)"
FT /evidence="ECO:0000269|PubMed:21850159"
FT /id="VAR_069227"
FT VARIANT 309
FT /note="W -> S (in MCOP6; dbSNP:rs387907095)"
FT /evidence="ECO:0000269|PubMed:21397065"
FT /id="VAR_065077"
FT VARIANT 320
FT /note="G -> R (in MCOP6; dbSNP:rs730882158)"
FT /evidence="ECO:0000269|PubMed:21850159"
FT /id="VAR_069228"
FT VARIANT 395
FT /note="C -> R (in MCOP6; dbSNP:rs730882161)"
FT /evidence="ECO:0000269|PubMed:21850159"
FT /id="VAR_069229"
FT VARIANT 599
FT /note="P -> A (in MCOP6; dbSNP:rs61744404)"
FT /evidence="ECO:0000269|PubMed:21532570"
FT /id="VAR_069230"
FT CONFLICT 162
FT /note="E -> K (in Ref. 2; CN280933)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 603 AA; 64597 MW; 72E33EDE6C495B81 CRC64;
MLLAVLLLLP LPSSWFAHGH PLYTRLPPSA LQVLSAQGTQ ALQAAQRSAQ WAINRVAMEI
QHRSHECRGS GRPRPQALLQ DPPEPGPCGE RRPSTANVTR AHGRIVGGSA APPGAWPWLV
RLQLGGQPLC GGVLVAASWV LTAAHCFVGA PNELLWTVTL AEGSRGEQAE EVPVNRILPH
PKFDPRTFHN DLALVQLWTP VSPGGSARPV CLPQEPQEPP AGTACAIAGW GALFEDGPEA
EAVREARVPL LSTDTCRRAL GPGLRPSTML CAGYLAGGVD SCQGDSGGPL TCSEPGPRPR
EVLFGVTSWG DGCGEPGKPG VYTRVAVFKD WLQEQMSASS SREPSCRELL AWDPPQELQA
DAARLCAFYA RLCPGSQGAC ARLAHQQCLQ RRRRCELRSL AHTLLGLLRN AQELLGPRPG
LRRLAPALAL PAPALRESPL HPARELRLHS GSRAAGTRFP KRRPEPRGEA NGCPGLEPLR
QKLAALQGAH AWILQVPSEH LAMNFHEVLA DLGSKTLTGL FRAWVRAGLG GRHVAFSGLV
GLEPATLARS LPRLLVQALQ AFRVAALAEG EPEGPWMDVG QGPGLERKGH HPLNPQVPPA
RQP
