PI16_HUMAN
ID PI16_HUMAN Reviewed; 463 AA.
AC Q6UXB8; Q6ZVG9; Q8IYL8; Q8NBK0; Q8TCB8;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Peptidase inhibitor 16;
DE Short=PI-16;
DE AltName: Full=Cysteine-rich secretory protein 9;
DE Short=CRISP-9;
DE AltName: Full=PSP94-binding protein;
DE AltName: CD_antigen=CD364;
DE Flags: Precursor;
GN Name=PI16; Synonyms=CRISP9, PSPBP; ORFNames=PSEC0164, UNQ289/PRO328;
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 MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-50.
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT PRO-50.
RC TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-50.
RC TISSUE=Blood, and Lung;
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 [6]
RP PROTEIN SEQUENCE OF 28-57, SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH MSMB.
RX PubMed=15344909; DOI=10.1042/bj20040290;
RA Reeves J.R., Xuan J.W., Arfanis K., Morin C., Garde S.V., Ruiz M.T.,
RA Wisniewski J., Panchal C., Tanner J.E.;
RT "Identification, purification and characterization of a novel human blood
RT protein with binding affinity for prostate secretory protein of 94 amino
RT acids.";
RL Biochem. J. 385:105-114(2005).
RN [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17062675; DOI=10.1158/1078-0432.ccr-06-0625;
RA Reeves J.R., Dulude H., Panchal C., Daigneault L., Ramnani D.M.;
RT "Prognostic value of prostate secretory protein of 94 amino acids and its
RT binding protein after radical prostatectomy.";
RL Clin. Cancer Res. 12:6018-6022(2006).
RN [8]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, STRUCTURE OF CARBOHYDRATES, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
CC -!- FUNCTION: May inhibit cardiomyocyte growth.
CC {ECO:0000250|UniProtKB:Q9ET66}.
CC -!- SUBUNIT: Interacts with PSP94/MSMB. {ECO:0000269|PubMed:15344909}.
CC -!- INTERACTION:
CC Q6UXB8; P27449: ATP6V0C; NbExp=3; IntAct=EBI-12810028, EBI-721179;
CC Q6UXB8; P60201-2: PLP1; NbExp=3; IntAct=EBI-12810028, EBI-12188331;
CC Q6UXB8; P0DN84: STRIT1; NbExp=3; IntAct=EBI-12810028, EBI-12200293;
CC Q6UXB8; P55061: TMBIM6; NbExp=3; IntAct=EBI-12810028, EBI-1045825;
CC Q6UXB8; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-12810028, EBI-2852148;
CC Q6UXB8; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-12810028, EBI-12015604;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15344909,
CC ECO:0000269|PubMed:17062675, ECO:0000269|PubMed:22171320}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6UXB8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UXB8-2; Sequence=VSP_025574;
CC -!- TISSUE SPECIFICITY: Expressed in prostate, testis, ovary and intestine.
CC Concentrates in prostate cancer patient's sera.
CC {ECO:0000269|PubMed:15344909, ECO:0000269|PubMed:17062675}.
CC -!- PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly core
CC 8 glycans. {ECO:0000269|PubMed:15344909, ECO:0000269|PubMed:22171320}.
CC -!- MISCELLANEOUS: May serve as a marker following prostatectomy for
CC prostate cancer.
CC -!- SIMILARITY: Belongs to the CRISP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH22399.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY358422; AAQ88788.1; -; mRNA.
DR EMBL; AK075470; BAC11640.1; -; mRNA.
DR EMBL; AK124589; BAC85892.1; -; mRNA.
DR EMBL; AL122034; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022399; AAH22399.2; ALT_FRAME; mRNA.
DR EMBL; BC035634; AAH35634.2; -; mRNA.
DR CCDS; CCDS34440.1; -. [Q6UXB8-1]
DR RefSeq; NP_001186088.1; NM_001199159.1. [Q6UXB8-1]
DR RefSeq; NP_699201.2; NM_153370.2. [Q6UXB8-1]
DR RefSeq; XP_005248974.1; XM_005248917.2. [Q6UXB8-2]
DR RefSeq; XP_011512677.1; XM_011514375.2. [Q6UXB8-1]
DR RefSeq; XP_016865919.1; XM_017010430.1. [Q6UXB8-2]
DR AlphaFoldDB; Q6UXB8; -.
DR SMR; Q6UXB8; -.
DR BioGRID; 128731; 6.
DR IntAct; Q6UXB8; 7.
DR MINT; Q6UXB8; -.
DR STRING; 9606.ENSP00000362778; -.
DR GlyGen; Q6UXB8; 15 sites, 4 O-linked glycans (12 sites).
DR iPTMnet; Q6UXB8; -.
DR PhosphoSitePlus; Q6UXB8; -.
DR BioMuta; PI16; -.
DR DMDM; 74749419; -.
DR jPOST; Q6UXB8; -.
DR MassIVE; Q6UXB8; -.
DR MaxQB; Q6UXB8; -.
DR PaxDb; Q6UXB8; -.
DR PeptideAtlas; Q6UXB8; -.
DR PRIDE; Q6UXB8; -.
DR ProteomicsDB; 67586; -. [Q6UXB8-1]
DR ProteomicsDB; 67587; -. [Q6UXB8-2]
DR Antibodypedia; 29743; 184 antibodies from 27 providers.
DR DNASU; 221476; -.
DR Ensembl; ENST00000373674.4; ENSP00000362778.3; ENSG00000164530.15. [Q6UXB8-1]
DR Ensembl; ENST00000611814.4; ENSP00000478888.1; ENSG00000164530.15. [Q6UXB8-1]
DR Ensembl; ENST00000647861.1; ENSP00000497550.1; ENSG00000164530.15. [Q6UXB8-1]
DR GeneID; 221476; -.
DR KEGG; hsa:221476; -.
DR MANE-Select; ENST00000373674.4; ENSP00000362778.3; NM_153370.3; NP_699201.2.
DR UCSC; uc003ona.3; human. [Q6UXB8-1]
DR CTD; 221476; -.
DR DisGeNET; 221476; -.
DR GeneCards; PI16; -.
DR HGNC; HGNC:21245; PI16.
DR HPA; ENSG00000164530; Tissue enhanced (cervix, urinary bladder, vagina).
DR neXtProt; NX_Q6UXB8; -.
DR OpenTargets; ENSG00000164530; -.
DR PharmGKB; PA134867616; -.
DR VEuPathDB; HostDB:ENSG00000164530; -.
DR eggNOG; KOG3017; Eukaryota.
DR GeneTree; ENSGT00940000162458; -.
DR HOGENOM; CLU_049124_0_0_1; -.
DR InParanoid; Q6UXB8; -.
DR OMA; AYAQQCI; -.
DR OrthoDB; 1528782at2759; -.
DR PhylomeDB; Q6UXB8; -.
DR TreeFam; TF316148; -.
DR PathwayCommons; Q6UXB8; -.
DR SignaLink; Q6UXB8; -.
DR BioGRID-ORCS; 221476; 14 hits in 1071 CRISPR screens.
DR GenomeRNAi; 221476; -.
DR Pharos; Q6UXB8; Tbio.
DR PRO; PR:Q6UXB8; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q6UXB8; protein.
DR Bgee; ENSG00000164530; Expressed in upper arm skin and 162 other tissues.
DR Genevisible; Q6UXB8; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030414; F:peptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.33.10; -; 1.
DR InterPro; IPR018244; Allrgn_V5/Tpx1_CS.
DR InterPro; IPR014044; CAP_domain.
DR InterPro; IPR035940; CAP_sf.
DR InterPro; IPR001283; CRISP-related.
DR PANTHER; PTHR10334; PTHR10334; 1.
DR Pfam; PF00188; CAP; 1.
DR PRINTS; PR00837; V5TPXLIKE.
DR SMART; SM00198; SCP; 1.
DR SUPFAM; SSF55797; SSF55797; 1.
DR PROSITE; PS01009; CRISP_1; 1.
DR PROSITE; PS01010; CRISP_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Glycoprotein;
KW Protease inhibitor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:15344909"
FT CHAIN 28..463
FT /note="Peptidase inhibitor 16"
FT /id="PRO_0000287633"
FT DOMAIN 37..165
FT /note="SCP"
FT REGION 262..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 303..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 383..408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 386..395
FT /note="O-glycosylated at one site"
FT COMPBIAS 387..408
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 403
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 231..423
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_025574"
FT VARIANT 50
FT /note="T -> P (in dbSNP:rs1405069)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16303743"
FT /id="VAR_032337"
FT VARIANT 416
FT /note="L -> V (in dbSNP:rs16889318)"
FT /id="VAR_032338"
FT CONFLICT 179
FT /note="E -> G (in Ref. 2; BAC11640)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="V -> A (in Ref. 2; BAC11640)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 463 AA; 49471 MW; 3B9E7565364CF0D2 CRC64;
MHGSCSFLML LLPLLLLLVA TTGPVGALTD EEKRLMVELH NLYRAQVSPT ASDMLHMRWD
EELAAFAKAY ARQCVWGHNK ERGRRGENLF AITDEGMDVP LAMEEWHHER EHYNLSAATC
SPGQMCGHYT QVVWAKTERI GCGSHFCEKL QGVEETNIEL LVCNYEPPGN VKGKRPYQEG
TPCSQCPSGY HCKNSLCEPI GSPEDAQDLP YLVTEAPSFR ATEASDSRKM GTPSSLATGI
PAFLVTEVSG SLATKALPAV ETQAPTSLAT KDPPSMATEA PPCVTTEVPS ILAAHSLPSL
DEEPVTFPKS THVPIPKSAD KVTDKTKVPS RSPENSLDPK MSLTGARELL PHAQEEAEAE
AELPPSSEVL ASVFPAQDKP GELQATLDHT GHTSSKSLPN FPNTSATANA TGGRALALQS
SLPGAEGPDK PSVVSGLNSG PGHVWGPLLG LLLLPPLVLA GIF
