PERF_HUMAN
ID PERF_HUMAN Reviewed; 555 AA.
AC P14222; B2R6X4; Q59F57; Q86WX7;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Perforin-1;
DE Short=P1;
DE AltName: Full=Cytolysin;
DE AltName: Full=Lymphocyte pore-forming protein;
DE Short=PFP;
DE Flags: Precursor;
GN Name=PRF1; Synonyms=PFP;
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 [MRNA].
RC TISSUE=Natural killer cell;
RX PubMed=3419519; DOI=10.1038/335448a0;
RA Lichtenheld M.G., Olsen K.J., Lu P., Lowrey D.M., Hameed A., Hengartner H.,
RA Podack E.R.;
RT "Structure and function of human perforin.";
RL Nature 335:448-451(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2592021; DOI=10.1007/bf02421177;
RA Shinkai Y., Yoshida C.M., Maeda K., Kobata T., Maruyama K., Yodoi J.,
RA Yagita H., Okumura K.;
RT "Molecular cloning and chromosomal assignment of a human perforin (PFP)
RT gene.";
RL Immunogenetics 30:452-457(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2480391;
RA Lichtenheld M.G., Podack E.R.;
RT "Structure of the human perforin gene. A simple gene organization with
RT interesting potential regulatory sequences.";
RL J. Immunol. 143:4267-4274(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 258-555.
RC TISSUE=Spleen;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 520-555, AND INDUCTION.
RC TISSUE=Natural killer cell;
RX PubMed=8676885; DOI=10.1016/0161-5890(95)00155-7;
RA Goebel W.S., Schloemer R.H., Brahmi Z.;
RT "Target cell-induced perforin mRNA turnover in NK3.3 cells is mediated by
RT multiple elements within the mRNA coding region.";
RL Mol. Immunol. 33:341-349(1996).
RN [10]
RP FUNCTION.
RX PubMed=9058810;
RA Vergelli M., Hemmer B., Muraro P.A., Tranquill L., Biddison W.E., Sarin A.,
RA McFarland H.F., Martin R.;
RT "Human autoreactive CD4+ T cell clones use perforin- or Fas/Fas ligand-
RT mediated pathways for target cell lysis.";
RL J. Immunol. 158:2756-2761(1997).
RN [11]
RP FUNCTION.
RX PubMed=9164947;
RA Ando K., Hiroishi K., Kaneko T., Moriyama T., Muto Y., Kayagaki N.,
RA Yagita H., Okumura K., Imawari M.;
RT "Perforin, Fas/Fas ligand, and TNF-alpha pathways as specific and bystander
RT killing mechanisms of hepatitis C virus-specific human CTL.";
RL J. Immunol. 158:5283-5291(1997).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-205.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20038786; DOI=10.1182/blood-2009-10-246116;
RA Thiery J., Keefe D., Saffarian S., Martinvalet D., Walch M., Boucrot E.,
RA Kirchhausen T., Lieberman J.;
RT "Perforin activates clathrin- and dynamin-dependent endocytosis, which is
RT required for plasma membrane repair and delivery of granzyme B for
RT granzyme-mediated apoptosis.";
RL Blood 115:1582-1593(2010).
RN [14]
RP FUNCTION, CALCIUM-DEPENDENT PORE FORMING ACTIVITY, SUBCELLULAR LOCATION,
RP SUBUNIT, AND ELECTRON MICROSCOPY.
RX PubMed=20889983; DOI=10.1074/jbc.m110.169417;
RA Praper T., Sonnen A., Viero G., Kladnik A., Froelich C.J., Anderluh G.,
RA Dalla Serra M., Gilbert R.J.;
RT "Human perforin employs different avenues to damage membranes.";
RL J. Biol. Chem. 286:2946-2955(2011).
RN [15]
RP FUNCTION.
RX PubMed=20225066; DOI=10.1007/s00109-010-0602-9;
RA Czystowska M., Strauss L., Bergmann C., Szajnik M., Rabinowich H.,
RA Whiteside T.L.;
RT "Reciprocal granzyme/perforin-mediated death of human regulatory and
RT responder T cells is regulated by interleukin-2 (IL-2).";
RL J. Mol. Med. 88:577-588(2010).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=24088571; DOI=10.1091/mbc.e13-05-0259;
RA Tuli A., Thiery J., James A.M., Michelet X., Sharma M., Garg S.,
RA Sanborn K.B., Orange J.S., Lieberman J., Brenner M.B.;
RT "Arf-like GTPase Arl8b regulates lytic granule polarization and natural
RT killer cell-mediated cytotoxicity.";
RL Mol. Biol. Cell 24:3721-3735(2013).
RN [17]
RP FUNCTION.
RX PubMed=32299851; DOI=10.1126/science.aaz7548;
RA Zhou Z., He H., Wang K., Shi X., Wang Y., Su Y., Wang Y., Li D., Liu W.,
RA Zhang Y., Shen L., Han W., Shen L., Ding J., Shao F.;
RT "Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis
RT in target cells.";
RL Science 368:0-0(2020).
RN [18]
RP 3D-STRUCTURE MODELING OF MEMBRANE-SPANNING DOMAIN (MSD).
RX PubMed=2395434; DOI=10.1016/0161-5890(90)90001-g;
RA Peitsch M.C., Amiguet P., Guy R., Brunner J., Maizel J.V. Jr., Tschopp J.;
RT "Localization and molecular modelling of the membrane-inserted domain of
RT the ninth component of human complement and perforin.";
RL Mol. Immunol. 27:589-602(1990).
RN [19]
RP ELECTRON MICROSCOPY OF PORE COMPLEX, FUNCTION, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
RX PubMed=21037563; DOI=10.1038/nature09518;
RA Law R.H., Lukoyanova N., Voskoboinik I., Caradoc-Davies T.T., Baran K.,
RA Dunstone M.A., D'Angelo M.E., Orlova E.V., Coulibaly F., Verschoor S.,
RA Browne K.A., Ciccone A., Kuiper M.J., Bird P.I., Trapani J.A., Saibil H.R.,
RA Whisstock J.C.;
RT "The structural basis for membrane binding and pore formation by lymphocyte
RT perforin.";
RL Nature 468:447-451(2010).
RN [20]
RP VARIANTS FHL2 GLY-183; TRP-225; SER-252; TYR-279; LEU-345 AND GLU-429.
RX PubMed=10583959; DOI=10.1126/science.286.5446.1957;
RA Stepp S.E., Dufourcq-Lagelouse R., Le Deist F., Bhawan S., Certain S.,
RA Mathew P.A., Henter J.-I., Bennett M., Fischer A., de Saint Basile G.,
RA Kumar V.;
RT "Perforin gene defects in familial hemophagocytic lymphohistiocytosis.";
RL Science 286:1957-1959(1999).
RN [21]
RP VARIANTS FHL2 MET-50; ASN-224 AND LYS-285 DEL.
RX PubMed=11179007; DOI=10.1086/318796;
RA Goeransdotter Ericson K., Fadeel B., Nilsson-Ardnor S., Soederhaell C.,
RA Samuelsson A., Janka G., Schneider M., Guergey A., Yalman N., Revesz T.,
RA Egeler R., Jahnukainen K., Storm-Mathiesen I., Haraldsson A., Poole J.,
RA de Saint Basile G., Nordenskjoeld M., Henter J.-I.;
RT "Spectrum of perforin gene mutations in familial hemophagocytic
RT lymphohistiocytosis.";
RL Am. J. Hum. Genet. 68:590-597(2001).
RN [22]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-123.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Pore-forming protein that plays a key role in secretory
CC granule-dependent cell death, and in defense against virus-infected or
CC neoplastic cells (PubMed:9058810, PubMed:9164947, PubMed:20889983,
CC PubMed:21037563). Plays an important role in killing other cells that
CC are recognized as non-self by the immune system, e.g. in transplant
CC rejection or some forms of autoimmune disease (PubMed:9058810). Can
CC insert into the membrane of target cells in its calcium-bound form,
CC oligomerize and form large pores (PubMed:20889983, PubMed:21037563).
CC Promotes cytolysis and apoptosis of target cells by facilitating the
CC uptake of cytotoxic granzymes (PubMed:20038786, PubMed:20225066,
CC PubMed:32299851). {ECO:0000269|PubMed:20038786,
CC ECO:0000269|PubMed:20225066, ECO:0000269|PubMed:20889983,
CC ECO:0000269|PubMed:21037563, ECO:0000269|PubMed:32299851,
CC ECO:0000269|PubMed:9058810, ECO:0000269|PubMed:9164947}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Monomer, as soluble protein (PubMed:20889983,
CC PubMed:21037563). Homooligomer. Oligomerization is required for pore
CC formation (PubMed:20889983, PubMed:21037563).
CC {ECO:0000269|PubMed:20889983, ECO:0000269|PubMed:21037563}.
CC -!- INTERACTION:
CC P14222; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-724466, EBI-3867333;
CC P14222; P10144: GZMB; NbExp=3; IntAct=EBI-724466, EBI-2505785;
CC P14222; Q15323: KRT31; NbExp=6; IntAct=EBI-724466, EBI-948001;
CC P14222; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-724466, EBI-22310682;
CC P14222; P14222: PRF1; NbExp=3; IntAct=EBI-724466, EBI-724466;
CC -!- SUBCELLULAR LOCATION: Cytolytic granule {ECO:0000269|PubMed:20038786,
CC ECO:0000269|PubMed:24088571}. Secreted. Cell membrane
CC {ECO:0000269|PubMed:20889983, ECO:0000269|PubMed:21037563}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:20889983,
CC ECO:0000269|PubMed:21037563}. Endosome lumen
CC {ECO:0000269|PubMed:20038786}. Note=Stored in cytolytic granules of
CC cytolytic T-lymphocytes and secreted into the cleft between T-
CC lymphocyte and target cell (PubMed:20038786). Inserts into the cell
CC membrane of target cells and forms pores (PubMed:20889983). Membrane
CC insertion and pore formation requires a major conformation change
CC (PubMed:20889983). May be taken up via endocytosis involving clathrin-
CC coated vesicles and accumulate in a first time in large early endosomes
CC (PubMed:20038786). {ECO:0000269|PubMed:20038786,
CC ECO:0000269|PubMed:20889983}.
CC -!- INDUCTION: Repressed by contact with target cells.
CC {ECO:0000269|PubMed:8676885}.
CC -!- DOMAIN: The C2 domain mediates calcium-dependent binding to lipid
CC membranes. A subsequent conformation change leads to membrane insertion
CC of beta-hairpin structures and pore formation. The pore is formed by
CC transmembrane beta-strands. {ECO:0000250|UniProtKB:P10820}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P10820}.
CC -!- DISEASE: Hemophagocytic lymphohistiocytosis, familial, 2 (FHL2)
CC [MIM:603553]: A rare disorder characterized by immune dysregulation
CC with hypercytokinemia, defective function of natural killer cell, and
CC massive infiltration of several organs by activated lymphocytes and
CC macrophages. The clinical features of the disease include fever,
CC hepatosplenomegaly, cytopenia, and less frequently neurological
CC abnormalities ranging from irritability and hypotonia to seizures,
CC cranial nerve deficits and ataxia. {ECO:0000269|PubMed:10583959,
CC ECO:0000269|PubMed:11179007}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complement C6/C7/C8/C9 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PRF1base; Note=PRF1 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/PRF1base/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Perforin entry;
CC URL="https://en.wikipedia.org/wiki/Perforin";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Our hollow architecture
CC - Issue 126 of February 2011;
CC URL="https://web.expasy.org/spotlight/back_issues/126";
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DR EMBL; X13224; CAA31612.1; -; mRNA.
DR EMBL; M28393; AAA60065.1; -; mRNA.
DR EMBL; M31951; AAA60167.1; -; Genomic_DNA.
DR EMBL; AK312754; BAG35621.1; -; mRNA.
DR EMBL; AL355344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54407.1; -; Genomic_DNA.
DR EMBL; BC047695; AAH47695.2; -; mRNA.
DR EMBL; BC063043; AAH63043.1; -; mRNA.
DR EMBL; AB209604; BAD92841.1; -; mRNA.
DR EMBL; L40557; AAA63618.1; -; mRNA.
DR CCDS; CCDS7305.1; -.
DR PIR; A45816; A37181.
DR RefSeq; NP_001076585.1; NM_001083116.1.
DR RefSeq; NP_005032.2; NM_005041.4.
DR AlphaFoldDB; P14222; -.
DR SMR; P14222; -.
DR BioGRID; 111542; 87.
DR DIP; DIP-53288N; -.
DR IntAct; P14222; 7.
DR STRING; 9606.ENSP00000398568; -.
DR BindingDB; P14222; -.
DR ChEMBL; CHEMBL5480; -.
DR GuidetoPHARMACOLOGY; 3100; -.
DR TCDB; 1.C.39.2.8; the membrane attack complex/perforin (macpf) family.
DR GlyGen; P14222; 2 sites.
DR iPTMnet; P14222; -.
DR PhosphoSitePlus; P14222; -.
DR BioMuta; PRF1; -.
DR DMDM; 129819; -.
DR jPOST; P14222; -.
DR MassIVE; P14222; -.
DR PaxDb; P14222; -.
DR PeptideAtlas; P14222; -.
DR PRIDE; P14222; -.
DR ProteomicsDB; 53040; -.
DR Antibodypedia; 3723; 602 antibodies from 44 providers.
DR DNASU; 5551; -.
DR Ensembl; ENST00000373209.2; ENSP00000362305.1; ENSG00000180644.8.
DR Ensembl; ENST00000441259.2; ENSP00000398568.1; ENSG00000180644.8.
DR GeneID; 5551; -.
DR KEGG; hsa:5551; -.
DR MANE-Select; ENST00000441259.2; ENSP00000398568.1; NM_001083116.3; NP_001076585.1.
DR UCSC; uc001jrf.5; human.
DR CTD; 5551; -.
DR DisGeNET; 5551; -.
DR GeneCards; PRF1; -.
DR GeneReviews; PRF1; -.
DR HGNC; HGNC:9360; PRF1.
DR HPA; ENSG00000180644; Group enriched (bone marrow, lung, lymphoid tissue).
DR MalaCards; PRF1; -.
DR MIM; 170280; gene.
DR MIM; 603553; phenotype.
DR neXtProt; NX_P14222; -.
DR OpenTargets; ENSG00000180644; -.
DR Orphanet; 540; Familial hemophagocytic lymphohistiocytosis.
DR Orphanet; 391343; Fatal post-viral neurodegenerative disorder.
DR Orphanet; 88; Idiopathic aplastic anemia.
DR PharmGKB; PA33732; -.
DR VEuPathDB; HostDB:ENSG00000180644; -.
DR eggNOG; ENOG502RQWS; Eukaryota.
DR GeneTree; ENSGT00530000063725; -.
DR HOGENOM; CLU_039516_2_0_1; -.
DR InParanoid; P14222; -.
DR OMA; LCKNALQ; -.
DR OrthoDB; 360042at2759; -.
DR PhylomeDB; P14222; -.
DR TreeFam; TF330498; -.
DR PathwayCommons; P14222; -.
DR SignaLink; P14222; -.
DR SIGNOR; P14222; -.
DR BioGRID-ORCS; 5551; 5 hits in 1075 CRISPR screens.
DR GeneWiki; Perforin; -.
DR GenomeRNAi; 5551; -.
DR Pharos; P14222; Tchem.
DR PRO; PR:P14222; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P14222; protein.
DR Bgee; ENSG00000180644; Expressed in granulocyte and 156 other tissues.
DR ExpressionAtlas; P14222; baseline and differential.
DR Genevisible; P14222; HS.
DR GO; GO:0044194; C:cytolytic granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031904; C:endosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0022829; F:wide pore channel activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0002357; P:defense response to tumor cell; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0002418; P:immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0001771; P:immunological synapse formation; IDA:UniProtKB.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0001913; P:T cell mediated cytotoxicity; IBA:GO_Central.
DR CDD; cd04032; C2_Perforin; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020864; MACPF.
DR InterPro; IPR020863; MACPF_CS.
DR InterPro; IPR037300; Perforin-1_C2.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF01823; MACPF; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00457; MACPF; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00279; MACPF_1; 1.
DR PROSITE; PS51412; MACPF_2; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cytolysis; Disease variant; Disulfide bond;
KW EGF-like domain; Endosome; Familial hemophagocytic lymphohistiocytosis;
KW Glycoprotein; Lysosome; Membrane; Metal-binding; Reference proteome;
KW Secreted; Signal; Transmembrane; Transmembrane beta strand.
FT SIGNAL 1..21
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT CHAIN 22..555
FT /note="Perforin-1"
FT /id="PRO_0000023609"
FT DOMAIN 27..375
FT /note="MACPF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00745"
FT DOMAIN 376..408
FT /note="EGF-like"
FT DOMAIN 397..519
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 436
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT BINDING 484
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT BINDING 486
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT BINDING 491
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT SITE 214
FT /note="Important for oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT SITE 344
FT /note="Important for oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 549
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 23..76
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 31..73
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 102..176
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 242..408
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 377..393
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 381..395
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 397..407
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 497..510
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 525..534
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT VARIANT 4
FT /note="R -> H (in dbSNP:rs35418374)"
FT /id="VAR_061504"
FT VARIANT 50
FT /note="V -> M (in FHL2; dbSNP:rs776299562)"
FT /evidence="ECO:0000269|PubMed:11179007"
FT /id="VAR_010772"
FT VARIANT 91
FT /note="A -> V (in dbSNP:rs35947132)"
FT /id="VAR_050482"
FT VARIANT 123
FT /note="R -> H (in dbSNP:rs139336186)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_010773"
FT VARIANT 135
FT /note="V -> M (in dbSNP:rs12263572)"
FT /id="VAR_029773"
FT VARIANT 183
FT /note="V -> G (in FHL2; dbSNP:rs104894183)"
FT /evidence="ECO:0000269|PubMed:10583959"
FT /id="VAR_010744"
FT VARIANT 224
FT /note="I -> N (in FHL2)"
FT /evidence="ECO:0000269|PubMed:11179007"
FT /id="VAR_010774"
FT VARIANT 225
FT /note="R -> W (in FHL2; dbSNP:rs28933973)"
FT /evidence="ECO:0000269|PubMed:10583959"
FT /id="VAR_010745"
FT VARIANT 252
FT /note="N -> S (in FHL2; dbSNP:rs28933375)"
FT /evidence="ECO:0000269|PubMed:10583959"
FT /id="VAR_010746"
FT VARIANT 279
FT /note="C -> Y (in FHL2; dbSNP:rs104894182)"
FT /evidence="ECO:0000269|PubMed:10583959"
FT /id="VAR_010747"
FT VARIANT 285
FT /note="Missing (in FHL2)"
FT /evidence="ECO:0000269|PubMed:11179007"
FT /id="VAR_010775"
FT VARIANT 345
FT /note="P -> L (in FHL2; dbSNP:rs28933374)"
FT /evidence="ECO:0000269|PubMed:10583959"
FT /id="VAR_010748"
FT VARIANT 429
FT /note="G -> E (in FHL2; dbSNP:rs104894181)"
FT /evidence="ECO:0000269|PubMed:10583959"
FT /id="VAR_010749"
FT CONFLICT 332
FT /note="L -> V (in Ref. 1; CAA31612)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="G -> S (in Ref. 1; CAA31612)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 555 AA; 61377 MW; DDEDE0D1CAB7586E CRC64;
MAARLLLLGI LLLLLPLPVP APCHTAARSE CKRSHKFVPG AWLAGEGVDV TSLRRSGSFP
VDTQRFLRPD GTCTLCENAL QEGTLQRLPL ALTNWRAQGS GCQRHVTRAK VSSTEAVARD
AARSIRNDWK VGLDVTPKPT SNVHVSVAGS HSQAANFAAQ KTHQDQYSFS TDTVECRFYS
FHVVHTPPLH PDFKRALGDL PHHFNASTQP AYLRLISNYG THFIRAVELG GRISALTALR
TCELALEGLT DNEVEDCLTV EAQVNIGIHG SISAEAKACE EKKKKHKMTA SFHQTYRERH
SEVVGGHHTS INDLLFGIQA GPEQYSAWVN SLPGSPGLVD YTLEPLHVLL DSQDPRREAL
RRALSQYLTD RARWRDCSRP CPPGRQKSPR DPCQCVCHGS AVTTQDCCPR QRGLAQLEVT
FIQAWGLWGD WFTATDAYVK LFFGGQELRT STVWDNNNPI WSVRLDFGDV LLATGGPLRL
QVWDQDSGRD DDLLGTCDQA PKSGSHEVRC NLNHGHLKFR YHARCLPHLG GGTCLDYVPQ
MLLGEPPGNR SGAVW
