PERF_RAT
ID PERF_RAT Reviewed; 554 AA.
AC P35763;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Perforin-1;
DE Short=P1;
DE AltName: Full=Cytolysin;
DE AltName: Full=Lymphocyte pore-forming protein;
DE Flags: Precursor;
GN Name=Prf1; Synonyms=Pfp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=2809217;
RA Ishikawa H., Shinkai Y., Yagita H., Yue C.C., Henkart P.A., Sawada S.,
RA Young H.A., Reynolds C.W., Okumura K.;
RT "Molecular cloning of rat cytolysin.";
RL J. Immunol. 143:3069-3073(1989).
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:2809217). Plays an important role in killing
CC other cells that are recognized as non-self by the immune system, e.g.
CC in transplant rejection or some forms of autoimmune disease. Can insert
CC into the membrane of target cells in its calcium-bound form,
CC oligomerize and form large pores. Promotes cytolysis and apoptosis of
CC target cells by facilitating the uptake of cytotoxic granzymes (By
CC similarity). {ECO:0000250|UniProtKB:P14222,
CC ECO:0000269|PubMed:2809217}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Monomer. Homooligomer. Oligomerization is required for pore
CC formation (By similarity). {ECO:0000250|UniProtKB:P14222}.
CC -!- SUBCELLULAR LOCATION: Cytolytic granule {ECO:0000269|PubMed:2809217}.
CC Secreted {ECO:0000269|PubMed:2809217}. Cell membrane
CC {ECO:0000269|PubMed:2809217}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:2809217}. Endosome lumen
CC {ECO:0000250|UniProtKB:P14222}. Note=Stored in cytolytic granules of
CC cytolytic T-lymphocytes and secreted into the cleft between T-
CC lymphocyte and target cell. Inserts into the cell membrane of target
CC cells and forms pores. Membrane insertion and pore formation requires a
CC major conformation change. May be taken up via endocytosis involving
CC clathrin-coated vesicles and accumulate in a first time in large early
CC endosomes (By similarity). {ECO:0000250|UniProtKB:P14222}.
CC -!- TISSUE SPECIFICITY: Detected in large granular lymphocytes and
CC lymphokine-activated killer cells. {ECO:0000269|PubMed:2809217}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:P10820}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P10820}.
CC -!- SIMILARITY: Belongs to the complement C6/C7/C8/C9 family.
CC {ECO:0000305}.
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DR EMBL; M33605; AAA41071.1; -; mRNA.
DR PIR; A45818; A45818.
DR AlphaFoldDB; P35763; -.
DR SMR; P35763; -.
DR STRING; 10116.ENSRNOP00000000681; -.
DR TCDB; 1.C.39.2.1; the membrane attack complex/perforin (macpf) family.
DR GlyGen; P35763; 3 sites.
DR PaxDb; P35763; -.
DR RGD; 708463; Prf1.
DR eggNOG; ENOG502RQWS; Eukaryota.
DR InParanoid; P35763; -.
DR PhylomeDB; P35763; -.
DR PRO; PR:P35763; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044194; C:cytolytic granule; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0031904; C:endosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISS: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; ISO:RGD.
DR GO; GO:0022829; F:wide pore channel activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:RGD.
DR GO; GO:0007623; P:circadian rhythm; IMP:RGD.
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; ISO:RGD.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; ISO:RGD.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0001913; P:T cell mediated cytotoxicity; ISO:RGD.
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 2: Evidence at transcript level;
KW Calcium; Cell membrane; Cytolysis; Disulfide bond; EGF-like domain;
KW Endosome; Glycoprotein; Lysosome; Membrane; Metal-binding;
KW Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane beta strand.
FT SIGNAL 1..20
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT CHAIN 21..554
FT /note="Perforin-1"
FT /id="PRO_0000023611"
FT DOMAIN 26..374
FT /note="MACPF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00745"
FT DOMAIN 375..407
FT /note="EGF-like"
FT DOMAIN 395..513
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT BINDING 483
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 485
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT BINDING 488
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT BINDING 490
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT SITE 213
FT /note="Important for oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT SITE 343
FT /note="Important for oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 548
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 22..75
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 30..72
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 101..175
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 241..407
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 376..392
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 380..394
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 396..406
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 496..509
FT /evidence="ECO:0000250|UniProtKB:P10820"
FT DISULFID 524..533
FT /evidence="ECO:0000250|UniProtKB:P10820"
SQ SEQUENCE 554 AA; 61513 MW; 7BB46B9EEDAB886F CRC64;
MAAYLFLLGL FLLLPRPVPA PCYTATRSEC KQNHKFVPGV WAAGEGVDVT TLRRSSSFPV
NTGKFLRPDR TCTLCKNALM NDGIQRLPVA IAHWRPHGSH CQRNVATTKV SSTEGVAREA
AANINNDWRA GLDVNPKPEA NVHVSVAGSH SKIANFAAEK AHQDQYNFNT DTVECRMYSF
RLAQKPPLHP DFRKALKNLP HNFNSSTEHA YRRLISSYGT HFITAVDLGG RVSVLTALRT
CQLTLDGLTA DEVGDCLSVE AQVSIGAQAS VSSEYKACEE KKKQHKIATS FHQTYRERHV
EVLGGPLDSS NDLLFGNQAT PEHFSTWIAS LPTRPDVVDY SLEPLHILLE DSDPKREALR
QAISHYVMSR ARWRDCNRPC RAGQHKSSRD SCQCVCQDSN VTNQDCCPRQ RGLAKLMVRN
FQAKGLWGDY ITSTDAYLKV FFGGQEIRTG VVWNNNHPSW SDKMDFGNVL LSTGGPLRVQ
VWDADNGWDD DLLGTCDKSP KSGFHEVNCP LNHGSIKFIY QANCLPDLTG ETCLEYAPQG
LLGDPRGNRS GAVW
