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Protein

Perforin-1

Gene

PRF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells. Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei214Important for oligomerizationBy similarity1
Sitei344Important for oligomerizationBy similarity1
Metal bindingi436Calcium 1By similarity1
Metal bindingi484Calcium 1By similarity1
Metal bindingi486Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi491Calcium 2By similarity1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • wide pore channel activity Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: ProtInc
  • cellular defense response Source: ProtInc
  • cytolysis Source: UniProtKB
  • defense response to tumor cell Source: UniProtKB
  • defense response to virus Source: UniProtKB
  • immune response to tumor cell Source: UniProtKB
  • immunological synapse formation Source: UniProtKB
  • positive regulation of killing of cells of other organism Source: UniProtKB
  • protein homooligomerization Source: UniProtKB

Keywordsi

Biological processCytolysis
LigandCalcium, Metal-binding

Protein family/group databases

TCDBi1.C.39.2.8. the membrane attack complex/perforin (macpf) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Perforin-1
Short name:
P1
Alternative name(s):
Cytolysin
Lymphocyte pore-forming protein
Short name:
PFP
Gene namesi
Name:PRF1
Synonyms:PFP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000180644.6.
HGNCiHGNC:9360. PRF1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Familial hemophagocytic lymphohistiocytosis 2 (FHL2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia.
See also OMIM:603553
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01077250V → M in FHL2. 1 Publication1
Natural variantiVAR_010744183V → G in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894183Ensembl.1
Natural variantiVAR_010774224I → N in FHL2. 1 Publication1
Natural variantiVAR_010745225R → W in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933973Ensembl.1
Natural variantiVAR_010746252N → S in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933375Ensembl.1
Natural variantiVAR_010747279C → Y in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894182Ensembl.1
Natural variantiVAR_010775285Missing in FHL2. 1 Publication1
Natural variantiVAR_010748345P → L in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933374Ensembl.1
Natural variantiVAR_010749429G → E in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894181Ensembl.1

Keywords - Diseasei

Disease mutation, Familial hemophagocytic lymphohistiocytosis

Organism-specific databases

DisGeNETi5551.
GeneReviewsiPRF1.
MalaCardsiPRF1.
MIMi603553. phenotype.
OpenTargetsiENSG00000180644.
Orphaneti540. Familial hemophagocytic lymphohistiocytosis.
391343. Fatal post-viral neurodegenerative disorder.
88. Idiopathic aplastic anemia.
PharmGKBiPA33732.

Chemistry databases

ChEMBLiCHEMBL5480.

Polymorphism and mutation databases

BioMutaiPRF1.
DMDMi129819.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Add BLAST21
ChainiPRO_000002360922 – 555Perforin-1Add BLAST534

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi23 ↔ 76By similarity
Disulfide bondi31 ↔ 73By similarity
Disulfide bondi102 ↔ 176By similarity
Glycosylationi205N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi242 ↔ 408By similarity
Disulfide bondi377 ↔ 393By similarity
Disulfide bondi381 ↔ 395By similarity
Disulfide bondi397 ↔ 407By similarity
Disulfide bondi497 ↔ 510By similarity
Disulfide bondi525 ↔ 534By similarity
Glycosylationi549N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP14222.
PeptideAtlasiP14222.
PRIDEiP14222.

PTM databases

iPTMnetiP14222.
PhosphoSitePlusiP14222.

Expressioni

Inductioni

Repressed by contact with target cells.1 Publication

Gene expression databases

BgeeiENSG00000180644.
CleanExiHS_PRF1.
GenevisibleiP14222. HS.

Organism-specific databases

HPAiCAB002436.
HPA037940.

Interactioni

Subunit structurei

Monomer, as sobluble protein. Homooligomer. Oligomerization is required for pore formation.2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111542. 5 interactors.
DIPiDIP-53288N.
IntActiP14222. 7 interactors.
MINTiMINT-1401322.
STRINGi9606.ENSP00000316746.

Chemistry databases

BindingDBiP14222.

Structurei

3D structure databases

ProteinModelPortaliP14222.
SMRiP14222.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 375MACPFPROSITE-ProRule annotationAdd BLAST349
Domaini376 – 408EGF-likeAdd BLAST33
Domaini416 – 498C2PROSITE-ProRule annotationAdd BLAST83

Domaini

The C2 domain mediates calcium-dependent binding to lipid membranes. A subsequent conformation change leads to membrane insertion of beta-hairpin structures and pore formation. The pore is formed by transmembrane beta-strands.

Sequence similaritiesi

Belongs to the complement C6/C7/C8/C9 family.Curated

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane beta strand

Phylogenomic databases

eggNOGiENOG410IGJ0. Eukaryota.
ENOG410XSHK. LUCA.
GeneTreeiENSGT00530000063725.
HOGENOMiHOG000236309.
HOVERGENiHBG008168.
InParanoidiP14222.
KOiK07818.
OMAiNYGTHFI.
OrthoDBiEOG091G03LE.
PhylomeDBiP14222.
TreeFamiTF330498.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiView protein in InterPro
IPR000008. C2_dom.
IPR020864. MACPF.
IPR020863. MACPF_CS.
PfamiView protein in Pfam
PF00168. C2. 1 hit.
PF01823. MACPF. 1 hit.
SMARTiView protein in SMART
SM00239. C2. 1 hit.
SM00457. MACPF. 1 hit.
SUPFAMiSSF49562. SSF49562. 1 hit.
PROSITEiView protein in PROSITE
PS50004. C2. 1 hit.
PS00279. MACPF_1. 1 hit.
PS51412. MACPF_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P14222-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAARLLLLGI LLLLLPLPVP APCHTAARSE CKRSHKFVPG AWLAGEGVDV
60 70 80 90 100
TSLRRSGSFP VDTQRFLRPD GTCTLCENAL QEGTLQRLPL ALTNWRAQGS
110 120 130 140 150
GCQRHVTRAK VSSTEAVARD AARSIRNDWK VGLDVTPKPT SNVHVSVAGS
160 170 180 190 200
HSQAANFAAQ KTHQDQYSFS TDTVECRFYS FHVVHTPPLH PDFKRALGDL
210 220 230 240 250
PHHFNASTQP AYLRLISNYG THFIRAVELG GRISALTALR TCELALEGLT
260 270 280 290 300
DNEVEDCLTV EAQVNIGIHG SISAEAKACE EKKKKHKMTA SFHQTYRERH
310 320 330 340 350
SEVVGGHHTS INDLLFGIQA GPEQYSAWVN SLPGSPGLVD YTLEPLHVLL
360 370 380 390 400
DSQDPRREAL RRALSQYLTD RARWRDCSRP CPPGRQKSPR DPCQCVCHGS
410 420 430 440 450
AVTTQDCCPR QRGLAQLEVT FIQAWGLWGD WFTATDAYVK LFFGGQELRT
460 470 480 490 500
STVWDNNNPI WSVRLDFGDV LLATGGPLRL QVWDQDSGRD DDLLGTCDQA
510 520 530 540 550
PKSGSHEVRC NLNHGHLKFR YHARCLPHLG GGTCLDYVPQ MLLGEPPGNR

SGAVW
Length:555
Mass (Da):61,377
Last modified:January 1, 1990 - v1
Checksum:iDDEDE0D1CAB7586E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti332L → V in CAA31612 (PubMed:3419519).Curated1
Sequence conflicti426G → S in CAA31612 (PubMed:3419519).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0615044R → H. Corresponds to variant dbSNP:rs35418374Ensembl.1
Natural variantiVAR_01077250V → M in FHL2. 1 Publication1
Natural variantiVAR_05048291A → V. Corresponds to variant dbSNP:rs35947132Ensembl.1
Natural variantiVAR_010773123R → H1 PublicationCorresponds to variant dbSNP:rs139336186Ensembl.1
Natural variantiVAR_029773135V → M. Corresponds to variant dbSNP:rs12263572Ensembl.1
Natural variantiVAR_010744183V → G in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894183Ensembl.1
Natural variantiVAR_010774224I → N in FHL2. 1 Publication1
Natural variantiVAR_010745225R → W in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933973Ensembl.1
Natural variantiVAR_010746252N → S in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933375Ensembl.1
Natural variantiVAR_010747279C → Y in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894182Ensembl.1
Natural variantiVAR_010775285Missing in FHL2. 1 Publication1
Natural variantiVAR_010748345P → L in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933374Ensembl.1
Natural variantiVAR_010749429G → E in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894181Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13224 mRNA. Translation: CAA31612.1.
M28393 mRNA. Translation: AAA60065.1.
M31951 Genomic DNA. Translation: AAA60167.1.
AK312754 mRNA. Translation: BAG35621.1.
AL355344 Genomic DNA. No translation available.
CH471083 Genomic DNA. Translation: EAW54407.1.
BC047695 mRNA. Translation: AAH47695.2.
BC063043 mRNA. Translation: AAH63043.1.
AB209604 mRNA. Translation: BAD92841.1.
L40557 mRNA. Translation: AAA63618.1.
CCDSiCCDS7305.1.
PIRiA45816. A37181.
RefSeqiNP_001076585.1. NM_001083116.1.
NP_005032.2. NM_005041.4.
UniGeneiHs.2200.

Genome annotation databases

EnsembliENST00000373209; ENSP00000362305; ENSG00000180644.
ENST00000441259; ENSP00000398568; ENSG00000180644.
GeneIDi5551.
KEGGihsa:5551.
UCSCiuc001jrf.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPERF_HUMAN
AccessioniPrimary (citable) accession number: P14222
Secondary accession number(s): B2R6X4, Q59F57, Q86WX7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: September 27, 2017
This is version 186 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  6. SIMILARITY comments
    Index of protein domains and families