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UniProtKB - P14222 (PERF_HUMAN)

Protein

Perforin-1

Gene

PRF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • identical protein binding Source: IntAct
  • wide pore channel activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processCytolysis
LigandCalcium, Metal-binding

Enzyme and pathway databases

SIGNORiP14222

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000180644.6
HGNCiHGNC:9360 PRF1
MIMi170280 gene
neXtProtiNX_P14222

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:rs104894183EnsemblClinVar.1
Natural variantiVAR_010774224I → N in FHL2. 1 Publication1
Natural variantiVAR_010745225R → W in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933973EnsemblClinVar.1
Natural variantiVAR_010746252N → S in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933375EnsemblClinVar.1
Natural variantiVAR_010747279C → Y in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894182EnsemblClinVar.1
Natural variantiVAR_010775285Missing in FHL2. 1 Publication1
Natural variantiVAR_010748345P → L in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933374EnsemblClinVar.1
Natural variantiVAR_010749429G → E in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894181EnsemblClinVar.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
ProteomicsDBi53040

PTM databases

iPTMnetiP14222
PhosphoSitePlusiP14222

Expressioni

Inductioni

Repressed by contact with target cells.1 Publication

Gene expression databases

BgeeiENSG00000180644 Expressed in 170 organ(s), highest expression level in mononuclear cell
CleanExiHS_PRF1
ExpressionAtlasiP14222 baseline and differential
GenevisibleiP14222 HS

Organism-specific databases

HPAiCAB002436
HPA037940

Interactioni

Subunit structurei

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

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi111542, 5 interactors
DIPiDIP-53288N
IntActiP14222, 7 interactors
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

CDDicd04032 C2_Perforin, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR020864 MACPF
IPR020863 MACPF_CS
IPR037300 Perforin-1_C2
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF01823 MACPF, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00457 MACPF, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS00279 MACPF_1, 1 hit
PS51412 MACPF_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1W2PR25A0A1W2PR25_HUMAN
Perforin-1
PRF1
232Annotation score:

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:rs35418374EnsemblClinVar.1
Natural variantiVAR_01077250V → M in FHL2. 1 Publication1
Natural variantiVAR_05048291A → V. Corresponds to variant dbSNP:rs35947132EnsemblClinVar.1
Natural variantiVAR_010773123R → H1 PublicationCorresponds to variant dbSNP:rs139336186Ensembl.1
Natural variantiVAR_029773135V → M. Corresponds to variant dbSNP:rs12263572EnsemblClinVar.1
Natural variantiVAR_010744183V → G in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894183EnsemblClinVar.1
Natural variantiVAR_010774224I → N in FHL2. 1 Publication1
Natural variantiVAR_010745225R → W in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933973EnsemblClinVar.1
Natural variantiVAR_010746252N → S in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933375EnsemblClinVar.1
Natural variantiVAR_010747279C → Y in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894182EnsemblClinVar.1
Natural variantiVAR_010775285Missing in FHL2. 1 Publication1
Natural variantiVAR_010748345P → L in FHL2. 1 PublicationCorresponds to variant dbSNP:rs28933374EnsemblClinVar.1
Natural variantiVAR_010749429G → E in FHL2. 1 PublicationCorresponds to variant dbSNP:rs104894181EnsemblClinVar.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

Cross-referencesi

Web resourcesi

PRF1base

PRF1 mutation db

Wikipedia

Perforin entry

Protein Spotlight

Our hollow architecture - Issue 126 of February 2011

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

3D structure databases

ProteinModelPortaliP14222
SMRiP14222
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiP14222
ChEMBLiCHEMBL5480

Protein family/group databases

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

PTM databases

iPTMnetiP14222
PhosphoSitePlusiP14222

Polymorphism and mutation databases

BioMutaiPRF1
DMDMi129819

Proteomic databases

PaxDbiP14222
PeptideAtlasiP14222
PRIDEiP14222
ProteomicsDBi53040

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5551
DisGeNETi5551
EuPathDBiHostDB:ENSG00000180644.6
GeneCardsiPRF1
GeneReviewsiPRF1
HGNCiHGNC:9360 PRF1
HPAiCAB002436
HPA037940
MalaCardsiPRF1
MIMi170280 gene
603553 phenotype
neXtProtiNX_P14222
OpenTargetsiENSG00000180644
Orphaneti540 Familial hemophagocytic lymphohistiocytosis
391343 Fatal post-viral neurodegenerative disorder
88 Idiopathic aplastic anemia
PharmGKBiPA33732
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

SIGNORiP14222

Miscellaneous databases

GeneWikiiPerforin
GenomeRNAii5551
PROiPR:P14222
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180644 Expressed in 170 organ(s), highest expression level in mononuclear cell
CleanExiHS_PRF1
ExpressionAtlasiP14222 baseline and differential
GenevisibleiP14222 HS

Family and domain databases

CDDicd04032 C2_Perforin, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR020864 MACPF
IPR020863 MACPF_CS
IPR037300 Perforin-1_C2
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF01823 MACPF, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00457 MACPF, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS00279 MACPF_1, 1 hit
PS51412 MACPF_2, 1 hit
ProtoNetiSearch...

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: October 10, 2018
This is version 196 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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