Reviewed, UniProtKB/Swiss-Prot P14222 (PERF_HUMAN)

Names and origin

Protein names

Recommended name:
    Perforin-1
      Short name=P1
Alternative name(s):
    Lymphocyte pore-forming protein
      Short name=PFP
    Cytolysin

Gene names

Name:	PRF1
Synonyms:	PFP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	555 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	In the presence of calcium, perforin polymerizes into transmembrane tubules and is capable of lysing non-specifically a variety of target cells.
Subcellular location	Cytoplasmic granule membrane; Multi-pass membrane protein. Note: Cytoplasmic granules of cytolytic T-lymphocytes.
Induction	Repressed by contact with target cells. Ref.7
Involvement in disease	Defects in PRF1 are the cause of familial hemophagocytic lymphohistiocytosis type 2 (FHL2) [MIM:603553]; also known as HPLH2. Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous, rare autosomal recessive disorder. It is characterized by immune dysregulation with hypercytokinemia and defective natural killer cell function. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits, and ataxia. Hemophagocytosis is a prominent feature of the disease, and a non-malignant infiltration of macrophages and activated T lymphocytes in lymph nodes, spleen, and other organs is also found. Ref.10 Ref.11
Sequence similarities	Belongs to the complement C6/C7/C8/C9 family. Contains 1 C2 domain. Contains 1 EGF-like domain. Contains 1 MACPF domain.

Ontologies

Keywords
Biological process	Cytolysis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Familial hemophagocytic lymphohistiocytosis
Domain	EGF-like domain Signal Transmembrane
Ligand	Calcium
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	apoptosis Traceable author statement. Source: ProtInc cellular defense response Traceable author statement. Source: ProtInc cytolysis Inferred from electronic annotation. Source: UniProtKB-KW pathogenesis Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21
	Chain	22 – 555	534	Perforin-1		PRO_0000023609
Regions
	Transmembrane	188 – 204	17	Potential
	Transmembrane	212 – 231	20	Potential
	Domain	27 – 375	349	MACPF
	Domain	376 – 408	33	EGF-like
	Domain	416 – 498	83	C2
Amino acid modifications
	Glycosylation	205	1	N-linked (GlcNAc...)
	Glycosylation	549	1	N-linked (GlcNAc...) Potential
	Disulfide bond	257 ↔ 279		By similarity
Natural variations
	Natural variant	50	1	V → M in FHL2. Ref.11		VAR_010772
	Natural variant	91	1	A → V: dbSNP rs35947132.		VAR_050482
	Natural variant	123	1	R → H Ref.12		VAR_010773
	Natural variant	135	1	V → M: dbSNP rs12263572.		VAR_029773
	Natural variant	183	1	V → G in FHL2. Ref.10		VAR_010744
	Natural variant	224	1	I → N in FHL2. Ref.11		VAR_010774
	Natural variant	225	1	R → W in FHL2. dbSNP rs28933973. Ref.10		VAR_010745
	Natural variant	252	1	N → S in FHL2. dbSNP rs28933375. Ref.10		VAR_010746
	Natural variant	279	1	C → Y in FHL2. Ref.10		VAR_010747
	Natural variant	285	1	Missing in FHL2. Ref.11		VAR_010775
	Natural variant	345	1	P → L in FHL2. dbSNP rs28933374. Ref.10		VAR_010748
	Natural variant	429	1	G → E in FHL2. Ref.10		VAR_010749
Experimental info
	Sequence conflict	332	1	L → V in CAA31612. Ref.1
	Sequence conflict	426	1	G → S in CAA31612. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P14222-1 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: DDEDE0D1CAB7586E	FASTA	555	61,377
	10 20 30 40 50 60 MAARLLLLGI LLLLLPLPVP APCHTAARSE CKRSHKFVPG AWLAGEGVDV TSLRRSGSFP 70 80 90 100 110 120 VDTQRFLRPD GTCTLCENAL QEGTLQRLPL ALTNWRAQGS GCQRHVTRAK VSSTEAVARD 130 140 150 160 170 180 AARSIRNDWK VGLDVTPKPT SNVHVSVAGS HSQAANFAAQ KTHQDQYSFS TDTVECRFYS 190 200 210 220 230 240 FHVVHTPPLH PDFKRALGDL PHHFNASTQP AYLRLISNYG THFIRAVELG GRISALTALR 250 260 270 280 290 300 TCELALEGLT DNEVEDCLTV EAQVNIGIHG SISAEAKACE EKKKKHKMTA SFHQTYRERH 310 320 330 340 350 360 SEVVGGHHTS INDLLFGIQA GPEQYSAWVN SLPGSPGLVD YTLEPLHVLL DSQDPRREAL 370 380 390 400 410 420 RRALSQYLTD RARWRDCSRP CPPGRQKSPR DPCQCVCHGS AVTTQDCCPR QRGLAQLEVT 430 440 450 460 470 480 FIQAWGLWGD WFTATDAYVK LFFGGQELRT STVWDNNNPI WSVRLDFGDV LLATGGPLRL 490 500 510 520 530 540 QVWDQDSGRD DDLLGTCDQA PKSGSHEVRC NLNHGHLKFR YHARCLPHLG GGTCLDYVPQ 550 MLLGEPPGNR SGAVW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and function of human perforin." Lichtenheld M.G., Olsen K.J., Lu P., Lowrey D.M., Hameed A., Hengartner H., Podack E.R. Nature 335:448-451(1988) [PubMed: 3419519] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Natural killer cell.
[2]	"Molecular cloning and chromosomal assignment of a human perforin (PFP) gene." Shinkai Y., Yoshida C.M., Maeda K., Kobata T., Maruyama K., Yodoi J., Yagita H., Okumura K. Immunogenetics 30:452-457(1989) [PubMed: 2592021] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structure of the human perforin gene. A simple gene organization with interesting potential regulatory sequences." Lichtenheld M.G., Podack E.R. J. Immunol. 143:4267-4274(1989) [PubMed: 2480391] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 258-555. Tissue: Spleen.
[7]	"Target cell-induced perforin mRNA turnover in NK3.3 cells is mediated by multiple elements within the mRNA coding region." Goebel W.S., Schloemer R.H., Brahmi Z. Mol. Immunol. 33:341-349(1996) [PubMed: 8676885] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 520-555, INDUCTION. Tissue: Natural killer cell.
[8]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-205, MASS SPECTROMETRY. Tissue: Liver.
[9]	"Localization and molecular modelling of the membrane-inserted domain of the ninth component of human complement and perforin." Peitsch M.C., Amiguet P., Guy R., Brunner J., Maizel J.V. Jr., Tschopp J. Mol. Immunol. 27:589-602(1990) [PubMed: 2395434] [Abstract] Cited for: 3D-STRUCTURE MODELING OF MEMBRANE-SPANNING DOMAIN (MSD).
[10]	"Perforin gene defects in familial hemophagocytic lymphohistiocytosis." Stepp S.E., Dufourcq-Lagelouse R., Le Deist F., Bhawan S., Certain S., Mathew P.A., Henter J.-I., Bennett M., Fischer A., de Saint Basile G., Kumar V. Science 286:1957-1959(1999) [PubMed: 10583959] [Abstract] Cited for: VARIANTS FHL2 GLY-183; TRP-225; SER-252; TYR-279; LEU-345 AND GLU-429.
[11]	"Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis." Goeransdotter Ericson K., Fadeel B., Nilsson-Ardnor S., Soederhaell C., Samuelsson A., Janka G., Schneider M., Guergey A., Yalman N., Revesz T., Egeler R., Jahnukainen K., Storm-Mathiesen I., Haraldsson A., Poole J., de Saint Basile G., Nordenskjoeld M., Henter J.-I. Am. J. Hum. Genet. 68:590-597(2001) [PubMed: 11179007] [Abstract] Cited for: VARIANTS FHL2 MET-50; ASN-224 AND LYS-285 DEL.
[12]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-123.
+	Additional computationally mapped references.

Web resources

PRF1base

PRF1 mutation db

GeneReviews

Wikipedia

Perforin entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	X13224 mRNA. Translation: CAA31612.1. M28393 mRNA. Translation: AAA60065.1. M31951 Genomic DNA. Translation: AAA60167.1. AL355344 Genomic DNA. Translation: CAI41276.1. BC047695 mRNA. Translation: AAH47695.2. BC063043 mRNA. Translation: AAH63043.1. AB209604 mRNA. Translation: BAD92841.1. L40557 mRNA. Translation: AAA63618.1.
IPI	IPI00293423.
PIR	A37181. A45816.
RefSeq	NP_001076585.1. NP_005032.2.
UniGene	Hs.2200
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P14222. 1 interaction.
Proteomic databases
PRIDE	P14222.
Genome annotation databases
Ensembl	ENSG00000180644. Homo sapiens. [Contig view]
GeneID	5551.
KEGG	hsa:5551.
Organism-specific databases
GeneCards	GC10M072027.
H-InvDB	HIX0035400.
HGNC	HGNC:9360. PRF1.
HPA	CAB002436.
MIM	170280. gene. 603553. phenotype.
Orphanet	88. Aplastic anemia. 540. Familial hemophagocytic lymphohistiocytosis.
PharmGKB	PA33732.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P14222.
HOVERGEN	P14222.
OMA	P14222. ACEEKKK.
Enzyme and pathway databases
Pathway_Interaction_DB	caspase_pathway. Caspase cascade in apoptosis. cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells. il12_stat4pathway. IL12 signaling mediated by STAT4. il2_stat5pathway. IL2 signaling events mediated by STAT5. cd8tcrpathway. TCR signaling in naive CD8+ T cells.
Gene expression databases
ArrayExpress	P14222.
Bgee	P14222.
CleanEx	HS_PRF1.
GermOnline	ENSG00000180644. Homo sapiens.
Family and domain databases
InterPro	IPR000008. C2_Ca-dep. IPR018029. C2_membr_targeting. IPR013032. EGF-like_reg_CS. IPR001862. MAC_perforin. [Graphical view]
Pfam	PF00168. C2. 1 hit. PF01823. MACPF. 1 hit. [Graphical view]
SMART	SM00239. C2. 1 hit. SM00457. MACPF. 1 hit. [Graphical view]
PROSITE	PS50004. C2. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. False negative. PS50026. EGF_3. False negative. PS00279. MACPF_1. 1 hit. PS51412. MACPF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	21512.
SOURCE	Search...

Entry information

Entry name

PERF_HUMAN

Accession

Primary (citable) accession number: P14222
Secondary accession number(s): Q59F57, Q86WX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	June 16, 2009
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)