Reviewed, UniProtKB/Swiss-Prot P05121 (PAI1_HUMAN)

Names and origin

Protein names

Recommended name:
    Plasminogen activator inhibitor 1
      Short name=PAI-1
      Short name=PAI
Alternative name(s):
    Endothelial plasminogen activator inhibitor

Gene names

Name:	SERPINE1
Synonyms:	PAI1, PLANH1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	402 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	This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, and protein C. Its rapid interaction with TPA may function as a major control point in the regulation of fibrinolysis.
Subunit structure	Interacts with VTN. Binds LRP1B; binding is followed by internalization and degradation. Ref.14 Ref.15
Subcellular location	Secreted.
Tissue specificity	Found in plasma and platelets and in endothelial, hepatoma and fibrosarcoma cells.
Post-translational modification	Inactivated by proteolytic attack of the urokinase-type (u-PA) and the tissue-type (TPA), cleaving the 369-Arg-|-Met-370 bond.
Involvement in disease	Defects in SERPINE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency) [MIM:173360]. This deficiency is characterized by abnormal bleeding due to SERPINE1 defect in the plasma. High concentrations of SERPINE1 have been associated with thrombophilia [MIM:188050]; an autosomal dominant disorder in which affected individuals are prone to develop serious spontaneous thrombosis.
Sequence similarities	Belongs to the serpin family.

Ontologies

Keywords
Biological process	Plasminogen activation
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: ProtInc chronological cell aging Inferred from expression pattern. Source: UniProtKB fibrinolysis Traceable author statement. Source: UniProtKB
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB plasma membrane Inferred from Experiment. Source: Reactome
Molecular function	protease binding Inferred from physical interaction. Source: UniProtKB serine-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase inhibitor activity Inferred from Experiment. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ORM1	P02763	1	EBI-953978,EBI-976767
VTN	P04004	1	EBI-953978,EBI-1036653

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Chain

24 – 402

379

Plasminogen activator inhibitor 1

PRO_0000032499

Sites

Site

369 – 370

2

Reactive bond

Amino acid modifications

Glycosylation

232

1

N-linked (GlcNAc...)

Glycosylation

288

1

N-linked (GlcNAc...)

Glycosylation

352

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

15

1

A → T: dbSNP rs6092. Ref.8 Ref.21 Ref.22

VAR_007099

Natural variant

17

1

V → I: dbSNP rs6090. Ref.8 Ref.22

VAR_011750

Natural variant

25

1

H → P: dbSNP rs2227647. Ref.8

VAR_013086

Natural variant

209

1

R → H: dbSNP rs2227669. Ref.8

VAR_013087

Natural variant

255

1

T → N: dbSNP rs2227685. Ref.8

VAR_013088

Experimental info

Sequence conflict

53

1

R → A in CAA31208. Ref.7

Sequence conflict

55

1

V → L in AAA60009. Ref.2

Sequence conflict

75

1

G → V in CAA31208. Ref.7

Sequence conflict

138

1

R → K in CAA31208. Ref.7

Sequence conflict

280 – 282

3

QLI → HVM in CAA31208. Ref.7

Secondary structure

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402

Helix Strand Turn

Details...

Helix

27 – 49

23

Turn

50 – 52

3

Beta strand

55 – 57

3

Helix

59 – 72

14

Helix

75 – 85

11

Helix

94 – 106

13

Helix

108 – 110

3

Beta strand

112 – 123

12

Helix

132 – 140

9

Beta strand

145 – 147

3

Helix

152 – 166

15

Turn

167 – 169

3

Beta strand

184 – 195

12

Beta strand

198 – 200

3

Helix

204 – 206

3

Beta strand

208 – 213

6

Beta strand

219 – 237

19

Beta strand

243 – 251

9

Beta strand

254 – 265

12

Helix

271 – 274

4

Helix

279 – 287

9

Beta strand

290 – 299

10

Beta strand

301 – 308

8

Helix

310 – 315

6

Helix

320 – 322

3

Turn

324 – 326

3

Turn

330 – 332

3

Beta strand

334 – 336

3

Beta strand

339 – 342

4

Beta strand

344 – 351

8

Beta strand

373 – 376

4

Beta strand

381 – 387

7

Turn

388 – 391

4

Beta strand

392 – 400

9

Sequences

	Sequence		Length	Mass (Da)
	P05121-1 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: A2E181ED28DD6082	FASTA	402	45,060
	10 20 30 40 50 60 MQMSPALTCL VLGLALVFGE GSAVHHPPSY VAHLASDFGV RVFQQVAQAS KDRNVVFSPY 70 80 90 100 110 120 GVASVLAMLQ LTTGGETQQQ IQAAMGFKID DKGMAPALRH LYKELMGPWN KDEISTTDAI 130 140 150 160 170 180 FVQRDLKLVQ GFMPHFFRLF RSTVKQVDFS EVERARFIIN DWVKTHTKGM ISNLLGKGAV 190 200 210 220 230 240 DQLTRLVLVN ALYFNGQWKT PFPDSSTHRR LFHKSDGSTV SVPMMAQTNK FNYTEFTTPD 250 260 270 280 290 300 GHYYDILELP YHGDTLSMFI AAPYEKEVPL SALTNILSAQ LISHWKGNMT RLPRLLVLPK 310 320 330 340 350 360 FSLETEVDLR KPLENLGMTD MFRQFQADFT SLSDQEPLHV AQALQKVKIE VNESGTVASS 370 380 390 400 STAVIVSARM APEEIIMDRP FLFVVRHNPT GTVLFMGQVM EP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family." Pannekoek H., Veerman H., Lambers H., Diergaarde P., Verweij C.L., van Zonneveld A.-J., van Mourik J.A. EMBO J. 5:2539-2544(1986) [PubMed: 2430793] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure of the human plasminogen activator inhibitor 1 gene: nonrandom distribution of introns." Loskutoff D.J., Linders M., Keijer J., Veerman H., van Heerikhuizen H., Pannekoek H. Biochemistry 26:3763-3768(1987) [PubMed: 2820474] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"cDNA cloning of human plasminogen activator-inhibitor from endothelial cells." Ginsburg D., Zeheb R., Yang A.Y., Rafferty U.M., Andreasen P.A., Nielsen L., Dano K., Lebo R.V., Gelehrter T.D. J. Clin. Invest. 78:1673-1680(1986) [PubMed: 3097076] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Structure and expression of the human gene encoding plasminogen activator inhibitor, PAI-1." Follo M., Ginsburg D. Gene 84:447-453(1989) [PubMed: 2612914] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The organization of the human-plasminogen-activator-inhibitor-1 gene. Implications on the evolution of the serine-protease inhibitor family." Strandberg L., Lawrence D., Ny T. Eur. J. Biochem. 176:609-616(1988) [PubMed: 3262512] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Human plasminogen activator inhibitor-1 gene. Promoter and structural gene nucleotide sequences." Bosma P.J., van den Berg E.A., Kooistra T., Siemieniak D.R., Slightom J.L. J. Biol. Chem. 263:9129-9141(1988) [PubMed: 3132455] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	Pannekoek H. Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[8]	SeattleSNPs variation discovery resource Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-15; ILE-17; PRO-25; HIS-209 AND ASN-255.
[9]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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]. Tissue: Lung.
[11]	"Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor." Ny T., Sawdey M., Lawrence D., Millan J.L., Loskutoff D.J. Proc. Natl. Acad. Sci. U.S.A. 83:6776-6780(1986) [PubMed: 3092219] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-402.
[12]	"Plasminogen activator inhibitor type-1: reactive center and amino-terminal heterogeneity determined by protein and cDNA sequencing." Andreasen P.A., Riccio A., Welinder K.G., Douglas R., Sartorio R., Nielsen L.S., Oppenheimer C., Blasi F., Danoe K. FEBS Lett. 209:213-218(1986) [PubMed: 3025016] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-47 AND 364-402.
[13]	"cDNA cloning and expression in E. coli of a plasminogen activator inhibitor (PAI) related to a PAI produced by Hep G2 hepatoma cell." Wun T.C., Kretzmer K.K. FEBS Lett. 210:11-16(1987) [PubMed: 3026837] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-402, PARTIAL PROTEIN SEQUENCE. Tissue: Placenta.
[14]	"Identification of a PAI-1 binding site in vitronectin." Sigurdardottir O., Wiman B. Biochim. Biophys. Acta 1208:104-110(1994) [PubMed: 7522053] [Abstract] Cited for: INTERACTION WITH VTN.
[15]	"The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein." Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G. J. Biol. Chem. 276:28889-28896(2001) [PubMed: 11384978] [Abstract] Cited for: INTERACTION WITH LRP1B.
[16]	"Structural basis of latency in plasminogen activator inhibitor-1." Mottonen J., Strand A., Symersky J., Sweet R.M., Danley D.E., Geoghegan K.F., Gerard R.D., Goldsmith E.J. Nature 355:270-273(1992) [PubMed: 1731226] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[17]	"Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1." Aertgeerts K., de Bondt H.L., de Ranter C.J., Declerck P.J. Nat. Struct. Biol. 2:891-897(1995) [PubMed: 7552714] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
[18]	"Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide." Xue Y., Bjoerquist P., Inghardt T., Linschoten M., Musil D., Sjoelin L., Deinum J. Structure 6:627-636(1998) [PubMed: 9634700] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
[19]	"The active conformation of plasminogen activator inhibitor 1, a target for drugs to control fibrinolysis and cell adhesion." Sharp A.M., Stein P.E., Pannu N.S., Carrell R.W., Berkenpas M.B., Ginsburg D., Lawrence D.A., Read R.J. Structure 7:111-118(1999) [PubMed: 10368279] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS).
[20]	"Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation." Nar H., Bauer M., Stassen J.M., Lang D., Gils A., Declerck P.J. J. Mol. Biol. 297:683-695(2000) [PubMed: 10731421] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
[21]	"Mutational analysis of the genes encoding urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in advanced ovarian cancer." Turkmen B., Schmitt M., Schmalfeldt B., Trommler P., Hell W., Creutzburg S., Graeff H., Magdolen V. Electrophoresis 18:686-689(1997) [PubMed: 9194591] [Abstract] Cited for: VARIANT THR-15.
[22]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANTS THR-15 AND ILE-17.
[23]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Plasminogen activator inhibitor-1 entry

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X04429 mRNA. Translation: CAA28025.1.
M14083 mRNA. Translation: AAA60008.1.
X04729 mRNA. Translation: CAA28438.1.
X04731 mRNA. Translation: CAA28442.1.
M16006 mRNA. Translation: AAA60003.1.
M22321 , M22314, M22315, M22316, M22317, M22318, M22319, M22320 Genomic DNA. Translation: AAA60009.1.
X13323 Genomic DNA. No translation available.
X13338 Genomic DNA. Translation: CAA31722.1.
X13339 Genomic DNA. Translation: CAB51639.1.
X13340 Genomic DNA. Translation: CAB51737.1.
X13341 Genomic DNA. Translation: CAB51606.1.
X13342 Genomic DNA. Translation: CAB51607.1.
X13343 Genomic DNA. Translation: CAB51738.1.
X13344 Genomic DNA. Translation: CAB51739.1.
X13345 Genomic DNA. Translation: CAA31729.1.
J03764 Genomic DNA. Translation: AAA60007.1.
X12701 mRNA. Translation: CAA31208.1.
AF386492 Genomic DNA. Translation: AAK60338.1.
AC004876 Genomic DNA. Translation: AAD45828.1.
BC010860 mRNA. Translation: AAH10860.1.
X04744 mRNA. Translation: CAA28444.1.

IPI

IPI00007118.

PIR

ITHUP1. A28107.

RefSeq

NP_000593.1.

UniGene

Hs.414795
Hs.713079

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A7C	X-ray	1.95	A	24-402	[»]
1B3K	X-ray	2.99	A/B/C/D	24-402	[»]
1C5G	X-ray	2.60	A	1-402	[»]
1DB2	X-ray	2.70	A/B	26-402	[»]
1DVM	X-ray	2.40	A/B/C/D	24-402	[»]
1DVN	X-ray	2.10	A	24-402	[»]
1LJ5	X-ray	1.80	A	24-402	[»]
1OC0	X-ray	2.28	A	24-402	[»]
3CVM	X-ray	2.02	A/B	21-402	[»]
3EOX	X-ray	2.61	A	24-402	[»]
9PAI	X-ray	2.70	A	24-369	[»]
			B	370-402	[»]

DisProt

DP00320.

ModBase

Search...

Protein-protein interaction databases

IntAct

P05121. 3 interactions.

STRING

P05121.

Protein family/group databases

MEROPS

I04.020.

2-D gel databases

SWISS-2DPAGE

P05121.

OGP

P05121.

Proteomic databases

PRIDE

P05121.

Genome annotation databases

Ensembl

ENST00000223095; ENSP00000223095; ENSG00000106366; Homo sapiens. [Genome view]
ENST00000441467; ENSP00000392435; ENSG00000106366; Homo sapiens. [Genome view]
ENST00000445463; ENSP00000396766; ENSG00000106366; Homo sapiens. [Genome view]

GeneID

5054.

KEGG

hsa:5054.

NMPDR

fig|9606.3.peg.29170.

UCSC

uc003uxt.2. human.

Organism-specific databases

CTD

5054.

GeneCards

GC07P100558.

H-InvDB

HIX0006944.

HGNC

HGNC:8583. SERPINE1.

HPA

CAB002516.

MIM

173360. gene.
188050. phenotype.

Orphanet

465. Congenital plasminogen activitor inhibitor type 1 deficiency.

PharmGKB

PA261.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P05121.

HOVERGEN

P05121.

OMA

DAIFVQR.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P05121.

Bgee

P05121.

CleanEx

HS_SERPINE1.

Genevestigator

P05121.

GermOnline

ENSG00000106366. Homo sapiens.

Family and domain databases

InterPro

IPR000215. Protease_inhib_I4_serpin.
[Graphical view]

PANTHER

PTHR11461. Prot_inh_serpin. 1 hit.

Pfam

PF00079. Serpin. 1 hit.
[Graphical view]

SMART

SM00093. SERPIN. 1 hit.
[Graphical view]

PROSITE

PS00284. SERPIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01076. Atorvastatin.
DB01093. Dimethyl sulfoxide.
DB00055. Drotrecogin alfa.
DB00641. Simvastatin.
DB00031. Tenecteplase.
DB00197. Troglitazone.
DB00013. Urokinase.

NextBio

19480.

PMAP-CutDB

P05121.

SOURCE

Search...

Entry information

Entry name

PAI1_HUMAN

Accession

Primary (citable) accession number: P05121

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	November 3, 2009
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.