P20918 (PLMN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Plasminogen
EC=3.4.21.7

Cleaved into the following 5 chains:

1. Plasmin heavy chain A
2. Activation peptide
3. Angiostatin
4. Plasmin heavy chain A, short form
5. Plasmin light chain B

Gene names

Name:

Plg

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	812 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	Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells By similarity. Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.
Catalytic activity	Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products.
Enzyme regulation	Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Cannot be activated with streptokinase.
Subunit structure	Interacts (both mature PLG and the angiostatin peptide) with AMOT and CSPG4. Interacts (via the Kringle domains) with HRG; the interaction tethers PLG to the cell surface and enhances its activation. Interacts (the angiostatin peptide) with ATP5A1; the interaction inhibits most of the angiogenic effects of angiostatin By similarity.
Subcellular location	Secreted By similarity. Note: Locates to the cell surface where it is proteolytically cleaved to produce the active plasmin. Interaction with HRG tethers it to the cell surface By similarity.
Domain	Kringle domains mediate interaction with CSPG4 By similarity.
Post-translational modification	In the presence of the inhibitor, the activation involves only cleavage after Arg-581, yielding two chains held together by two disulfide bonds. In the absence of the inhibitor, the activation involves additionally the removal of the activation peptide By similarity.
Miscellaneous	Plasmin is inactivated by alpha-2-antiplasmin immediately after dissociation from the clot. In the presence of the inhibitor, the activation involves only cleavage after Arg-581, resulting in 2 chains held together by 2 disulfide bonds. Without the inhibitor, the activation involves also removal of the activation peptide.
Sequence similarities	Belongs to the peptidase S1 family. Plasminogen subfamily. Contains 5 kringle domains. Contains 1 PAN domain. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Blood coagulation Fibrinolysis Hemostasis Tissue remodeling
Cellular component	Secreted
Domain	Kringle Repeat Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Phosphoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from direct assay PubMed 12167431. Source: MGI blood coagulation Inferred from sequence or structural similarity. Source: HGNC extracellular matrix disassembly Inferred from electronic annotation. Source: Compara fibrinolysis Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Inferred from direct assay PubMed 12167431. Source: MGI labyrinthine layer blood vessel development Inferred from mutant phenotype PubMed 12900459. Source: MGI mononuclear cell migration Inferred from mutant phenotype PubMed 17690254. Source: MGI muscle cell homeostasis Inferred from mutant phenotype PubMed 11929773. Source: MGI myoblast differentiation Inferred from mutant phenotype PubMed 11929773. Source: MGI negative regulation of angiogenesis Traceable author statement PubMed 12167431. Source: MGI negative regulation of cell-substrate adhesion Inferred from electronic annotation. Source: Compara negative regulation of fibrinolysis Inferred from electronic annotation. Source: Compara positive regulation of fibrinolysis Inferred from electronic annotation. Source: Compara proteolysis involved in cellular protein catabolic process Inferred from electronic annotation. Source: Compara tissue regeneration Inferred from mutant phenotype PubMed 11929773. Source: MGI tissue remodeling Inferred from electronic annotation. Source: UniProtKB-KW trophoblast giant cell differentiation Inferred from mutant phenotype PubMed 12900459. Source: MGI
Cellular_component	extracellular space Inferred from sequence or structural similarity. Source: HGNC extrinsic to external side of plasma membrane Inferred from electronic annotation. Source: Compara extrinsic to plasma membrane Inferred from direct assay PubMed 17690254. Source: MGI intracellular membrane-bounded organelle Inferred from electronic annotation. Source: Compara
Molecular_function	cell surface binding Inferred from electronic annotation. Source: Compara serine-type endopeptidase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19
	Chain	20 – 812	793	Plasminogen		PRO_0000028069
	Chain	20 – 581	562	Plasmin heavy chain A		PRO_0000028070
	Peptide	20 – 97	78	Activation peptide		PRO_0000028071
	Chain	98 – 581	484	Plasmin heavy chain A, short form		PRO_0000028072
	Chain	98 – ?436	339	Angiostatin		PRO_0000028073
	Chain	582 – 812	231	Plasmin light chain B		PRO_0000028074
Regions
	Domain	20 – 98	79	PAN
	Domain	103 – 181	79	Kringle 1
	Domain	184 – 262	79	Kringle 2
	Domain	275 – 352	78	Kringle 3
	Domain	377 – 454	78	Kringle 4
	Domain	481 – 560	80	Kringle 5
	Domain	582 – 810	229	Peptidase S1
Sites
	Active site	624	1	Charge relay system By similarity
	Active site	667	1	Charge relay system By similarity
	Active site	762	1	Charge relay system By similarity
Amino acid modifications
	Modified residue	598	1	Phosphoserine By similarity
	Disulfide bond	49 ↔ 73		By similarity
	Disulfide bond	53 ↔ 61		By similarity
	Disulfide bond	103 ↔ 181		By similarity
	Disulfide bond	124 ↔ 164		By similarity
	Disulfide bond	152 ↔ 176		By similarity
	Disulfide bond	185 ↔ 262		By similarity
	Disulfide bond	188 ↔ 316		By similarity
	Disulfide bond	206 ↔ 245		By similarity
	Disulfide bond	234 ↔ 257		By similarity
	Disulfide bond	275 ↔ 352		By similarity
	Disulfide bond	296 ↔ 335		By similarity
	Disulfide bond	324 ↔ 347		By similarity
	Disulfide bond	377 ↔ 454		By similarity
	Disulfide bond	398 ↔ 437		By similarity
	Disulfide bond	426 ↔ 449		By similarity
	Disulfide bond	481 ↔ 560		By similarity
	Disulfide bond	502 ↔ 543		By similarity
	Disulfide bond	531 ↔ 555		By similarity
	Disulfide bond	568 ↔ 687		Interchain (between A and B chains) By similarity
	Disulfide bond	578 ↔ 586		Interchain (between A and B chains) By similarity
	Disulfide bond	609 ↔ 625		By similarity
	Disulfide bond	701 ↔ 768		By similarity
	Disulfide bond	731 ↔ 747		By similarity
	Disulfide bond	758 ↔ 786		By similarity
Experimental info
	Sequence conflict	235	1	R → H in AAA50168. Ref.1
	Sequence conflict	525	1	G → D in AAA50168. Ref.1
	Sequence conflict	649	1	L → S in AAM22156. Ref.2
	Sequence conflict	649	1	L → S in AAH14773. Ref.4
	Sequence conflict	649	1	L → S in AAH57186. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P20918 [UniParc]. Last modified June 28, 2011. Version 3. Checksum: E70E1AC8E52844E9	FASTA	812	90,808
	10 20 30 40 50 60 MDHKEVILLF LLLLKPGQGD SLDGYISTQG ASLFSLTKKQ LAAGGVSDCL AKCEGETDFV 70 80 90 100 110 120 CRSFQYHSKE QQCVIMAENS KTSSIIRMRD VILFEKRVYL SECKTGIGNG YRGTMSRTKS 130 140 150 160 170 180 GVACQKWGAT FPHVPNYSPS THPNEGLEEN YCRNPDNDEQ GPWCYTTDPD KRYDYCNIPE 190 200 210 220 230 240 CEEECMYCSG EKYEGKISKT MSGLDCQAWD SQSPHAHGYI PAKFPSKNLK MNYCRNPDGE 250 260 270 280 290 300 PRPWCFTTDP TKRWEYCDIP RCTTPPPPPS PTYQCLKGRG ENYRGTVSVT VSGKTCQRWS 310 320 330 340 350 360 EQTPHRHNRT PENFPCKNLE ENYCRNPDGE TAPWCYTTDS QLRWEYCEIP SCESSASPDQ 370 380 390 400 410 420 SDSSVPPEEQ TPVVQECYQS DGQSYRGTSS TTITGKKCQS WAAMFPHRHS KTPENFPDAG 430 440 450 460 470 480 LEMNYCRNPD GDKGPWCYTT DPSVRWEYCN LKRCSETGGS VVELPTVSQE PSGPSDSETD 490 500 510 520 530 540 CMYGNGKDYR GKTAVTAAGT PCQGWAAQEP HRHSIFTPQT NPRAGLEKNY CRNPDGDVNG 550 560 570 580 590 600 PWCYTTNPRK LYDYCDIPLC ASASSFECGK PQVEPKKCPG RVVGGCVANP HSWPWQISLR 610 620 630 640 650 660 TRFTGQHFCG GTLIAPEWVL TAAHCLEKSS RPEFYKVILG AHEEYIRGLD VQEISVAKLI 670 680 690 700 710 720 LEPNNRDIAL LKLSRPATIT DKVIPACLPS PNYMVADRTI CYITGWGETQ GTFGAGRLKE 730 740 750 760 770 780 AQLPVIENKV CNRVEYLNNR VKSTELCAGQ LAGGVDSCQG DSGGPLVCFE KDKYILQGVT 790 800 810 SWGLGCARPN KPGVYVRVSR FVDWIEREMR NN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the cDNA coding for mouse plasminogen and localization of the gene to mouse chromosome 17." Degen S.J., Bell S.M., Schaefer L.A., Elliott R.W. Genomics 8:49-61(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic sequence analysis in the mouse T-complex region." Brathwaite M.E., Waeltz P., Qian Y., Dudekula D., Schlessinger D., Nagaraja R. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: 129/Sv.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[5]	"Localization of regulatory elements mediating constitutive and cytokine-stimulated plasminogen gene expression." Bannach F.G., Gutierrez A., Fowler B.J., Bugge T.H., Degen J.L., Parmer R.J., Miles L.A. J. Biol. Chem. 277:38579-38588(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. Strain: 129/SvJ. Tissue: Liver.
[6]	"Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma." O'Reilly M.S., Holmgren L., Shing Y., Chen C., Rosenthal R.A., Moses M., Lane W.S., Cao Y., Sage E.H., Folkman J. Cell 79:315-328(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF ANGIOSTATIN, PARTIAL PROTEIN SEQUENCE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J04766 mRNA. Translation: AAA50168.1. AF481053 Genomic DNA. Translation: AAM22156.1. AC087901 Genomic DNA. No translation available. BC014773 mRNA. Translation: AAH14773.1. BC057186 mRNA. Translation: AAH57186.1. AY134430 Genomic DNA. Translation: AAN15805.1.
IPI	IPI00322936.
PIR	PLMS. A38514.
RefSeq	NP_032903.3. NM_008877.3.
UniGene	Mm.971.
3D structure databases
ProteinModelPortal	P20918.
SMR	P20918. Positions 20-812.
ModBase	Search...
Protein-protein interaction databases
IntAct	P20918. 1 interaction.
Protein family/group databases
MEROPS	S01.233.
PTM databases
PhosphoSite	P20918.
2D gel databases
REPRODUCTION-2DPAGE	P20918.
Proteomic databases
PaxDb	P20918.
PRIDE	P20918.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000014578; ENSMUSP00000014578; ENSMUSG00000059481.
GeneID	18815.
KEGG	mmu:18815.
Organism-specific databases
CTD	5340.
MGI	MGI:97620. Plg.
Phylogenomic databases
eggNOG	COG5640.
GeneTree	ENSGT00700000104191.
HOGENOM	HOG000112892.
HOVERGEN	HBG004381.
InParanoid	P20918.
KO	K01315.
OMA	PSKFPNK.
OrthoDB	EOG4RR6GQ.
Gene expression databases
ArrayExpress	P20918.
Bgee	P20918.
CleanEx	MM_PLG.
Genevestigator	P20918.
GermOnline	ENSMUSG00000059481. Mus musculus.
Family and domain databases
Gene3D	2.40.20.10. 5 hits.
InterPro	IPR000001. Kringle. IPR013806. Kringle-like. IPR018056. Kringle_CS. IPR003014. PAN-1_domain. IPR003609. Pan_app. IPR023317. Pept_S1A_plasmin. IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00051. Kringle. 5 hits. PF00024. PAN_1. 1 hit. PF00089. Trypsin. 1 hit. [Graphical view]
PIRSF	PIRSF001150. Plasmin. 1 hit.
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00130. KR. 5 hits. SM00473. PAN_AP. 1 hit. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF57440. Kringle-like. 5 hits. SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS00021. KRINGLE_1. 5 hits. PS50070. KRINGLE_2. 5 hits. PS50948. PAN. 1 hit. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1075299.
ChiTaRS	PLG. mouse.
NextBio	295166.
PMAP-CutDB	P20918.
SOURCE	Search...

Entry information

Entry name

PLMN_MOUSE

Accession

Primary (citable) accession number: P20918
Secondary accession number(s): Q8CIS2, Q91WJ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	June 28, 2011
Last modified:	May 1, 2013
This is version 151 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program