P07225 (PROS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vitamin K-dependent protein S

Gene names

Name:	PROS1
Synonyms:	PROS

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	676 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	Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.
Subcellular location	Secreted.
Tissue specificity	Plasma.
Post-translational modification	The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains By similarity.
Involvement in disease	Thrombophilia due to protein S deficiency, autosomal dominant (THPH5) [MIM:612336]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Based on the plasma levels of total and free PROS1 as well as the serine protease-activated protein C cofactor activity, three types of THPH5 have been described: type I, characterized by reduced total and free PROS1 levels together with reduced anticoagulant activity; type III, in which only free PROS1 antigen and PROS1 activity levels are reduced; and the rare type II which is characterized by normal concentrations of both total and free PROS1 antigen, but low cofactor activity. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Thrombophilia due to protein S deficiency, autosomal recessive (THPH6) [MIM:614514]: A very rare and severe hematologic disorder resulting in thrombosis and secondary hemorrhage usually beginning in early infancy. Some affected individuals develop neonatal purpura fulminans, multifocal thrombosis, or intracranial hemorrhage. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Contains 4 EGF-like domains. Contains 1 Gla (gamma-carboxy-glutamate) domain. Contains 2 laminin G-like domains.
Sequence caution	The sequence AAP45054.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Blood coagulation Fibrinolysis Hemostasis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Thrombophilia
Domain	EGF-like domain Repeat Signal
Ligand	Calcium
PTM	Cleavage on pair of basic residues Disulfide bond Gamma-carboxyglutamic acid Glycoprotein Hydroxylation Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fibrinolysis Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome peptidyl-glutamic acid carboxylation Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome post-translational protein modification Traceable author statement. Source: Reactome proteolysis Traceable author statement. Source: Reactome regulation of complement activation Traceable author statement. Source: Reactome
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome Golgi membrane Traceable author statement. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: Reactome extracellular region Non-traceable author statement PubMed 14718574. Source: UniProtKB platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro endopeptidase inhibitor activity Traceable author statement PubMed 8146182. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Propeptide

25 – 41

17

PRO_0000022119

Chain

42 – 676

635

Vitamin K-dependent protein S

PRO_0000022120

Regions

Domain

42 – 87

46

Gla

Domain

117 – 155

39

EGF-like 1

Domain

157 – 200

44

EGF-like 2; calcium-binding Potential

Domain

201 – 242

42

EGF-like 3; calcium-binding Potential

Domain

243 – 283

41

EGF-like 4; calcium-binding Potential

Domain

299 – 475

177

Laminin G-like 1

Domain

484 – 666

183

Laminin G-like 2

Region

88 – 116

29

Thrombin-sensitive

Sites

Site

499

1

Not glycosylated; in variant Heerlen

Amino acid modifications

Modified residue

47

1

4-carboxyglutamate

Modified residue

48

1

4-carboxyglutamate

Modified residue

55

1

4-carboxyglutamate

Modified residue

57

1

4-carboxyglutamate

Modified residue

60

1

4-carboxyglutamate

Modified residue

61

1

4-carboxyglutamate

Modified residue

66

1

4-carboxyglutamate

Modified residue

67

1

4-carboxyglutamate

Modified residue

70

1

4-carboxyglutamate

Modified residue

73

1

4-carboxyglutamate

Modified residue

77

1

4-carboxyglutamate

Modified residue

136

1

(3R)-3-hydroxyaspartate By similarity

Glycosylation

499

1

N-linked (GlcNAc...)

Glycosylation

509

1

N-linked (GlcNAc...) Potential

Glycosylation

530

1

N-linked (GlcNAc...) Ref.11

Disulfide bond

58 ↔ 63

By similarity

Disulfide bond

121 ↔ 134

By similarity

Disulfide bond

126 ↔ 143

By similarity

Disulfide bond

145 ↔ 154

By similarity

Disulfide bond

161 ↔ 175

By similarity

Disulfide bond

171 ↔ 184

By similarity

Disulfide bond

186 ↔ 199

By similarity

Disulfide bond

205 ↔ 217

Ref.12

Disulfide bond

212 ↔ 226

Ref.12

Disulfide bond

228 ↔ 241

Ref.12

Disulfide bond

247 ↔ 256

Ref.12

Disulfide bond

252 ↔ 265

Ref.12

Disulfide bond

267 ↔ 282

Ref.12

Disulfide bond

449 ↔ 475

By similarity

Disulfide bond

639 ↔ 666

By similarity

Natural variations

Natural variant

15

1

L → H in THPH5. Ref.30

VAR_046802

Natural variant

18

1

V → E in THPH5; expresses very low/undetectable PROS1 levels compared to wild-type; has impaired secretion; intracellular degradation of unsecreted material is found. Ref.34

VAR_046803

Natural variant

40

1

R → L in THPH5. Ref.16
Corresponds to variant rs7614835 [ dbSNP | Ensembl ].

VAR_046804

Natural variant

41

1

R → H in THPH5. Ref.16

VAR_046805

Natural variant

50

1

K → E in THPH5. Ref.22

VAR_046806

Natural variant

52

1

G → D in THPH5; does not affect PROS1 production but results in 15.2-fold reduced PROS1 activity; has 5.4 fold reduced affinity for anionic phospholipid vesicles (P < 0.0001) and decreased affinity for an antibody specific for the Ca(2+)-dependent conformation of the PROS1 Gla domain. Ref.33

VAR_046807

Natural variant

67

1

E → A in THPH5. Ref.16 Ref.22 Ref.28 Ref.38

VAR_046808

Natural variant

68

1

A → D in THPH5. Ref.26

VAR_046809

Natural variant

72

1

F → C in THPH5. Ref.16

VAR_046810

Natural variant

76

1

P → L. Ref.16 Ref.28 Ref.38

VAR_046811

Natural variant

78

1

T → M in THPH5; reduces expression of PROS1 by 33.2% (P < 0.001) and activity by 3.6-fold; has only a modest 1.5-fold (P < 0.001) reduced affinity for phospholipid and an antibody specific for the Ca(2+)-dependent conformation of the PROS1 Gla domain. Ref.16 Ref.33
Corresponds to variant rs6122 [ dbSNP | Ensembl ].

VAR_014666

Natural variant

87

1

V → L in THPH5. Ref.37

VAR_046812

Natural variant

88

1

C → Y in THPH5. Ref.38

VAR_046813

Natural variant

90

1

R → C in THPH5; produces around 50% of PROS1 levels compared to wild-type; has impaired secretion; intracellular degradation of unsecreted material is found. Ref.34

VAR_046814

Natural variant

90

1

R → H in THPH5. Ref.16

VAR_046815

Natural variant

95

1

G → E in THPH5. Ref.22

VAR_046816

Natural variant

95

1

G → R in THPH5; the activated protein cofactor activity is inhibited by C4BPB with a dose dependency similar to that of wild-type PROS1. Ref.26 Ref.35

VAR_046817

Natural variant

98

1

T → S. Ref.30

VAR_046818

Natural variant

101

1

R → C in THPH5. Ref.36

VAR_046819

Natural variant

111

1

R → S in THPH5. Ref.23

VAR_046820

Natural variant

121

1

C → Y in THPH5. Ref.37

VAR_046821

Natural variant

129

1

D → G in THPH5. Ref.28 Ref.38

VAR_046822

Natural variant

144

1

T → N in THPH5. Ref.16 Ref.36 Ref.38

VAR_046823

Natural variant

149

1

W → C in THPH5. Ref.32

VAR_046824

Natural variant

157

1

D → G in THPH5. Ref.23

VAR_046825

Natural variant

161

1

C → G in THPH5. Ref.23

VAR_046826

Natural variant

166

1

N → Y in THPH5. Ref.29

VAR_046827

Natural variant

168

1

N → S. Ref.36

VAR_046828

Natural variant

175

1

C → F in THPH5. Ref.28 Ref.38

VAR_046829

Natural variant

186

1

C → Y in THPH5. Ref.21 Ref.22

VAR_046830

Natural variant

196

1

K → E in THPH5; Tokushima; the specific activity decreases to 58% of that of the wild-type PROS1; the activated protein cofactor activity is inhibited by C4BPB with a dose dependency similar to that of wild-type PROS1. Ref.15 Ref.35 Ref.37

VAR_005566

Natural variant

204

1

E → G in THPH5. Ref.38

VAR_046831

Natural variant

233

1

R → K in THPH5; expresses lower (p < 0.05) PROS1 levels compared to wild-type; has impaired secretion. Ref.30 Ref.34
Corresponds to variant rs41267007 [ dbSNP | Ensembl ].

VAR_046832

Natural variant

234

1

Y → C in THPH6. Ref.40

VAR_067302

Natural variant

241

1

C → S in THPH5. Ref.22

VAR_046833

Natural variant

243

1

D → N in THPH5. Ref.31

VAR_046834

Natural variant

245

1

D → G in THPH5. Ref.16

VAR_046835

Natural variant

247

1

C → G in THPH5. Ref.29

VAR_046836

Natural variant

249

1

E → K in THPH5. Ref.16

VAR_046837

Natural variant

258

1

N → S in THPH5; produces around 30% of PROS1 levels compared to wild-type; has impaired secretion; intracellular degradation of unsecreted material is found. Ref.14 Ref.17 Ref.34

VAR_005567

Natural variant

265

1

C → R in THPH5. Ref.16

VAR_046838

Natural variant

265

1

C → W in THPH5. Ref.16

VAR_046839

Natural variant

266

1

Y → C in THPH5. Ref.38

VAR_046840

Natural variant

267

1

C → S in THPH5. Ref.38

VAR_046841

Natural variant

300

1

L → P in THPH5. Ref.24

VAR_046842

Natural variant

324

1

S → P in THPH5. Ref.22

VAR_046843

Natural variant

336

1

G → D in THPH5. Ref.38

VAR_046844

Natural variant

336

1

G → S in THPH5. Ref.26

VAR_046845

Natural variant

336

1

G → V in THPH5; expresses very low/undetectable PROS1 levels compared to wild-type; has impaired secretion; intracellular degradation of unsecreted material is found. Ref.34

VAR_046846

Natural variant

339

1

L → P in THPH5. Ref.31

VAR_046847

Natural variant

351

1

L → P in THPH5. Ref.18

VAR_046848

Natural variant

355

1

R → H in THPH5. Ref.37

VAR_046849

Natural variant

357

1

G → R in THPH5. Ref.38

VAR_046850

Natural variant

364

1

K → E in THPH5. Ref.23

VAR_046851

Natural variant

376

1

D → N in THPH5. Ref.16

VAR_046852

Natural variant

381

1

G → D in THPH5. Ref.22

VAR_046853

Natural variant

381

1

G → V in THPH5. Ref.10

VAR_046854

Natural variant

383

1

W → R in THPH5. Ref.32

VAR_046855

Natural variant

385

1

M → V. Ref.16

VAR_046856

Natural variant

390

1

E → K in THPH5. Ref.32

VAR_046857

Natural variant

446

1

L → P in THPH5. Ref.23 Ref.38

VAR_046858

Natural variant

449

1

C → S in THPH5. Ref.22

VAR_046859

Natural variant

475

1

C → R in THPH5. Ref.23

VAR_046860

Natural variant

482

1

G → C in THPH5. Ref.27

VAR_014116

Natural variant

485

1

Y → C in THPH5. Ref.27

VAR_014117

Natural variant

495

1

I → V.
Corresponds to variant rs5017712 [ dbSNP | Ensembl ].

VAR_046861

Natural variant

501

1

S → A in THPH5. Ref.23

VAR_046862

Natural variant

501

1

S → P Variant Heerlen; could be associated with THPH5. Ref.13 Ref.22 Ref.23 Ref.27 Ref.38

VAR_005568

Natural variant

508

1

V → G in THPH5. Ref.10

VAR_046863

Natural variant

508

1

V → M in THPH5. Ref.23

VAR_046864

Natural variant

515

1

R → C in THPH5; secretion of the mutant markedly decreased compared with that of the wild-type; intracellular degradation and impaired secretion of the mutant. Ref.20 Ref.23

VAR_046865

Natural variant

515

1

R → P in THPH5. Ref.28 Ref.38

VAR_046866

Natural variant

521

1

G → D in THPH5. Ref.38

VAR_046867

Natural variant

525

1

A → P in THPH5. Ref.23

VAR_046868

Natural variant

526

1

L → S in THPH5. Ref.32

VAR_046869

Natural variant

532

1

T → A in THPH5. Ref.23

VAR_046870

Natural variant

545

1

E → G in a colorectal cancer sample; somatic mutation. Ref.39

VAR_035981

Natural variant

552

1

L → S in THPH5. Ref.18

VAR_046871

Natural variant

559

1

I → M. Ref.27 Ref.30 Ref.38

VAR_014118

Natural variant

561

1

R → G in THPH5. Ref.27

VAR_014119

Natural variant

562

1

I → L in THPH5; unknown pathological significance. Ref.28 Ref.38

VAR_046872

Natural variant

568

1

C → Y in THPH5. Ref.23

VAR_046873

Natural variant

575

1

L → R in THPH5. Ref.23

VAR_046874

Natural variant

583

1

N → H. Ref.38

VAR_046875

Natural variant

584

1

L → Q in THPH5. Ref.18

VAR_046876

Natural variant

611

1

M → K in THPH5. Ref.38

VAR_046877

Natural variant

611

1

M → T in THPH5. Ref.17 Ref.21 Ref.29

VAR_046878

Natural variant

616

1

A → P in THPH5. Ref.18

VAR_046879

Natural variant

622

1

L → R in THPH5. Ref.29

VAR_046880

Natural variant

630

1

T → I in THPH5; the activated protein cofactor activity is inhibited by C4BPB with a dose dependency similar to that of wild-type PROS1. Ref.35

VAR_046881

Natural variant

636

1

Y → C in THPH5; shows intracellular degradation and decreased secretion. Ref.35

VAR_046882

Natural variant

638

1

G → D in THPH5. Ref.28 Ref.38

VAR_046883

Natural variant

639

1

C → F in THPH5. Ref.25

VAR_046884

Natural variant

639

1

C → Y in THPH5. Ref.38

VAR_046885

Natural variant

640

1

M → T in THPH5. Ref.30

VAR_046886

Natural variant

644

1

I → S in THPH5. Ref.19

VAR_046887

Natural variant

664

1

H → P in THPH5; expresses very low/undetectable PROS1 levels compared to wild-type; has impaired secretion; intracellular degradation of unsecreted material is found. Ref.34

VAR_046888

Natural variant

665

1

S → L in THPH5. Ref.21

VAR_046889

Natural variant

666

1

C → R in THPH5. Ref.22 Ref.23 Ref.24 Ref.29

VAR_046890

Natural variant

667

1

P → L in THPH5. Ref.30 Ref.37

VAR_046891

Experimental info

Mutagenesis

515

1

R → A or E: Markedly reduced secretion of the mutant. Ref.20

Mutagenesis

515

1

R → K: No change in secretion of the mutant. Ref.20

Sequence conflict

11

1

L → P in AAA36479. Ref.2

Sequence conflict

26

1

F → L in AAA36479. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

676

Helix Strand Turn

Details...

Beta strand

204 – 212

9

Beta strand

227 – 229

3

Beta strand

233 – 235

3

Turn

236 – 239

4

Beta strand

240 – 242

3

Helix

246 – 249

4

Beta strand

253 – 256

4

Beta strand

260 – 262

3

Beta strand

269 – 271

3

Beta strand

279 – 281

3

Sequences

	Sequence		Length	Mass (Da)
	P07225 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 2B88A04F85403F25	FASTA	676	75,123
	10 20 30 40 50 60 MRVLGGRCGA LLACLLLVLP VSEANFLSKQ QASQVLVRKR RANSLLEETK QGNLERECIE 70 80 90 100 110 120 ELCNKEEARE VFENDPETDY FYPKYLVCLR SFQTGLFTAA RQSTNAYPDL RSCVNAIPDQ 130 140 150 160 170 180 CSPLPCNEDG YMSCKDGKAS FTCTCKPGWQ GEKCEFDINE CKDPSNINGG CSQICDNTPG 190 200 210 220 230 240 SYHCSCKNGF VMLSNKKDCK DVDECSLKPS ICGTAVCKNI PGDFECECPE GYRYNLKSKS 250 260 270 280 290 300 CEDIDECSEN MCAQLCVNYP GGYTCYCDGK KGFKLAQDQK SCEVVSVCLP LNLDTKYELL 310 320 330 340 350 360 YLAEQFAGVV LYLKFRLPEI SRFSAEFDFR TYDSEGVILY AESIDHSAWL LIALRGGKIE 370 380 390 400 410 420 VQLKNEHTSK ITTGGDVINN GLWNMVSVEE LEHSISIKIA KEAVMDINKP GPLFKPENGL 430 440 450 460 470 480 LETKVYFAGF PRKVESELIK PINPRLDGCI RSWNLMKQGA SGIKEIIQEK QNKHCLVTVE 490 500 510 520 530 540 KGSYYPGSGI AQFHIDYNNV SSAEGWHVNV TLNIRPSTGT GVMLALVSGN NTVPFAVSLV 550 560 570 580 590 600 DSTSEKSQDI LLSVENTVIY RIQALSLCSD QQSHLEFRVN RNNLELSTPL KIETISHEDL 610 620 630 640 650 660 QRQLAVLDKA MKAKVATYLG GLPDVPFSAT PVNAFYNGCM EVNINGVQLD LDEAISKHND 670 IRAHSCPSVW KKTKNS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human protein S cDNA encodes Phe-16 and Tyr 222 in consensus sequences for the post-translational processing." Ploos van Amstel H.K., van der Zanden A.L., Reitsma P.H., Bertina R.M. FEBS Lett. 222:186-190(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and characterization of human liver cDNA encoding a protein S precursor." Hoskins J., Norman D.K., Beckmann R.J., Long G.L. Proc. Natl. Acad. Sci. U.S.A. 84:349-353(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Organization of the human protein S genes." Schmidel D.K., Tatro A.V., Phelps L.G., Tomczak J.A., Long G.L. Biochemistry 29:7845-7852(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Intron-exon organization of the active human protein S gene PS alpha and its pseudogene PS beta: duplication and silencing during primate evolution." Ploos van Amstel H.K., Reitsma P.H., der Logt C.P., Bertina R.M. Biochemistry 29:7853-7861(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Trachea.
[6]	SeattleSNPs variation discovery resource Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: Uterus.
[9]	"Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation." Lundwall A., Dackowski W., Cohen E., Shaffer M., Mahr A., Dahlback B., Stenflo J., Wydro R. Proc. Natl. Acad. Sci. U.S.A. 83:6716-6720(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 27-676.
[10]	"Identification of eight point mutations in protein S deficiency type I -- analysis of 15 pedigrees." Gomez E., Poort S.R., Bertina R.M., Reitsma P.H. Thromb. Haemost. 73:750-755(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-519, VARIANTS THPH5 VAL-381 AND GLY-508.
[11]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-530, MASS SPECTROMETRY. Tissue: Plasma.
[12]	"Solution structure of the Ca2+-binding EGF3-4 pair from vitamin K-dependent protein S: identification of an unusual fold in EGF3." Drakenberg T., Ghasriani H., Thulin E., Thamlitz A.M., Muranyi A., Annila A., Stenflo J. Biochemistry 44:8782-8789(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 200-286, DISULFIDE BONDS.
[13]	"Heerlen polymorphism of protein S, an immunologic polymorphism due to dimorphism of residue 460." Bertina R.M., Ploos van Amstel H.K., van Wijngaarden A., Coenen J., Leemhuis M.P., Deutz-Terlouw P.P., van der Linden I.K., Reitsma P.H. Blood 76:538-548(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PRO-501.
[14]	Cooper D.N. Unpublished observations (SEP-1993) Cited for: VARIANT THPH5 SER-258.
[15]	"Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S." Hayashi T., Nishioka J., Shigekiyo T., Saito S., Suzuki K. Blood 83:683-690(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THPH5 TOKUSHIMA GLU-196.
[16]	"Identification of 15 different candidate causal point mutations and three polymorphisms in 19 patients with protein S deficiency using a scanning method for the analysis of the protein S active gene." Gandrille S., Borgel D., Eschwege-Gufflet V., Aillaud M., Dreyfus M., Matheron C., Gaussem P., Abgrall J.F., Jude B., Sie P., Toulon P., Aiach M. Blood 85:130-138(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 LEU-40; HIS-41; ALA-67; CYS-72; MET-78; HIS-90; ASN-144; GLY-245; LYS-249; TRP-265; ARG-265 AND ASN-376, VARIANTS LEU-76 AND VAL-385.
[17]	"Detection and characterization of seven novel protein S (PROS) gene lesions: evaluation of reverse transcript-polymerase chain reaction as a mutation screening strategy." Formstone C.J., Wacey A.I., Berg L.-P., Rahman S., Bevan D., Rowley M., Voke J., Bernardi F., Legnani C., Simioni P., Girolami A., Tuddenham E.G.D., Kakkar V.V., Cooper D.N. Blood 86:2632-2641(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 SER-258 AND THR-611.
[18]	"Protein S deficiency type I: identification of point mutations in 9 of 10 families." Mustafa S., Pabinger I., Mannhalter C. Blood 86:3444-3451(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 PRO-351; SER-552; GLN-584 AND PRO-616.
[19]	"Identification of two novel point mutations in the human protein S gene associated with familial protein S deficiency and thrombosis." Li M., Long G.L. Arterioscler. Thromb. Vasc. Biol. 16:1407-1415(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THPH5 SER-644.
[20]	"Molecular basis of a hereditary type I protein S deficiency caused by a substitution of Cys for Arg474." Yamazaki T., Katsumi A., Kagami K., Okamoto Y., Sugiura I., Hamaguchi M., Kojima T., Takamatsu J., Saito H. Blood 87:4643-4650(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THPH5 CYS-515, CHARACTERIZATION OF VARIANT PROS1 DEFICIENCY CYS-515, MUTAGENESIS OF ARG-515.
[21]	"Molecular basis of protein S deficiency in three families also showing independent inheritance of factor V Leiden." Beauchamp N.J., Daly M.E., Cooper P.C., Makris M., Preston F.E., Peake I.R. Blood 88:1700-1707(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 TYR-186; THR-611 AND LEU-665.
[22]	"Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis." Protein S study group Simmonds R.E., Ireland H., Kunz G., Lane D.A. Blood 88:4195-4204(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 GLU-50; ALA-67; GLU-95; TYR-186; SER-241; PRO-324; ASP-381; SER-449 AND ARG-666, VARIANT PRO-501.
[23]	"Molecular basis for protein S hereditary deficiency: genetic defects observed in 118 patients with type I and type IIa deficiencies." The French network on molecular abnormalities responsible for protein C and protein S deficiencies Borgel D., Duchemin J., Alhenc-Gelas M., Matheron C., Aiach M., Gandrille S. J. Lab. Clin. Med. 128:218-227(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 SER-111; GLY-157; GLY-161; GLU-364; PRO-446; ARG-475; ALA-501; MET-508; CYS-515; PRO-525; ALA-532; TYR-568; ARG-575 AND ARG-666, VARIANT PRO-501.
[24]	"Five novel mutations of the protein S active gene (PROS 1) in 8 Norman families." Duchemin J., Borg J.-Y., Borgel D., Vasse M., Leveque H., Aiach M., Gandrille S. Thromb. Haemost. 75:437-444(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 PRO-300 AND ARG-666.
[25]	"Identification of three novel mutations in hereditary protein S deficiency." Bustorff T.C., Freire I., Gago T., Crespo F., David D. Thromb. Haemost. 77:21-25(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THPH5 PHE-639.
[26]	"Protein S deficiency: a database of mutations." Plasma coagulation inhibitors subcommittee of the scientific and standardization committee of the international society on thrombosis and haemostasis Gandrille S., Borgel D., Ireland H., Lane D.A., Simmonds R., Reitsma P.H., Mannhalter C., Pabinger I., Saito H., Suzuki K., Formstone C., Cooper D.N., Espinosa Y., Sala N., Bernardi F., Aiach M. Thromb. Haemost. 77:1201-1214(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 ASP-68; ARG-95 AND SER-336.
[27]	"Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency." Espinosa-Parrilla Y., Morell M., Souto J.C., Tirado I., Fontcuberta J., Estivill X., Sala N. Hum. Mutat. 14:30-39(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 CYS-482; CYS-485 AND GLY-561, VARIANTS PRO-501 AND MET-559.
[28]	"Poor relationship between phenotypes of protein S deficiency and mutations in the protein S alpha gene." Hermida J., Faioni E.M., Mannucci P.M. Thromb. Haemost. 82:1634-1638(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 ALA-67; GLY-129; PHE-175; PRO-515; LEU-562 AND ASP-638, VARIANTS LEU-76 AND ASP-638.
[29]	"Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S." Makris M., Leach M., Beauchamp N.J., Daly M.E., Cooper P.C., Hampton K.K., Bayliss P., Peake I.R., Miller G.J., Preston F.E. Blood 95:1935-1941(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 TYR-166; GLY-247; THR-611; ARG-622 AND ARG-666.
[30]	"Optimization of a simple and rapid single-strand conformation analysis for detection of mutations in the PROS1 gene: identification of seven novel mutations and three novel, apparently neutral, variants." Espinosa-Parrilla Y., Morell M., Borrell M., Souto J.C., Fontcuberta J., Estivill X., Sala N. Hum. Mutat. 15:463-473(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 HIS-15; LYS-233; THR-640 AND LEU-667, VARIANTS SER-98 AND MET-559.
[31]	"DNA sequence analysis of protein S deficiency -- identification of four point mutations in twelve Japanese subjects." Iwaki T., Mastushita T., Kobayashi T., Yamamoto Y., Nomura Y., Kagami K., Nakayama T., Sugiura I., Kojima T., Takamatsu J., Kanayama N., Saito H. Semin. Thromb. Hemost. 27:155-160(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 ASN-243 AND PRO-339.
[32]	"Characterization and structural impact of five novel PROS1 mutations in eleven protein S-deficient families." Andersen B.D., Bisgaard M.L., Lind B., Philips M., Villoutreix B.O., Thorsen S. Thromb. Haemost. 86:1392-1399(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 CYS-149; ARG-383; LYS-390 AND SER-526.
[33]	"Protein S Gla-domain mutations causing impaired Ca(2+)-induced phospholipid binding and severe functional protein S deficiency." Rezende S.M., Lane D.A., Mille-Baker B., Samama M.M., Conard J., Simmonds R.E. Blood 100:2812-2819(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 ASP-52 AND MET-78, CHARACTERIZATION OF VARIANTS THPH5 ASP-52 AND MET-78.
[34]	"Genetic and phenotypic variability between families with hereditary protein S deficiency." Rezende S.M., Lane D.A., Zoeller B., Mille-Baker B., Laffan M., Dalhbaeck B., Simmonds R.E. Thromb. Haemost. 87:258-265(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 GLU-18; CYS-90; LYS-233; SER-258; VAL-336 AND PRO-664, CHARACTERIZATION OF VARIANTS THPH5 GLU-18; CYS-90; LYS-233; SER-258 VAL-336 AND PRO-664.
[35]	"Four missense mutations identified in the protein S gene of thrombosis patients with protein S deficiency: effects on secretion and anticoagulant activity of protein S." Tsuda H., Urata M., Tsuda T., Wakiyama M., Iida H., Nakahara M., Kinoshita S., Hamasaki N. Thromb. Res. 105:233-239(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 ARG-95; GLU-196; ILE-630 AND CYS-636, CHARACTERIZATION OF VARIANTS THPH5 ARG-95; GLU-196; ILE-630 AND CYS-636.
[36]	"Familial thrombophilia is an oligogenetic disease: involvement of the prothrombin G20210A, PROC and PROS gene mutations." Boinot C., Borgel D., Kitzis A., Guicheteau M., Aiach M., Alhenc-Gelas M. Blood Coagul. Fibrinolysis 14:191-196(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 CYS-101 AND ASN-144, VARIANT SER-168.
[37]	"Identification of protein Salpha gene mutations including four novel mutations in eight unrelated patients with protein S deficiency." Okada H., Takagi A., Murate T., Adachi T., Yamamoto K., Matsushita T., Takamatsu J., Sugita K., Sugimoto M., Yoshioka A., Yamazaki T., Saito H., Kojima T. Br. J. Haematol. 126:219-225(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 LEU-87; TYR-121; GLU-196; HIS-355 AND LEU-667.
[38]	"Molecular diversity and thrombotic risk in protein S deficiency: the PROSIT study." Protein S Italian team (PROSIT) Biguzzi E., Razzari C., Lane D.A., Castaman G., Cappellari A., Bucciarelli P., Fontana G., Margaglione M., D'Andrea G., Simmonds R.E., Rezende S.M., Preston R., Prisco D., Faioni E.M. Hum. Mutat. 25:259-269(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THPH5 ALA-67; TYR-88; GLY-129; ASN-144; PHE-175; GLY-204; CYS-266; SER-267; ASP-336; ARG-357; PRO-446; PRO-515; ASP-521; LYS-611; ASP-638 AND TYR-639, VARIANTS LEU-76; PRO-501; MET-559; LEU-562 AND HIS-583, CHARACTERIZATION OF VARIANTS PROS1 DEFICIENCY ALA-67; TYR-88; GLY-129; PHE-175; GLY-204; CYS-266; SER-267; ASP-336; ARG-357; PRO-446; PRO-515; ASP-521; LYS-611; ASP-638 AND TYR-639, CHARACTERIZATION OF VARIANTS LEU-76; LEU-562 AND HIS-583.
[39]	"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] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLY-545.
[40]	"Intracerebral mass bleeding in a term neonate: manifestation of hereditary protein S deficiency with a new mutation in the PROS1 gene." Fischer D., Porto L., Stoll H., Geisen C., Schloesser R.L. Neonatology 98:337-340(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THPH6 CYS-234.
+	Additional computationally mapped references.

Web resources

GeneReviews

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00692 mRNA. Translation: CAA68687.1.
Y00692 mRNA. Translation: CAA68688.1. Sequence problems.
M15036 mRNA. Translation: AAA36479.1.
M57853 , M57840, M57841, M57842, M57844, M57845, M57846, M57847, M57848, M57849, M57850, M57851, M57852 Genomic DNA. Translation: AAA60357.1.
AH002948 Genomic DNA. Translation: AAA60180.1.
AK292994 mRNA. Translation: BAF85683.1.
AY308744 Genomic DNA. Translation: AAP45054.1. Sequence problems.
CH471052 Genomic DNA. Translation: EAW79903.1.
CH471052 Genomic DNA. Translation: EAW79905.1.
BC015801 mRNA. Translation: AAH15801.1.

IPI

IPI00294004.

PIR

KXHUS. A35610.

RefSeq

NP_000304.2. NM_000313.3.

UniGene

Hs.64016.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z6C	NMR	-	A	200-286	[»]

ProteinModelPortal

P07225.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07225. 3 interactions.

STRING

9606.ENSP00000377783.

PTM databases

PhosphoSite

P07225.

Polymorphism databases

DMDM

131086.

Proteomic databases

PaxDb

P07225.

PeptideAtlas

P07225.

PRIDE

P07225.

Protocols and materials databases

DNASU

5627.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000394236; ENSP00000377783; ENSG00000184500.

GeneID

5627.

KEGG

hsa:5627.

UCSC

uc003dqz.4. human.

Organism-specific databases

CTD

5627.

GeneCards

GC03M093591.

HGNC

HGNC:9456. PROS1.

HPA

HPA007724.
HPA023974.

MIM

176880. gene.
612336. phenotype.
614514. phenotype.

neXtProt

NX_P07225.

Orphanet

743. Hereditary thrombophilia due to congenital protein S deficiency.

PharmGKB

PA33809.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG124763.

HOGENOM

HOG000065758.

HOVERGEN

HBG051702.

InParanoid

P07225.

KO

K03908.

OMA

WNMVSVE.

OrthoDB

EOG4PRSQB.

PhylomeDB

P07225.

Enzyme and pathway databases

Reactome

REACT_17015. Metabolism of proteins.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P07225.

Bgee

P07225.

CleanEx

HS_PROS1.

Genevestigator

P07225.

GermOnline

ENSG00000184500. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.200. 2 hits.
4.10.740.10. 1 hit.

InterPro

IPR017857. Coagulation_fac_subgr_Gla_dom.
IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR001791. Laminin_G.
[Graphical view]

Pfam

PF00008. EGF. 1 hit.
PF07645. EGF_CA. 2 hits.
PF00594. Gla. 1 hit.
PF00054. Laminin_G_1. 1 hit.
PF02210. Laminin_G_2. 1 hit.
[Graphical view]

PRINTS

PR00001. GLABLOOD.

SMART

SM00181. EGF. 1 hit.
SM00179. EGF_CA. 3 hits.
SM00069. GLA. 1 hit.
SM00282. LamG. 2 hits.
[Graphical view]

SUPFAM

SSF49899. ConA_like_lec_gl. 2 hits.
SSF57630. VitK_dep_GLA. 1 hit.

PROSITE

PS00010. ASX_HYDROXYL. 4 hits.
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 3 hits.
PS50026. EGF_3. 4 hits.
PS01187. EGF_CA. 3 hits.
PS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS50025. LAM_G_DOMAIN. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PROS1. human.

DrugBank

DB00025. Antihemophilic Factor.
DB00055. Drotrecogin alfa.
DB00170. Menadione.

EvolutionaryTrace

P07225.

GenomeRNAi

5627.

NextBio

21872.

SOURCE

Search...

Entry information

Entry name

PROS_HUMAN

Accession

Primary (citable) accession number: P07225
Secondary accession number(s): A8KAC9 , D3DN28, Q15518, Q7Z715, Q9UCZ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	April 1, 1988
Last modified:	May 1, 2013
This is version 170 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.