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P07225 (PROS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 184. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Vitamin K-dependent protein S
Gene names
Name:PROS1
Synonyms:PROS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length676 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processBlood coagulation
Fibrinolysis
Hemostasis
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Thrombophilia
   DomainEGF-like domain
Repeat
Signal
   LigandCalcium
   PTMCleavage on pair of basic residues
Disulfide bond
Gamma-carboxyglutamic acid
Glycoprotein
Hydroxylation
Zymogen
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

cellular protein metabolic process

Traceable author statement. Source: Reactome

fibrinolysis

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

leukocyte migration

Traceable author statement. Source: Reactome

negative regulation of endopeptidase activity

Traceable author statement PubMed 8146182. Source: GOC

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_componentGolgi lumen

Traceable author statement. Source: Reactome

Golgi membrane

Traceable author statement. Source: Reactome

blood microparticle

Inferred from direct assay PubMed 22516433. Source: UniProt

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

extracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 14607961. Source: BHF-UCL

platelet alpha granule lumen

Traceable author statement. Source: Reactome

   Molecular_functioncalcium 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Propeptide25 – 4117
PRO_0000022119
Chain42 – 676635Vitamin K-dependent protein S
PRO_0000022120

Regions

Domain42 – 8746Gla
Domain117 – 15539EGF-like 1
Domain157 – 20044EGF-like 2; calcium-binding Potential
Domain201 – 24242EGF-like 3; calcium-binding Potential
Domain243 – 28341EGF-like 4; calcium-binding Potential
Domain299 – 475177Laminin G-like 1
Domain484 – 666183Laminin G-like 2
Region88 – 11629Thrombin-sensitive

Sites

Site4991Not glycosylated; in variant Heerlen

Amino acid modifications

Modified residue4714-carboxyglutamate Ref.1
Modified residue4814-carboxyglutamate Ref.1
Modified residue5514-carboxyglutamate Ref.1
Modified residue5714-carboxyglutamate Ref.1
Modified residue6014-carboxyglutamate Ref.1
Modified residue6114-carboxyglutamate Ref.1
Modified residue6614-carboxyglutamate Ref.1
Modified residue6714-carboxyglutamate Ref.1
Modified residue7014-carboxyglutamate Ref.1
Modified residue7314-carboxyglutamate Ref.1
Modified residue7714-carboxyglutamate Ref.1
Modified residue1361(3R)-3-hydroxyaspartate By similarity
Glycosylation4991N-linked (GlcNAc...)
Glycosylation5091N-linked (GlcNAc...) Potential
Glycosylation5301N-linked (GlcNAc...) Ref.11
Disulfide bond58 ↔ 63 By similarity
Disulfide bond121 ↔ 134 By similarity
Disulfide bond126 ↔ 143 By similarity
Disulfide bond145 ↔ 154 By similarity
Disulfide bond161 ↔ 175 By similarity
Disulfide bond171 ↔ 184 By similarity
Disulfide bond186 ↔ 199 By similarity
Disulfide bond205 ↔ 217 Ref.12
Disulfide bond212 ↔ 226 Ref.12
Disulfide bond228 ↔ 241 Ref.12
Disulfide bond247 ↔ 256 Ref.12
Disulfide bond252 ↔ 265 Ref.12
Disulfide bond267 ↔ 282 Ref.12
Disulfide bond449 ↔ 475 By similarity
Disulfide bond639 ↔ 666 By similarity

Natural variations

Natural variant151L → H in THPH5. Ref.30
VAR_046802
Natural variant181V → 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 variant401R → L in THPH5. Ref.16
Corresponds to variant rs7614835 [ dbSNP | Ensembl ].
VAR_046804
Natural variant411R → H in THPH5. Ref.16
VAR_046805
Natural variant501K → E in THPH5. Ref.22
VAR_046806
Natural variant521G → 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 variant671E → A in THPH5. Ref.16 Ref.22 Ref.28 Ref.38
VAR_046808
Natural variant681A → D in THPH5. Ref.26
VAR_046809
Natural variant721F → C in THPH5. Ref.16
VAR_046810
Natural variant761P → L. Ref.16 Ref.28 Ref.38
Corresponds to variant rs73846070 [ dbSNP | Ensembl ].
VAR_046811
Natural variant781T → 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 variant871V → L in THPH5. Ref.37
VAR_046812
Natural variant881C → Y in THPH5. Ref.38
VAR_046813
Natural variant901R → 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 variant901R → H in THPH5. Ref.16
VAR_046815
Natural variant951G → E in THPH5. Ref.22
VAR_046816
Natural variant951G → 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 variant981T → S. Ref.30
Corresponds to variant rs142805170 [ dbSNP | Ensembl ].
VAR_046818
Natural variant1011R → C in THPH5. Ref.36
VAR_046819
Natural variant1111R → S in THPH5. Ref.23
VAR_046820
Natural variant1211C → Y in THPH5. Ref.37
VAR_046821
Natural variant1291D → G in THPH5. Ref.28 Ref.38
VAR_046822
Natural variant1441T → N in THPH5. Ref.16 Ref.36 Ref.38
VAR_046823
Natural variant1491W → C in THPH5. Ref.32
VAR_046824
Natural variant1571D → G in THPH5. Ref.23
VAR_046825
Natural variant1611C → G in THPH5. Ref.23
VAR_046826
Natural variant1661N → Y in THPH5. Ref.29
VAR_046827
Natural variant1681N → S. Ref.36
VAR_046828
Natural variant1751C → F in THPH5. Ref.28 Ref.38
VAR_046829
Natural variant1861C → Y in THPH5. Ref.21 Ref.22
VAR_046830
Natural variant1961K → 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
Corresponds to variant rs121918474 [ dbSNP | Ensembl ].
VAR_005566
Natural variant2041E → G in THPH5. Ref.38
VAR_046831
Natural variant2331R → 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 variant2341Y → C in THPH6. Ref.40
VAR_067302
Natural variant2411C → S in THPH5. Ref.22
VAR_046833
Natural variant2431D → N in THPH5. Ref.31
VAR_046834
Natural variant2451D → G in THPH5. Ref.16
VAR_046835
Natural variant2471C → G in THPH5. Ref.29
VAR_046836
Natural variant2491E → K in THPH5. Ref.16
VAR_046837
Natural variant2581N → 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 variant2651C → R in THPH5. Ref.16
VAR_046838
Natural variant2651C → W in THPH5. Ref.16
VAR_046839
Natural variant2661Y → C in THPH5. Ref.38
VAR_046840
Natural variant2671C → S in THPH5. Ref.38
VAR_046841
Natural variant3001L → P in THPH5. Ref.24
VAR_046842
Natural variant3241S → P in THPH5. Ref.22
VAR_046843
Natural variant3361G → D in THPH5. Ref.38
VAR_046844
Natural variant3361G → S in THPH5. Ref.26
VAR_046845
Natural variant3361G → 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 variant3391L → P in THPH5. Ref.31
VAR_046847
Natural variant3511L → P in THPH5. Ref.18
VAR_046848
Natural variant3551R → H in THPH5. Ref.37
VAR_046849
Natural variant3571G → R in THPH5. Ref.38
VAR_046850
Natural variant3641K → E in THPH5. Ref.23
VAR_046851
Natural variant3761D → N in THPH5. Ref.16
VAR_046852
Natural variant3811G → D in THPH5. Ref.22
VAR_046853
Natural variant3811G → V in THPH5. Ref.10
VAR_046854
Natural variant3831W → R in THPH5. Ref.32
VAR_046855
Natural variant3851M → V. Ref.16
VAR_046856
Natural variant3901E → K in THPH5. Ref.32
VAR_046857
Natural variant4461L → P in THPH5. Ref.23 Ref.38
VAR_046858
Natural variant4491C → S in THPH5. Ref.22
VAR_046859
Natural variant4751C → R in THPH5. Ref.23
VAR_046860
Natural variant4821G → C in THPH5. Ref.27
VAR_014116
Natural variant4851Y → C in THPH5. Ref.27
VAR_014117
Natural variant4951I → V.
Corresponds to variant rs5017712 [ dbSNP | Ensembl ].
VAR_046861
Natural variant5011S → A in THPH5. Ref.23
Corresponds to variant rs121918472 [ dbSNP | Ensembl ].
VAR_046862
Natural variant5011S → P Variant Heerlen; could be associated with THPH5. Ref.13 Ref.22 Ref.23 Ref.27 Ref.38
Corresponds to variant rs121918472 [ dbSNP | Ensembl ].
VAR_005568
Natural variant5081V → G in THPH5. Ref.10
VAR_046863
Natural variant5081V → M in THPH5. Ref.23
VAR_046864
Natural variant5151R → 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 variant5151R → P in THPH5. Ref.28 Ref.38
VAR_046866
Natural variant5211G → D in THPH5. Ref.38
VAR_046867
Natural variant5251A → P in THPH5. Ref.23
VAR_046868
Natural variant5261L → S in THPH5. Ref.32
VAR_046869
Natural variant5321T → A in THPH5. Ref.23
VAR_046870
Natural variant5451E → G in a colorectal cancer sample; somatic mutation. Ref.39
VAR_035981
Natural variant5521L → S in THPH5. Ref.18
VAR_046871
Natural variant5591I → M. Ref.27 Ref.30 Ref.38
Corresponds to variant rs184798444 [ dbSNP | Ensembl ].
VAR_014118
Natural variant5611R → G in THPH5. Ref.27
VAR_014119
Natural variant5621I → L in THPH5; unknown pathological significance. Ref.28 Ref.38
VAR_046872
Natural variant5681C → Y in THPH5. Ref.23
VAR_046873
Natural variant5751L → R in THPH5. Ref.23
VAR_046874
Natural variant5831N → H. Ref.38
VAR_046875
Natural variant5841L → Q in THPH5. Ref.18
VAR_046876
Natural variant6111M → K in THPH5. Ref.38
VAR_046877
Natural variant6111M → T in THPH5. Ref.17 Ref.21 Ref.29
VAR_046878
Natural variant6161A → P in THPH5. Ref.18
VAR_046879
Natural variant6221L → R in THPH5. Ref.29
VAR_046880
Natural variant6301T → 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 variant6361Y → C in THPH5; shows intracellular degradation and decreased secretion. Ref.35
VAR_046882
Natural variant6381G → D in THPH5. Ref.28 Ref.38
VAR_046883
Natural variant6391C → F in THPH5. Ref.25
VAR_046884
Natural variant6391C → Y in THPH5. Ref.38
VAR_046885
Natural variant6401M → T in THPH5. Ref.30
VAR_046886
Natural variant6441I → S in THPH5. Ref.19
VAR_046887
Natural variant6641H → 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 variant6651S → L in THPH5. Ref.21
VAR_046889
Natural variant6661C → R in THPH5. Ref.22 Ref.23 Ref.24 Ref.29
VAR_046890
Natural variant6671P → L in THPH5. Ref.30 Ref.37
VAR_046891

Experimental info

Mutagenesis5151R → A or E: Markedly reduced secretion of the mutant. Ref.20
Mutagenesis5151R → K: No change in secretion of the mutant. Ref.20
Sequence conflict111L → P in AAA36479. Ref.2
Sequence conflict261F → L in AAA36479. Ref.2

Secondary structure

................... 676
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07225 [UniParc].

Last modified April 1, 1988. Version 1.
Checksum: 2B88A04F85403F25

FASTA67675,123
        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 

« Hide

References

« Hide '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], GAMMA-CARBOXYGLUTAMATION AT GLU-47; GLU-48; GLU-55; GLU-57; GLU-60; GLU-61; GLU-66; GLU-67; GLU-70; GLU-73 AND GLU-77.
[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. expand/collapse author list , 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. expand/collapse author list , 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.
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. expand/collapse author list , 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

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 expand/collapse EMBL AC list , 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.
CCDSCCDS2923.1.
PIRKXHUS. A35610.
RefSeqNP_000304.2. NM_000313.3.
UniGeneHs.64016.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Z6CNMR-A200-286[»]
ProteinModelPortalP07225.
SMRP07225. Positions 42-669.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111611. 7 interactions.
IntActP07225. 3 interactions.
STRING9606.ENSP00000377783.

Chemistry

DrugBankDB00025. Antihemophilic Factor.
DB00055. Drotrecogin alfa.
DB00170. Menadione.

PTM databases

PhosphoSiteP07225.

Polymorphism databases

DMDM131086.

Proteomic databases

MaxQBP07225.
PaxDbP07225.
PeptideAtlasP07225.
PRIDEP07225.

Protocols and materials databases

DNASU5627.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000394236; ENSP00000377783; ENSG00000184500.
GeneID5627.
KEGGhsa:5627.
UCSCuc003dqz.4. human.

Organism-specific databases

CTD5627.
GeneCardsGC03M093591.
HGNCHGNC:9456. PROS1.
HPAHPA007724.
HPA023974.
MIM176880. gene.
612336. phenotype.
614514. phenotype.
neXtProtNX_P07225.
Orphanet743. Hereditary thrombophilia due to congenital protein S deficiency.
PharmGKBPA33809.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG124763.
HOGENOMHOG000065758.
HOVERGENHBG051702.
InParanoidP07225.
KOK03908.
OMAWNMVSVE.
OrthoDBEOG7R2BJ0.
PhylomeDBP07225.
TreeFamTF352157.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP07225.
BgeeP07225.
CleanExHS_PROS1.
GenevestigatorP07225.

Family and domain databases

Gene3D2.60.120.200. 2 hits.
4.10.740.10. 1 hit.
InterProIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR009030. Growth_fac_rcpt_N_dom.
IPR001791. Laminin_G.
[Graphical view]
PfamPF00008. EGF. 1 hit.
PF07645. EGF_CA. 1 hit.
PF00594. Gla. 1 hit.
PF00054. Laminin_G_1. 1 hit.
PF02210. Laminin_G_2. 1 hit.
[Graphical view]
PRINTSPR00001. GLABLOOD.
SMARTSM00181. EGF. 1 hit.
SM00179. EGF_CA. 3 hits.
SM00069. GLA. 1 hit.
SM00282. LamG. 2 hits.
[Graphical view]
SUPFAMSSF49899. SSF49899. 2 hits.
SSF57184. SSF57184. 1 hit.
SSF57630. SSF57630. 1 hit.
PROSITEPS00010. 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]
ProtoNetSearch...

Other

ChiTaRSPROS1. human.
EvolutionaryTraceP07225.
GeneWikiProtein_S.
GenomeRNAi5627.
NextBio21872.
PROP07225.
SOURCESearch...

Entry information

Entry namePROS_HUMAN
AccessionPrimary (citable) accession number: P07225
Secondary accession number(s): A8KAC9 expand/collapse secondary AC list , D3DN28, Q15518, Q7Z715, Q9UCZ8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: July 9, 2014
This is version 184 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM