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P05187 (PPB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 168. 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:
Alkaline phosphatase, placental type

EC=3.1.3.1
Alternative name(s):
Alkaline phosphatase Regan isozyme
Placental alkaline phosphatase 1
Short name=PLAP-1
Gene names
Name:ALPP
Synonyms:PLAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length535 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

A phosphate monoester + H2O = an alcohol + phosphate.

Cofactor

Binds 1 magnesium ion. Ref.14 Ref.15 Ref.16 Ref.17

Binds 2 zinc ions. Ref.14 Ref.15 Ref.16 Ref.17

Subunit structure

Homodimer. Ref.14 Ref.15 Ref.16 Ref.17

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor Ref.10 Ref.11.

Tissue specificity

Detected in placenta (at protein level). Ref.17

Polymorphism

Placental ALP is highly polymorphic, there are at least three common alleles.

Miscellaneous

In most mammals there are four different isozymes: placental, placental-like, intestinal and tissue non-specific (liver/bone/kidney).

Sequence similarities

Belongs to the alkaline phosphatase family.

Sequence caution

The sequence AAA51708.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.7
Chain23 – 506484Alkaline phosphatase, placental type
PRO_0000024031
Propeptide507 – 53529Removed in mature form
PRO_0000024032

Regions

Transmembrane513 – 52917Helical

Sites

Active site1141Phosphoserine intermediate
Metal binding641Magnesium
Metal binding641Zinc 1
Metal binding1141Zinc 1
Metal binding1771Magnesium
Metal binding3331Magnesium
Metal binding3381Zinc 2
Metal binding3421Zinc 2; via tele nitrogen
Metal binding3791Zinc 1
Metal binding3801Zinc 1; via tele nitrogen
Metal binding4541Zinc 2; via tele nitrogen

Amino acid modifications

Lipidation5061GPI-anchor amidated aspartate Ref.10 Ref.11
Glycosylation1441N-linked (GlcNAc...) Ref.15 Ref.16 Ref.17
Glycosylation2711N-linked (GlcNAc...) Ref.15 Ref.16 Ref.17
Disulfide bond143 ↔ 205 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17
Disulfide bond489 ↔ 496 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17

Natural variations

Natural variant251P → L. Ref.3 Ref.6
Corresponds to variant rs1130335 [ dbSNP | Ensembl ].
VAR_017419
Natural variant891I → L. Ref.5
Corresponds to variant rs13026692 [ dbSNP | Ensembl ].
VAR_050520
Natural variant2311R → P. Ref.2
Corresponds to variant rs1048988 [ dbSNP | Ensembl ].
VAR_050521
Natural variant2631R → H. Ref.3
Corresponds to variant rs2853378 [ dbSNP | Ensembl ].
VAR_050522
Natural variant4511E → G.
Corresponds to variant rs1048994 [ dbSNP | Ensembl ].
VAR_050523

Experimental info

Sequence conflict661M → V in AAA51709. Ref.3
Sequence conflict261 – 2622AK → GE in AAA51706. Ref.6
Sequence conflict2771Q → R in AAA51709. Ref.3
Sequence conflict2851T → A in AAA51709. Ref.3
Sequence conflict3241N → H in AAA51706. Ref.6
Sequence conflict3891Y → C in AAA51709. Ref.3
Sequence conflict3941S → G in AAA51709. Ref.3
Sequence conflict396 – 3972IF → FI in AAA51706. Ref.6
Sequence conflict4011P → A in AAA51706. Ref.6
Sequence conflict4361S → T Ref.8

Secondary structure

................................................................................... 535
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05187 [UniParc].

Last modified July 1, 1989. Version 2.
Checksum: 13C136679A70C76B

FASTA53557,954
        10         20         30         40         50         60 
MLGPCMLLLL LLLGLRLQLS LGIIPVEEEN PDFWNREAAE ALGAAKKLQP AQTAAKNLII 

        70         80         90        100        110        120 
FLGDGMGVST VTAARILKGQ KKDKLGPEIP LAMDRFPYVA LSKTYNVDKH VPDSGATATA 

       130        140        150        160        170        180 
YLCGVKGNFQ TIGLSAAARF NQCNTTRGNE VISVMNRAKK AGKSVGVVTT TRVQHASPAG 

       190        200        210        220        230        240 
TYAHTVNRNW YSDADVPASA RQEGCQDIAT QLISNMDIDV ILGGGRKYMF RMGTPDPEYP 

       250        260        270        280        290        300 
DDYSQGGTRL DGKNLVQEWL AKRQGARYVW NRTELMQASL DPSVTHLMGL FEPGDMKYEI 

       310        320        330        340        350        360 
HRDSTLDPSL MEMTEAALRL LSRNPRGFFL FVEGGRIDHG HHESRAYRAL TETIMFDDAI 

       370        380        390        400        410        420 
ERAGQLTSEE DTLSLVTADH SHVFSFGGYP LRGSSIFGLA PGKARDRKAY TVLLYGNGPG 

       430        440        450        460        470        480 
YVLKDGARPD VTESESGSPE YRQQSAVPLD EETHAGEDVA VFARGPQAHL VHGVQEQTFI 

       490        500        510        520        530 
AHVMAFAACL EPYTACDLAP PAGTTDAAHP GRSVVPALLP LLAGTLLLLE TATAP 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the human placental alkaline phosphatase gene. Evolution of the 5' flanking region by deletion/substitution."
Knoll B.J., Rothblum K.N., Longley M.A.
J. Biol. Chem. 263:12020-12027(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Molecular cloning and sequence analysis of human placental alkaline phosphatase."
Millan J.L.
J. Biol. Chem. 261:3112-3115(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-231.
[3]"Products of two common alleles at the locus for human placental alkaline phosphatase differ by seven amino acids."
Henthorn P.S., Knoll B.J., Raducha M., Rothblum K.N., Slaughter C., Weiss M., Lafferty M.A., Fischer T., Harris H.
Proc. Natl. Acad. Sci. U.S.A. 83:5597-5601(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANTS LEU-25 AND HIS-263.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-89.
Tissue: Cervix and Placenta.
[6]"Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA."
Kam W., Clauser E., Kim Y.S., Kan Y.W., Rutter W.J.
Proc. Natl. Acad. Sci. U.S.A. 82:8715-8719(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-535, VARIANT LEU-25.
[7]"Purification and partial sequencing of human placental alkaline phosphatase."
Ezra E., Blacher R., Udenfriend S.
Biochem. Biophys. Res. Commun. 116:1076-1083(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-64.
[8]"Expression of different-sized placental alkaline phosphatase mRNAs in placenta and choriocarcinoma cells."
Ovitt C.E., Strauss A.W., Alpers D.H., Chou J.Y., Boime I.
Proc. Natl. Acad. Sci. U.S.A. 83:3781-3785(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 382-535.
[9]"Aspartic acid-484 of nascent placental alkaline phosphatase condenses with a phosphatidylinositol glycan to become the carboxyl terminus of the mature enzyme."
Micanovic R., Bailey C.A., Brink L., Gerber L., Pan Y.C.E., Hulmes J.D., Udenfriend S.
Proc. Natl. Acad. Sci. U.S.A. 85:1398-1402(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 485-535.
[10]"Selectivity of the cleavage/attachment site of phosphatidylinositol-glycan-anchored membrane proteins determined by site-specific mutagenesis at Asp-484 of placental alkaline phosphatase."
Micanovic R., Gerber L.D., Berger J., Kodukula K., Udenfriend S.
Proc. Natl. Acad. Sci. U.S.A. 87:157-161(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: GPI-ANCHOR AT ASP-506.
[11]"Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein."
Lowe M.E.
J. Cell Biol. 116:799-807(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: EFFECT OF MUTAGENESIS OF C-TERMINAL PEPTIDE ON GPI-ANCHORING.
[12]"Function assignment to conserved residues in mammalian alkaline phosphatases."
Kozlenkov A., Manes T., Hoylaerts M.F., Millan J.L.
J. Biol. Chem. 277:22992-22999(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Crystal structure of alkaline phosphatase from human placenta at 1.8 A resolution. Implication for a substrate specificity."
Le Du M.H., Stigbrand T., Taussig M.J., Menez A., Stura E.A.
J. Biol. Chem. 276:9158-9165(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 23-535 IN COMPLEX WITH MAGNESIUM AND ZINC, COFACTOR, DISULFIDE BOND, SUBUNIT.
[15]"Structural studies of human placental alkaline phosphatase in complex with functional ligands."
Llinas P., Stura E.A., Menez A., Kiss Z., Stigbrand T., Millan J.L., Le Du M.H.
J. Mol. Biol. 350:441-451(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 23-506 IN COMPLEX WITH MAGNESIUM AND ZINC, GLYCOSYLATION AT ASN-144 AND ASN-271, COFACTOR, DISULFIDE BOND, SUBUNIT.
[16]"Structural studies of human alkaline phosphatase in complex with strontium: implication for its secondary effect in bones."
Llinas P., Masella M., Stigbrand T., Menez A., Stura E.A., Le Du M.H.
Protein Sci. 15:1691-1700(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 23-506 IN COMPLEX WITH MAGNESIUM AND ZINC, GLYCOSYLATION AT ASN-144 AND ASN-271, COFACTOR, DISULFIDE BOND, SUBUNIT.
[17]"Refined structures of placental alkaline phosphatase show a consistent pattern of interactions at the peripheral site."
Stec B., Cheltsov A., Millan J.L.
Acta Crystallogr. F 66:866-870(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 23-506 IN COMPLEX WITH MAGNESIUM AND ZINC, GLYCOSYLATION AT ASN-144 AND ASN-271, COFACTOR, DISULFIDE BOND, SUBUNIT, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Web resources

Wikipedia

Alkaline phosphatase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M19159 Genomic DNA. Translation: AAA51710.1.
M13077 mRNA. Translation: AAC97139.1.
M14169 mRNA. Translation: AAA51708.1. Different initiation.
M14170 mRNA. Translation: AAA51709.1.
AC068134 Genomic DNA. Translation: AAY24087.1.
BC009647 mRNA. Translation: AAH09647.1.
BC068501 mRNA. Translation: AAH68501.1.
BC094743 mRNA. Translation: AAH94743.1.
M12551 mRNA. Translation: AAA51706.1.
CCDSCCDS2490.1.
PIRPAHUA. A31074.
RefSeqNP_001623.3. NM_001632.3.
UniGeneHs.284255.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EW2X-ray1.82A23-535[»]
1ZEBX-ray1.90A23-506[»]
1ZEDX-ray1.57A23-506[»]
1ZEFX-ray1.90A23-506[»]
2GLQX-ray1.60A23-506[»]
3MK0X-ray1.90A23-506[»]
3MK1X-ray1.57A23-506[»]
3MK2X-ray1.89A23-503[»]
ProteinModelPortalP05187.
SMRP05187. Positions 23-503.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106751. 21 interactions.
IntActP05187. 9 interactions.
MINTMINT-4054397.
STRING9606.ENSP00000375881.

Chemistry

BindingDBP05187.
ChEMBLCHEMBL4458.

PTM databases

PhosphoSiteP05187.

Polymorphism databases

DMDM130737.

Proteomic databases

MaxQBP05187.
PaxDbP05187.
PRIDEP05187.

Protocols and materials databases

DNASU250.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000392027; ENSP00000375881; ENSG00000163283.
GeneID250.
KEGGhsa:250.
UCSCuc002vsq.3. human.

Organism-specific databases

CTD250.
GeneCardsGC02P233244.
HGNCHGNC:439. ALPP.
HPACAB026327.
HPA038764.
HPA038765.
HPA051699.
MIM171800. gene.
neXtProtNX_P05187.
PharmGKBPA24730.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1785.
HOGENOMHOG000099118.
HOVERGENHBG007345.
InParanoidP05187.
KOK01077.
OMALNAQPAY.
OrthoDBEOG7SN8CH.
PhylomeDBP05187.
TreeFamTF323513.

Gene expression databases

BgeeP05187.
CleanExHS_ALPP.
GenevestigatorP05187.

Family and domain databases

Gene3D3.40.720.10. 1 hit.
InterProIPR017849. Alkaline_Pase-like_a/b/a.
IPR001952. Alkaline_phosphatase.
IPR018299. Alkaline_phosphatase_AS.
IPR017850. Alkaline_phosphatase_core.
[Graphical view]
PfamPF00245. Alk_phosphatase. 1 hit.
[Graphical view]
PRINTSPR00113. ALKPHPHTASE.
SMARTSM00098. alkPPc. 1 hit.
[Graphical view]
SUPFAMSSF53649. SSF53649. 1 hit.
PROSITEPS00123. ALKALINE_PHOSPHATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSALPP. human.
EvolutionaryTraceP05187.
GeneWikiPlacental_alkaline_phosphatase.
GenomeRNAi250.
NextBio1001.
PROP05187.
SOURCESearch...

Entry information

Entry namePPB1_HUMAN
AccessionPrimary (citable) accession number: P05187
Secondary accession number(s): P05188 expand/collapse secondary AC list , P06861, Q53S78, Q96DB7
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 168 of the entry and version 2 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 2

Human chromosome 2: entries, gene names and cross-references to MIM