P36955 (PEDF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pigment epithelium-derived factor
Short name=PEDF

Alternative name(s):
Cell proliferation-inducing gene 35 protein
EPC-1
Serpin F1

Gene names

Name:	SERPINF1
Synonyms:	PEDF
ORF Names:	PIG35

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	418 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	Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells. Potent inhibitor of angiogenesis. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity. Ref.12 Ref.13
Subcellular location	Secreted. Melanosome. Note: Enriched in stage I melanosomes. Ref.16
Tissue specificity	Retinal pigment epithelial cells and blood plasma. Ref.10
Developmental stage	Expressed in quiescent cells.
Domain	The N-terminal (AA 44-121) exhibits neurite outgrowth-inducing activity. The C-terminal exposed loop (AA 382-418) is essential for serpin activity.
Post-translational modification	The N-terminus is blocked. Extracellular phosphorylation enhances antiangiogenic activity. N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan. Ref.15 Ref.17 Ref.18 Ref.20
Involvement in disease	Defects in SERPINF1 are the cause of osteogenesis imperfecta type 12 (OI12) [MIM:613982]. OI12 is a connective tissue disorder characterized by bone fragility, low bone mass, and recurrent fractures. OI12 is characterized by features compatible with osteogenesis imperfecta type III in the Sillence classification. Patients have normal grayish sclerae and fractures of long bones and severe vertebral compression fractures, with resulting deformities observed as early as the first year of life. Ref.19
Sequence similarities	Belongs to the serpin family.
Sequence caution	The sequence AAA84914.1 differs from that shown. Reason: Frameshift at position 356. The sequence AAA93524.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Osteogenesis imperfecta
Domain	Signal
PTM	Glycoprotein Phosphoprotein Pyrrolidone carboxylic acid
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell proliferation Traceable author statement. Source: ProtInc negative regulation of angiogenesis Inferred from direct assay Ref.20. Source: UniProtKB positive regulation of neurogenesis Inferred from direct assay Ref.12. Source: UniProtKB regulation of proteolysis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	extracellular space Inferred from direct assay. Source: BHF-UCL melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	serine-type endopeptidase inhibitor activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Chain

20 – 418

399

Pigment epithelium-derived factor

PRO_0000032508

Regions

Region

371 – 383

13

O-glycosylated at one site

Amino acid modifications

Modified residue

20

1

Pyrrolidone carboxylic acid

Modified residue

24

1

Phosphoserine; by CK2 Ref.14

Modified residue

114

1

Phosphoserine; by CK2 Ref.14

Modified residue

227

1

Phosphoserine; by PKA Ref.14

Glycosylation

285

1

N-linked (GlcNAc...) Ref.15 Ref.17 Ref.20

Natural variations

Natural variant

72

1

T → M. Ref.1 Ref.2 Ref.3 Ref.5 Ref.7 Ref.8 Ref.9 Ref.11 Ref.21
Corresponds to variant rs1136287 [ dbSNP | Ensembl ].

VAR_009126

Natural variant

132

1

P → R. Ref.8
Corresponds to variant rs1804145 [ dbSNP | Ensembl ].

VAR_025500

Experimental info

Sequence conflict

97 – 98

2

EQ → DE in AAA60058. Ref.1

Sequence conflict

97 – 98

2

EQ → DE in AAB38685. Ref.9

Secondary structure

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418

Helix Strand Turn

Details...

Helix

45 – 48

4

Helix

50 – 72

23

Beta strand

78 – 80

3

Helix

82 – 92

11

Helix

93 – 95

3

Helix

98 – 107

10

Helix

110 – 112

3

Helix

118 – 129

12

Beta strand

136 – 144

9

Helix

152 – 162

11

Helix

173 – 187

15

Turn

188 – 190

3

Beta strand

204 – 214

11

Beta strand

217 – 219

3

Helix

223 – 225

3

Beta strand

227 – 236

10

Beta strand

238 – 256

19

Turn

257 – 260

4

Beta strand

261 – 268

8

Turn

269 – 271

3

Beta strand

272 – 281

10

Helix

287 – 290

4

Helix

295 – 304

10

Beta strand

306 – 315

10

Beta strand

317 – 324

8

Helix

326 – 330

5

Turn

331 – 335

5

Helix

336 – 339

4

Turn

344 – 346

3

Beta strand

353 – 364

12

Beta strand

368 – 370

3

Beta strand

387 – 389

3

Beta strand

394 – 400

7

Turn

401 – 403

3

Beta strand

406 – 413

8

Sequences

	Sequence		Length	Mass (Da)
	P36955 [UniParc]. Last modified November 30, 2010. Version 4. Checksum: 7630DD2B4026A0D3	FASTA	418	46,312
	10 20 30 40 50 60 MQALVLLLCI GALLGHSSCQ NPASPPEEGS PDPDSTGALV EEEDPFFKVP VNKLAAAVSN 70 80 90 100 110 120 FGYDLYRVRS STSPTTNVLL SPLSVATALS ALSLGAEQRT ESIIHRALYY DLISSPDIHG 130 140 150 160 170 180 TYKELLDTVT APQKNLKSAS RIVFEKKLRI KSSFVAPLEK SYGTRPRVLT GNPRLDLQEI 190 200 210 220 230 240 NNWVQAQMKG KLARSTKEIP DEISILLLGV AHFKGQWVTK FDSRKTSLED FYLDEERTVR 250 260 270 280 290 300 VPMMSDPKAV LRYGLDSDLS CKIAQLPLTG SMSIIFFLPL KVTQNLTLIE ESLTSEFIHD 310 320 330 340 350 360 IDRELKTVQA VLTVPKLKLS YEGEVTKSLQ EMKLQSLFDS PDFSKITGKP IKLTQVEHRA 370 380 390 400 410 GFEWNEDGAG TTPSPGLQPA HLTFPLDYHL NQPFIFVLRD TDTGALLFIG KILDPRGP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family." Steele F.R., Chader G.J., Johnson L.V., Tombran-Tink J. Proc. Natl. Acad. Sci. U.S.A. 90:1526-1530(1993) [PubMed: 8434014] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT MET-72. Tissue: Fetal eye.
[2]	"Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin." Tombran-Tink J., Mazuruk K., Rodriguez I.R., Chung D., Linker T., Englander E., Chader G.J. Mol. Vis. 2:11-11(1996) [PubMed: 9238088] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-72.
[3]	Yin B., Peng X., Yuan J., Qiang B. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-72.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Identification of a human cell proliferation inducing gene." Kim J.W. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-72. Tissue: Liver cancer.
[6]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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], VARIANT MET-72.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS MET-72 AND ARG-132. Tissue: Muscle.
[9]	Coljee V.W. Thesis (1996), Medical College of Pennsylvania, United States Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-332, VARIANT MET-72. Tissue: Fetal lung fibroblast.
[10]	"Pigment-epithelium-derived factor (PEDF) occurs at a physiologically relevant concentration in human blood: purification and characterization." Petersen S.V., Valnickova Z., Enghild J.J. Biochem. J. 374:199-206(2003) [PubMed: 12737624] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-29; 253-262 AND 282-303, TISSUE SPECIFICITY, PYROGLUTAMATE FORMATION AT GLN-20. Tissue: Plasma.
[11]	"Senescent WI-38 cells fail to express EPC-1, a gene induced in young cells upon entry into the G0 state." Pignolo R.J., Cristofalo V.J., Rotenberg M.O. J. Biol. Chem. 268:8949-8957(1993) [PubMed: 8473338] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-418, VARIANT MET-72. Tissue: Fetal lung fibroblast.
[12]	"Overexpression of fetal human pigment epithelium-derived factor in Escherichia coli. A functionally active neurotrophic factor." Becerra S.P., Palmer I., Kumar A., Steele F.R., Shiloach J., Notario V., Chader G.J. J. Biol. Chem. 268:23148-23156(1993) [PubMed: 8226833] [Abstract] Cited for: FUNCTION.
[13]	"Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop." Becerra S.P., Sagasti A., Spinella P., Notario V. J. Biol. Chem. 270:25992-25999(1995) [PubMed: 7592790] [Abstract] Cited for: FUNCTION.
[14]	"Extracellular phosphorylation converts pigment epithelium-derived factor from a neurotrophic to an antiangiogenic factor." Maik-Rachline G., Shaltiel S., Seger R. Blood 105:670-678(2005) [PubMed: 15374885] [Abstract] Cited for: PHOSPHORYLATION AT SER-24; SER-114 AND SER-227.
[15]	"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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-285, MASS SPECTROMETRY. Tissue: Plasma.
[16]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[17]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-285, MASS SPECTROMETRY. Tissue: Liver.
[18]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed: 19838169] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS], STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[19]	"Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta." Becker J., Semler O., Gilissen C., Li Y., Bolz H.J., Giunta C., Bergmann C., Rohrbach M., Koerber F., Zimmermann K., de Vries P., Wirth B., Schoenau E., Wollnik B., Veltman J.A., Hoischen A., Netzer C. Am. J. Hum. Genet. 88:362-371(2011) [PubMed: 21353196] [Abstract] Cited for: INVOLVEMENT IN OI12.
[20]	"Crystal structure of human PEDF, a potent anti-angiogenic and neurite growth-promoting factor." Simonovic M., Gettins P.G.W., Volz K. Proc. Natl. Acad. Sci. U.S.A. 98:11131-11135(2001) [PubMed: 11562499] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 21-418, GLYCOSYLATION AT ASN-285.
[21]	"Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis." Koenekoop R., Pina A.L., Loyer M., Davidson J., Robitaille J., Maumenee I., Tombran-Tink J. Mol. Vis. 5:10-10(1999) [PubMed: 10398730] [Abstract] Cited for: VARIANT MET-72.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M76979 mRNA. Translation: AAA60058.1.
U29953 Genomic DNA. Translation: AAA84914.1. Frameshift.
AF400442 mRNA. Translation: AAK92491.1.
BT007222 mRNA. Translation: AAP35886.1.
AY513280 mRNA. Translation: AAT08033.1.
AC130343 Genomic DNA. No translation available.
AC130689 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW90577.1.
BC000522 mRNA. Translation: AAH00522.1.
BC013984 mRNA. Translation: AAH13984.1.
U57450 , U57445, U57446, U57447, U57448, U57449 Genomic DNA. Translation: AAB38685.1.
M90439 mRNA. Translation: AAA93524.1. Different initiation.

IPI

IPI00006114.

PIR

A46046.
A47281.

RefSeq

NP_002606.3. NM_002615.5.

UniGene

Hs.532768.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IMV	X-ray	2.85	A	21-418	[»]

ProteinModelPortal

P36955.

SMR

P36955. Positions 36-418.

ModBase

Search...

Protein-protein interaction databases

IntAct

P36955. 1 interaction.

STRING

P36955.

Protein family/group databases

MEROPS

I04.979.

PTM databases

PhosphoSite

P36955.

Polymorphism databases

DMDM

20178323.

2D gel databases

Cornea-2DPAGE

P36955.

REPRODUCTION-2DPAGE

IPI00006114.

Proteomic databases

PeptideAtlas

P36955.

PRIDE

P36955.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000254722; ENSP00000254722; ENSG00000132386.

GeneID

5176.

KEGG

hsa:5176.

Organism-specific databases

CTD

5176.

GeneCards

GC17P001612.

H-InvDB

HIX0013408.

HGNC

HGNC:8824. SERPINF1.

HPA

CAB004785.
HPA005825.

MIM

172860. gene.
613982. phenotype.

neXtProt

NX_P36955.

PharmGKB

PA35508.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09045.

GeneTree

ENSGT00560000076649.

HOGENOM

HBG278447.

HOVERGEN

HBG106911.

InParanoid

P36955.

OMA

LNCKIAQ.

OrthoDB

EOG44J2JG.

PhylomeDB

P36955.

Gene expression databases

ArrayExpress

P36955.

Bgee

P36955.

CleanEx

HS_SERPINF1.

Genevestigator

P36955.

GermOnline

ENSG00000132386. Homo sapiens.

Family and domain databases

InterPro

IPR000215. Protease_inhib_I4_serpin.
IPR023795. Protease_inhib_I4_serpin_CS.
IPR023796. Sepin_dom.
[Graphical view]

PANTHER

PTHR11461. Prot_inh_serpin. 1 hit.

Pfam

PF00079. Serpin. 1 hit.
[Graphical view]

SMART

SM00093. SERPIN. 1 hit.
[Graphical view]

SUPFAM

SSF56574. Prot_inh_serpin. 1 hit.

PROSITE

PS00284. SERPIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

SOURCE

Search...

Entry information

Entry name

PEDF_HUMAN

Accession

Primary (citable) accession number: P36955
Secondary accession number(s): Q13236 , Q2TU83, Q96CT1, Q96R01, Q9BWA4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 30, 2010
Last modified:	December 14, 2011
This is version 127 of the entry and version 4 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.