P07093 (GDN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glia-derived nexin
Short name=GDN

Alternative name(s):
Peptidase inhibitor 7
Short name=PI-7
Protease nexin 1
Short name=PN-1
Protease nexin I
Serpin E2

Gene names

Name:	SERPINE2
Synonyms:	PI7, PN1

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	398 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	Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase. Promotes neurite extension by inhibiting thrombin. Binds heparin.
Subcellular location	Secreted › extracellular space.
Sequence similarities	Belongs to the serpin family.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Heparin-binding
Molecular function	Developmental protein Protease inhibitor Serine protease inhibitor
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Inferred from electronic annotation. Source: Compara cerebellar granular layer morphogenesis Inferred from electronic annotation. Source: Compara detection of mechanical stimulus involved in sensory perception Inferred from electronic annotation. Source: Compara innervation Inferred from electronic annotation. Source: Compara long-term synaptic potentiation Inferred from electronic annotation. Source: Compara mating plug formation Inferred from electronic annotation. Source: Compara negative regulation of blood coagulation Inferred from direct assay PubMed 17379830. Source: BHF-UCL negative regulation of cell growth Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of phosphatidylinositol 3-kinase cascade Inferred from electronic annotation. Source: Compara negative regulation of plasminogen activation Inferred from mutant phenotype PubMed 19855083. Source: BHF-UCL negative regulation of platelet activation Inferred from electronic annotation. Source: Compara negative regulation of platelet aggregation Inferred from sequence or structural similarity PubMed 19855083. Source: BHF-UCL negative regulation of protein catabolic process Inferred from electronic annotation. Source: Compara negative regulation of proteolysis Inferred from direct assay PubMed 17379830Ref.8. Source: BHF-UCL negative regulation of smoothened signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of sodium ion transport Inferred from electronic annotation. Source: Compara positive regulation of astrocyte differentiation Inferred from direct assay PubMed 1691280. Source: BHF-UCL regulation of cell migration Non-traceable author statement Ref.2. Source: UniProtKB regulation of synaptic transmission, glutamatergic Inferred from electronic annotation. Source: Compara regulation of timing of cell differentiation Inferred from electronic annotation. Source: Compara secretion by cell Inferred from electronic annotation. Source: Compara secretory granule organization Inferred from electronic annotation. Source: Compara seminal vesicle epithelium development Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay PubMed 19855083. Source: BHF-UCL extracellular matrix Inferred from direct assay PubMed 3279057. Source: BHF-UCL extracellular space Inferred from Biological aspect of Ancestor. Source: RefGenome extrinsic to external side of plasma membrane Inferred from direct assay PubMed 19855083. Source: BHF-UCL neuromuscular junction Inferred from sequence or structural similarity PubMed 2037625. Source: BHF-UCL platelet alpha granule Inferred from mutant phenotype PubMed 19855083. Source: BHF-UCL
Molecular_function	heparin binding Inferred from direct assay PubMed 1939253Ref.8. Source: BHF-UCL serine-type endopeptidase inhibitor activity Inferred from direct assay PubMed 19249338Ref.8. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P07093-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P07093-2)

The sequence of this isoform differs from the canonical sequence as follows:
     329-330: TG → R

Isoform 3 (identifier: P07093-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSDCRSSLVEGTM
     329-330: TG → R

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.8 Ref.9

Chain

20 – 398

379

Glia-derived nexin

PRO_0000032504

Sites

Site

365 – 366

2

Reactive bond Potential

Amino acid modifications

Glycosylation

118

1

N-linked (GlcNAc...) Potential

Glycosylation

159

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1

1

M → MSDCRSSLVEGTM in isoform 3.

VSP_043668

Alternative sequence

329 – 330

2

TG → R in isoform 2 and isoform 3.

VSP_038367

Natural variant

51

1

I → M.
Corresponds to variant rs3795875 [ dbSNP | Ensembl ].

VAR_051955

Natural variant

204

1

K → N in a breast cancer sample; somatic mutation. Ref.10

VAR_036027

Experimental info

Sequence conflict

159

1

N → D in BAG35401. Ref.4

Sequence conflict

261

1

S → E Ref.2

Secondary structure

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398

Helix Strand Turn

Details...

Helix

24 – 45

22

Beta strand

51 – 53

3

Helix

55 – 66

12

Helix

71 – 81

11

Turn

86 – 88

3

Helix

89 – 100

12

Helix

102 – 104

3

Beta strand

109 – 117

9

Helix

124 – 134

11

Beta strand

136 – 140

5

Helix

146 – 160

15

Turn

161 – 163

3

Helix

171 – 173

3

Turn

176 – 178

3

Beta strand

181 – 189

9

Beta strand

193 – 195

3

Helix

199 – 201

3

Beta strand

203 – 208

6

Beta strand

210 – 212

3

Beta strand

214 – 232

19

Beta strand

238 – 246

9

Beta strand

249 – 260

12

Helix

265 – 267

3

Helix

269 – 271

3

Helix

274 – 281

8

Beta strand

285 – 294

10

Beta strand

296 – 303

8

Helix

305 – 310

6

Helix

315 – 317

3

Turn

319 – 321

3

Turn

325 – 327

3

Beta strand

328 – 330

3

Beta strand

338 – 347

10

Beta strand

354 – 356

3

Helix

357 – 360

4

Beta strand

370 – 372

3

Beta strand

377 – 383

7

Turn

384 – 387

4

Beta strand

388 – 396

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 2A165604E2CBE6B8	FASTA	398	44,002
	10 20 30 40 50 60 MNWHLPLFLL ASVTLPSICS HFNPLSLEEL GSNTGIQVFN QIVKSRPHDN IVISPHGIAS 70 80 90 100 110 120 VLGMLQLGAD GRTKKQLAMV MRYGVNGVGK ILKKINKAIV SKKNKDIVTV ANAVFVKNAS 130 140 150 160 170 180 EIEVPFVTRN KDVFQCEVRN VNFEDPASAC DSINAWVKNE TRDMIDNLLS PDLIDGVLTR 190 200 210 220 230 240 LVLVNAVYFK GLWKSRFQPE NTKKRTFVAA DGKSYQVPML AQLSVFRCGS TSAPNDLWYN 250 260 270 280 290 300 FIELPYHGES ISMLIALPTE SSTPLSAIIP HISTKTIDSW MSIMVPKRVQ VILPKFTAVA 310 320 330 340 350 360 QTDLKEPLKV LGITDMFDSS KANFAKITTG SENLHVSHIL QKAKIEVSED GTKASAATTA 370 380 390 ILIARSSPPW FIVDRPFLFF IRHNPTGAVL FMGQINKP
	Isoform 2 [UniParc]. Checksum: 45A9C934A800D7EB	FASTA	397	44,000
	10 20 30 40 50 60 MNWHLPLFLL ASVTLPSICS HFNPLSLEEL GSNTGIQVFN QIVKSRPHDN IVISPHGIAS 70 80 90 100 110 120 VLGMLQLGAD GRTKKQLAMV MRYGVNGVGK ILKKINKAIV SKKNKDIVTV ANAVFVKNAS 130 140 150 160 170 180 EIEVPFVTRN KDVFQCEVRN VNFEDPASAC DSINAWVKNE TRDMIDNLLS PDLIDGVLTR 190 200 210 220 230 240 LVLVNAVYFK GLWKSRFQPE NTKKRTFVAA DGKSYQVPML AQLSVFRCGS TSAPNDLWYN 250 260 270 280 290 300 FIELPYHGES ISMLIALPTE SSTPLSAIIP HISTKTIDSW MSIMVPKRVQ VILPKFTAVA 310 320 330 340 350 360 QTDLKEPLKV LGITDMFDSS KANFAKITRS ENLHVSHILQ KAKIEVSEDG TKASAATTAI 370 380 390 LIARSSPPWF IVDRPFLFFI RHNPTGAVLF MGQINKP
	Isoform 3 [UniParc]. Checksum: 6315691891B53A7B	FASTA	409	45,267
	10 20 30 40 50 60 MSDCRSSLVE GTMNWHLPLF LLASVTLPSI CSHFNPLSLE ELGSNTGIQV FNQIVKSRPH 70 80 90 100 110 120 DNIVISPHGI ASVLGMLQLG ADGRTKKQLA MVMRYGVNGV GKILKKINKA IVSKKNKDIV 130 140 150 160 170 180 TVANAVFVKN ASEIEVPFVT RNKDVFQCEV RNVNFEDPAS ACDSINAWVK NETRDMIDNL 190 200 210 220 230 240 LSPDLIDGVL TRLVLVNAVY FKGLWKSRFQ PENTKKRTFV AADGKSYQVP MLAQLSVFRC 250 260 270 280 290 300 GSTSAPNDLW YNFIELPYHG ESISMLIALP TESSTPLSAI IPHISTKTID SWMSIMVPKR 310 320 330 340 350 360 VQVILPKFTA VAQTDLKEPL KVLGITDMFD SSKANFAKIT RSENLHVSHI LQKAKIEVSE 370 380 390 400 DGTKASAATT AILIARSSPP WFIVDRPFLF FIRHNPTGAV LFMGQINKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA sequence coding for a rat glia-derived nexin and its homology to members of the serpin superfamily." Sommer J., Gloor S.M., Rovelli G.F., Hofsteenge J., Nick H., Meier R., Monard D. Biochemistry 26:6407-6410(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"A glia-derived neurite promoting factor with protease inhibitory activity belongs to the protease nexins." Gloor S.M., Odink K., Guenther J., Nick H., Monard D. Cell 47:687-693(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Molecular cloning and expression of two forms of human protease nexin I." McGrogan M., Kennedy J., Li M.P., Hsu C., Scott R.W., Simonsen C.C., Baker J.B. Biotechnology (N.Y.) 6:172-177(1988) Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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] (ISOFORMS 1 AND 3). Tissue: Hippocampus and Thalamus.
[5]	"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. , 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].
[6]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORMS 1 AND 2). Tissue: Skin and Testis.
[8]	"Protease nexin. Properties and a modified purification procedure." Scott R.W., Bergman B.L., Bajpai A., Hersh R.T., Rodriguez H., Jones B.N., Barreda C., Watts S., Baker J.B. J. Biol. Chem. 260:7029-7034(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-47, CHARACTERIZATION.
[9]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-34.
[10]	"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] ASN-204.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M17783 mRNA. Translation: AAA35883.1.
AK295564 mRNA. Translation: BAG58464.1.
AK312499 mRNA. Translation: BAG35401.1.
AC073641 Genomic DNA. Translation: AAY14926.1.
CH471063 Genomic DNA. Translation: EAW70821.1.
CH471063 Genomic DNA. Translation: EAW70823.1.
BC015663 mRNA. Translation: AAH15663.1.
BC042628 mRNA. Translation: AAH42628.1.

IPI

IPI00009890.
IPI00914848.
IPI00917938.

PIR

A37274.

RefSeq

NP_001130000.1. NM_001136528.1.
NP_001130002.1. NM_001136530.1.
NP_006207.1. NM_006216.3.

UniGene

Hs.38449.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4DY0	X-ray	2.35	A/B	20-398	[»]
4DY7	X-ray	2.80	C/F	20-398	[»]

ProteinModelPortal

P07093.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000415786.

Protein family/group databases

MEROPS

I04.021.

PTM databases

PhosphoSite

P07093.

Polymorphism databases

DMDM

121110.

Proteomic databases

PaxDb

P07093.

PeptideAtlas

P07093.

PRIDE

P07093.

Protocols and materials databases

DNASU

5270.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000258405; ENSP00000258405; ENSG00000135919.
ENST00000409304; ENSP00000386412; ENSG00000135919.
ENST00000409840; ENSP00000386969; ENSG00000135919.
ENST00000447280; ENSP00000415786; ENSG00000135919.

GeneID

5270.

KEGG

hsa:5270.

UCSC

uc002vnu.2. human.
uc002vnv.2. human.

Organism-specific databases

CTD

5270.

GeneCards

GC02M224839.

HGNC

HGNC:8951. SERPINE2.

MIM

177010. gene.

neXtProt

NX_P07093.

PharmGKB

PA269.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4826.

HOGENOM

HOG000238519.

HOVERGEN

HBG106493.

InParanoid

P07093.

KO

K16643.

OMA

IQVFNQI.

OrthoDB

EOG4V4383.

PhylomeDB

P07093.

Gene expression databases

ArrayExpress

P07093.

Bgee

P07093.

CleanEx

HS_SERPINE2.

Genevestigator

P07093.

GermOnline

ENSG00000135919. Homo sapiens.

Family and domain databases

InterPro

IPR023795. Protease_inhib_I4_serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]

PANTHER

PTHR11461. PTHR11461. 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

ChiTaRS

SERPINE2. human.

GenomeRNAi

5270.

NextBio

20360.

PMAP-CutDB

P07093.

SOURCE

Search...

Entry information

Entry name

GDN_HUMAN

Accession

Primary (citable) accession number: P07093
Secondary accession number(s): B2R6A4 , B4DIF2, Q53S15, Q5D0C4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	April 1, 1988
Last modified:	May 1, 2013
This is version 136 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.