Neuroserpin Human E. coli

Cat. No.	Size	Price 1 - 4 pcs / 5 - 9 pcs / 10+ pcs
RD172326100	0.1 mg	$300 / $266 / On request

Technical Data

Type

Recombinant protein

Description

Total 404 AA. MW: 45.9 kDa (calculated). UniProtKB acc.no. Q99574 (Thr17-Leu410). N-Terminal His-tag (10 extra AA). Protein identity confirmed by MS.

Amino Acid Sequence

MKHHHHHHASTGATFPEEAIADLSVNMYNRLRATGEDENILFSPLSIALAMGMMELGAQGSTQKEIRHSMGYDSLKNGEEFSFLKEFSNMVTAKESQYVMKIANSLFVQNGFHVNEEFLQMMKKYFNAAVNHVDFSQNVAVANYINKWVENNTNNLVKDLVSPRDFDAATYLALINAVYFKGNWKSQFRPENTRTFSFTKDDESEVQIPMMYQQGEFYYGEFSDGSNEAGGIYQVLEIPYEGDEISMMLVLSRQEVPLATLEPLVKAQLVEEWANSVKKQKVEVYLPRFTVEQEIDLKDVLKALGITEIFIKDANLTGLSDNKEIFLSKAIHKSFLEVNEEGSEAAAVSGMIAISRMAVLYPQVIVDHPFFFLIRNRRTGTILFMGRVMHPETMNTSGHDFEEL

Source

E. coli

Purity

˃ 90 % by SDS-PAGE

SDS-PAGE Gel

12% SDS-PAGE separation of Human Neuroserpin:
1. MW marker – 97, 66, 45, 31, 21, 14 kDa
2. non reduced and non boiled sample, 2.5 μg / lane
3. reduced and boiled sample, 2.5 μg / lane

Endotoxin

< 1.0 EU/µg

Formulation

Filtered (0.4 μm) and lyophilized in 0.5 mg/mL in 0.025M phosphate buffer, 0.035M NaCl, pH 7.4

Reconstitution

Add 200ul of deionized water to prepare a working stock solution of 0.5 mg/mL and let the lyophilized pellet dissolve completely.

Applications

Western blotting, ELISA

Shipping

At ambient temperature. Upon receipt, store the product at the temperature recommended below.

Storage/Expiration

Store protein at -80°C. Protein remains stable until the expiry date when stored at -80°C. Avoid repeated freezing/thawing cycles. Defrosted protein can be stored at 4°C for a week.

Quality Control Test

BCA to determine quantity of the protein.
SDS PAGE to determine purity of the protein. Endotoxin level determination.

Note

This product is intended for research use only.

Summary

Research topic

Neural tissue markers, Oncology

Summary

Neuroserpin (NSP; alternative names: serpin I1, peptidase inhibitor 12, PI-12) is a secreted glycoprotein which consists of 410 amino acid residues (46.4 kDa – if taken without glycosylation) including 16 amino acids of potential signal peptide. Neuroserpin-coding gene (PI12) consists of 9 exons and 8 introns and has a strongly conserved gene organization. Neuroserpin is a serine protease inhibitor of the serpin family that has been identified as an axonally secreted glycoprotein in neuronal cultures of chicken dorsal root ganglia. Neuroserpin-coding gene was later identified also in human; it was cloned, expressed and characterised. Human neuroserpin exhibits high amino acid identity with some other neuroserpins from mammals, e.g. 88%, 86% and 80% identity with neuroserpin of rat, mouse and chicken, respectively. Two secreted forms were observed with molecular weights of 49 and 50 kDa which may represent alternative glycosylation at three putative N-linked glycosylation sites. PI12 transcript (neuroserpin mRNA) was observed mainly in the brain, where the gene is ubiquitously expressed. Expression of neuroserpin was also detected in the spinal cord and, with much weaker signals, in some other tissues such as pancreas, heart, kidney, testis and placenta. NSP mRNA was detected extensively in normal brain tissue, but not in brain tumors. Neuroserpin has been suggested to be a critical regulator of tissue-type plasminogen activator (tPA) activity in the central nervous system, and as such may play an important role in neuronal plasticity and/or maintenance. Expression of tPA in some brain regions (choroid plexus, Purkyně cells of the cerebellum, discrete neuron areas of the hypothalamus and hippocampus, and in the myelinated axons of the commissura) is reported to be high and has previously been correlated with both motor learning and neuronal survival. Tissue plasminogen activator (tPA) is commonly used as a thrombolytic agent to remove fibrin blood clots but it has also been directly implicated in neurovascular breakdown in ischemic stroke. It was suggested that neuroprotective properties of neuroserpin, the inhibitor of tPA, may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke. Some point mutations in the neuroserpin gene cause familial encephalopathy with neuroserpin inclusion bodies (FENIB). FENIB is characterized by intraneuronal accumulation of neuroserpin polymers and consequent dementia with different age of onset, ranging from before age of 20 years to old age. To date, six autosomal dominantly inherited mutations have been described. It has been shown that neuroserpin is a plaque-associated protein in brains of patients with Alzheimer disease and that it forms a specific binary complex with Aß1–42 peptide which is also characteristic for Alzheimer disease (AD). The neuroprotective nature of this interaction has been indicated in cell culture and on Drosophila models of disease. Higher CSF levels of neuroserpin together with α1-antichymotrypsin have been shown to be associated with the clinical diagnosis of Alzheimer disease vs healthy controls. The neuroserpin gene was reported among genes which are overexpressed at some types of cancer – e.g. hepatocellular cancer and prostatic cancer.

Summary References (17)

References to Neuroserpin

Belorgey D, Hagglof P, Karlsson-Li S, Lomas DA. Protein misfolding and the serpinopathies. Prion. 2007 Jan-Mar;1 (1):15-20
Chang WS, Chang NT, Lin SC, Wu CW, Wu FY. Tissue-specific cancer-related serpin gene cluster at human chromosome band 3q26. Genes Chromosomes Cancer. 2000 Nov;29 (3):240-55
Davis RL, Shrimpton AE, Carrell RW, Lomas DA, Gerhard L, Baumann B, Lawrence DA, Yepes M, Kim TS, Ghetti B, Piccardo P, Takao M, Lacbawan F, Muenke M, Sifers RN, Bradshaw CB, Kent PF, Collins GH, Larocca D, Holohan PD. Association between conformational mutations in neuroserpin and onset and severity of dementia. Lancet. 2002 Jun 29;359 (9325):2242-7
Hastings GA, Coleman TA, Haudenschild CC, Stefansson S, Smith EP, Barthlow R, Cherry S, Sandkvist M, Lawrence DA. Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival. J Biol Chem. 1997 Dec 26;272 (52):33062-7
Hasumi H, Ishiguro H, Nakamura M, Sugiura S, Osada Y, Miyoshi Y, Fujinami K, Yao M, Hamada K, Yamada-Okabe H, Kubota Y, Uemura H. Neuroserpin (PI-12) is upregulated in high-grade prostate cancer and is associated with survival. Int J Cancer. 2005 Jul 20;115 (6):911-6
Hill RM, Brennan SO, Birch NP. Expression, purification, and functional characterization of the serine protease inhibitor neuroserpin expressed in Drosophila S2 cells. Protein Expr Purif. 2001 Aug;22 (3):406-13
Hill RM, Parmar PK, Coates LC, Mezey E, Pearson JF, Birch NP. Neuroserpin is expressed in the pituitary and adrenal glands and induces the extension of neurite-like processes in AtT-20 cells. Biochem J. 2000 Feb 1;345 Pt 3:595-601
Jia HL, Ye QH, Qin LX, Budhu A, Forgues M, Chen Y, Liu YK, Sun HC, Wang L, Lu HZ, Shen F, Tang ZY, Wang XW. Gene expression profiling reveals potential biomarkers of human hepatocellular carcinoma. Clin Cancer Res. 2007 Feb 15;13 (4):1133-9
Kinghorn KJ, Crowther DC, Sharp LK, Nerelius C, Davis RL, Chang HT, Green C, Gubb DC, Johansson J, Lomas DA. Neuroserpin binds Abeta and is a neuroprotective component of amyloid plaques in Alzheimer disease. J Biol Chem. 2006 Sep 29;281 (39):29268-77
Krueger SR, Ghisu GP, Cinelli P, Gschwend TP, Osterwalder T, Wolfer DP, Sonderegger P. Expression of neuroserpin, an inhibitor of tissue plasminogen activator, in the developing and adult nervous system of the mouse. J Neurosci. 1997 Dec 1;17 (23):8984-96
Nielsen HM, Minthon L, Londos E, Blennow K, Miranda E, Perez J, Crowther DC, Lomas DA, Janciauskiene SM. Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies. Neurology. 2007 Oct 16;69 (16):1569-79
Osterwalder T, Contartese J, Stoeckli ET, Kuhn TB, Sonderegger P. Neuroserpin, an axonally secreted serine protease inhibitor. EMBO J. 1996 Jun 17;15 (12):2944-53
Ozaki K, Nagata M, Suzuki M, Fujiwara T, Miyoshi Y, Ishikawa O, Ohigashi H, Imaoka S, Takahashi E, Nakamura Y. Isolation and characterization of a novel human pancreas-specific gene, pancpin, that is down-regulated in pancreatic cancer cells. Genes Chromosomes Cancer. 1998 Jul;22 (3):179-85
Robinson T, Zaheer Z, Mistri AK. Thrombolysis in acute ischaemic stroke: an update. Ther Adv Chronic Dis. 2011 Mar;2 (2):119-31
Rodriguez-Gonzalez R, Sobrino T, Rodriguez-Yanez M, Millan M, Brea D, Miranda E, Moldes O, Perez J, Lomas DA, Leira R, Davalos A, Castillo J. Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke. J Transl Med. 2011;9:58
Schipanski A, Lange S, Segref A, Gutschmidt A, Lomas DA, Miranda E, Schweizer M, Hoppe T, Glatzel M. A novel interaction between aging and ER overload in a protein conformational dementia. Genetics. 2013 Mar;193 (3):865-76
Schrimpf SP, Bleiker AJ, Brecevic L, Kozlov SV, Berger P, Osterwalder T, Krueger SR, Schinzel A, Sonderegger P. Human neuroserpin (PI12): cDNA cloning and chromosomal localization to 3q26. Genomics. 1997

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