Q99574 (NEUS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuroserpin

Alternative name(s):
Peptidase inhibitor 12
Short name=PI-12
Serpin I1

Gene names

Name:	SERPINI1
Synonyms:	PI12

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	410 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 that inhibits plasminogen activators and plasmin but not thrombin. May be involved in the formation or reorganization of synaptic connections as well as for synaptic plasticity in the adult nervous system. May protect neurons from cell damage by tissue-type plasminogen activator.
Subcellular location	Secreted.
Tissue specificity	Predominantly expressed in the brain.
Involvement in disease	Familial encephalopathy with neuroserpin inclusion bodies (FEN1B) [MIM:604218]: Characterized clinically as an autosomal dominantly inherited dementia, histologically by unique neuronal inclusion bodies and biochemically by polymers of neuroserpin. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the serpin family.

Ontologies

Keywords
Cellular component	Secreted
Disease	Disease mutation
Domain	Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	central nervous system development Traceable author statement Ref.1. Source: ProtInc peripheral nervous system development Traceable author statement Ref.1. Source: ProtInc regulation of cell adhesion Inferred from electronic annotation. Source: Compara regulation of proteolysis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	extracellular region 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 – 16

16

Potential

Chain

17 – 410

394

Neuroserpin

PRO_0000032521

Sites

Site

362 – 363

2

Reactive bond By similarity

Amino acid modifications

Glycosylation

157

1

N-linked (GlcNAc...) Potential

Glycosylation

321

1

N-linked (GlcNAc...) Potential

Glycosylation

401

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

49

1

S → P in FEN1B; Syracuse. Ref.7

VAR_008520

Natural variant

52

1

S → R in FEN1B; Portland. Ref.7

VAR_008521

Experimental info

Sequence conflict

70

1

K → E in AAH18043. Ref.6

Sequence conflict

326

1

S → Y in AAH18043. Ref.6

Secondary structure

1

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410

Helix Strand Turn

Details...

Helix

25 – 40

16

Beta strand

46 – 48

3

Helix

50 – 63

14

Helix

66 – 76

11

Helix

85 – 89

5

Helix

90 – 97

8

Turn

101 – 103

3

Beta strand

104 – 115

12

Helix

122 – 131

10

Beta strand

134 – 139

6

Helix

144 – 158

15

Turn

159 – 161

3

Helix

169 – 172

4

Beta strand

177 – 188

12

Beta strand

190 – 192

3

Helix

196 – 198

3

Beta strand

200 – 205

6

Beta strand

211 – 229

19

Beta strand

238 – 246

9

Beta strand

249 – 257

9

Helix

264 – 266

3

Helix

268 – 270

3

Helix

273 – 282

10

Beta strand

284 – 293

10

Beta strand

295 – 302

8

Helix

303 – 308

6

Turn

309 – 311

3

Helix

314 – 316

3

Turn

323 – 325

3

Beta strand

335 – 344

10

Helix

360 – 366

7

Beta strand

369 – 371

3

Beta strand

376 – 382

7

Turn

383 – 385

3

Beta strand

388 – 395

8

Sequences

	Sequence		Length	Mass (Da)
	Q99574 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: D966E9036BB21943	FASTA	410	46,427
	10 20 30 40 50 60 MAFLGLFSLL VLQSMATGAT FPEEAIADLS VNMYNRLRAT GEDENILFSP LSIALAMGMM 70 80 90 100 110 120 ELGAQGSTQK EIRHSMGYDS LKNGEEFSFL KEFSNMVTAK ESQYVMKIAN SLFVQNGFHV 130 140 150 160 170 180 NEEFLQMMKK YFNAAVNHVD FSQNVAVANY INKWVENNTN NLVKDLVSPR DFDAATYLAL 190 200 210 220 230 240 INAVYFKGNW KSQFRPENTR TFSFTKDDES EVQIPMMYQQ GEFYYGEFSD GSNEAGGIYQ 250 260 270 280 290 300 VLEIPYEGDE ISMMLVLSRQ EVPLATLEPL VKAQLVEEWA NSVKKQKVEV YLPRFTVEQE 310 320 330 340 350 360 IDLKDVLKAL GITEIFIKDA NLTGLSDNKE IFLSKAIHKS FLEVNEEGSE AAAVSGMIAI 370 380 390 400 410 SRMAVLYPQV IVDHPFFFLI RNRRTGTILF MGRVMHPETM NTSGHDFEEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human neuroserpin (PI12): cDNA cloning and chromosomal localization to 3q26." Schrimpf S.P., Bleiker A.J., Brecevic L., Kozlov S.V., Berger P., Osterwalder T., Krueger S.R., Schinzel A., Sonderegger P. Genomics 40:55-62(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[2]	"Genomic organization of the human neuroserpin (PI12) gene." Kinter J., Berger P., Kozlov S.V., Sonderegger P. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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]. Tissue: Subthalamic nucleus.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain cortex.
[5]	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].
[6]	"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: Brain.
[7]	"Familial dementia caused by polymerization of mutant neuroserpin." Davis R.L., Shrimpton A.E., Holohan P.D., Bradshaw C., Feiglin D., Collins G.H., Sonderegger P., Kinter J., Becker L.M., Lacbawan F., Krasnewich D., Muenke M., Lawrence D.A., Yerby M.S., Shaw C.M., Gooptu B., Elliott P.R., Finch J.T., Carrell R.W., Lomas D.A. Nature 401:376-379(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FEN1B PRO-49 AND ARG-52.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z81326 mRNA. Translation: CAB03626.1.
AF248246, AF248244, AF248245 Genomic DNA. Translation: AAG01089.1.
AK290082 mRNA. Translation: BAF82771.1.
CR627434 mRNA. Translation: CAH10520.1.
CH471052 Genomic DNA. Translation: EAW78571.1.
CH471052 Genomic DNA. Translation: EAW78572.1.
CH471052 Genomic DNA. Translation: EAW78573.1.
BC018043 mRNA. Translation: AAH18043.1.

IPI

IPI00016150.

RefSeq

NP_001116224.1. NM_001122752.1.
NP_005016.1. NM_005025.4.

UniGene

Hs.478153.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3F02	X-ray	1.80	A/B	17-362	[»]
			C/D	363-410	[»]
3F5N	X-ray	3.15	A/B/C/D/E	17-410	[»]
3FGQ	X-ray	2.09	A/B	17-400	[»]

ProteinModelPortal

Q99574.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99574. 1 interaction.

STRING

9606.ENSP00000295777.

Protein family/group databases

MEROPS

I04.025.

PTM databases

PhosphoSite

Q99574.

Polymorphism databases

DMDM

3183087.

Proteomic databases

PaxDb

Q99574.

PRIDE

Q99574.

Protocols and materials databases

DNASU

5274.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000295777; ENSP00000295777; ENSG00000163536.
ENST00000446050; ENSP00000397373; ENSG00000163536.

GeneID

5274.

KEGG

hsa:5274.

UCSC

uc003ffa.4. human.

Organism-specific databases

CTD

5274.

GeneCards

GC03P167453.

HGNC

HGNC:8943. SERPINI1.

HPA

CAB026059.
HPA001565.

MIM

602445. gene.
604218. phenotype.

neXtProt

NX_Q99574.

Orphanet

85110. Familial encephalopathy with neuroserpin inclusion bodies.

PharmGKB

PA35511.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4826.

HOGENOM

HOG000238519.

HOVERGEN

HBG005957.

InParanoid

Q99574.

OMA

EFSNMVT.

PhylomeDB

Q99574.

Gene expression databases

ArrayExpress

Q99574.

Bgee

Q99574.

CleanEx

HS_SERPINI1.

Genevestigator

Q99574.

GermOnline

ENSG00000163536. 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

EvolutionaryTrace

Q99574.

GenomeRNAi

5274.

NextBio

20380.

PMAP-CutDB

Q99574.

SOURCE

Search...

Entry information

Entry name

NEUS_HUMAN

Accession

Primary (citable) accession number: Q99574
Secondary accession number(s): A8K217, D3DNP1, Q6AHZ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 116 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.