P56730 (NETR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neurotrypsin
EC=3.4.21.-

Alternative name(s):
Leydin
Motopsin
Serine protease 12

Gene names

Name:

PRSS12

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	875 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Plays a role in neuronal plasticity and the proteolytic action may subserve structural reorganizations associated with learning and memory operations By similarity.
Subcellular location	Secreted.
Tissue specificity	Brain and Leydig cells of the testis.
Involvement in disease	Mental retardation, autosomal recessive 1 (MRT1) [MIM:249500]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Belongs to the peptidase S1 family. Contains 1 kringle domain. Contains 1 peptidase S1 domain. Contains 4 SRCR domains.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Mental retardation
Domain	Kringle Repeat Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	exocytosis Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW zymogen activation Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from sequence or structural similarity. Source: UniProtKB cytoplasmic vesicle Inferred from electronic annotation. Source: Compara dendrite Inferred from electronic annotation. Source: Compara extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB synaptic cleft Inferred from electronic annotation. Source: Compara terminal bouton Inferred from electronic annotation. Source: Compara
Molecular_function	scavenger receptor activity Inferred from electronic annotation. Source: InterPro serine-type endopeptidase activity Inferred from electronic annotation. Source: Compara serine-type peptidase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 875	855	Neurotrypsin		PRO_0000027663
Regions
	Domain	93 – 165	73	Kringle
	Domain	170 – 271	102	SRCR 1
	Domain	280 – 381	102	SRCR 2
	Domain	387 – 487	101	SRCR 3
	Domain	500 – 601	102	SRCR 4
	Domain	631 – 874	244	Peptidase S1
	Region	619 – 630	12	Zymogen activation region
	Compositional bias	23 – 92	70	Pro-rich
Sites
	Active site	676	1	Charge relay system By similarity
	Active site	726	1	Charge relay system By similarity
	Active site	825	1	Charge relay system By similarity
	Site	630 – 631	2	Reactive bond homolog Potential
Amino acid modifications
	Glycosylation	26	1	N-linked (GlcNAc...) Potential
	Glycosylation	683	1	N-linked (GlcNAc...) Potential
	Disulfide bond	93 ↔ 165		By similarity
	Disulfide bond	109 ↔ 149		By similarity
	Disulfide bond	138 ↔ 163		By similarity
	Disulfide bond	195 ↔ 259		By similarity
	Disulfide bond	208 ↔ 269		By similarity
	Disulfide bond	239 ↔ 249		By similarity
	Disulfide bond	305 ↔ 369		By similarity
	Disulfide bond	318 ↔ 379		By similarity
	Disulfide bond	349 ↔ 359		By similarity
	Disulfide bond	412 ↔ 475		By similarity
	Disulfide bond	425 ↔ 485		By similarity
	Disulfide bond	455 ↔ 465		By similarity
	Disulfide bond	525 ↔ 589		By similarity
	Disulfide bond	538 ↔ 599		By similarity
	Disulfide bond	569 ↔ 579		By similarity
	Disulfide bond	619 ↔ 750		Potential
	Disulfide bond	661 ↔ 677		By similarity
	Disulfide bond	765 ↔ 831		By similarity
	Disulfide bond	794 ↔ 808		By similarity
	Disulfide bond	821 ↔ 850		By similarity
Natural variations
	Natural variant	606	1	A → S. Corresponds to variant rs28661939 [ dbSNP | Ensembl ].		VAR_051835
	Natural variant	833	1	R → Q. Corresponds to variant rs17594503 [ dbSNP | Ensembl ].		VAR_051836
Experimental info
	Sequence conflict	55	1	R → T in CAA04816. Ref.1
	Sequence conflict	663	1	A → V in AAD25919. Ref.3
	Sequence conflict	701	1	E → V in AAD25919. Ref.3
	Sequence conflict	839 – 841	3	VVY → AAL in AAD25919. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P56730 [UniParc]. Last modified September 22, 2009. Version 2. Checksum: EB357047C39371BC	FASTA	875	97,067
	10 20 30 40 50 60 MTLARFVLAL MLGALPEVVG FDSVLNDSLH HSHRHSPPAG PHYPYYLPTQ QRPPRTRPPP 70 80 90 100 110 120 PLPRFPRPPR ALPAQRPHAL QAGHTPRPHP WGCPAGEPWV SVTDFGAPCL RWAEVPPFLE 130 140 150 160 170 180 RSPPASWAQL RGQRHNFCRS PDGAGRPWCF YGDARGKVDW GYCDCRHGSV RLRGGKNEFE 190 200 210 220 230 240 GTVEVYASGV WGTVCSSHWD DSDASVICHQ LQLGGKGIAK QTPFSGLGLI PIYWSNVRCR 250 260 270 280 290 300 GDEENILLCE KDIWQGGVCP QKMAAAVTCS FSHGPTFPII RLAGGSSVHE GRVELYHAGQ 310 320 330 340 350 360 WGTVCDDQWD DADAEVICRQ LGLSGIAKAW HQAYFGEGSG PVMLDEVRCT GNELSIEQCP 370 380 390 400 410 420 KSSWGEHNCG HKEDAGVSCT PLTDGVIRLA GGKGSHEGRL EVYYRGQWGT VCDDGWTELN 430 440 450 460 470 480 TYVVCRQLGF KYGKQASANH FEESTGPIWL DDVSCSGKET RFLQCSRRQW GRHDCSHRED 490 500 510 520 530 540 VSIACYPGGE GHRLSLGFPV RLMDGENKKE GRVEVFINGQ WGTICDDGWT DKDAAVICRQ 550 560 570 580 590 600 LGYKGPARAR TMAYFGEGKG PIHVDNVKCT GNERSLADCI KQDIGRHNCR HSEDAGVICD 610 620 630 640 650 660 YFGKKASGNS NKESLSSVCG LRLLHRRQKR IIGGKNSLRG GWPWQVSLRL KSSHGDGRLL 670 680 690 700 710 720 CGATLLSSCW VLTAAHCFKR YGNSTRSYAV RVGDYHTLVP EEFEEEIGVQ QIVIHREYRP 730 740 750 760 770 780 DRSDYDIALV RLQGPEEQCA RFSSHVLPAC LPLWRERPQK TASNCYITGW GDTGRAYSRT 790 800 810 820 830 840 LQQAAIPLLP KRFCEERYKG RFTGRMLCAG NLHEHKRVDS CQGDSGGPLM CERPGESWVV 850 860 870 YGVTSWGYGC GVKDSPGVYT KVSAFVPWIK SVTKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of the cDNA encoding human neurotrypsin." Proba K., Gschwend T.P., Sonderegger P. Biochim. Biophys. Acta 1396:143-147(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"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].
[3]	"Cloning and structural analysis of leydin, a novel human serine protease expressed by the Leydig cells of the testis." Poorafshar M., Hellman L. Eur. J. Biochem. 261:244-250(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 615-875. Tissue: Testis.
[4]	"Truncating neurotrypsin mutation in autosomal recessive nonsyndromic mental retardation." Molinari F., Rio M., Meskenaite V., Encha-Razavi F., Auge J., Bacq D., Briault S., Vekemans M., Munnich A., Attie-Bitach T., Sonderegger P., Colleaux L. Science 298:1779-1781(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DISEASE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ001531 mRNA. Translation: CAA04816.1. AC096762 Genomic DNA. No translation available. AF077298 mRNA. Translation: AAD25919.1.
IPI	IPI00011063.
RefSeq	NP_003610.2. NM_003619.3.
UniGene	Hs.445857.
3D structure databases
ProteinModelPortal	P56730.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000296498.
Protein family/group databases
MEROPS	S01.237.
PTM databases
PhosphoSite	P56730.
Polymorphism databases
DMDM	259016287.
Proteomic databases
PaxDb	P56730.
PRIDE	P56730.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296498; ENSP00000296498; ENSG00000164099.
GeneID	8492.
KEGG	hsa:8492.
UCSC	uc003ica.2. human.
Organism-specific databases
CTD	8492.
GeneCards	GC04M119201.
HGNC	HGNC:9477. PRSS12.
HPA	HPA035054.
MIM	249500. phenotype. 606709. gene.
neXtProt	NX_P56730.
Orphanet	88616. Autosomal recessive nonsyndromic intellectual deficit.
PharmGKB	PA33830.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5640.
HOGENOM	HOG000113767.
HOVERGEN	HBG006465.
InParanoid	P56730.
KO	K09624.
OMA	DWGYCDC.
OrthoDB	EOG46WZ7R.
PhylomeDB	P56730.
Gene expression databases
Bgee	P56730.
CleanEx	HS_PRSS12.
Genevestigator	P56730.
GermOnline	ENSG00000164099. Homo sapiens.
Family and domain databases
Gene3D	2.40.20.10. 1 hit.
InterPro	IPR000001. Kringle. IPR013806. Kringle-like. IPR018056. Kringle_CS. IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR001190. Srcr_rcpt. IPR017448. Srcr_rcpt-rel. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00051. Kringle. 1 hit. PF00530. SRCR. 4 hits. PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN. PR00258. SPERACTRCPTR.
SMART	SM00130. KR. 1 hit. SM00202. SR. 4 hits. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF57440. Kringle-like. 1 hit. SSF50494. Pept_Ser_Cys. 1 hit. SSF56487. Srcr_receptor. 4 hits.
PROSITE	PS00021. KRINGLE_1. 1 hit. PS50070. KRINGLE_2. 1 hit. PS00420. SRCR_1. 3 hits. PS50287. SRCR_2. 4 hits. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8492.
NextBio	31771.
SOURCE	Search...

Entry information

Entry name

NETR_HUMAN

Accession

Primary (citable) accession number: P56730
Secondary accession number(s): Q9UP16

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	September 22, 2009
Last modified:	May 1, 2013
This is version 119 of the entry and version 2 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.