P91953 (HE_HEMPU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: 50 kDa hatching enzyme Short name=HE Short name=HEZ EC=3.4.24.12 Alternative name(s): Envelysin Sea-urchin-hatching proteinase Cleaved into the following 3 chains: 38 kDa hatching enzyme 32 kDa hatching enzyme non-specific 15 kDa peptide
Organism	Hemicentrotus pulcherrimus (Sea urchin) (Strongylocentrotus pulcherrimus)
Taxonomic identifier	7650 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Echinodermata › Eleutherozoa › Echinozoa › Echinoidea › Euechinoidea › Echinacea › Echinoida › Strongylocentrotidae › Hemicentrotus

Protein attributes

Sequence length	591 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	Allows the sea urchin to digest the protective envelope derived from the egg extracellular matrix; thus allowing the sea urchin to swim freely.
Catalytic activity	Hydrolysis of proteins of the fertilization envelope and dimethylcasein.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	During hatching, the 50 kDa mature enzyme is autocatalytically cleaved to produce a major 38 kDa and a minor 15 kDa form which may be disulfide linked. Subsequent cleavage of the 38 kDa species yields a 32 kDa non-specific protease.
Developmental stage	Embryo, blastula stage. Highest activity at 12.5 hours embryo stage.
Domain	There are two distinct domains in this protein; the catalytic N-terminal, and the C-terminal which is involved in substrate specificity. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Sequence similarities	Belongs to the peptidase M10A family. Contains 4 hemopexin-like domains.

Ontologies

Keywords
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Autocatalytic cleavage Disulfide bond Glycoprotein Zymogen
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular matrix Inferred from electronic annotation. Source: InterPro
Molecular_function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Probable
	Propeptide	19 – 169	151	Activation peptide By similarity		PRO_0000028859
	Chain	170 – 591	422	50 kDa hatching enzyme		PRO_0000028860
	Chain	170 – 503	334	38 kDa hatching enzyme		PRO_0000028861
	Chain	170 – 450	281	32 kDa hatching enzyme non-specific		PRO_0000028862
	Chain	504 – 591	88	15 kDa peptide		PRO_0000028863
Regions
	Domain	387 – 429	43	Hemopexin-like 1
	Domain	431 – 473	43	Hemopexin-like 2
	Domain	475 – 519	45	Hemopexin-like 3
	Domain	525 – 569	45	Hemopexin-like 4
	Motif	160 – 167	8	Cysteine switch By similarity
	Compositional bias	62 – 76	15	Asp/Glu-rich (acidic)
	Compositional bias	336 – 380	45	Arg/Thr-rich (hinge region)
	Compositional bias	448 – 451	4	Poly-Tyr
Sites
	Active site	287	1	By similarity
	Metal binding	162	1	Zinc; in inhibited form By similarity
	Metal binding	286	1	Zinc; catalytic By similarity
	Metal binding	290	1	Zinc; catalytic By similarity
	Metal binding	296	1	Zinc; catalytic By similarity
	Site	450 – 451	2	Cleavage; by autolysis
	Site	503 – 504	2	Cleavage; by autolysis
Amino acid modifications
	Glycosylation	129	1	N-linked (GlcNAc...) Potential
	Glycosylation	144	1	N-linked (GlcNAc...) Potential
	Glycosylation	578	1	N-linked (GlcNAc...) Potential
	Glycosylation	588	1	N-linked (GlcNAc...) Potential
	Disulfide bond	383 ↔ 586		By similarity
Experimental info
	Sequence conflict	195	1	S → N AA sequence Ref.1
	Sequence conflict	197	1	T → N AA sequence Ref.1
	Sequence conflict	203	1	L → I AA sequence Ref.1
	Sequence conflict	215 – 216	2	SL → GN AA sequence Ref.1
	Sequence conflict	220	1	E → N AA sequence Ref.1
	Sequence conflict	509	1	P → R AA sequence Ref.1
	Sequence conflict	511 – 512	2	SS → RR AA sequence Ref.1
	Sequence conflict	518	1	P → L AA sequence Ref.1
	Sequence conflict	522	1	R → I AA sequence Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P91953 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 5DCB448C6758C70D	FASTA	591	66,126
	10 20 30 40 50 60 MANFCLIFAA VFLTRLTTVL NTPISVTFGP TQLTDITKLV SETGDDFGLT TPRSAILTTV 70 80 90 100 110 120 SEDDSDDDDG GESVEDTTIL QTTTSSEIVI SGIVVDEDID ESKVVKLKAN LEQFGYVPLG 130 140 150 160 170 180 STFGEANINY TSAILEYQQN GGINQTGILD AETAALLDTP RCGVPDILPY VTGGIAWPRN 190 200 210 220 230 240 VAVTYSFGTL SNDLSQTAIK NELRRAFQVW DDVSSLTFRE VVDSSSVDIR IKFGSYEHGD 250 260 270 280 290 300 GISFDGQGGV LAHAFLPRNG DAHFDDSERW TIGTNSGTNL FQVAAHEFGH SLGLYHSDVQ 310 320 330 340 350 360 SALMYPYYRG YNPNFNLDRD DIAGITSLYG RNTGSTTTTT RRPTITRTTT RRTTTRRTTT 370 380 390 400 410 420 QLATTQTTTI RPPTYPTPPR QACTGSFDAV IKDNSDRIYA LAGRYYWRLD QASPSWGVVR 430 440 450 460 470 480 NRFGFDLPEN VDASFQNGIF SYFFSGCYYY YQTSTRRRFP RTPFNRRWVG LPCDIDAVYK 490 500 510 520 530 540 SGDSGTTYFF KGRFVYKFSS SNQLQRRSPI SSYFRNTPYA LRDGVEAVVR VDDVYLHFYR 550 560 570 580 590 DGRYYRMIES TKQFVNFPNG LSYRDVIDTL IPQCRSLNLS VEIESCSNSS E

References

[1]	"Sea urchin hatching enzyme (envelysin): cDNA cloning and deprivation of protein substrate specificity by autolytic degradation." Nomura K., Shimizu T., Kinoh H., Sendai Y., Inomata M., Suzuki N. Biochemistry 36:7225-7238(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 170-220 AND 504-528. Tissue: Blastula.
[2]	"The specificity of sea urchin hatching enzyme (envelysin) places it in the mammalian matrix metalloproteinase family." Nomura K., Tanaka H., Kikkawa Y., Yamaguchi M., Suzuki N. Biochemistry 30:6115-6123(1991) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE SPECIFICITY.
[3]	"Stereo-specific inhibition of sea urchin envelysin (hatching enzyme) by a synthetic autoinhibitor peptide with a cysteine-switch consensus sequence." Nomura K., Suzuki N. FEBS Lett. 321:84-88(1993) [PubMed] [Europe PMC] [Abstract] Cited for: STEREOSPECIFICITY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB000719 mRNA. Translation: BAA19171.1.
3D structure databases
ProteinModelPortal	P91953.
ModBase	Search...
Protein family/group databases
MEROPS	M10.010.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	2.110.10.10. 1 hit. 3.40.390.10. 1 hit.
InterPro	IPR000585. Hemopexin-like_dom. IPR018487. Hemopexin-like_repeat. IPR018486. Hemopexin_CS. IPR024079. MetalloPept_cat_dom. IPR001818. Pept_M10_metallopeptidase. IPR021190. Pept_M10A. IPR021158. Pept_M10A_Zn_BS. IPR006026. Peptidase_Metallo. IPR002477. Peptidoglycan-bd-like. [Graphical view]
Pfam	PF00045. Hemopexin. 2 hits. PF00413. Peptidase_M10. 1 hit. PF01471. PG_binding_1. 1 hit. [Graphical view]
PRINTS	PR00138. MATRIXIN.
SMART	SM00120. HX. 4 hits. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF50923. Hemopexin. 1 hit. SSF47090. PGBD_like. 1 hit.
PROSITE	PS00546. CYSTEINE_SWITCH. 1 hit. PS00024. HEMOPEXIN. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
PMAP-CutDB	P91953.

Entry information

Entry name

HE_HEMPU

Accession

Primary (citable) accession number: P91953

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)