UniProt functional annotation for P08473



	UniProt functional annotation for P08473

UniProt code: P08473.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1- 32)) (PubMed:2531377, PubMed:2972276, PubMed:16254193). Displays UV- inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573). {ECO:0000269|PubMed:15283675, ECO:0000269|PubMed:17101991, ECO:0000269|PubMed:20876573, ECO:0000269|PubMed:2531377, ECO:0000269|PubMed:27588448, ECO:0000269|PubMed:2972276}.

Catalytic activity: Reaction=Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.; EC=3.4.24.11; Evidence={ECO:0000269|PubMed:15283675, ECO:0000269|PubMed:27588448, ECO:0000269|PubMed:8168535};

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:14747736, ECO:0000269|PubMed:17704566}; Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:14747736, ECO:0000269|PubMed:17704566};

Activity regulation: Inhibited in a dose dependent manner by opiorphin (PubMed:17101991). Activated by K49-P1-20, a twenty-residue synthetic peptide shortened from the snake B.asper myotoxin II (PubMed:26931059). {ECO:0000269|PubMed:17101991, ECO:0000269|PubMed:26931059}.

Biophysicochemical properties: Kinetic parameters: KM=55.1 uM for angiotensin-1 {ECO:0000269|PubMed:15283675}; KM=179 uM for angiotensin-2 {ECO:0000269|PubMed:15283675}; KM=111.4 uM for angiotensin 1-9 {ECO:0000269|PubMed:15283675};

Subcellular location: Cell membrane; Single-pass type II membrane protein.

Ptm: Myristoylation is a determinant of membrane targeting. {ECO:0000269|PubMed:19756956}.

Ptm: Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity. {ECO:0000269|PubMed:10669592, ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14747736, ECO:0000269|PubMed:17704566, ECO:0000269|PubMed:22766194}.

Disease: Charcot-Marie-Tooth disease 2T (CMT2T) [MIM:617017]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:26991897, ECO:0000269|PubMed:27588448}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Spinocerebellar ataxia 43 (SCA43) [MIM:617018]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA43 is a slowly progressive, autosomal dominant form. {ECO:0000269|PubMed:27583304}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Important cell surface marker in the diagnostic of human acute lymphocytic leukemia.

Similarity: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE- ProRule:PRU01233, ECO:0000305}.

Sequence caution: Sequence=CAA30157.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1- 32)) (PubMed:2531377, PubMed:2972276, PubMed:16254193). Displays UV- inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573). {ECO:0000269\|PubMed:15283675, ECO:0000269\|PubMed:17101991, ECO:0000269\|PubMed:20876573, ECO:0000269\|PubMed:2531377, ECO:0000269\|PubMed:27588448, ECO:0000269\|PubMed:2972276}.


Catalytic activity:		Reaction=Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.; EC=3.4.24.11; Evidence={ECO:0000269\|PubMed:15283675, ECO:0000269\|PubMed:27588448, ECO:0000269\|PubMed:8168535};
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269\|PubMed:14747736, ECO:0000269\|PubMed:17704566}; Note=Binds 1 zinc ion per subunit. {ECO:0000269\|PubMed:14747736, ECO:0000269\|PubMed:17704566};
Activity regulation:		Inhibited in a dose dependent manner by opiorphin (PubMed:17101991). Activated by K49-P1-20, a twenty-residue synthetic peptide shortened from the snake B.asper myotoxin II (PubMed:26931059). {ECO:0000269\|PubMed:17101991, ECO:0000269\|PubMed:26931059}.
Biophysicochemical properties:		Kinetic parameters: KM=55.1 uM for angiotensin-1 {ECO:0000269\|PubMed:15283675}; KM=179 uM for angiotensin-2 {ECO:0000269\|PubMed:15283675}; KM=111.4 uM for angiotensin 1-9 {ECO:0000269\|PubMed:15283675};
Subcellular location:		Cell membrane; Single-pass type II membrane protein.
Ptm:		Myristoylation is a determinant of membrane targeting. {ECO:0000269\|PubMed:19756956}.
Ptm:		Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity. {ECO:0000269\|PubMed:10669592, ECO:0000269\|PubMed:12754519, ECO:0000269\|PubMed:14747736, ECO:0000269\|PubMed:17704566, ECO:0000269\|PubMed:22766194}.
Disease:		Charcot-Marie-Tooth disease 2T (CMT2T) [MIM:617017]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269\|PubMed:26991897, ECO:0000269\|PubMed:27588448}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Spinocerebellar ataxia 43 (SCA43) [MIM:617018]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA43 is a slowly progressive, autosomal dominant form. {ECO:0000269\|PubMed:27583304}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Important cell surface marker in the diagnostic of human acute lymphocytic leukemia.
Similarity:		Belongs to the peptidase M13 family. {ECO:0000255\|PROSITE- ProRule:PRU01233, ECO:0000305}.
Sequence caution:		Sequence=CAA30157.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};