Q16819 (MEP1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Meprin A subunit alpha
EC=3.4.24.18

Alternative name(s):
Endopeptidase-2
N-benzoyl-L-tyrosyl-P-amino-benzoic acid hydrolase subunit alpha
PABA peptide hydrolase
PPH alpha

Gene names

Name:

MEP1A

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	746 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)

Catalytic activity	Hydrolysis of protein and peptide substrates preferentially on carboxyl side of hydrophobic residues.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Inhibited by several hydroxamate compounds, the most potent inhibitor is actinonin. Ref.8
Subunit structure	Homotetramer consisting of disulfide-linked alpha subunits, homooligomer consisting of disulfide-linked alpha subunit homodimers, or heterotetramer of two alpha and two beta subunits formed by non-covalent association of two disulfide-linked heterodimers By similarity. Interacts with MBL2 through its carbohydrate moiety. This interaction may inhibit its catalytic activity By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	N-glycosylated; contains GlcNAc, galactose, mannose and a small amount of fucose By similarity.
Sequence similarities	Belongs to the peptidase M12A family. Contains 1 EGF-like domain. Contains 1 MAM domain. Contains 1 MATH domain.
Biophysicochemical properties	Kinetic parameters: KM=110 µM for GRP Ref.8 KM=18.0 µM for PTH 12-34 KM=33.9 µM for secretin KM=41.3 µM for substance P KM=56.5 µM for LHRH KM=73.2 µM for orcokinin KM=292 µM for alpha-MSH KM=125 µM for bradykinin KM=200 µM for gastrin

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	digestion Traceable author statement PubMed 9288916. Source: ProtInc proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Traceable author statement Ref.7. Source: ProtInc integral to plasma membrane Traceable author statement Ref.7. Source: ProtInc meprin A complex Inferred from electronic annotation. Source: Compara
Molecular_function	metalloendopeptidase activity Traceable author statement PubMed 9288916. Source: ProtInc 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 – 21	21	By similarity
	Propeptide	22 – 65	44	By similarity		PRO_0000028877
	Chain	66 – 746	681	Meprin A subunit alpha		PRO_0000028878
Regions
	Topological domain	66 – 712	647	Extracellular Potential
	Transmembrane	713 – 740	28	Helical; Potential
	Topological domain	741 – 746	6	Cytoplasmic Potential
	Domain	264 – 433	170	MAM
	Domain	434 – 593	160	MATH
	Domain	670 – 710	41	EGF-like
	Region	66 – 263	198	Metalloprotease
Sites
	Active site	156	1	By similarity
	Metal binding	155	1	Zinc; catalytic By similarity
	Metal binding	159	1	Zinc; catalytic By similarity
	Metal binding	165	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	140	1	N-linked (GlcNAc...) Potential
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
	Glycosylation	258	1	N-linked (GlcNAc...) Potential
	Glycosylation	414	1	N-linked (GlcNAc...) Potential
	Glycosylation	440	1	N-linked (GlcNAc...) Potential
	Glycosylation	447	1	N-linked (GlcNAc...) Potential
	Glycosylation	539	1	N-linked (GlcNAc...) Potential
	Disulfide bond	107 ↔ 259		By similarity
	Disulfide bond	128 ↔ 147		By similarity
	Disulfide bond	269 ↔ 431		By similarity
	Disulfide bond	277		Interchain By similarity
	Disulfide bond	308		Interchain By similarity
	Disulfide bond	674 ↔ 685		By similarity
	Disulfide bond	679 ↔ 694		By similarity
	Disulfide bond	696 ↔ 709		By similarity
Natural variations
	Natural variant	469	1	V → L. Ref.3 Ref.6 Corresponds to variant rs2274658 [ dbSNP | Ensembl ].		VAR_020056
	Natural variant	476	1	R → G. Ref.6 Corresponds to variant rs12197930 [ dbSNP | Ensembl ].		VAR_033492
	Natural variant	606	1	T → S. Ref.1 Ref.7 Corresponds to variant rs2297020 [ dbSNP | Ensembl ].		VAR_051583
	Natural variant	634	1	M → V. Corresponds to variant rs2297019 [ dbSNP | Ensembl ].		VAR_021846
	Natural variant	726	1	T → M. Ref.3 Corresponds to variant rs1804211 [ dbSNP | Ensembl ].		VAR_033493
Experimental info
	Sequence conflict	26	1	Y → H in AAA21338. Ref.1
	Sequence conflict	162	1	G → V in AAL85339. Ref.2
	Sequence conflict	306	1	G → E in BAF98731. Ref.3
	Sequence conflict	426	1	L → P in BAF98731. Ref.3
	Sequence conflict	518	1	R → Q in BAG37669. Ref.3
	Sequence conflict	546	1	R → S in BAF98731. Ref.3
	Sequence conflict	638	1	A → V in BAF98731. Ref.3
	Sequence conflict	711 – 713	3	AVQ → SAE in AAA21338. Ref.1
	Sequence conflict	711 – 713	3	AVQ → SAE no nucleotide entry Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q16819 [UniParc]. Last modified July 22, 2008. Version 2. Checksum: B5F0812F2850F958	FASTA	746	84,419
	10 20 30 40 50 60 MAWIRSTCIL FFTLLFAHIA AVPIKYLPEE NVHDADFGEQ KDISEINLAA GLDLFQGDIL 70 80 90 100 110 120 LQKSRNGLRD PNTRWTFPIP YILADNLGLN AKGAILYAFE MFRLKSCVDF KPYEGESSYI 130 140 150 160 170 180 IFQQFDGCWS EVGDQHVGQN ISIGQGCAYK AIIEHEILHA LGFYHEQSRT DRDDYVNIWW 190 200 210 220 230 240 DQILSGYQHN FDTYDDSLIT DLNTPYDYES LMHYQPFSFN KNASVPTITA KIPEFNSIIG 250 260 270 280 290 300 QRLDFSAIDL ERLNRMYNCT TTHTLLDHCT FEKANICGMI QGTRDDTDWA HQDSAQAGEV 310 320 330 340 350 360 DHTLLGQCTG AGYFMQFSTS SGSAEEAALL ESRILYPKRK QQCLQFFYKM TGSPSDRLVV 370 380 390 400 410 420 WVRRDDSTGN VRKLVKVQTF QGDDDHNWKI AHVVLKEEQK FRYLFQGTKG DPQNSTGGIY 430 440 450 460 470 480 LDDITLTETP CPTGVWTVRN FSQVLENTSK GDKLQSPRFY NSEGYGFGVT LYPNSRESSG 490 500 510 520 530 540 YLRLAFHVCS GENDAILEWP VENRQVIITI LDQEPDVRNR MSSSMVFTTS KSHTSPAIND 550 560 570 580 590 600 TVIWDRPSRV GTYHTDCNCF RSIDLGWSGF ISHQMLKRRS FLKNDDLIIF VDFEDITHLS 610 620 630 640 650 660 QTEVPTKGKR LSPQGLILQG QEQQVSEEGS GKAMLEEALP VSLSQGQPSR QKRSVENTGP 670 680 690 700 710 720 LEDHNWPQYF RDPCDPNPCQ NDGICVNVKG MASCRCISGH AFFYTGERCQ AVQVHGSVLG 730 740 MVIGGTAGVI FLTFSIIAIL SQRPRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Sterchi E.E. Submitted (AUG-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-606. Tissue: Jejunum.
[2]	"Expression of human meprin alpha." Haun R.S. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Small intestine.
[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], VARIANTS LEU-469 AND MET-726. Tissue: Colon and Small intestine.
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 (JUL-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], VARIANTS LEU-469 AND GLY-476.
[7]	"Cloning of the PABA peptide hydrolase alpha subunit (PPH alpha) from human small intestine and its expression in COS-1 cells." Dumermuth E., Eldering J.A., Gruenberg J., Jiang W., Sterchi E.E. FEBS Lett. 335:367-375(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-746, VARIANT SER-606. Tissue: Jejunum.
[8]	"Human and mouse homo-oligomeric meprin A metalloendopeptidase: substrate and inhibitor specificities." Bylander J.E., Bertenshaw G.P., Matters G.L., Hubbard S.J., Bond J.S. Biol. Chem. 388:1163-1172(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M82962 mRNA. Translation: AAA21338.1. AF478685 mRNA. Translation: AAL85339.1. AK290282 mRNA. Translation: BAF82971.1. AK315246 mRNA. Translation: BAG37669.1. AK315840 mRNA. Translation: BAF98731.1. AL161618 Genomic DNA. Translation: CAC21508.1. CH471081 Genomic DNA. Translation: EAX04306.1. BC131714 mRNA. Translation: AAI31715.1.
IPI	IPI00004372.
PIR	HYHUMA. S60193.
RefSeq	NP_005579.2. NM_005588.2.
UniGene	Hs.179704.
3D structure databases
ProteinModelPortal	Q16819.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000230588.
Protein family/group databases
MEROPS	M12.002.
PTM databases
PhosphoSite	Q16819.
Polymorphism databases
DMDM	205830902.
Proteomic databases
PaxDb	Q16819.
PRIDE	Q16819.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000230588; ENSP00000230588; ENSG00000112818.
GeneID	4224.
KEGG	hsa:4224.
UCSC	uc010jzh.1. human.
Organism-specific databases
CTD	4224.
GeneCards	GC06P046807.
H-InvDB	HIX0032798.
HGNC	HGNC:7015. MEP1A.
HPA	HPA029416.
MIM	600388. gene.
neXtProt	NX_Q16819.
PharmGKB	PA30749.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG322115.
HOVERGEN	HBG052457.
InParanoid	Q16819.
KO	K01395.
OMA	MIQGTRD.
OrthoDB	EOG4S4PFJ.
PhylomeDB	Q16819.
Gene expression databases
Bgee	Q16819.
CleanEx	HS_MEP1A.
Genevestigator	Q16819.
GermOnline	ENSG00000112818. Homo sapiens.
Family and domain databases
Gene3D	3.40.390.10. 1 hit.
InterPro	IPR008985. ConA-like_lec_gl_sf. IPR000742. EG-like_dom. IPR000998. MAM_dom. IPR002083. MATH. IPR024079. MetalloPept_cat_dom. IPR008294. Pept_M12A_Meprin. IPR001506. Peptidase_M12A. IPR006026. Peptidase_Metallo. IPR008974. TRAF-like. [Graphical view]
Pfam	PF01400. Astacin. 1 hit. PF00008. EGF. 1 hit. PF00629. MAM. 1 hit. PF00917. MATH. 1 hit. [Graphical view]
PIRSF	PIRSF001196. Meprin. 1 hit.
PRINTS	PR00480. ASTACIN. PR00020. MAMDOMAIN.
SMART	SM00181. EGF. 1 hit. SM00137. MAM. 1 hit. SM00061. MATH. 1 hit. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF49899. ConA_like_lec_gl. 1 hit. SSF49599. Traf_like. 1 hit.
PROSITE	PS00022. EGF_1. False negative. PS01186. EGF_2. False negative. PS50026. EGF_3. 1 hit. PS00740. MAM_1. 1 hit. PS50060. MAM_2. 1 hit. PS50144. MATH. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4224.
NextBio	16671.
SOURCE	Search...

Entry information

Entry name

MEP1A_HUMAN

Accession

Primary (citable) accession number: Q16819
Secondary accession number(s): A2RRM4 , B0AZP9, B2RCS2, Q8TDC9, Q9H1R1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 22, 2008
Last modified:	May 1, 2013
This is version 132 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.