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Q16819 (MEP1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length746 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MMP9P147802EBI-8153734,EBI-1382326

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 By similarity
Propeptide22 – 6544 By similarity
PRO_0000028877
Chain66 – 746681Meprin A subunit alpha
PRO_0000028878

Regions

Topological domain66 – 712647Extracellular Potential
Transmembrane713 – 74028Helical; Potential
Topological domain741 – 7466Cytoplasmic Potential
Domain264 – 433170MAM
Domain434 – 593160MATH
Domain670 – 71041EGF-like
Region66 – 263198Metalloprotease

Sites

Active site1561 By similarity
Metal binding581Zinc; catalytic By similarity
Metal binding1551Zinc; via tele nitrogen; catalytic By similarity
Metal binding1591Zinc; via tele nitrogen; catalytic By similarity
Metal binding1651Zinc; via tele nitrogen; catalytic By similarity

Amino acid modifications

Glycosylation1401N-linked (GlcNAc...) Potential
Glycosylation2221N-linked (GlcNAc...) Potential
Glycosylation2581N-linked (GlcNAc...) Potential
Glycosylation4141N-linked (GlcNAc...) Potential
Glycosylation4401N-linked (GlcNAc...) Potential
Glycosylation4471N-linked (GlcNAc...) Potential
Glycosylation5391N-linked (GlcNAc...) Potential
Disulfide bond107 ↔ 259 By similarity
Disulfide bond128 ↔ 147 By similarity
Disulfide bond269 ↔ 431 By similarity
Disulfide bond277Interchain By similarity
Disulfide bond308Interchain By similarity
Disulfide bond674 ↔ 685 By similarity
Disulfide bond679 ↔ 694 By similarity
Disulfide bond696 ↔ 709 By similarity

Natural variations

Natural variant4691V → L. Ref.3 Ref.6
Corresponds to variant rs2274658 [ dbSNP | Ensembl ].
VAR_020056
Natural variant4761R → G. Ref.6
Corresponds to variant rs12197930 [ dbSNP | Ensembl ].
VAR_033492
Natural variant6061T → S. Ref.1 Ref.7
Corresponds to variant rs2297020 [ dbSNP | Ensembl ].
VAR_051583
Natural variant6341M → V.
Corresponds to variant rs2297019 [ dbSNP | Ensembl ].
VAR_021846
Natural variant7261T → M. Ref.3
Corresponds to variant rs1804211 [ dbSNP | Ensembl ].
VAR_033493

Experimental info

Sequence conflict261Y → H in AAA21338. Ref.1
Sequence conflict1621G → V in AAL85339. Ref.2
Sequence conflict3061G → E in BAF98731. Ref.3
Sequence conflict4261L → P in BAF98731. Ref.3
Sequence conflict5181R → Q in BAG37669. Ref.3
Sequence conflict5461R → S in BAF98731. Ref.3
Sequence conflict6381A → V in BAF98731. Ref.3
Sequence conflict711 – 7133AVQ → SAE in AAA21338. Ref.1
Sequence conflict711 – 7133AVQ → SAE no nucleotide entry Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q16819 [UniParc].

Last modified July 22, 2008. Version 2.
Checksum: B5F0812F2850F958

FASTA74684,419
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS4918.1.
PIRHYHUMA. S60193.
RefSeqNP_005579.2. NM_005588.2.
UniGeneHs.179704.

3D structure databases

ProteinModelPortalQ16819.
SMRQ16819. Positions 62-259, 435-589.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110387. 11 interactions.
IntActQ16819. 1 interaction.
STRING9606.ENSP00000230588.

Protein family/group databases

MEROPSM12.002.

PTM databases

PhosphoSiteQ16819.

Polymorphism databases

DMDM205830902.

Proteomic databases

PaxDbQ16819.
PRIDEQ16819.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000230588; ENSP00000230588; ENSG00000112818.
GeneID4224.
KEGGhsa:4224.
UCSCuc010jzh.1. human.

Organism-specific databases

CTD4224.
GeneCardsGC06P046807.
H-InvDBHIX0032798.
HGNCHGNC:7015. MEP1A.
HPAHPA029416.
MIM600388. gene.
neXtProtNX_Q16819.
PharmGKBPA30749.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322115.
HOVERGENHBG052457.
InParanoidQ16819.
KOK01395.
OMAMIQGTRD.
OrthoDBEOG73V6MT.
PhylomeDBQ16819.
TreeFamTF315280.

Enzyme and pathway databases

SignaLinkQ16819.

Gene expression databases

BgeeQ16819.
CleanExHS_MEP1A.
GenevestigatorQ16819.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR000742. EG-like_dom.
IPR000998. MAM_dom.
IPR002083. MATH.
IPR008294. Meprin.
IPR024079. MetalloPept_cat_dom.
IPR001506. Peptidase_M12A.
IPR006026. Peptidase_Metallo.
IPR008974. TRAF-like.
[Graphical view]
PfamPF01400. Astacin. 1 hit.
PF00008. EGF. 1 hit.
PF00629. MAM. 1 hit.
PF00917. MATH. 1 hit.
[Graphical view]
PIRSFPIRSF001196. Meprin. 1 hit.
PRINTSPR00480. ASTACIN.
PR00020. MAMDOMAIN.
SMARTSM00181. EGF. 1 hit.
SM00137. MAM. 1 hit.
SM00061. MATH. 1 hit.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF49599. SSF49599. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEPS50026. 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]
ProtoNetSearch...

Other

GeneWikiMEP1A.
GenomeRNAi4224.
NextBio16671.
PROQ16819.
SOURCESearch...

Entry information

Entry nameMEP1A_HUMAN
AccessionPrimary (citable) accession number: Q16819
Secondary accession number(s): A2RRM4 expand/collapse secondary AC list , B0AZP9, B2RCS2, Q8TDC9, Q9H1R1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 22, 2008
Last modified: July 9, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM