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P0DJD7 (PEPA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 23. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pepsin A-4

EC=3.4.23.1
Alternative name(s):
Pepsinogen-4
Gene names
Name:PGA4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length388 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Shows particularly broad specificity; although bonds involving phenylalanine and leucine are preferred, many others are also cleaved to some extent.

Catalytic activity

Preferential cleavage: hydrophobic, preferably aromatic, residues in P1 and P1' positions. Cleaves 1-Phe-|-Val-2, 4-Gln-|-His-5, 13-Glu-|-Ala-14, 14-Ala-|-Leu-15, 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17, 23-Gly-|-Phe-24, 24-Phe-|-Phe-25 and 25-Phe-|-Tyr-26 bonds in the B chain of insulin.

Subcellular location

Secreted.

Sequence similarities

Belongs to the peptidase A1 family.

Ontologies

Keywords
   Biological processDigestion
   Cellular componentSecreted
   DomainSignal
   Molecular functionAspartyl protease
Hydrolase
Protease
   PTMDisulfide bond
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processdigestion

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionaspartic-type endopeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1515 Ref.6 Ref.7
Propeptide16 – 6247Activation peptide
PRO_0000415757
Chain63 – 388326Pepsin A-4
PRO_0000415758

Sites

Active site941 Ref.10
Active site2771 Ref.10

Amino acid modifications

Disulfide bond107 ↔ 112 Ref.10
Disulfide bond268 ↔ 272 Ref.10
Disulfide bond311 ↔ 344 Ref.10

Experimental info

Sequence conflict2911A → T in BAF84553. Ref.2
Sequence conflict371 – 3722YF → FY AA sequence Ref.8

Secondary structure

......................................................................... 388
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P0DJD7 [UniParc].

Last modified February 22, 2012. Version 1.
Checksum: C9CB89BA08F4D78B

FASTA38841,977
        10         20         30         40         50         60 
MKWLLLLGLV ALSECIMYKV PLIRKKSLRR TLSERGLLKD FLKKHNLNPA RKYFPQWEAP 

        70         80         90        100        110        120 
TLVDEQPLEN YLDMEYFGTI GIGTPAQDFT VVFDTGSSNL WVPSVYCSSL ACTNHNRFNP 

       130        140        150        160        170        180 
EDSSTYQSTS ETVSITYGTG SMTGILGYDT VQVGGISDTN QIFGLSETEP GSFLYYAPFD 

       190        200        210        220        230        240 
GILGLAYPSI SSSGATPVFD NIWNQGLVSQ DLFSVYLSAD DQSGSVVIFG GIDSSYYTGS 

       250        260        270        280        290        300 
LNWVPVTVEG YWQITVDSIT MNGEAIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS 

       310        320        330        340        350        360 
ENSDGDMVVS CSAISSLPDI VFTINGVQYP VPPSAYILQS EGSCISGFQG MNLPTESGEL 

       370        380 
WILGDVFIRQ YFTVFDRANN QVGLAPVA 

« Hide

References

« Hide 'large scale' references
[1]"Primary structure of human pepsinogen gene."
Sogawa K., Fujii-Kuriyama Y., Mizukami Y., Ichihara Y., Takahashi K.
J. Biol. Chem. 258:5306-5311(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"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].
Tissue: Skeletal muscle.
[3]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
Tissue: Colon and Kidney.
[5]"Isolation of human, swine, and rat prepepsinogens and calf preprochymosin, and determination of the primary structures of their NH2-terminal signal sequences."
Ichihara Y., Sogawa K., Takahashi K.
J. Biochem. 98:483-492(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE OF 1-28.
[6]"A comparative study on the NH2-terminal amino acid sequences and some other properties of six isozymic forms of human pepsinogens and pepsins."
Athauda S.B.P., Tanji M., Kageyama T., Takahashi K.
J. Biochem. 106:920-927(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 16-100.
[7]"Activation of human pepsinogens."
Foltmann B.
FEBS Lett. 241:69-72(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 16-68.
[8]"Carboxyl-terminal sequence of human gastricsin and pepsin."
Huang W.-Y., Tang J.
J. Biol. Chem. 245:2189-2193(1970) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 362-388.
[9]"Nucleotide sequence comparison of five human pepsinogen A (PGA) genes: evolution of the PGA multigene family."
Evers M.P.J., Zelle B., Bebelman J.-P., van Beusechem V., Kraakman L., Hoffer M.J.V., Pronk J.C., Mager W.H., Planta R.J., Eriksson A.W., Frants R.R.
Genomics 4:232-239(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
Tissue: Placenta.
[10]"Crystal structure of human pepsin and its complex with pepstatin."
Fujinaga M., Chernaia M.M., Tarasova N.I., Mosimann S.C., James M.N.G.
Protein Sci. 4:960-972(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 63-388, ACTIVE SITES, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J00287 expand/collapse EMBL AC list , J00279, J00280, J00281, J00282, J00283, J00284, J00285, J00286 Genomic DNA. Translation: AAA98529.1.
AK291864 mRNA. Translation: BAF84553.1.
AP000437 Genomic DNA. No translation available.
AP003037 Genomic DNA. No translation available.
BC150659 mRNA. Translation: AAI50660.1.
BC171910 mRNA. Translation: AAI71910.1.
BC171920 mRNA. Translation: AAI71920.1.
CCDSCCDS31575.1.
PIRPEHU. A00980.
A30142.
A92058.
B30142.
RefSeqNP_001073276.1. NM_001079808.2.
UniGeneHs.432854.
Hs.661883.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FLHX-ray2.45A63-388[»]
1PSNX-ray2.20A63-388[»]
1PSOX-ray2.00E63-388[»]
1QRPX-ray1.96E63-388[»]
3UTLX-ray2.61A63-388[»]
ProteinModelPortalP0DJD7.
SMRP0DJD7. Positions 17-388.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP0DJD7.

Protein family/group databases

MEROPSA01.070.

PTM databases

PhosphoSiteP0DJD7.

Polymorphism databases

DMDM378521995.

Proteomic databases

PRIDEP0DJD7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000378149; ENSP00000367391; ENSG00000229183.
GeneID643847.
KEGGhsa:643847.
UCSCuc001nqy.3. human.

Organism-specific databases

CTD643847.
GeneCardsGC11P060989.
HGNCHGNC:8886. PGA4.
HPACAB026358.
HPA046875.
MIM169700. gene.
169720. gene.
neXtProtNX_P0DJD7.
GenAtlasSearch...

Phylogenomic databases

KOK06002.
OMAAYFGTIS.
OrthoDBEOG7HQN88.
PhylomeDBP0DJD7.
TreeFamTF314990.

Gene expression databases

BgeeP0DJD7.
CleanExHS_PGA4.

Family and domain databases

Gene3D2.40.70.10. 2 hits.
InterProIPR001461. Aspartic_peptidase.
IPR001969. Aspartic_peptidase_AS.
IPR012848. Aspartic_peptidase_N.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERPTHR13683. PTHR13683. 1 hit.
PfamPF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]
PRINTSPR00792. PEPSIN.
SUPFAMSSF50630. SSF50630. 1 hit.
PROSITEPS00141. ASP_PROTEASE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi643847.
NextBio115463.
PROP0DJD7.
SOURCESearch...

Entry information

Entry namePEPA4_HUMAN
AccessionPrimary (citable) accession number: P0DJD7
Secondary accession number(s): A8K749 expand/collapse secondary AC list , B7ZW75, P00790, Q7M4R0, Q8N1E3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 22, 2012
Last sequence update: February 22, 2012
Last modified: July 9, 2014
This is version 23 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM