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P0DJD7

- PEPA4_HUMAN

UniProt

P0DJD7 - PEPA4_HUMAN

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Protein

Pepsin A-4

Gene
PGA4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei94 – 9411 Publication
Active sitei277 – 27711 Publication

GO - Molecular functioni

  1. aspartic-type endopeptidase activity Source: UniProtKB-KW

GO - Biological processi

  1. digestion Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Aspartyl protease, Hydrolase, Protease

Keywords - Biological processi

Digestion

Protein family/group databases

MEROPSiA01.070.

Names & Taxonomyi

Protein namesi
Recommended name:
Pepsin A-4 (EC:3.4.23.1)
Alternative name(s):
Pepsinogen-4
Gene namesi
Name:PGA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:8886. PGA4.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 15152 PublicationsAdd
BLAST
Propeptidei16 – 6247Activation peptidePRO_0000415757Add
BLAST
Chaini63 – 388326Pepsin A-4PRO_0000415758Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi107 ↔ 1121 Publication
Disulfide bondi268 ↔ 2721 Publication
Disulfide bondi311 ↔ 3441 Publication

Keywords - PTMi

Disulfide bond, Zymogen

Proteomic databases

PRIDEiP0DJD7.

PTM databases

PhosphoSiteiP0DJD7.

Expressioni

Gene expression databases

BgeeiP0DJD7.
CleanExiHS_PGA4.

Organism-specific databases

HPAiCAB026358.
HPA046875.

Interactioni

Structurei

Secondary structure

1
388
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi65 – 673
Beta strandi69 – 713
Turni72 – 743
Beta strandi75 – 828
Turni83 – 864
Beta strandi87 – 948
Beta strandi100 – 1023
Helixi110 – 1134
Helixi120 – 1223
Beta strandi127 – 13610
Beta strandi141 – 15313
Beta strandi156 – 16813
Helixi172 – 1765
Beta strandi180 – 1845
Helixi188 – 1903
Helixi192 – 1943
Helixi198 – 2047
Beta strandi209 – 2168
Beta strandi226 – 2294
Helixi234 – 2363
Beta strandi237 – 2393
Beta strandi242 – 2454
Turni249 – 2524
Beta strandi253 – 2564
Beta strandi258 – 2614
Beta strandi264 – 2674
Beta strandi272 – 2765
Beta strandi282 – 2854
Helixi287 – 29610
Beta strandi307 – 3093
Helixi311 – 3166
Beta strandi320 – 3245
Beta strandi327 – 3315
Helixi333 – 3364
Beta strandi337 – 3404
Beta strandi343 – 3508
Beta strandi361 – 3633
Helixi365 – 3706
Beta strandi371 – 3766
Turni377 – 3804
Beta strandi381 – 3877

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FLHX-ray2.45A63-388[»]
1PSNX-ray2.20A63-388[»]
1PSOX-ray2.00E63-388[»]
1QRPX-ray1.96E63-388[»]
3UTLX-ray2.61A63-388[»]
ProteinModelPortaliP0DJD7.
SMRiP0DJD7. Positions 17-388.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase A1 family.

Keywords - Domaini

Signal

Phylogenomic databases

KOiK06002.
OMAiAYFGTIS.
OrthoDBiEOG7HQN88.
PhylomeDBiP0DJD7.
TreeFamiTF314990.

Family and domain databases

Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase.
IPR001969. Aspartic_peptidase_AS.
IPR012848. Aspartic_peptidase_N.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERiPTHR13683. PTHR13683. 1 hit.
PfamiPF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]
PRINTSiPR00792. PEPSIN.
SUPFAMiSSF50630. SSF50630. 1 hit.
PROSITEiPS00141. ASP_PROTEASE. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P0DJD7-1 [UniParc]FASTAAdd to Basket

« Hide

MKWLLLLGLV ALSECIMYKV PLIRKKSLRR TLSERGLLKD FLKKHNLNPA    50
RKYFPQWEAP TLVDEQPLEN YLDMEYFGTI GIGTPAQDFT VVFDTGSSNL 100
WVPSVYCSSL ACTNHNRFNP EDSSTYQSTS ETVSITYGTG SMTGILGYDT 150
VQVGGISDTN QIFGLSETEP GSFLYYAPFD GILGLAYPSI SSSGATPVFD 200
NIWNQGLVSQ DLFSVYLSAD DQSGSVVIFG GIDSSYYTGS LNWVPVTVEG 250
YWQITVDSIT MNGEAIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS 300
ENSDGDMVVS CSAISSLPDI VFTINGVQYP VPPSAYILQS EGSCISGFQG 350
MNLPTESGEL WILGDVFIRQ YFTVFDRANN QVGLAPVA 388
Length:388
Mass (Da):41,977
Last modified:February 22, 2012 - v1
Checksum:iC9CB89BA08F4D78B
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti291 – 2911A → T in BAF84553. 1 Publication
Sequence conflicti371 – 3722YF → FY AA sequence 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J00287
, 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.
CCDSiCCDS31575.1.
PIRiA00980. PEHU.
A30142.
A92058.
B30142.
RefSeqiNP_001073276.1. NM_001079808.2.
UniGeneiHs.432854.
Hs.661883.

Genome annotation databases

EnsembliENST00000378149; ENSP00000367391; ENSG00000229183.
GeneIDi643847.
KEGGihsa:643847.
UCSCiuc001nqy.3. human.

Polymorphism databases

DMDMi378521995.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J00287
, 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 .
CCDSi CCDS31575.1.
PIRi A00980. PEHU.
A30142.
A92058.
B30142.
RefSeqi NP_001073276.1. NM_001079808.2.
UniGenei Hs.432854.
Hs.661883.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1FLH X-ray 2.45 A 63-388 [» ]
1PSN X-ray 2.20 A 63-388 [» ]
1PSO X-ray 2.00 E 63-388 [» ]
1QRP X-ray 1.96 E 63-388 [» ]
3UTL X-ray 2.61 A 63-388 [» ]
ProteinModelPortali P0DJD7.
SMRi P0DJD7. Positions 17-388.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P0DJD7.

Protein family/group databases

MEROPSi A01.070.

PTM databases

PhosphoSitei P0DJD7.

Polymorphism databases

DMDMi 378521995.

Proteomic databases

PRIDEi P0DJD7.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000378149 ; ENSP00000367391 ; ENSG00000229183 .
GeneIDi 643847.
KEGGi hsa:643847.
UCSCi uc001nqy.3. human.

Organism-specific databases

CTDi 643847.
GeneCardsi GC11P060989.
HGNCi HGNC:8886. PGA4.
HPAi CAB026358.
HPA046875.
MIMi 169700. gene.
169720. gene.
neXtProti NX_P0DJD7.
GenAtlasi Search...

Phylogenomic databases

KOi K06002.
OMAi AYFGTIS.
OrthoDBi EOG7HQN88.
PhylomeDBi P0DJD7.
TreeFami TF314990.

Miscellaneous databases

GenomeRNAii 643847.
NextBioi 115463.
PROi P0DJD7.
SOURCEi Search...

Gene expression databases

Bgeei P0DJD7.
CleanExi HS_PGA4.

Family and domain databases

Gene3Di 2.40.70.10. 2 hits.
InterProi IPR001461. Aspartic_peptidase.
IPR001969. Aspartic_peptidase_AS.
IPR012848. Aspartic_peptidase_N.
IPR021109. Peptidase_aspartic_dom.
[Graphical view ]
PANTHERi PTHR13683. PTHR13683. 1 hit.
Pfami PF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view ]
PRINTSi PR00792. PEPSIN.
SUPFAMi SSF50630. SSF50630. 1 hit.
PROSITEi PS00141. ASP_PROTEASE. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiPEPA4_HUMAN
AccessioniPrimary (citable) accession number: P0DJD7
Secondary accession number(s): A8K749
, B7ZW75, P00790, Q7M4R0, Q8N1E3
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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