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Protein

Pepsin A-4

Gene

PGA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei94PROSITE-ProRule annotation1 Publication1
Active sitei277PROSITE-ProRule annotation1 Publication1

GO - Molecular functioni

  • aspartic-type endopeptidase activity Source: GO_Central
  • peptidase activity Source: Reactome

GO - Biological processi

Keywordsi

Molecular functionAspartyl protease, Hydrolase, Protease
Biological processDigestion

Enzyme and pathway databases

ReactomeiR-HSA-5683826 Surfactant metabolism

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
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000229183.8
HGNCiHGNC:8886 PGA4
MIMi169700 gene
169720 gene
neXtProtiNX_P0DJD7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000229183

Polymorphism and mutation databases

BioMutaiPGA4
DMDMi378521995

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 152 PublicationsAdd BLAST15
PropeptideiPRO_000041575716 – 62Activation peptideAdd BLAST47
ChainiPRO_000041575863 – 388Pepsin A-4Add BLAST326

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi107 ↔ 1121 Publication
Modified residuei130PhosphoserineBy similarity1
Disulfide bondi268 ↔ 2721 Publication
Disulfide bondi311 ↔ 3441 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiP0DJD7
PeptideAtlasiP0DJD7
PRIDEiP0DJD7
ProteomicsDBi52544

PTM databases

iPTMnetiP0DJD7
PhosphoSitePlusiP0DJD7

Expressioni

Gene expression databases

BgeeiENSG00000229183 Expressed in 80 organ(s), highest expression level in fundus of stomach
CleanExiHS_PGA4
ExpressionAtlasiP0DJD7 baseline and differential
GenevisibleiP0DJD7 HS

Organism-specific databases

HPAiHPA046875

Interactioni

Protein-protein interaction databases

IntActiP0DJD7, 9 interactors
STRINGi9606.ENSP00000367391

Chemistry databases

BindingDBiP0DJD7

Structurei

Secondary structure

1388
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP0DJD7
SMRiP0DJD7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini76 – 385Peptidase A1PROSITE-ProRule annotationAdd BLAST310

Sequence similaritiesi

Belongs to the peptidase A1 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1339 Eukaryota
ENOG410XNV7 LUCA
GeneTreeiENSGT00760000118929
InParanoidiP0DJD7
KOiK06002
OMAiDADPFFW
OrthoDBiEOG091G0JP7
PhylomeDBiP0DJD7
TreeFamiTF314990

Family and domain databases

CDDicd05478 pepsin_A, 1 hit
Gene3Di2.40.70.10, 2 hits
InterProiView protein in InterPro
IPR001461 Aspartic_peptidase_A1
IPR001969 Aspartic_peptidase_AS
IPR012848 Aspartic_peptidase_N
IPR034162 Pepsin_A
IPR033121 PEPTIDASE_A1
IPR021109 Peptidase_aspartic_dom_sf
PANTHERiPTHR13683 PTHR13683, 1 hit
PfamiView protein in Pfam
PF07966 A1_Propeptide, 1 hit
PF00026 Asp, 1 hit
PRINTSiPR00792 PEPSIN
SUPFAMiSSF50630 SSF50630, 1 hit
PROSITEiView protein in PROSITE
PS00141 ASP_PROTEASE, 2 hits
PS51767 PEPTIDASE_A1, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P0DJD7-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKWLLLLGLV ALSECIMYKV PLIRKKSLRR TLSERGLLKD FLKKHNLNPA
60 70 80 90 100
RKYFPQWEAP TLVDEQPLEN YLDMEYFGTI GIGTPAQDFT VVFDTGSSNL
110 120 130 140 150
WVPSVYCSSL ACTNHNRFNP EDSSTYQSTS ETVSITYGTG SMTGILGYDT
160 170 180 190 200
VQVGGISDTN QIFGLSETEP GSFLYYAPFD GILGLAYPSI SSSGATPVFD
210 220 230 240 250
NIWNQGLVSQ DLFSVYLSAD DQSGSVVIFG GIDSSYYTGS LNWVPVTVEG
260 270 280 290 300
YWQITVDSIT MNGEAIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS
310 320 330 340 350
ENSDGDMVVS CSAISSLPDI VFTINGVQYP VPPSAYILQS EGSCISGFQG
360 370 380
MNLPTESGEL WILGDVFIRQ YFTVFDRANN QVGLAPVA
Length:388
Mass (Da):41,977
Last modified:February 22, 2012 - v1
Checksum:iC9CB89BA08F4D78B
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H842F5H842_HUMAN
Pepsin A-3
PGA3
265Annotation score:
F5GXL4F5GXL4_HUMAN
Pepsin A-3
PGA3 PGA4
234Annotation score:
F5H0H6F5H0H6_HUMAN
Pepsin A-3
PGA4 PGA3
128Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti291A → T in BAF84553 (PubMed:14702039).Curated1
Sequence conflicti371 – 372YF → FY AA sequence (PubMed:4909888).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_001079808.3
XP_016854970.1, XM_016999481.1
UniGeneiHs.432854
Hs.661883

Genome annotation databases

EnsembliENST00000378149; ENSP00000367391; ENSG00000229183
GeneIDi643847
KEGGihsa:643847
UCSCiuc001nqy.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_001079808.3
XP_016854970.1, XM_016999481.1
UniGeneiHs.432854
Hs.661883

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP0DJD7, 9 interactors
STRINGi9606.ENSP00000367391

Chemistry databases

BindingDBiP0DJD7

Protein family/group databases

MEROPSiA01.070

PTM databases

iPTMnetiP0DJD7
PhosphoSitePlusiP0DJD7

Polymorphism and mutation databases

BioMutaiPGA4
DMDMi378521995

Proteomic databases

PaxDbiP0DJD7
PeptideAtlasiP0DJD7
PRIDEiP0DJD7
ProteomicsDBi52544

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378149; ENSP00000367391; ENSG00000229183
GeneIDi643847
KEGGihsa:643847
UCSCiuc001nqy.4 human

Organism-specific databases

CTDi643847
EuPathDBiHostDB:ENSG00000229183.8
GeneCardsiPGA4
HGNCiHGNC:8886 PGA4
HPAiHPA046875
MIMi169700 gene
169720 gene
neXtProtiNX_P0DJD7
OpenTargetsiENSG00000229183
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1339 Eukaryota
ENOG410XNV7 LUCA
GeneTreeiENSGT00760000118929
InParanoidiP0DJD7
KOiK06002
OMAiDADPFFW
OrthoDBiEOG091G0JP7
PhylomeDBiP0DJD7
TreeFamiTF314990

Enzyme and pathway databases

ReactomeiR-HSA-5683826 Surfactant metabolism

Miscellaneous databases

ChiTaRSiPGA4 human
GenomeRNAii643847
PROiPR:P0DJD7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000229183 Expressed in 80 organ(s), highest expression level in fundus of stomach
CleanExiHS_PGA4
ExpressionAtlasiP0DJD7 baseline and differential
GenevisibleiP0DJD7 HS

Family and domain databases

CDDicd05478 pepsin_A, 1 hit
Gene3Di2.40.70.10, 2 hits
InterProiView protein in InterPro
IPR001461 Aspartic_peptidase_A1
IPR001969 Aspartic_peptidase_AS
IPR012848 Aspartic_peptidase_N
IPR034162 Pepsin_A
IPR033121 PEPTIDASE_A1
IPR021109 Peptidase_aspartic_dom_sf
PANTHERiPTHR13683 PTHR13683, 1 hit
PfamiView protein in Pfam
PF07966 A1_Propeptide, 1 hit
PF00026 Asp, 1 hit
PRINTSiPR00792 PEPSIN
SUPFAMiSSF50630 SSF50630, 1 hit
PROSITEiView protein in PROSITE
PS00141 ASP_PROTEASE, 2 hits
PS51767 PEPTIDASE_A1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPEPA4_HUMAN
AccessioniPrimary (citable) accession number: P0DJD7
Secondary accession number(s): A8K749
, B7ZW75, P00790, Q7M4R0, Q8N1E3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 22, 2012
Last sequence update: February 22, 2012
Last modified: November 7, 2018
This is version 58 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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