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Protein

Pepsin A-4

Gene

PGA4

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

Sites

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

GO - Molecular functioni

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.

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.
PRIDEiP0DJD7.

PTM databases

iPTMnetiP0DJD7.
PhosphoSitePlusiP0DJD7.

Expressioni

Gene expression databases

BgeeiENSG00000229183.
CleanExiHS_PGA4.
ExpressionAtlasiP0DJD7. baseline and differential.
GenevisibleiP0DJD7. HS.

Organism-specific databases

HPAiHPA046875.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
SPAG4Q9NPE64EBI-12957629,EBI-10819434

Protein-protein interaction databases

IntActiP0DJD7. 4 interactors.
STRINGi9606.ENSP00000367391.

Chemistry databases

BindingDBiP0DJD7.

Structurei

Secondary structure

1388
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi65 – 67Combined sources3
Beta strandi69 – 71Combined sources3
Turni72 – 74Combined sources3
Beta strandi75 – 82Combined sources8
Turni83 – 86Combined sources4
Beta strandi87 – 94Combined sources8
Beta strandi100 – 102Combined sources3
Helixi110 – 113Combined sources4
Helixi120 – 122Combined sources3
Beta strandi127 – 136Combined sources10
Beta strandi141 – 153Combined sources13
Beta strandi156 – 168Combined sources13
Helixi172 – 176Combined sources5
Beta strandi180 – 184Combined sources5
Helixi188 – 190Combined sources3
Helixi192 – 194Combined sources3
Helixi198 – 204Combined sources7
Beta strandi209 – 216Combined sources8
Beta strandi226 – 229Combined sources4
Helixi234 – 236Combined sources3
Beta strandi237 – 239Combined sources3
Beta strandi242 – 245Combined sources4
Turni249 – 252Combined sources4
Beta strandi253 – 256Combined sources4
Beta strandi258 – 261Combined sources4
Beta strandi264 – 267Combined sources4
Beta strandi272 – 276Combined sources5
Beta strandi282 – 285Combined sources4
Helixi287 – 296Combined sources10
Beta strandi307 – 309Combined sources3
Helixi311 – 316Combined sources6
Beta strandi320 – 324Combined sources5
Beta strandi327 – 331Combined sources5
Helixi333 – 336Combined sources4
Beta strandi337 – 340Combined sources4
Beta strandi343 – 350Combined sources8
Beta strandi361 – 363Combined sources3
Helixi365 – 370Combined sources6
Beta strandi371 – 376Combined sources6
Turni377 – 380Combined sources4
Beta strandi381 – 387Combined sources7

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...

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.
OMAiECKTIVA.
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.

Sequencei

Sequence statusi: Complete.

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

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

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

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 22, 2017
This is version 52 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. 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