Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Proprotein convertase subtilisin/kexin type 5

Gene

Pcsk5

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Plays an essential role in pregnancy establishment by proteolytic activation of a number of important factors such as BMP2, CALD1 and alpha-integrins. Likely to represent a widespread endoprotease activity within the constitutive and regulated secretory pathway. Capable of cleavage at the RX(K/R)R consensus motif. May be responsible for the maturation of gastrointestinal peptides. May be involved in the cellular proliferation of adrenal cortex via the activation of growth factors (By similarity).By similarity

Catalytic activityi

Release of mature proteins from their proproteins by cleavage of Arg-Xaa-Yaa-Arg-|-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei173Charge relay systemBy similarity1
Active sitei214Charge relay systemBy similarity1
Active sitei388Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Pregnancy

Enzyme and pathway databases

BRENDAi3.4.21.B26. 5301.
ReactomeiR-RNO-167060. NGF processing.
R-RNO-174800. Chylomicron-mediated lipid transport.

Protein family/group databases

MEROPSiS08.076.

Names & Taxonomyi

Protein namesi
Recommended name:
Proprotein convertase subtilisin/kexin type 5 (EC:3.4.21.-)
Alternative name(s):
Proprotein convertase 5
Short name:
PC5
Proprotein convertase 6
Short name:
PC6
Subtilisin/kexin-like protease PC5
Short name:
rPC5
Gene namesi
Name:Pcsk5
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi620326. Pcsk5.

Subcellular locationi

Isoform PC5A :
  • Secreted By similarity

  • Note: Secreted through the regulated secretory pathway.By similarity
Isoform PC5B :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini117 – 1700ExtracellularSequence analysisAdd BLAST1584
Transmembranei1701 – 1721HelicalSequence analysisAdd BLAST21
Topological domaini1722 – 1809CytoplasmicSequence analysisAdd BLAST88

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34By similarityAdd BLAST34
PropeptideiPRO_000002710635 – 116By similarityAdd BLAST82
ChainiPRO_0000027107117 – 1809Proprotein convertase subtilisin/kexin type 5Add BLAST1693

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi227N-linked (GlcNAc...)Sequence analysis1
Glycosylationi383N-linked (GlcNAc...)Sequence analysis1
Glycosylationi667N-linked (GlcNAc...)Sequence analysis1
Glycosylationi754N-linked (GlcNAc...)Sequence analysis1
Glycosylationi804N-linked (GlcNAc...)Sequence analysis1
Glycosylationi854N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1642N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1664N-linked (GlcNAc...)Sequence analysis1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei116 – 117Cleavage; by autolysisBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP41413.
PRIDEiP41413.

Expressioni

Tissue specificityi

Expressed in the intestine, brain, adrenal gland, anterior pituitary, thyroid, ovaries, testis and lung. Highest levels are found in the gut, duodenum, jejunum and ileum. Expression is higher in female than in male reproductive organs.1 Publication

Developmental stagei

First detected at E9 in highly restricted regions of the neural tube, in caudal myotomes, and at the materno-embryonic junction of the uterus. At E10, restricted expression is detected in the optic and otic vesicles, the roof of midbrain, and trunk myotomes. By midgestation (E13-E16), expression in the developing nervous system has expanded to multiple regions including hippocampus, thalamus, hypothalamus, brain stem, and spinal cord. Expression is also detected in several peripheral organ systems, including gut, lung, adrenal and kydney primordia.1 Publication

Gene expression databases

BgeeiENSRNOG00000012036.
GenevisibleiP41413. RN.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000016164.

Structurei

3D structure databases

ProteinModelPortaliP41413.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini168 – 455Peptidase S8Add BLAST288
Repeati632 – 682FU 1Add BLAST51
Repeati685 – 732FU 2Add BLAST48
Repeati736 – 779FU 3Add BLAST44
Repeati781 – 826FU 4Add BLAST46
Repeati834 – 881FU 5Add BLAST48
Repeati884 – 929FU 6Add BLAST46
Repeati931 – 964FU 7Add BLAST34
Repeati965 – 1010FU 8Add BLAST46
Repeati1012 – 1054FU 9Add BLAST43
Repeati1058 – 1099FU 10Add BLAST42
Repeati1137 – 1179FU 11Add BLAST43
Repeati1183 – 1230FU 12Add BLAST48
Repeati1232 – 1276FU 13Add BLAST45
Repeati1278 – 1321FU 14Add BLAST44
Repeati1323 – 1369FU 15Add BLAST47
Repeati1373 – 1418FU 16Add BLAST46
Repeati1422 – 1467FU 17Add BLAST46
Repeati1471 – 1516FU 18Add BLAST46
Repeati1520 – 1567FU 19Add BLAST48
Repeati1571 – 1616FU 20Add BLAST46
Repeati1622 – 1669FU 21Add BLAST48

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni638 – 1685CRM (Cys-rich motif)Add BLAST1048
Regioni1757 – 1776AC 1Add BLAST20
Regioni1788 – 1809AC 2Add BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi521 – 523Cell attachment siteSequence analysis3

Domaini

The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum.
AC 1 and AC 2 (clusters of acidic amino acids) contain sorting information. AC 1 directs TGN localization and interacts with the TGN sorting protein PACS-1.

Sequence similaritiesi

Belongs to the peptidase S8 family.Curated
Contains 21 FU (furin-like) repeats.Curated
Contains 1 peptidase S8 domain.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP41413.
KOiK08654.
OMAiVCTECKP.
OrthoDBiEOG091G05HI.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR000742. EGF-like_dom.
IPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR000209. Peptidase_S8/S53_dom.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR009020. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 3 hits.
PfamiPF14843. GF_recep_IV. 2 hits.
PF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SMARTiSM00181. EGF. 16 hits.
SM01411. Ephrin_rec_like. 7 hits.
SM00261. FU. 21 hits.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 9 hits.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform PC5B (identifier: P41413-1) [UniParc]FASTAAdd to basket
Also known as: Long

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDWGWGSRCC RPGRRDLLCV LALLAGCLLP VCRTRVYTNH WAVKIAGGFA
60 70 80 90 100
EADRIASKYG FINVGQIGAL KDYYHFYHSR TIKRSVLSSR GTHSFISMEP
110 120 130 140 150
KVEWIQQQVV KKRTKRDYDL SRAQSTYFND PKWPSMWYMH CSDNTHPCQS
160 170 180 190 200
DMNIEGAWKR GYTGKNIVVT ILDDGIERTH PDLMQNYDAL ASCDVNGNDL
210 220 230 240 250
DPMPRYDASN ENKHGTRCAG EVAATANNSH CTVGIAFNAK IGGVRMLDGD
260 270 280 290 300
VTDMVEAKSV SYNPQHVHIY SASWGPDDDG KTVDGPAPLT RQAFENGVRM
310 320 330 340 350
GRRGLGSVFV WASGNGGRSK DHCSCDGYTN SIYTISISST AESGKKPWYL
360 370 380 390 400
EECSSTLATT YSSGESYDKK IITTDLRQRC TDNHTGTSAS APMAAGIIAL
410 420 430 440 450
ALEANPFLTW RDVQHVIVRT SRAGHLNAND WKTNAAGFKV SHLYGFGLMD
460 470 480 490 500
AEAMVMEAEK WTTVPQQHVC VESTDRQIKT IRPNSAVRSI YKASGCSDNP
510 520 530 540 550
NHHVNYLEHV VVRITITHPR RGDLAIYLTS PSGTRSQLLA NRLFDHSMEG
560 570 580 590 600
FKNWEFMTIH CWGERAAGDW VLEVYDTPSQ LRNFKTPGKL KEWSLVLYGT
610 620 630 640 650
SVQPYSPTNE FPKVERFRYS RVEDPTDDYG AEDYAGPCDP ECSEVGCDGP
660 670 680 690 700
GPDHCTDCLH YHYKLKNNTR ICVSSCPPGH FHADKKRCRK CAPNCESCFG
710 720 730 740 750
SHADQCLSCK YGYFLNEETS SCVAQCPEGS YQDIKKNICG KCSENCKTCT
760 770 780 790 800
GFHNCTECKG GLSLQGSRCS VTCEDGQFFS GHDCQPCHRF CATCAGAGAD
810 820 830 840 850
GCINCTEGYV MEEGRCVQSC SVSYYLDHSL EGGYKSCKRC DNSCLTCNGP
860 870 880 890 900
GFKNCSSCPS GYLLDLGMCQ MGAICKDGEY IDEQGHCQIC DASCAKCWGP
910 920 930 940 950
TQDDCISCPI TRVFDDGRCV MNCPSWKFEL KKQCHPCHHT CQGCQGSGPS
960 970 980 990 1000
NCTSCKAGEF QDSEYGECMP CEEGCVGCTV DDPGACTSCA TGYYMFERHC
1010 1020 1030 1040 1050
YKACPEKTFG EKWECKACGT NCGSCDQHEC YWCEEGFFLS SGSCVQDCDP
1060 1070 1080 1090 1100
GFYGDQELGE CKPCHRACET CTGLGYNQCS SCPEGLQLWH GTCIWPTWPH
1110 1120 1130 1140 1150
VEGKVWNEAV PTEKPSLVRS LPQDRRKWKV QIKRDATRQY QPCHSSCKTC
1160 1170 1180 1190 1200
NGSLCTSCPA GTYLWLQACV PSCPQGTWLS VRSSSCEKCA EGCASCSGDD
1210 1220 1230 1240 1250
LCQRCLSQPS NTLLLHEGRC YHSCPEGFYA KDGVCEHCSS PCKTCKGNAT
1260 1270 1280 1290 1300
SCHSCEGDFV LDHGVCWETC PEKHVAVEGV CKHCPERCQD CIHEKTCKEC
1310 1320 1330 1340 1350
MPDFFLYNDM CHHSCPKNFY PDMRQCVPCH KNCLGCNGPK EDDCKACADT
1360 1370 1380 1390 1400
SKVLHNGLCL DECPKGTYKD EVNDECRDCP ESCLICSSAW TCLTCREGFT
1410 1420 1430 1440 1450
VVQDVCTAPK ECAAIEYWDV GSHRCQPCHR KCSRCSGPSE NQCYTCPRET
1460 1470 1480 1490 1500
FLLNTTCVKE CPEGYHTDKD SHQCVPCHSS CRTCEGPHSM QCLSCRPGWF
1510 1520 1530 1540 1550
QLGKECLLQC RDGYYGESTS GRCEKCDKSC KTCRGPQPTD CQSCDTFFFL
1560 1570 1580 1590 1600
LRSKGQCHLA CPEHYYADQH AQTCERCHPT CDKCSGKEAW NCLSCVWSYH
1610 1620 1630 1640 1650
LLKGICTPEC IVGEYRDGKG ENFNCKKCHE SCMECKGPGS KNCTGCSAGL
1660 1670 1680 1690 1700
LLQMDDSRCL RCCNASHPHR SQDCCDCQSS TDECILPASD DTVFHEHTKT
1710 1720 1730 1740 1750
ALLVTSGAML LLLLGAAVVV WRKSRSQPVA KGRYEKLAEP TVSYSSYRSS
1760 1770 1780 1790 1800
YLDEDQVIEY RDRDYDEDDE DDIVYMGQDG TVYRKFKYGL LDEAEDDELE

YDDESYSYQ
Length:1,809
Mass (Da):201,308
Last modified:October 19, 2011 - v3
Checksum:i726855D09F929ADE
GO
Isoform PC5A (identifier: P41413-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     878-915: GEYIDEQGHC...ISCPITRVFD → ATEESWAEGG...LCCKTCTFQG
     916-1809: Missing.

Show »
Length:915
Mass (Da):101,454
Checksum:i63B032ACF0E28654
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005440878 – 915GEYID…TRVFD → ATEESWAEGGFCMLVKKNNL CQRKVLQQLCCKTCTFQG in isoform PC5A. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_005441916 – 1809Missing in isoform PC5A. 1 PublicationAdd BLAST894

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14933 mRNA. Translation: AAA99906.2.
U47014 mRNA. Translation: AAA87888.1.
PIRiB48225.
RefSeqiNP_446275.1. NM_053823.1. [P41413-2]
UniGeneiRn.104002.
Rn.234318.

Genome annotation databases

EnsembliENSRNOT00000016164; ENSRNOP00000016164; ENSRNOG00000012036. [P41413-2]
GeneIDi116548.
KEGGirno:116548.
UCSCiRGD:620326. rat. [P41413-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14933 mRNA. Translation: AAA99906.2.
U47014 mRNA. Translation: AAA87888.1.
PIRiB48225.
RefSeqiNP_446275.1. NM_053823.1. [P41413-2]
UniGeneiRn.104002.
Rn.234318.

3D structure databases

ProteinModelPortaliP41413.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000016164.

Protein family/group databases

MEROPSiS08.076.

Proteomic databases

PaxDbiP41413.
PRIDEiP41413.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000016164; ENSRNOP00000016164; ENSRNOG00000012036. [P41413-2]
GeneIDi116548.
KEGGirno:116548.
UCSCiRGD:620326. rat. [P41413-1]

Organism-specific databases

CTDi5125.
RGDi620326. Pcsk5.

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP41413.
KOiK08654.
OMAiVCTECKP.
OrthoDBiEOG091G05HI.

Enzyme and pathway databases

BRENDAi3.4.21.B26. 5301.
ReactomeiR-RNO-167060. NGF processing.
R-RNO-174800. Chylomicron-mediated lipid transport.

Miscellaneous databases

PROiP41413.

Gene expression databases

BgeeiENSRNOG00000012036.
GenevisibleiP41413. RN.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR000742. EGF-like_dom.
IPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR000209. Peptidase_S8/S53_dom.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR009020. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 3 hits.
PfamiPF14843. GF_recep_IV. 2 hits.
PF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SMARTiSM00181. EGF. 16 hits.
SM01411. Ephrin_rec_like. 7 hits.
SM00261. FU. 21 hits.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 9 hits.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPCSK5_RAT
AccessioniPrimary (citable) accession number: P41413
Secondary accession number(s): D3ZVZ3, Q62914
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 19, 2011
Last modified: October 5, 2016
This is version 143 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.