P29122 (PCSK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proprotein convertase subtilisin/kexin type 6
EC=3.4.21.-

Alternative name(s):
Paired basic amino acid cleaving enzyme 4
Subtilisin-like proprotein convertase 4
Short name=SPC4
Subtilisin/kexin-like protease PACE4

Gene names

Name:	PCSK6
Synonyms:	PACE4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	969 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Likely to represent an endoprotease activity within the constitutive secretory pathway, with unique restricted distribution in both neuroendocrine and non-neuroendocrine tissues and capable of cleavage at the RX(K/R)R consensus motif.
Catalytic activity	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.
Cofactor	Calcium Potential.
Subunit structure	The PACE4A-I precursor protein seems to exist in the reticulum endoplasmic as both a monomer and a dimer-sized complex whereas mature PACE4A-I exists only as a monomer, suggesting that propeptide cleavage affects its tertiary or quaternary structure.
Subcellular location	Isoform PACE4A-I: Secreted. Isoform PACE4A-II: Secreted. Isoform PACE4C: Endoplasmic reticulum. Note: Not secreted, remains probably in zymogen form in endoplasmic reticulum. Isoform PACE4CS: Endoplasmic reticulum. Note: Not secreted, remains probably in zymogen form in endoplasmic reticulum. Isoform PACE4E-I: Endomembrane system; Peripheral membrane protein. Note: Retained intracellularly probably through a hydrophobic cluster in their C-terminus. Isoform PACE4E-II: Endomembrane system; Peripheral membrane protein. Note: Retained intracellularly probably through a hydrophobic cluster in their C-terminus. Isoform PACE4B: Secreted.
Tissue specificity	Each PACE4 isoform exhibits a unique restricted distribution. Isoform PACE4A-I is expressed in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, but at comparatively higher levels in the liver. Isoform PACE4A-II is at least expressed in placenta. Isoform PACE4B was only found in the embryonic kidney cell line from which it was isolated. Isoform PACE4C and isoform PACE4D are expressed in placenta. Isoform PACE4E-I is expressed in cerebellum, placenta and pituitary. Isoform PACE4E-II is at least present in cerebellum.
Domain	The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum. Isoform PACE4D lacks the propeptide domain.
Sequence similarities	Belongs to the peptidase S8 family. Contains 1 homo B/P domain. Contains 1 PLAC domain.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Ligand	Calcium
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	determination of left/right symmetry Inferred from electronic annotation. Source: Compara glycoprotein metabolic process Inferred from direct assay PubMed 8218226. Source: BHF-UCL nerve growth factor processing Traceable author statement. Source: Reactome nerve growth factor production Inferred from direct assay PubMed 8615794. Source: BHF-UCL nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of BMP signaling pathway Traceable author statement PubMed 10467177. Source: BHF-UCL secretion by cell Inferred from direct assay PubMed 8615794. Source: BHF-UCL zygotic determination of anterior/posterior axis, embryo Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome cell surface Inferred from direct assay PubMed 12535616. Source: BHF-UCL endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular matrix Inferred from direct assay PubMed 12535616. Source: BHF-UCL extracellular space Inferred from direct assay Ref.7. Source: BHF-UCL membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	eukaryotic cell surface binding Inferred from direct assay PubMed 12535616. Source: BHF-UCL heparin binding Inferred from direct assay PubMed 12535616. Source: BHF-UCL nerve growth factor binding Inferred from direct assay PubMed 8615794. Source: BHF-UCL serine-type endopeptidase activity Inferred from direct assay PubMed 8218226PubMed 8615794Ref.7. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]

Isoform PACE4A-I (identifier: P29122-1)

Also known as: PACE4;

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.

Isoform PACE4A-II (identifier: P29122-2)

The sequence of this isoform differs from the canonical sequence as follows:
     680-693: AQSTPGSANILQTS → G

Isoform PACE4B (identifier: P29122-3)

Also known as: PACE4.1;

The sequence of this isoform differs from the canonical sequence as follows:
     471-471: K → KGAAVAFWWTIGWPWNV
     472-969: Missing.

Note: Probably enzymatically inactive.

Isoform PACE4C (identifier: P29122-4)

The sequence of this isoform differs from the canonical sequence as follows:
     621-652: KLKEWSLILYGTAEHPYHTFSAHQSRSRMLEL → DLETPVANQLTTEEREPGLKHVFRWQIEQELW
     653-969: Missing.

Note: Probably enzymatically inactive.

Isoform PACE4CS (identifier: P29122-5)

The sequence of this isoform differs from the canonical sequence as follows:
     621-623: KLK → NLD
     624-969: Missing.

Note: Probably enzymatically inactive.

Isoform PACE4D (identifier: P29122-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-167: Missing.
     621-664: KLKEWSLILY...PELEPPKAAL → DLETPVANQL...YHIVLITVAL
     665-969: Missing.

Note: Probably enzymatically inactive.

Isoform PACE4E-I (identifier: P29122-7)

The sequence of this isoform differs from the canonical sequence as follows:
     901-969: CDENCLSCAG...FCCRTCLLAG → YGPPGGERQA...AVGRHRAAAG

Isoform PACE4E-II (identifier: P29122-8)

The sequence of this isoform differs from the canonical sequence as follows:
     680-693: AQSTPGSANILQTS → G
     901-969: CDENCLSCAG...FCCRTCLLAG → YGPPGGERQA...AVGRHRAAAG

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 63	63	Potential
	Propeptide	64 – 149	86			PRO_0000027110
	Chain	150 – 969	820	Proprotein convertase subtilisin/kexin type 6		PRO_0000027111
Regions
	Domain	496 – 634	139	Homo B/P
	Domain	931 – 969	39	PLAC
	Region	150 – 454	305	Catalytic
	Region	695 – 930	236	CRM (Cys-rich motif)
	Motif	553 – 555	3	Cell attachment site Potential
Sites
	Active site	205	1	Charge relay system By similarity
	Active site	246	1	Charge relay system By similarity
	Active site	420	1	Charge relay system By similarity
	Site	149 – 150	2	Cleavage; by autolysis
Amino acid modifications
	Glycosylation	259	1	N-linked (GlcNAc...) Potential
	Glycosylation	914	1	N-linked (GlcNAc...) Potential
	Glycosylation	932	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 167	167	Missing in isoform PACE4D.		VSP_005427
	Alternative sequence	471	1	K → KGAAVAFWWTIGWPWNV in isoform PACE4B.		VSP_005428
	Alternative sequence	472 – 969	498	Missing in isoform PACE4B.		VSP_005429
	Alternative sequence	621 – 664	44	KLKEW…PKAAL → DLETPVANQLTTEERFVSTP SILFHWSVYLSWSQYHIVLI TVAL in isoform PACE4D.		VSP_005434
	Alternative sequence	621 – 652	32	KLKEW…RMLEL → DLETPVANQLTTEEREPGLK HVFRWQIEQELW in isoform PACE4C.		VSP_005432
	Alternative sequence	621 – 623	3	KLK → NLD in isoform PACE4CS.		VSP_005430
	Alternative sequence	624 – 969	346	Missing in isoform PACE4CS.		VSP_005431
	Alternative sequence	653 – 969	317	Missing in isoform PACE4C.		VSP_005433
	Alternative sequence	665 – 969	305	Missing in isoform PACE4D.		VSP_005435
	Alternative sequence	680 – 693	14	AQSTP…ILQTS → G in isoform PACE4A-II and isoform PACE4E-II.		VSP_005436
	Alternative sequence	901 – 969	69	CDENC…CLLAG → YGPPGGERQATVSSKGVPGG QSLSASSPGAGEGMLHHPTV DRSPFTELLRGLRPFVHWMH ICWVPAVGRHRAAAG in isoform PACE4E-I and isoform PACE4E-II.		VSP_005437
	Natural variant	502	1	C → R. Corresponds to variant rs1058260 [ dbSNP | Ensembl ].		VAR_051824
Experimental info
	Sequence conflict	639	1	T → I in BAA21624. Ref.6
	Sequence conflict	639	1	T → I in BAA21625. Ref.6
	Sequence conflict	639	1	T → I in BAA21626. Ref.6
	Sequence conflict	639	1	T → I in BAA21627. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform PACE4A-I (PACE4) [UniParc]. Last modified December 1, 1992. Version 1. Checksum: A3599CC278D09B05	FASTA	969	106,420
	10 20 30 40 50 60 MPPRAPPAPG PRPPPRAAAA TDTAAGAGGA GGAGGAGGPG FRPLAPRPWR WLLLLALPAA 70 80 90 100 110 120 CSAPPPRPVY TNHWAVQVLG GPAEADRVAA AHGYLNLGQI GNLEDYYHFY HSKTFKRSTL 130 140 150 160 170 180 SSRGPHTFLR MDPQVKWLQQ QEVKRRVKRQ VRSDPQALYF NDPIWSNMWY LHCGDKNSRC 190 200 210 220 230 240 RSEMNVQAAW KRGYTGKNVV VTILDDGIER NHPDLAPNYD SYASYDVNGN DYDPSPRYDA 250 260 270 280 290 300 SNENKHGTRC AGEVAASANN SYCIVGIAYN AKIGGIRMLD GDVTDVVEAK SLGIRPNYID 310 320 330 340 350 360 IYSASWGPDD DGKTVDGPGR LAKQAFEYGI KKGRQGLGSI FVWASGNGGR EGDYCSCDGY 370 380 390 400 410 420 TNSIYTISVS SATENGYKPW YLEECASTLA TTYSSGAFYE RKIVTTDLRQ RCTDGHTGTS 430 440 450 460 470 480 VSAPMVAGII ALALEANSQL TWRDVQHLLV KTSRPAHLKA SDWKVNGAGH KVSHFYGFGL 490 500 510 520 530 540 VDAEALVVEA KKWTAVPSQH MCVAASDKRP RSIPLVQVLR TTALTSACAE HSDQRVVYLE 550 560 570 580 590 600 HVVVRTSISH PRRGDLQIYL VSPSGTKSQL LAKRLLDLSN EGFTNWEFMT VHCWGEKAEG 610 620 630 640 650 660 QWTLEIQDLP SQVRNPEKQG KLKEWSLILY GTAEHPYHTF SAHQSRSRML ELSAPELEPP 670 680 690 700 710 720 KAALSPSQVE VPEDEEDYTA QSTPGSANIL QTSVCHPECG DKGCDGPNAD QCLNCVHFSL 730 740 750 760 770 780 GSVKTSRKCV SVCPLGYFGD TAARRCRRCH KGCETCSSRA ATQCLSCRRG FYHHQEMNTC 790 800 810 820 830 840 VTLCPAGFYA DESQKNCLKC HPSCKKCVDE PEKCTVCKEG FSLARGSCIP DCEPGTYFDS 850 860 870 880 890 900 ELIRCGECHH TCGTCVGPGR EECIHCAKNF HFHDWKCVPA CGEGFYPEEM PGLPHKVCRR 910 920 930 940 950 960 CDENCLSCAG SSRNCSRCKT GFTQLGTSCI TNHTCSNADE TFCEMVKSNR LCERKLFIQF CCRTCLLAG
	Isoform PACE4A-II [UniParc]. Checksum: BA240E3EEBCC862F	FASTA	956	105,121
	10 20 30 40 50 60 MPPRAPPAPG PRPPPRAAAA TDTAAGAGGA GGAGGAGGPG FRPLAPRPWR WLLLLALPAA 70 80 90 100 110 120 CSAPPPRPVY TNHWAVQVLG GPAEADRVAA AHGYLNLGQI GNLEDYYHFY HSKTFKRSTL 130 140 150 160 170 180 SSRGPHTFLR MDPQVKWLQQ QEVKRRVKRQ VRSDPQALYF NDPIWSNMWY LHCGDKNSRC 190 200 210 220 230 240 RSEMNVQAAW KRGYTGKNVV VTILDDGIER NHPDLAPNYD SYASYDVNGN DYDPSPRYDA 250 260 270 280 290 300 SNENKHGTRC AGEVAASANN SYCIVGIAYN AKIGGIRMLD GDVTDVVEAK SLGIRPNYID 310 320 330 340 350 360 IYSASWGPDD DGKTVDGPGR LAKQAFEYGI KKGRQGLGSI FVWASGNGGR EGDYCSCDGY 370 380 390 400 410 420 TNSIYTISVS SATENGYKPW YLEECASTLA TTYSSGAFYE RKIVTTDLRQ RCTDGHTGTS 430 440 450 460 470 480 VSAPMVAGII ALALEANSQL TWRDVQHLLV KTSRPAHLKA SDWKVNGAGH KVSHFYGFGL 490 500 510 520 530 540 VDAEALVVEA KKWTAVPSQH MCVAASDKRP RSIPLVQVLR TTALTSACAE HSDQRVVYLE 550 560 570 580 590 600 HVVVRTSISH PRRGDLQIYL VSPSGTKSQL LAKRLLDLSN EGFTNWEFMT VHCWGEKAEG 610 620 630 640 650 660 QWTLEIQDLP SQVRNPEKQG KLKEWSLILY GTAEHPYHTF SAHQSRSRML ELSAPELEPP 670 680 690 700 710 720 KAALSPSQVE VPEDEEDYTG VCHPECGDKG CDGPNADQCL NCVHFSLGSV KTSRKCVSVC 730 740 750 760 770 780 PLGYFGDTAA RRCRRCHKGC ETCSSRAATQ CLSCRRGFYH HQEMNTCVTL CPAGFYADES 790 800 810 820 830 840 QKNCLKCHPS CKKCVDEPEK CTVCKEGFSL ARGSCIPDCE PGTYFDSELI RCGECHHTCG 850 860 870 880 890 900 TCVGPGREEC IHCAKNFHFH DWKCVPACGE GFYPEEMPGL PHKVCRRCDE NCLSCAGSSR 910 920 930 940 950 NCSRCKTGFT QLGTSCITNH TCSNADETFC EMVKSNRLCE RKLFIQFCCR TCLLAG
	Isoform PACE4B (PACE4.1) [UniParc]. Checksum: 10DB376359A7F1AF	FASTA	487	53,044
	10 20 30 40 50 60 MPPRAPPAPG PRPPPRAAAA TDTAAGAGGA GGAGGAGGPG FRPLAPRPWR WLLLLALPAA 70 80 90 100 110 120 CSAPPPRPVY TNHWAVQVLG GPAEADRVAA AHGYLNLGQI GNLEDYYHFY HSKTFKRSTL 130 140 150 160 170 180 SSRGPHTFLR MDPQVKWLQQ QEVKRRVKRQ VRSDPQALYF NDPIWSNMWY LHCGDKNSRC 190 200 210 220 230 240 RSEMNVQAAW KRGYTGKNVV VTILDDGIER NHPDLAPNYD SYASYDVNGN DYDPSPRYDA 250 260 270 280 290 300 SNENKHGTRC AGEVAASANN SYCIVGIAYN AKIGGIRMLD GDVTDVVEAK SLGIRPNYID 310 320 330 340 350 360 IYSASWGPDD DGKTVDGPGR LAKQAFEYGI KKGRQGLGSI FVWASGNGGR EGDYCSCDGY 370 380 390 400 410 420 TNSIYTISVS SATENGYKPW YLEECASTLA TTYSSGAFYE RKIVTTDLRQ RCTDGHTGTS 430 440 450 460 470 480 VSAPMVAGII ALALEANSQL TWRDVQHLLV KTSRPAHLKA SDWKVNGAGH KGAAVAFWWT IGWPWNV
	Isoform PACE4C [UniParc]. Checksum: 880D99278881942C	FASTA	652	71,771
	10 20 30 40 50 60 MPPRAPPAPG PRPPPRAAAA TDTAAGAGGA GGAGGAGGPG FRPLAPRPWR WLLLLALPAA 70 80 90 100 110 120 CSAPPPRPVY TNHWAVQVLG GPAEADRVAA AHGYLNLGQI GNLEDYYHFY HSKTFKRSTL 130 140 150 160 170 180 SSRGPHTFLR MDPQVKWLQQ QEVKRRVKRQ VRSDPQALYF NDPIWSNMWY LHCGDKNSRC 190 200 210 220 230 240 RSEMNVQAAW KRGYTGKNVV VTILDDGIER NHPDLAPNYD SYASYDVNGN DYDPSPRYDA 250 260 270 280 290 300 SNENKHGTRC AGEVAASANN SYCIVGIAYN AKIGGIRMLD GDVTDVVEAK SLGIRPNYID 310 320 330 340 350 360 IYSASWGPDD DGKTVDGPGR LAKQAFEYGI KKGRQGLGSI FVWASGNGGR EGDYCSCDGY 370 380 390 400 410 420 TNSIYTISVS SATENGYKPW YLEECASTLA TTYSSGAFYE RKIVTTDLRQ RCTDGHTGTS 430 440 450 460 470 480 VSAPMVAGII ALALEANSQL TWRDVQHLLV KTSRPAHLKA SDWKVNGAGH KVSHFYGFGL 490 500 510 520 530 540 VDAEALVVEA KKWTAVPSQH MCVAASDKRP RSIPLVQVLR TTALTSACAE HSDQRVVYLE 550 560 570 580 590 600 HVVVRTSISH PRRGDLQIYL VSPSGTKSQL LAKRLLDLSN EGFTNWEFMT VHCWGEKAEG 610 620 630 640 650 QWTLEIQDLP SQVRNPEKQG DLETPVANQL TTEEREPGLK HVFRWQIEQE LW
	Isoform PACE4CS [UniParc]. Checksum: 19BCB5350278C621	FASTA	623	68,238
	10 20 30 40 50 60 MPPRAPPAPG PRPPPRAAAA TDTAAGAGGA GGAGGAGGPG FRPLAPRPWR WLLLLALPAA 70 80 90 100 110 120 CSAPPPRPVY TNHWAVQVLG GPAEADRVAA AHGYLNLGQI GNLEDYYHFY HSKTFKRSTL 130 140 150 160 170 180 SSRGPHTFLR MDPQVKWLQQ QEVKRRVKRQ VRSDPQALYF NDPIWSNMWY LHCGDKNSRC 190 200 210 220 230 240 RSEMNVQAAW KRGYTGKNVV VTILDDGIER NHPDLAPNYD SYASYDVNGN DYDPSPRYDA 250 260 270 280 290 300 SNENKHGTRC AGEVAASANN SYCIVGIAYN AKIGGIRMLD GDVTDVVEAK SLGIRPNYID 310 320 330 340 350 360 IYSASWGPDD DGKTVDGPGR LAKQAFEYGI KKGRQGLGSI FVWASGNGGR EGDYCSCDGY 370 380 390 400 410 420 TNSIYTISVS SATENGYKPW YLEECASTLA TTYSSGAFYE RKIVTTDLRQ RCTDGHTGTS 430 440 450 460 470 480 VSAPMVAGII ALALEANSQL TWRDVQHLLV KTSRPAHLKA SDWKVNGAGH KVSHFYGFGL 490 500 510 520 530 540 VDAEALVVEA KKWTAVPSQH MCVAASDKRP RSIPLVQVLR TTALTSACAE HSDQRVVYLE 550 560 570 580 590 600 HVVVRTSISH PRRGDLQIYL VSPSGTKSQL LAKRLLDLSN EGFTNWEFMT VHCWGEKAEG 610 620 QWTLEIQDLP SQVRNPEKQG NLD
	Isoform PACE4D [UniParc]. Checksum: 46C1F64CAEA0E3EB	FASTA	497	54,900
	10 20 30 40 50 60 MWYLHCGDKN SRCRSEMNVQ AAWKRGYTGK NVVVTILDDG IERNHPDLAP NYDSYASYDV 70 80 90 100 110 120 NGNDYDPSPR YDASNENKHG TRCAGEVAAS ANNSYCIVGI AYNAKIGGIR MLDGDVTDVV 130 140 150 160 170 180 EAKSLGIRPN YIDIYSASWG PDDDGKTVDG PGRLAKQAFE YGIKKGRQGL GSIFVWASGN 190 200 210 220 230 240 GGREGDYCSC DGYTNSIYTI SVSSATENGY KPWYLEECAS TLATTYSSGA FYERKIVTTD 250 260 270 280 290 300 LRQRCTDGHT GTSVSAPMVA GIIALALEAN SQLTWRDVQH LLVKTSRPAH LKASDWKVNG 310 320 330 340 350 360 AGHKVSHFYG FGLVDAEALV VEAKKWTAVP SQHMCVAASD KRPRSIPLVQ VLRTTALTSA 370 380 390 400 410 420 CAEHSDQRVV YLEHVVVRTS ISHPRRGDLQ IYLVSPSGTK SQLLAKRLLD LSNEGFTNWE 430 440 450 460 470 480 FMTVHCWGEK AEGQWTLEIQ DLPSQVRNPE KQGDLETPVA NQLTTEERFV STPSILFHWS 490 VYLSWSQYHI VLITVAL
	Isoform PACE4E-I [UniParc]. Checksum: 31983E526116A67C	FASTA	975	106,674
	10 20 30 40 50 60 MPPRAPPAPG PRPPPRAAAA TDTAAGAGGA GGAGGAGGPG FRPLAPRPWR WLLLLALPAA 70 80 90 100 110 120 CSAPPPRPVY TNHWAVQVLG GPAEADRVAA AHGYLNLGQI GNLEDYYHFY HSKTFKRSTL 130 140 150 160 170 180 SSRGPHTFLR MDPQVKWLQQ QEVKRRVKRQ VRSDPQALYF NDPIWSNMWY LHCGDKNSRC 190 200 210 220 230 240 RSEMNVQAAW KRGYTGKNVV VTILDDGIER NHPDLAPNYD SYASYDVNGN DYDPSPRYDA 250 260 270 280 290 300 SNENKHGTRC AGEVAASANN SYCIVGIAYN AKIGGIRMLD GDVTDVVEAK SLGIRPNYID 310 320 330 340 350 360 IYSASWGPDD DGKTVDGPGR LAKQAFEYGI KKGRQGLGSI FVWASGNGGR EGDYCSCDGY 370 380 390 400 410 420 TNSIYTISVS SATENGYKPW YLEECASTLA TTYSSGAFYE RKIVTTDLRQ RCTDGHTGTS 430 440 450 460 470 480 VSAPMVAGII ALALEANSQL TWRDVQHLLV KTSRPAHLKA SDWKVNGAGH KVSHFYGFGL 490 500 510 520 530 540 VDAEALVVEA KKWTAVPSQH MCVAASDKRP RSIPLVQVLR TTALTSACAE HSDQRVVYLE 550 560 570 580 590 600 HVVVRTSISH PRRGDLQIYL VSPSGTKSQL LAKRLLDLSN EGFTNWEFMT VHCWGEKAEG 610 620 630 640 650 660 QWTLEIQDLP SQVRNPEKQG KLKEWSLILY GTAEHPYHTF SAHQSRSRML ELSAPELEPP 670 680 690 700 710 720 KAALSPSQVE VPEDEEDYTA QSTPGSANIL QTSVCHPECG DKGCDGPNAD QCLNCVHFSL 730 740 750 760 770 780 GSVKTSRKCV SVCPLGYFGD TAARRCRRCH KGCETCSSRA ATQCLSCRRG FYHHQEMNTC 790 800 810 820 830 840 VTLCPAGFYA DESQKNCLKC HPSCKKCVDE PEKCTVCKEG FSLARGSCIP DCEPGTYFDS 850 860 870 880 890 900 ELIRCGECHH TCGTCVGPGR EECIHCAKNF HFHDWKCVPA CGEGFYPEEM PGLPHKVCRR 910 920 930 940 950 960 YGPPGGERQA TVSSKGVPGG QSLSASSPGA GEGMLHHPTV DRSPFTELLR GLRPFVHWMH 970 ICWVPAVGRH RAAAG
	Isoform PACE4E-II [UniParc]. Checksum: F16ABF9230DE5F01	FASTA	962	105,375
	10 20 30 40 50 60 MPPRAPPAPG PRPPPRAAAA TDTAAGAGGA GGAGGAGGPG FRPLAPRPWR WLLLLALPAA 70 80 90 100 110 120 CSAPPPRPVY TNHWAVQVLG GPAEADRVAA AHGYLNLGQI GNLEDYYHFY HSKTFKRSTL 130 140 150 160 170 180 SSRGPHTFLR MDPQVKWLQQ QEVKRRVKRQ VRSDPQALYF NDPIWSNMWY LHCGDKNSRC 190 200 210 220 230 240 RSEMNVQAAW KRGYTGKNVV VTILDDGIER NHPDLAPNYD SYASYDVNGN DYDPSPRYDA 250 260 270 280 290 300 SNENKHGTRC AGEVAASANN SYCIVGIAYN AKIGGIRMLD GDVTDVVEAK SLGIRPNYID 310 320 330 340 350 360 IYSASWGPDD DGKTVDGPGR LAKQAFEYGI KKGRQGLGSI FVWASGNGGR EGDYCSCDGY 370 380 390 400 410 420 TNSIYTISVS SATENGYKPW YLEECASTLA TTYSSGAFYE RKIVTTDLRQ RCTDGHTGTS 430 440 450 460 470 480 VSAPMVAGII ALALEANSQL TWRDVQHLLV KTSRPAHLKA SDWKVNGAGH KVSHFYGFGL 490 500 510 520 530 540 VDAEALVVEA KKWTAVPSQH MCVAASDKRP RSIPLVQVLR TTALTSACAE HSDQRVVYLE 550 560 570 580 590 600 HVVVRTSISH PRRGDLQIYL VSPSGTKSQL LAKRLLDLSN EGFTNWEFMT VHCWGEKAEG 610 620 630 640 650 660 QWTLEIQDLP SQVRNPEKQG KLKEWSLILY GTAEHPYHTF SAHQSRSRML ELSAPELEPP 670 680 690 700 710 720 KAALSPSQVE VPEDEEDYTG VCHPECGDKG CDGPNADQCL NCVHFSLGSV KTSRKCVSVC 730 740 750 760 770 780 PLGYFGDTAA RRCRRCHKGC ETCSSRAATQ CLSCRRGFYH HQEMNTCVTL CPAGFYADES 790 800 810 820 830 840 QKNCLKCHPS CKKCVDEPEK CTVCKEGFSL ARGSCIPDCE PGTYFDSELI RCGECHHTCG 850 860 870 880 890 900 TCVGPGREEC IHCAKNFHFH DWKCVPACGE GFYPEEMPGL PHKVCRRYGP PGGERQATVS 910 920 930 940 950 960 SKGVPGGQSL SASSPGAGEG MLHHPTVDRS PFTELLRGLR PFVHWMHICW VPAVGRHRAA AG

References

[1]	"Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15." Kiefer M.C., Tucker J.E., Joh R., Landsberg K.E., Saltman D., Barr P.J. DNA Cell Biol. 10:757-769(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PACE4A-I AND PACE4B). Tissue: Hepatoma and Kidney.
[2]	"Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms." Tsuji A., Higashine K., Hine C., Mori K., Tamai Y., Nagamune H., Matsuda Y. Biochem. Biophys. Res. Commun. 200:943-950(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PACE4C AND PACE4D). Tissue: Placenta.
[3]	Erratum Tsuji A., Higashine K., Hine C., Mori K., Tamai Y., Nagamune H., Matsuda Y. Biochem. Biophys. Res. Commun. 204:1381-1382(1994) [PubMed] [Europe PMC] [Abstract]
[4]	"Identification of a novel PACE4 isoform, PACE4E." Mori K., Imamaki A., Kii S., Nagamune H., Nagahama M., Tsuji A., Matsuda Y. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM PACE4A-II). Tissue: Placenta.
[5]	"A novel human PACE4 isoform, PACE4E is an active processing protease containing a hydrophobic cluster at the carboxy terminus." Mori K., Kii S., Tsuji A., Nagahama M., Imamaki A., Hayashi K., Akamatsu T., Nagamune H., Matsuda Y. J. Biochem. 121:941-948(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PACE4E-I AND PACE4E-II). Tissue: Cerebellum.
[6]	"Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease." Tsuji A., Hine C., Tamai Y., Yonemoto K., Mori K., Yoshida S., Bando M., Sakai E., Mori K., Akamatsu T., Matsuda Y. J. Biochem. 122:438-452(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS PACE4A-I; PACE4A-II; PACE4CS; PACE4D; PACE4E-I AND PACE4E-II).
[7]	"Functional analysis of human PACE4-A and PACE4-C isoforms: identification of a new PACE4-CS isoform." Zhong M., Benjannet S., Lazure C., Munzer S., Seidah N.G. FEBS Lett. 396:31-36(1996) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM PACE4CS).
[8]	"Endoprotease PACE4 is Ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain." Sucic J.F., Moehring J.M., Inocencio N.M., Luchini J.W., Moehring T.J. Biochem. J. 339:639-647(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[9]	"Biosynthetic processing and quaternary interactions of proprotein convertase SPC4 (PACE4)." Nagahama M., Taniguchi T., Hashimoto E., Imamaki A., Mori K., Tsuji A., Matsuda Y. FEBS Lett. 434:155-159(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M80482 mRNA. Translation: AAA59998.1. AB001914 Genomic DNA. Translation: BAA21620.1. AB001914 Genomic DNA. Translation: BAA21621.1. AB001914 Genomic DNA. Translation: BAA21622.1. AB001914 Genomic DNA. Translation: BAA21623.1. AB001914 Genomic DNA. Translation: BAA21624.1. AB001914 Genomic DNA. Translation: BAA21625.1. AB001914 Genomic DNA. Translation: BAA21626.1. AB001914 Genomic DNA. Translation: BAA21627.1. D28513 mRNA. Translation: BAA05871.1. D28514 mRNA. Translation: BAA05872.1. D87995 mRNA. Translation: BAA21793.1. D87993 mRNA. Translation: BAA21791.1. D87994 mRNA. Translation: BAA21792.1.
IPI	IPI00020396. IPI00217331. IPI00217332. IPI00217333. IPI00217334. IPI00293159. IPI00332449. IPI00982047.
PIR	A39490. B39490. JC2191. JC2192. JC5570. JC5571.
RefSeq	NP_002561.1. NM_002570.3. NP_612192.1. NM_138319.2. NP_612193.1. NM_138320.1. NP_612194.1. NM_138321.1. NP_612195.1. NM_138322.2. NP_612196.1. NM_138323.1. NP_612197.1. NM_138324.1. NP_612198.2. NM_138325.2.
UniGene	Hs.498494. Hs.665989.
3D structure databases
ProteinModelPortal	P29122.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29903N.
IntAct	P29122. 3 interactions.
Protein family/group databases
MEROPS	S08.075.
PTM databases
PhosphoSite	P29122.
Polymorphism databases
DMDM	129542.
Proteomic databases
PaxDb	P29122.
PRIDE	P29122.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000348070; ENSP00000305056; ENSG00000140479.
GeneID	5046.
KEGG	hsa:5046.
UCSC	uc002bwy.3. human. uc002bxa.2. human. uc002bxb.2. human. uc002bxc.1. human. uc002bxd.1. human. uc002bxg.1. human. uc010bpe.3. human.
Organism-specific databases
CTD	5046.
GeneCards	GC15M101844.
HGNC	HGNC:8569. PCSK6.
HPA	HPA004774.
MIM	167405. gene.
neXtProt	NX_P29122.
PharmGKB	PA32895.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4935.
HOVERGEN	HBG008705.
InParanoid	P29122.
KO	K08672.
OrthoDB	EOG44MXR9.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P29122.
Bgee	P29122.
Genevestigator	P29122.
GermOnline	ENSG00000140479. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.200. 1 hit.
InterPro	IPR006212. Furin_repeat. IPR008979. Galactose-bd-like. 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. IPR010909. PLAC. IPR009020. Prot_inh_propept. IPR002884. PrprotnconvertsP. [Graphical view]
PANTHER	PTHR10795. PTHR10795. 1 hit.
Pfam	PF01483. P_proprotein. 1 hit. PF00082. Peptidase_S8. 1 hit. PF08686. PLAC. 1 hit. [Graphical view]
PRINTS	PR00723. SUBTILISIN.
SMART	SM00261. FU. 5 hits. [Graphical view]
SUPFAM	SSF49785. Gal_bind_like. 1 hit. SSF57184. Grow_fac_recept. 2 hits. SSF52743. Pept_S8_S53. 1 hit. SSF54897. Prot_inh_propept. 1 hit.
PROSITE	PS50900. PLAC. 1 hit. PS00136. SUBTILASE_ASP. 1 hit. PS00137. SUBTILASE_HIS. 1 hit. PS00138. SUBTILASE_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P29122.
ChEMBL	CHEMBL2951.
GenomeRNAi	5046.
NextBio	19426.
SOURCE	Search...

Entry information

Entry name

PCSK6_HUMAN

Accession

Primary (citable) accession number: P29122
Secondary accession number(s): Q15099 , Q15100, Q9UEG7, Q9UEJ1, Q9UEJ2, Q9UEJ7, Q9UEJ8, Q9UEJ9, Q9Y4G9, Q9Y4H0, Q9Y4H1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	May 1, 2013
This is version 138 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.