PCSK6 (proprotein convertase subtilisin/kexin type 6)

Gene

• Entrez ID: 5046
• Gene name: Proprotein convertase subtilisin/kexin type 6
• Gene symbol: PCSK6
• Synonyms: PACE4, SPC4
• Chromosome: 15
• Chromosome location: 15q26.3
• Summary: This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein under

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT039239	hsa-miR-454-3p	CLASH	23622248
MIRT701011	hsa-miR-302f	HITS-CLIP	23313552
MIRT701010	hsa-miR-6782-3p	HITS-CLIP	23313552
MIRT701009	hsa-miR-3190-5p	HITS-CLIP	23313552
MIRT701008	hsa-miR-219b-3p	HITS-CLIP	23313552
MIRT701007	hsa-miR-4529-5p	HITS-CLIP	23313552
MIRT701006	hsa-miR-3652	HITS-CLIP	23313552
MIRT701005	hsa-miR-4430	HITS-CLIP	23313552
MIRT701004	hsa-miR-4505	HITS-CLIP	23313552
MIRT701003	hsa-miR-5787	HITS-CLIP	23313552
MIRT701002	hsa-miR-1273e	HITS-CLIP	23313552
MIRT701001	hsa-miR-548s	HITS-CLIP	23313552
MIRT701000	hsa-miR-4701-5p	HITS-CLIP	23313552
MIRT700999	hsa-miR-588	HITS-CLIP	23313552
MIRT700998	hsa-miR-4435	HITS-CLIP	23313552
MIRT700997	hsa-miR-3187-3p	HITS-CLIP	23313552
MIRT700996	hsa-miR-647	HITS-CLIP	23313552
MIRT700995	hsa-miR-6842-3p	HITS-CLIP	23313552
MIRT701011	hsa-miR-302f	HITS-CLIP	23313552
MIRT701010	hsa-miR-6782-3p	HITS-CLIP	23313552
MIRT701009	hsa-miR-3190-5p	HITS-CLIP	23313552
MIRT701008	hsa-miR-219b-3p	HITS-CLIP	23313552
MIRT701007	hsa-miR-4529-5p	HITS-CLIP	23313552
MIRT701006	hsa-miR-3652	HITS-CLIP	23313552
MIRT701005	hsa-miR-4430	HITS-CLIP	23313552
MIRT701004	hsa-miR-4505	HITS-CLIP	23313552
MIRT701003	hsa-miR-5787	HITS-CLIP	23313552
MIRT701002	hsa-miR-1273e	HITS-CLIP	23313552
MIRT701001	hsa-miR-548s	HITS-CLIP	23313552
MIRT701000	hsa-miR-4701-5p	HITS-CLIP	23313552
MIRT700999	hsa-miR-588	HITS-CLIP	23313552
MIRT700998	hsa-miR-4435	HITS-CLIP	23313552
MIRT700997	hsa-miR-3187-3p	HITS-CLIP	23313552
MIRT700996	hsa-miR-647	HITS-CLIP	23313552
MIRT700995	hsa-miR-6842-3p	HITS-CLIP	23313552
MIRT1218527	hsa-miR-1271	CLIP-seq
MIRT1218528	hsa-miR-182	CLIP-seq
MIRT1218529	hsa-miR-21	CLIP-seq
MIRT1218530	hsa-miR-3163	CLIP-seq
MIRT1218531	hsa-miR-340	CLIP-seq
MIRT1218532	hsa-miR-3662	CLIP-seq
MIRT1218533	hsa-miR-4464	CLIP-seq
MIRT1218534	hsa-miR-4672	CLIP-seq
MIRT1218535	hsa-miR-4748	CLIP-seq
MIRT1218536	hsa-miR-4773	CLIP-seq
MIRT1218537	hsa-miR-548c-3p	CLIP-seq
MIRT1218538	hsa-miR-590-5p	CLIP-seq
MIRT1218539	hsa-miR-96	CLIP-seq
MIRT1218540	hsa-miR-103a	CLIP-seq
MIRT1218541	hsa-miR-107	CLIP-seq
MIRT1218542	hsa-miR-15a	CLIP-seq
MIRT1218543	hsa-miR-15b	CLIP-seq
MIRT1218544	hsa-miR-16	CLIP-seq
MIRT1218545	hsa-miR-195	CLIP-seq
MIRT1218546	hsa-miR-424	CLIP-seq
MIRT1218547	hsa-miR-4310	CLIP-seq
MIRT1218548	hsa-miR-497	CLIP-seq
MIRT1218549	hsa-miR-3920	CLIP-seq
MIRT1218550	hsa-miR-3921	CLIP-seq
MIRT1218551	hsa-miR-4653-5p	CLIP-seq
MIRT1218552	hsa-miR-4768-5p	CLIP-seq
MIRT1218553	hsa-miR-146a	CLIP-seq
MIRT1218554	hsa-miR-146b-5p	CLIP-seq
MIRT1218555	hsa-miR-218	CLIP-seq
MIRT1218530	hsa-miR-3163	CLIP-seq
MIRT1218532	hsa-miR-3662	CLIP-seq
MIRT1218556	hsa-miR-3908	CLIP-seq
MIRT1218557	hsa-miR-3910	CLIP-seq
MIRT1218558	hsa-miR-3942-5p	CLIP-seq
MIRT1218559	hsa-miR-4703-5p	CLIP-seq
MIRT1218560	hsa-miR-4766-3p	CLIP-seq
MIRT1218536	hsa-miR-4773	CLIP-seq
MIRT1218561	hsa-miR-589	CLIP-seq
MIRT1218562	hsa-miR-636	CLIP-seq
MIRT2439230	hsa-miR-375	CLIP-seq
MIRT2439231	hsa-miR-4320	CLIP-seq
MIRT2439232	hsa-miR-4326	CLIP-seq
MIRT2439233	hsa-miR-4760-3p	CLIP-seq
MIRT2439234	hsa-miR-579	CLIP-seq
MIRT2439235	hsa-miR-664	CLIP-seq
MIRT2439230	hsa-miR-375	CLIP-seq
MIRT2439231	hsa-miR-4320	CLIP-seq
MIRT2439232	hsa-miR-4326	CLIP-seq
MIRT2439233	hsa-miR-4760-3p	CLIP-seq
MIRT2439234	hsa-miR-579	CLIP-seq
MIRT2439235	hsa-miR-664	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ASCL1	Repression	11736660
E2F1	Activation	17825503

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004175	Function	Endopeptidase activity	IDA	9242664
GO:0004252	Function	Serine-type endopeptidase activity	IBA	21873635
GO:0004252	Function	Serine-type endopeptidase activity	IDA	8218226, 8615794, 8906861
GO:0005515	Function	Protein binding	IPI	16433634, 32296183
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	8906861
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005796	Component	Golgi lumen	TAS
GO:0005886	Component	Plasma membrane	TAS
GO:0008201	Function	Heparin binding	IDA	12535616
GO:0009100	Process	Glycoprotein metabolic process	IDA	8218226
GO:0009986	Component	Cell surface	IBA	21873635
GO:0009986	Component	Cell surface	IDA	12535616
GO:0016020	Component	Membrane	IBA	21873635
GO:0016485	Process	Protein processing	IBA	21873635
GO:0016485	Process	Protein processing	IDA	8218226, 9242664, 9738469
GO:0016486	Process	Peptide hormone processing	IBA	21873635
GO:0016486	Process	Peptide hormone processing	IDA	9242664
GO:0030510	Process	Regulation of BMP signaling pathway	TAS	10467177
GO:0032455	Process	Nerve growth factor processing	TAS
GO:0032902	Process	Nerve growth factor production	IDA	8615794
GO:0032940	Process	Secretion by cell	IDA	8615794
GO:0048406	Function	Nerve growth factor binding	IDA	8615794
GO:0051004	Process	Regulation of lipoprotein lipase activity	TAS
GO:0062023	Component	Collagen-containing extracellular matrix	IBA	21873635
GO:0062023	Component	Collagen-containing extracellular matrix	IDA	12535616
GO:0070268	Process	Cornification	TAS

Other IDs

• MIM: 167405
• HGNC: 8569
• e!Ensembl: ENSG00000140479

Protein

• UniProt ID: P29122
• Protein name: Proprotein convertase subtilisin/kexin type 6 (EC 3.4.21.-) (Paired basic amino acid cleaving enzyme 4) (Subtilisin-like proprotein convertase 4) (SPC4) (Subtilisin/kexin-like protease PACE4)
• Protein function: Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive secretory pathway, with unique restricted distribution in both neuroe
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16470	S8_pro-domain	73 → 149	Peptidase S8 pro-domain	Domain
  PF00082	Peptidase_S8	196 → 479	Subtilase family	Domain
  PF01483	P_proprotein	539 → 629	Proprotein convertase P-domain	Family
  PF14843	GF_recep_IV	694 → 812	Growth factor receptor domain IV	Domain
  PF08686	PLAC	935 → 966	PLAC (protease and lacunin) domain	Domain

• Sequence:

  MPPRAPPAPGPRPPPRAAAATDTAAGAGGAGGAGGAGGPGFRPLAPRPWRWLLLLALPAA
  CSAPPPRPVYTNHWAVQVLGGPAEADRVAAAHGYLNLGQIGNLEDYYHFYHSKTFKRSTL
  SSRGPHTFLRMDPQVKWLQQQEVKRRVKRQVRSDPQALYFNDPIWSNMWYLHCGDKNSRC
  RSEMNVQAAWKRGYTGKNVVVTILDDGIERNHPDLAPNYDSYASYDVNGNDYDPSPRYDA
  SNENKHGTRCAGEVAASANNSYCIVGIAYNAKIGGIRMLDGDVTDVVEAKSLGIRPNYID
  IYSASWGPDDDGKTVDGPGRLAKQAFEYGIKKGRQGLGSIFVWASGNGGREGDYCSCDGY
  TNSIYTISVSSATENGYKPWYLEECASTLATTYSSGAFYERKIVTTDLRQRCTDGHTGTS
  VSAPMVAGIIALALEANSQLTWRDVQHLLVKTSRPAHLKASDWKVNGAGHKVSHFYGFGL
  VDAEALVVEAKKWTAVPSQHMCVAASDKRPRSIPLVQVLRTTALTSACAEHSDQRVVYLE
  HVVVRTSISHPRRGDLQIYLVSPSGTKSQLLAKRLLDLSNEGFTNWEFMTVHCWGEKAEG
  QWTLEIQDLPSQVRNPEKQGKLKEWSLILYGTAEHPYHTFSAHQSRSRMLELSAPELEPP
  KAALSPSQVEVPEDEEDYTAQSTPGSANILQTSVCHPECGDKGCDGPNADQCLNCVHFSL
  GSVKTSRKCVSVCPLGYFGDTAARRCRRCHKGCETCSSRAATQCLSCRRGFYHHQEMNTC
  VTLCPAGFYADESQKNCLKCHPSCKKCVDEPEKCTVCKEGFSLARGSCIPDCEPGTYFDS
  ELIRCGECHHTCGTCVGPGREECIHCAKNFHFHDWKCVPACGEGFYPEEMPGLPHKVCRR
  CDENCLSCAGSSRNCSRCKTGFTQLGTSCITNHTCSNADETFCEMVKSNRLCERKLFIQF
  CCRTCLLAG

• Sequence length: 969

Pathways

Reactome:

NGF processing
Formation of the cornified envelope
Assembly of active LPL and LIPC lipase complexes

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Diabetes mellitus	Diabetes Mellitus, Non-Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs1553638903, rs1553638909, rs948820149, rs371977235, rs1553784995, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	30470734
Leukemia	Leukemia, Myelocytic, Acute	rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297, rs11978267, rs4132601	27903959

Unknown
Disease name	Disease term	dbSNP ID	References
Dyslexia	Dyslexia		21051773, 24068947