PCOLCE

Summary

PCOLCE (procollagen C-endopeptidase enhancer, HGNC:8738) is a protein-coding gene on chromosome 7q22.1, encoding Procollagen C-endopeptidase enhancer 1 (Q15113). Binds to the C-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity.

Fibrillar collagen types I-III are synthesized as precursor molecules known as procollagens. These precursors contain amino- and carboxyl-terminal peptide extensions known as N- and C-propeptides, respectively, which are cleaved, upon secretion of procollagen from the cell, to yield the mature triple helical, highly structured fibrils. This gene encodes a glycoprotein which binds and drives the enzymatic cleavage of type I procollagen and heightens C-proteinase activity.

Source: NCBI Gene 5118 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 81 total
• GTEx eGene: eQTL in 7 tissues, sQTL in 3 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.07 (unconstrained)
• MANE Select transcript: NM_002593
• Notable: 81 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8738
Approved symbol	PCOLCE
Name	procollagen C-endopeptidase enhancer
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	PCPE, PCPE1
Ensembl gene	ENSG00000106333
Ensembl biotype	protein_coding
OMIM	600270
Entrez	5118

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 8 protein_coding, 7 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000223061

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 2, TSL 4: 2

ENST00000223061, ENST00000460002, ENST00000462260, ENST00000468214, ENST00000472348, ENST00000482863, ENST00000486440, ENST00000487172, ENST00000490909, ENST00000496269, ENST00000862594, ENST00000862595, ENST00000937380, ENST00000965183, ENST00000965184, ENST00000965185, ENST00001013738, ENST00001013739, ENST00001013740, ENST00001073989, ENST00001137226

RefSeq mRNA: 1 — MANE Select: NM_002593 NM_002593

CCDS: CCDS5700

Canonical transcript exons

ENST00000223061 — 9 exons

Exon	Start	End
ENSE00000710689	100605676	100605812
ENSE00000710690	100605091	100605215
ENSE00001861120	100602363	100602551
ENSE00001871599	100607937	100608175
ENSE00003524395	100607452	100607523
ENSE00003528702	100606416	100606630
ENSE00003592467	100603959	100604217
ENSE00003626772	100607637	100607807
ENSE00003687690	100603430	100603538

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 219.7107 / max 4445.8183, expressed in 1619 samples.

Highest expression (Bgee): stromal cell of endometrium, periodontal ligament, endocervix, tendon of biceps brachii, tibia.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PCOLCE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

10 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	4.4e-03	-0.10	7:100609146:T:C
Thyroid	eqtl	8.6e-03	+0.16	7:100601973:G:T
Small Intestine Terminal Ileum	sqtl	1.7e-02	-3.49	7:101350168:C:G
Testis	eqtl	1.9e-02	+0.56	7:101213448:G:A
Brain Amygdala	eqtl	2.2e-02	-0.24	7:101520550:G:A
Brain Cerebellum	eqtl	2.3e-02	+0.34	7:100838585:T:C
Nerve Tibial	eqtl	2.4e-02	+0.07	7:100642568:A:G
Adrenal Gland	eqtl	3.0e-02	-1.52	7:100738331:C:T
Adipose Visceral Omentum	sqtl	3.0e-02	+1.11	7:99970576:C:T
Brain Cerebellar Hemisphere	sqtl	3.7e-02	+2.59	7:101495959:C:T

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
80011	204.2556	1078
80012	8.4480	776
80019	1.8669	925
80021	1.6855	765
80013	1.1775	545
80022	1.1558	496
80017	0.4814	259
80020	0.4396	244
80016	0.2004	112

Top tissues by expression

showing 100 of 290 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.54	gold quality
periodontal ligament	UBERON:0008266	99.50	gold quality
endocervix	UBERON:0000458	98.84	gold quality
tendon of biceps brachii	UBERON:0008188	98.67	gold quality
tibia	UBERON:0000979	98.60	gold quality
cartilage tissue	UBERON:0002418	98.57	gold quality
apex of heart	UBERON:0002098	98.37	gold quality
gall bladder	UBERON:0002110	98.25	gold quality
right coronary artery	UBERON:0001625	98.11	gold quality
layer of synovial tissue	UBERON:0007616	97.96	gold quality
body of uterus	UBERON:0009853	97.92	gold quality
nerve	UBERON:0001021	97.84	gold quality
tibial nerve	UBERON:0001323	97.84	gold quality
right ovary	UBERON:0002118	97.81	gold quality
descending thoracic aorta	UBERON:0002345	97.77	gold quality
synovial joint	UBERON:0002217	97.75	gold quality
coronary artery	UBERON:0001621	97.66	gold quality
left coronary artery	UBERON:0001626	97.63	gold quality
ectocervix	UBERON:0012249	97.60	gold quality
metanephros cortex	UBERON:0010533	97.57	gold quality
right atrium auricular region	UBERON:0006631	97.56	gold quality
left uterine tube	UBERON:0001303	97.52	gold quality
decidua	UBERON:0002450	97.45	gold quality
pericardium	UBERON:0002407	97.43	gold quality
thoracic aorta	UBERON:0001515	97.32	gold quality
left ovary	UBERON:0002119	97.32	gold quality
omental fat pad	UBERON:0010414	97.32	gold quality
ascending aorta	UBERON:0001496	97.30	gold quality
peritoneum	UBERON:0002358	97.26	gold quality
parietal pleura	UBERON:0002400	97.20	gold quality
skin of hip	UBERON:0001554	96.97	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.91	gold quality
right lobe of thyroid gland	UBERON:0001119	96.78	gold quality
upper lobe of left lung	UBERON:0008952	96.66	gold quality
cardiac atrium	UBERON:0002081	96.62	gold quality
myometrium	UBERON:0001296	96.51	gold quality
upper lobe of lung	UBERON:0008948	96.41	gold quality
left adrenal gland cortex	UBERON:0035825	96.38	gold quality
right lobe of liver	UBERON:0001114	96.36	gold quality
smooth muscle tissue	UBERON:0001135	96.29	gold quality
right adrenal gland	UBERON:0001233	96.28	gold quality
adenohypophysis	UBERON:0002196	96.28	gold quality
vena cava	UBERON:0004087	96.21	gold quality
left adrenal gland	UBERON:0001234	96.18	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.01	gold quality
left lobe of thyroid gland	UBERON:0001120	95.99	gold quality
right adrenal gland cortex	UBERON:0035827	95.80	gold quality
adrenal cortex	UBERON:0001235	95.56	gold quality
aorta	UBERON:0000947	95.49	gold quality
nipple	UBERON:0002030	95.34	gold quality
right uterine tube	UBERON:0001302	95.18	gold quality
adipose tissue	UBERON:0001013	95.13	gold quality
connective tissue	UBERON:0002384	94.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.81	gold quality
vermiform appendix	UBERON:0001154	94.76	gold quality
thyroid gland	UBERON:0002046	94.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.75	gold quality
pleura	UBERON:0000977	94.74	gold quality
urethra	UBERON:0000057	94.61	gold quality
cerebellar hemisphere	UBERON:0002245	94.60	gold quality
adrenal gland	UBERON:0002369	94.59	gold quality
heart	UBERON:0000948	94.49	gold quality
skin of leg	UBERON:0001511	94.47	gold quality
cerebellar cortex	UBERON:0002129	94.35	gold quality
skin of abdomen	UBERON:0001416	94.26	gold quality
tibial artery	UBERON:0007610	94.22	gold quality
popliteal artery	UBERON:0002250	94.21	gold quality
saphenous vein	UBERON:0007318	94.21	gold quality
heart left ventricle	UBERON:0002084	94.19	gold quality
caecum	UBERON:0001153	94.09	gold quality
cardiac ventricle	UBERON:0002082	94.01	gold quality
right lung	UBERON:0002167	93.95	gold quality
cauda epididymis	UBERON:0004360	93.94	gold quality
colonic epithelium	UBERON:0000397	93.93	gold quality
upper arm skin	UBERON:0004263	93.89	gold quality
vagina	UBERON:0000996	93.88	gold quality
zone of skin	UBERON:0000014	93.81	gold quality
pituitary gland	UBERON:0000007	93.68	gold quality
ovary	UBERON:0000992	93.67	gold quality
mammalian vulva	UBERON:0000997	93.49	gold quality
mammary duct	UBERON:0001765	93.45	gold quality
mucosa of stomach	UBERON:0001199	93.28	gold quality
lymph node	UBERON:0000029	93.24	gold quality
breast	UBERON:0000310	93.09	gold quality
thoracic mammary gland	UBERON:0005200	93.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.05	gold quality
mammary gland	UBERON:0001911	92.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.86	gold quality
minor salivary gland	UBERON:0001830	92.72	gold quality
lung	UBERON:0002048	92.65	gold quality
right testis	UBERON:0004534	92.63	gold quality
prostate gland	UBERON:0002367	92.56	gold quality
fundus of stomach	UBERON:0001160	92.55	gold quality
liver	UBERON:0002107	92.47	gold quality
lower esophagus	UBERON:0013473	92.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.40	gold quality
left testis	UBERON:0004533	92.36	gold quality
superficial temporal artery	UBERON:0001614	92.34	gold quality
uterus	UBERON:0000995	92.29	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	2777.31
E-MTAB-6701	yes	1945.60
E-MTAB-8322	yes	1621.10
E-MTAB-6678	yes	1503.00
E-HCAD-10	yes	1229.07
E-MTAB-10287	yes	929.59
E-GEOD-124472	yes	756.99
E-GEOD-114530	yes	713.89
E-ANND-5	yes	617.67
E-GEOD-135922	yes	589.82
E-HCAD-56	yes	565.94
E-HCAD-1	yes	97.45
E-MTAB-8410	yes	71.35
E-HCAD-11	yes	56.72
E-HCAD-4	yes	23.26

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cervix	tissue	152.8	low
Spinal cord	tissue	106.9
Gallbladder	tissue	105.4	medium
Vagina	tissue	101.3	not detected
Adipose tissue	tissue	95.1	low
Urinary bladder	tissue	80.6	low
Heart muscle	tissue	67.2	low
Ovary	tissue	64.5	medium
Superior colliculi	tissue	62.7
Smooth muscle	tissue	55.9	low
Placenta	tissue	55.9	low
Liver	tissue	55.9	low
Appendix	tissue	48.6	not detected
Endometrium 1	tissue	47.8	medium
Breast	tissue	44.3	high
Skin 1	tissue	42.6	low
Adrenal gland	tissue	40.8	medium
Lymph node	tissue	38.8	not detected
Pituitary gland	tissue	37.0
Fallopian tube	tissue	33.7	not detected
Seminal vesicle	tissue	31.6	not detected
Prostate	tissue	31.3	not detected
Tongue	tissue	30.6
Substantia nigra	tissue	29.5
Lung	tissue	27.3	low
Esophagus	tissue	25.3	medium
Salivary gland	tissue	23.4	not detected
Colon	tissue	23.4	low
Medulla oblongata	tissue	20.3
Pancreas	tissue	19.4	low
Tonsil	tissue	16.3	medium
Small intestine	tissue	16.2	low
Skeletal muscle	tissue	15.9	not detected
Rectum	tissue	15.7	not detected
Pons	tissue	14.4
Hippocampal formation	tissue	13.7
Midbrain	tissue	13.1
Entorhinal cortex	tissue	12.9
Testis	tissue	12.8	medium
Thalamus	tissue	12.8
Stomach 1	tissue	12.4	medium
Spleen	tissue	11.2	low
Thyroid gland	tissue	10.4	low
Epididymis	tissue	10.3	not detected
Thymus	tissue	9.8
Parathyroid gland	tissue	9.6	not detected
Frontal cortex	tissue	8.9
Hypothalamus	tissue	8.4
Cerebellum	tissue	8.4	not detected
Cerebral cortex	tissue	7.5	low
Temporal cortex	tissue	7.5
Kidney	tissue	7.3	low
Duodenum	tissue	7.3	low
Olfactory bulb	tissue	7.0
Choroid plexus	tissue	6.7
Caudate putamen	tissue	6.6
Motor cortex	tissue	6.5
Septum	tissue	6.4
Ventral forebrain	tissue	6.3
Somatosensory cortex	tissue	6.0

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (110.2), Dorsal spinal cord (106.9), Ventral spinal cord (56.4), Subiculum (13.7), Anterior insular cortex, dorsal (6.4).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 7.43e-09, LOEUF 1.07, missense Z -0.116 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000223061 — one region, missense o/e 1.00.

Literature-anchored findings (GeneRIF, showing 30)

• PCPE binds to sites on either side of the procollagen cleavage site, thereby facilitating the action of procollagen C-proteinases. (PMID:12105202)
• PCPE1 and PCPE2 were found to be collagen-binding proteins, capable of binding at multiple sites on the triple helical portions of fibrillar collagens and also capable of competing for such binding with procollagen C-proteinases (PMID:12393877)
• procollagen C-proteinase enhancer is an elongated multidomain glycoprotein as shown by small angle x-ray scattering (PMID:12486138)
• the three-dimensional structure of the NTR domain of human PCOLCE1 is the first example of a structural domain with the canonical features of an NTR module (PMID:12670942)
• chordinase activity of BMP1 is not enhanced by PCPE-1 (PMID:15817489)
• tolloid-like 1 binds procollagen C-proteinase enhancer protein 1 and differs from bone morphogenetic protein 1 in the functional roles of homologous protein domains (PMID:16507574)
• PCPE-stimulating activity requires a calcium binding motif in the CUB1 domain that is highly conserved among CUB-containing proteins (PMID:17446170)
• in bone fracture patients, 12 proteins were related to bone/cartilage metabolism, including: TGF-beta induced protein IG-H(3), cartilage acidic protein 1, procollagen C proteinase enhancer protein and TGF-beta receptor III. (PMID:17602227)
• PCPE-1 interacts with beta2-microglobulin (beta2-m) and may help initiate beta2-m amyloid fibril formation in connective tissues (PMID:18164932)
• Procollagen I mRNA expression was decreased by synovial fluid from patients with prosthesis loosening. (PMID:18350290)
• the sPCPE1 glycopattern appears to be associated with the physiological and pathological states of bone (PMID:19361460)
• Data show that only those containing both PCPE1 CUB1 and CUB2 were capable of enhancing BMP-1 activity and binding to a mini-procollagen substrate with nanomolar affinity. (PMID:19801683)
• Role of the netrin-like domain of procollagen C-proteinase enhancer-1 in the control of metalloproteinase activity. (PMID:20207734)
• procollagen C-proteinase enhancer-1 (PCPE-1) binds to heparin/heparan sulfate and has a role in interaction with cells (PMID:20729553)
• data generated by our system, support our hypothesis that combined data on PCPE concentration and isoforms may be useful for the diagnosis and follow-up of bone diseases (PMID:21569766)
• Procollagen C-proteinase enhancer stimulates procollagen processing by binding to the C-propeptide region only. (PMID:21940633)
• Procollagen C-proteinase enhancer grasps the stalk of the C-propeptide trimer to boost collagen precursor maturation. (PMID:23550162)
• The results of this study suggested that nuclear entrapment of PCOLCE and its extracellular depletion represents a novel molecular mechanism in late-onset muscle fibrosis. (PMID:23815790)
• The analysis of the PCPE-1 interaction network based on Gene Ontology terms suggests that, besides its role in collagen deposition, PCPE-1 might be involved in tumour growth, neurodegenerative diseases and angiogenesis. (PMID:24117177)
• Results suggest that PCPE-1 binding to syndecans and/or fibronectin may control collagen fibril assembly on the cell surface. (PMID:25286301)
• Serum PCPE-1 might be used as a noninvasive marker of liver fibrosis in chronic hepatitis B. (PMID:29683980)
• Study shows that the two CUB domains bind to two different chains of C-propeptide trimer of procollagen III (CPIII) and that the N-terminal region of one CPIII chain, close to the proteolytic cleavage site, lies in the cleft between CUB1 and CUB2. This suggests that enhancing activity involves unraveling of this chain from the rest of the trimer, thus facilitating the action of the proteinase involved. (PMID:30078642)
• PCPE-1 levels are elevated in chronic kidney disease patients and that this elevation associated with declining glomerular filtration rate. (PMID:30393914)
• Up-regulation of PCOLCE by TWIST1 promotes metastasis in Osteosarcoma. (PMID:31285765)
• Procollagen C-Proteinase Enhancer-1 (PCPE-1) deficiency in mice reduces liver fibrosis but not NASH progression. (PMID:35148334)
• Procollagen C-proteinase enhancer-1 and renal failure in multiple myeloma. (PMID:36173536)
• Expression of procollagen C-proteinase enhancer 1 in human trabecular meshwork tissues and cells. (PMID:36252654)
• A pan-cancer analysis of the oncogenic role of procollagen C-endopeptidase enhancer (PCOLCE) in human. (PMID:36596064)
• High expression of PCOLCE gene indicate poor prognosis in patients and are associated with immune infiltration in glioma. (PMID:36882457)
• SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma. (PMID:38436832)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcolceb	ENSDARG00000052057
danio_rerio	pcolcea	ENSDARG00000056913
mus_musculus	Pcolce	ENSMUSG00000029718
rattus_norvegicus	Pcolce	ENSRNOG00000025001

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:105099) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal trabecular bone morphology	1
abnormal femur morphology	1
abnormal skeleton physiology	1
abnormal long bone morphology	1
abnormal bone structure	1
abnormal compact bone morphology	1
increased compact bone thickness	1
abnormal tendon morphology	1
increased compact bone area	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RDI1	98.5%	Diamond
Oryctolagus cuniculus	P98065	93.5%	Diamond
Gallus gallus	P0DJJ2	93.2%	Diamond
Coturnix japonica	P42662	93.2%	Diamond
Bos taurus	Q5E9P5	90.8%	Diamond
Xenopus laevis	Q8JI28	87.1%	Diamond
Canis lupus familiaris	Q9TU53	83.0%	Diamond
Sus scrofa	F1RWC3	81.9%	Diamond
Paracentrotus lividus	P42674	71.1%	Diamond
Strongylocentrotus purpuratus	P98069	65.1%	Diamond
Drosophila melanogaster	Q9VC47	56.4%	Diamond
Caenorhabditis elegans	Q20176	48.8%	Diamond
Riftia pachyptila	Q9NH13	38.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SAP25	protein-coding	100316904
FBXO24	protein-coding	26261
LRCH4	protein-coding	4034
MOSPD3	protein-coding	64598
TFR2	protein-coding	7036
PCOLCE-AS1	ncRNA	100129845
ACTL6B	protein-coding	51412

Protein

Protein identifiers

Procollagen C-endopeptidase enhancer 1 — Q15113 (reviewed: Q15113)

Alternative names: Procollagen COOH-terminal proteinase enhancer 1, Type 1 procollagen C-proteinase enhancer protein, Type I procollagen COOH-terminal proteinase enhancer

All UniProt accessions (1): Q15113

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the C-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity. C-terminal processed part of PCPE (CT-PCPE) may have an metalloproteinase inhibitory activity.

Subunit / interactions. Interacts with EFEMP2.

Subcellular location. Secreted.

Post-translational modifications. C-terminally processed at multiple positions.

RefSeq proteins (1): NP_002584* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000859	CUB_dom	Domain
IPR001134	Netrin_domain	Domain
IPR008993	TIMP-like_OB-fold	Homologous_superfamily
IPR018933	Netrin_module_non-TIMP	Domain
IPR035814	NTR_PCOLCE	Domain
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily

Pfam: PF00431, PF01759

UniProt features (55 total): strand 24, disulfide bond 7, helix 7, site 5, domain 3, turn 3, glycosylation site 2, signal peptide 1, chain 1, modified residue 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
9EN2	Crystal structure of the metalloproteinase enhancer PCPE-1 complexed with nanobodies …	X-RAY DIFFRACTION	2.2
6FZV	Crystal structure of the metalloproteinase enhancer PCPE-1 bound to the procollagen C …	X-RAY DIFFRACTION	2.7
6FZW	Crystal structure of the metalloproteinase enhancer PCPE-1 bound to the procollagen C …	X-RAY DIFFRACTION	2.78
1UAP	NMR structure of the NTR domain from human PCOLCE1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15113-F1	79.96	0.45

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 9EN2

Human Protein Atlas

Protein class: Predicted secreted proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; vesicles

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (5)

Position	Role
303–304	cleavage
287–288	cleavage
288–289	cleavage
293–294	cleavage
299–300	cleavage

Post-translational modifications (1)

Type	Positions
Phosphoserine	50

Disulfide bonds (7)

Type	Positions
Disulfide bond	37–63, 90–112, 159–186, 213–236, 318–386, 322–389, 333–437

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	29, 431

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-1650814	Collagen biosynthesis and modifying enzymes	curated
R-HSA-2243919	Crosslinking of collagen fibrils	curated
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures	—
R-HSA-1474290	Collagen formation	—
R-HSA-1474244	Extracellular matrix organization	—

MSigDB gene sets: 210 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, RNGTGGGC_UNKNOWN, MODULE_52, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, MARTINEZ_RB1_TARGETS_UP, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, SASAI_RESISTANCE_TO_NEOPLASTIC_TRANSFROMATION, ROZANOV_MMP14_TARGETS_UP

GO Biological Process (2): proteolysis (GO:0006508), collagen biosynthetic process (GO:0032964)

GO Molecular Function (5): collagen binding (GO:0005518), heparin binding (GO:0008201), peptidase activator activity (GO:0016504), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), extracellular exosome (GO:0070062), extracellular matrix (GO:0031012)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Collagen formation	2
Assembly of collagen fibrils and other multimeric structures	1
Extracellular matrix organization	1

GO top-level categories

15 GO namespaces:

Category	Terms
protein metabolic process	1
biosynthetic process	1
collagen metabolic process	1
protein-containing complex binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
enzyme activator activity	1
peptidase activity	1
peptidase regulator activity	1
structural molecule activity	1
extracellular matrix	1
binding	1
cellular anatomical structure	1
extracellular vesicle	1
external encapsulating structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay
extracellular region	CC	high-throughput assay
collagen binding	MF	direct assay
heparin binding	MF	direct assay
peptidase activator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 904 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCOLCE	NTSR1	P30989	735
PCOLCE	COL1A2	P02464	731
PCOLCE	BMP1	P13497	600
PCOLCE	IGFBP7	Q16270	553
PCOLCE	COL12A1	Q99715	518
PCOLCE	PLS1	Q14651	500
PCOLCE	COL11A2	P13942	471
PCOLCE	COL5A1	P20908	470
PCOLCE	COL22A1	Q8NFW1	461
PCOLCE	LAMA4	Q16363	459
PCOLCE	CHRD	Q9H2X0	457
PCOLCE	FMOD	Q06828	454
PCOLCE	LAMA3	Q16787	452
PCOLCE	COL6A2	P12110	451
PCOLCE	LUM	P51884	443

IntAct

Human interaction partners of PCOLCE in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

20 partners by confidence:

Partner	Interaction type	MIscore	Records
APP	direct interaction	0.680	4
COL18A1	direct interaction	0.620	4
BMP1	physical association	0.610	2
THBS1	direct interaction	0.560	3
FN1	direct interaction	0.560	2
COL5A1	direct interaction	0.530	2
ACAN	direct interaction	0.440	1
ANTXR1	direct interaction	0.440	1
B2M	direct interaction	0.440	1
BGN	direct interaction	0.440	1
EGF	direct interaction	0.440	1
F10	direct interaction	0.440	1
LTBP1	direct interaction	0.440	1
MMP2	cleavage reaction	0.440	1
PLG	direct interaction	0.440	1
TGM2	direct interaction	0.440	1
TNXB	direct interaction	0.440	1
SDC1	physical association	0.400	1
HMGB1	physical association	0.370	1
S100A9	physical association	0.370	1

BioGRID (7 interactions; top human partners by supporting records): AGRN (Affinity Capture-MS), DDX39A (Affinity Capture-RNA), ECT2 (Two-hybrid), HMGB1 (Two-hybrid), POLI (Reconstituted Complex), TGOLN2 (Proximity Label-MS), TRIM67 (Affinity Capture-MS)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
ECM proteoglycans	6	47.5×	4e-07
Degradation of the extracellular matrix	5	31.0×	3e-05
Platelet degranulation	5	23.1×	8e-05
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	5	22.8×	8e-05
Extracellular matrix organization	6	19.9×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
cell adhesion	7	13.1×	2e-04
proteolysis	6	10.3×	2e-03

Disease & clinical

Genetic variants

Variant evidence for PCOLCE: 81 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

81 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	5
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 743):

Position(s)	Effect	Δscore	Sites
7:100605786	donor_gain	1.0000
7:100606400	acceptor_gain	1.0000
7:100606631–100606632	donor_loss	1.0000	5
7:100607635–100607636	acceptor_loss	1.0000	3
7:100607808–100607809	donor_loss	1.0000	4
7:100602552–100602553	donor_loss	0.9900	3
7:100603957–100603958	acceptor_loss	0.9900	6
7:100604218–100604219	donor_loss	0.9900	5
7:100605090	acceptor_gain	0.9900
7:100605813–100605814	donor_loss	0.9900	6

AlphaMissense

826 missense substitutions predicted likely pathogenic (of 2,864 scored), across 229 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D216	8	0.996	0.999
D258	8	0.991	0.999
F266	8	0.986	1.000
D93	8	0.985	0.997
F202	8	0.973	0.999
F142	8	0.972	0.999
F255	8	0.965	0.998
F205	8	0.939	0.996
F82	8	0.932	0.991
F79	8	0.926	0.990
D134	8	0.923	0.988
D83	8	0.868	0.969
D210	8	0.834	0.970
C186	7	0.997	0.999
C236	7	0.996	0.998
C112	7	0.995	0.998
C159	7	0.994	0.998
F53	7	0.993	0.998
C63	7	0.993	0.998
W188	7	0.993	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Skin Cutaneous Melanoma (TCGA)	unfavorable	0.000205
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	0.000307

Disease associations

OMIM: gene MIM:600270 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST003818_67	Resting heart rate	1e-41
GCST010703_241	Brain morphology (MOSTest)	6e-15
GCST006585_2834	Blood protein levels	2e-12
GCST010702_30	Subcortical volume (MOSTest)	6e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Air Pollutants	decreases expression, increases abundance, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	increases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
entinostat	increases expression, affects cotreatment	2
bisphenol AF	decreases expression, increases expression	2
Estradiol	decreases expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
trichostatin A	increases expression	1
sulforaphane	decreases expression	1
benzo(e)pyrene	decreases methylation	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	decreases expression	1
jinfukang	increases expression	1
Arsenic Trioxide	decreases expression	1
Panobinostat	affects cotreatment, increases expression	1
Arsenic	increases abundance, decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Carmustine	decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.