Q16769 (QPCT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutaminyl-peptide cyclotransferase
EC=2.3.2.5

Alternative name(s):
Glutaminyl cyclase
Short name=QC
Short name=sQC
Glutaminyl-tRNA cyclotransferase
Glutamyl cyclase
Short name=EC

Gene names

Name:

QPCT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	361 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	Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-beta-amyloid. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides. Ref.4 Ref.5 Ref.9
Catalytic activity	L-glutaminyl-peptide = 5-oxoprolyl-peptide + NH3. Ref.5 Ref.6 Ref.7 Ref.9
Cofactor	Binds 1 zinc ion per subunit. Ref.7 Ref.9
Subcellular location	Secreted Ref.5.
Sequence similarities	Belongs to the glutaminyl-peptide cyclotransferase family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Acyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase Inferred from direct assay Ref.9. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	glutaminyl-peptide cyclotransferase activity Inferred from direct assay Ref.9. Source: UniProtKB peptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q16769-1)

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 2 (identifier: Q16769-2)

The sequence of this isoform differs from the canonical sequence as follows:
     41-89: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Potential

Chain

29 – 361

333

Glutaminyl-peptide cyclotransferase

PRO_0000022195

Sites

Active site

201

1

Proton acceptor Ref.7

Active site

248

1

Proton acceptor Ref.7

Metal binding

159

1

Zinc; catalytic

Metal binding

202

1

Zinc; catalytic

Metal binding

330

1

Zinc; catalytic

Amino acid modifications

Glycosylation

49

1

N-linked (GlcNAc...) Ref.8

Glycosylation

296

1

N-linked (GlcNAc...) Potential

Disulfide bond

139 ↔ 164

Ref.8

Natural variations

Alternative sequence

41 – 89

49

Missing in isoform 2.

VSP_038487

Natural variant

54

1

R → W Lowers activity by approximately 30%. Ref.6
Corresponds to variant rs2255991 [ dbSNP | Ensembl ].

VAR_053956

Natural variant

71

1

Q → R.

VAR_005569

Natural variant

360

1

H → P. Ref.3
Corresponds to variant rs4670696 [ dbSNP | Ensembl ].

VAR_053957

Experimental info

Mutagenesis

144

1

K → A: Lowers activity by approximately 40%. Ref.6

Mutagenesis

146

1

F → A: Lowers activity by approximately 30%. Ref.6

Mutagenesis

160

1

S → A: Reduces activity by about 50%. Ref.7

Mutagenesis

160

1

S → G: Reduces activity by 96%. Ref.7

Mutagenesis

201

1

E → D: Reduces activity by about 98%. Ref.6 Ref.7

Mutagenesis

201

1

E → L or Q: Abolishes activity. Ref.6 Ref.7

Mutagenesis

207

1

W → L: Greatly lowers activity. Ref.6

Mutagenesis

248

1

D → A: Reduces activity by 99%. Ref.6 Ref.7

Mutagenesis

248

1

D → Q: Abolishes activity. Ref.6 Ref.7

Mutagenesis

304

1

Q → L: Lowers activity by approximately 35%. Ref.6

Mutagenesis

305

1

D → A, E or L: Abolishes activity. Ref.6 Ref.7

Mutagenesis

305

1

D → N: Reduces activity by 99%. Ref.6 Ref.7

Mutagenesis

319

1

H → L: Reduces activity by 87%. Ref.7

Mutagenesis

325

1

F → A: Greatly lowers activity. Ref.6

Mutagenesis

329

1

W → A: Abolishes activity. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

361

Helix Strand Turn

Details...

Helix

36 – 38

3

Helix

39 – 42

4

Helix

50 – 59

10

Helix

62 – 68

7

Helix

71 – 73

3

Helix

82 – 96

15

Beta strand

98 – 100

3

Beta strand

103 – 111

9

Beta strand

116 – 128

13

Beta strand

131 – 140

10

Turn

157 – 160

4

Helix

161 – 173

13

Helix

175 – 179

5

Beta strand

191 – 199

9

Beta strand

204 – 206

3

Beta strand

209 – 212

4

Helix

214 – 224

11

Beta strand

226 – 229

4

Turn

237 – 240

4

Beta strand

241 – 247

7

Beta strand

252 – 254

3

Helix

262 – 264

3

Helix

265 – 280

16

Beta strand

284 – 286

3

Helix

308 – 311

4

Turn

312 – 314

3

Beta strand

317 – 320

4

Turn

327 – 330

4

Helix

336 – 338

3

Helix

341 – 359

19

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 32C26041BCF5ED75	FASTA	361	40,877
	10 20 30 40 50 60 MAGGRHRRVV GTLHLLLLVA ALPWASRGVS PSASAWPEEK NYHQPAILNS SALRQIAEGT 70 80 90 100 110 120 SISEMWQNDL QPLLIERYPG SPGSYAARQH IMQRIQRLQA DWVLEIDTFL SQTPYGYRSF 130 140 150 160 170 180 SNIISTLNPT AKRHLVLACH YDSKYFSHWN NRVFVGATDS AVPCAMMLEL ARALDKKLLS 190 200 210 220 230 240 LKTVSDSKPD LSLQLIFFDG EEAFLHWSPQ DSLYGSRHLA AKMASTPHPP GARGTSQLHG 250 260 270 280 290 300 MDLLVLLDLI GAPNPTFPNF FPNSARWFER LQAIEHELHE LGLLKDHSLE GRYFQNYSYG 310 320 330 340 350 360 GVIQDDHIPF LRRGVPVLHL IPSPFPEVWH TMDDNEENLD ESTIDNLNKI LQVFVLEYLH L
	Isoform 2 [UniParc]. Checksum: 21EF984B639F5DEE	FASTA	312	35,421
	10 20 30 40 50 60 MAGGRHRRVV GTLHLLLLVA ALPWASRGVS PSASAWPEEK HIMQRIQRLQ ADWVLEIDTF 70 80 90 100 110 120 LSQTPYGYRS FSNIISTLNP TAKRHLVLAC HYDSKYFSHW NNRVFVGATD SAVPCAMMLE 130 140 150 160 170 180 LARALDKKLL SLKTVSDSKP DLSLQLIFFD GEEAFLHWSP QDSLYGSRHL AAKMASTPHP 190 200 210 220 230 240 PGARGTSQLH GMDLLVLLDL IGAPNPTFPN FFPNSARWFE RLQAIEHELH ELGLLKDHSL 250 260 270 280 290 300 EGRYFQNYSY GGVIQDDHIP FLRRGVPVLH LIPSPFPEVW HTMDDNEENL DESTIDNLNK 310 ILQVFVLEYL HL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, sequence analysis and expression of human pituitary glutaminyl cyclase." Song I., Chuang C.Z., Bateman R.C. Jr. J. Mol. Endocrinol. 13:77-86(1994) [PubMed: 7999256] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Pituitary.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT PRO-360. Tissue: Lung and Pancreas.
[4]	"Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions." Schilling S., Hoffmann T., Manhart S., Hoffmann M., Demuth H.U. FEBS Lett. 563:191-196(2004) [PubMed: 15063747] [Abstract] Cited for: FUNCTION AS GLUTAMYL CYCLASE.
[5]	"Isolation of an isoenzyme of human glutaminyl cyclase: retention in the Golgi complex suggests involvement in the protein maturation machinery." Cynis H., Rahfeld J.U., Stephan A., Kehlen A., Koch B., Wermann M., Demuth H.U., Schilling S. J. Mol. Biol. 379:966-980(2008) [PubMed: 18486145] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
[6]	"Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation." Huang K.-F., Liu Y.-L., Cheng W.-J., Ko T.-P., Wang A.H.-J. Proc. Natl. Acad. Sci. U.S.A. 102:13117-13122(2005) [PubMed: 16135565] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 33-361, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-144; PHE-146; GLU-201; TRP-207; ASP-248; GLN-304; ASP-305; PHE-325 AND TRP-329, CHARACTERIZATION OF VARIANT TRP-54.
[7]	"A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl cyclases is critical for catalysis." Huang K.F., Wang Y.R., Chang E.C., Chou T.L., Wang A.H. Biochem. J. 411:181-190(2008) [PubMed: 18072935] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 33-361 OF MUTANTS ALA-160; GLY-160; ASP-201; LEU-201; GLN-201; ALA-248; GLN-248; ALA-305; GLU-305 AND LEU-319 IN COMPLEX WITH ZINC IONS, CATALYTIC ACTIVITY, COFACTOR, ACTIVE SITE, MUTAGENESIS OF SER-160; GLU-201; ASP-248; ASP-305 AND HIS-319.
[8]	"Structures of glycosylated mammalian glutaminyl cyclases reveal conformational variability near the active center." Ruiz-Carrillo D., Koch B., Parthier C., Wermann M., Dambe T., Buchholz M., Ludwig H.H., Heiser U., Rahfeld J.U., Stubbs M.T., Schilling S., Demuth H.U. Biochemistry 50:6280-6288(2011) [PubMed: 21671571] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 38-361, GLYCOSYLATION AT ASN-49, DISULFIDE BOND.
[9]	"Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding." Huang K.F., Liaw S.S., Huang W.L., Chia C.Y., Lo Y.C., Chen Y.L., Wang A.H. J. Biol. Chem. 286:12439-12449(2011) [PubMed: 21288892] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 33-361 IN COMPLEX WITH ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, COFACTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X71125 mRNA. Translation: CAA50438.1.
X67731 mRNA. Translation: CAA47961.1.
AC007391 Genomic DNA. No translation available.
BC036721 mRNA. Translation: AAH36721.1.
BC047756 mRNA. Translation: AAH47756.1.

IPI

IPI00003919.
IPI00954591.

PIR

I37421.

RefSeq

NP_036545.1. NM_012413.3.

UniGene

Hs.79033.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MOI	model	-	A	1-361	[»]
2AFM	X-ray	1.66	A/B	33-361	[»]
2AFO	X-ray	2.35	A/B	33-361	[»]
2AFS	X-ray	2.22	A/B	33-361	[»]
2AFU	X-ray	2.22	A/B	33-361	[»]
2AFW	X-ray	1.56	A/B	33-361	[»]
2AFX	X-ray	1.64	A/B	33-361	[»]
2AFZ	X-ray	1.68	A/B	33-361	[»]
2ZED	X-ray	1.70	A/B	33-361	[»]
2ZEE	X-ray	1.99	A/B	33-361	[»]
2ZEF	X-ray	1.67	A/B	33-361	[»]
2ZEG	X-ray	2.08	A/B	33-361	[»]
2ZEH	X-ray	1.80	A/B	33-361	[»]
2ZEL	X-ray	1.97	A/B	33-361	[»]
2ZEM	X-ray	2.18	A/B	33-361	[»]
2ZEN	X-ray	1.78	A/B	33-361	[»]
2ZEO	X-ray	1.66	A/B	33-361	[»]
2ZEP	X-ray	2.10	A/B	33-361	[»]
3PBB	X-ray	1.95	A/B	33-361	[»]
3PBE	X-ray	1.95	A/B	33-361	[»]
3SI0	X-ray	2.10	A	38-361	[»]

ProteinModelPortal

Q16769.

SMR

Q16769. Positions 33-361.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16769. 2 interactions.

STRING

Q16769.

Protein family/group databases

MEROPS

M28.974.

Polymorphism databases

DMDM

2498824.

Proteomic databases

PeptideAtlas

Q16769.

PRIDE

Q16769.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338415; ENSP00000344829; ENSG00000115828.

GeneID

25797.

KEGG

hsa:25797.

UCSC

uc002rqg.1. human.

Organism-specific databases

CTD

25797.

GeneCards

GC02P037571.

H-InvDB

HIX0023907.

HGNC

HGNC:9753. QPCT.

HPA

HPA008406.

MIM

607065. gene.

neXtProt

NX_Q16769.

PharmGKB

PA34095.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09871.

HOGENOM

HBG314483.

HOVERGEN

HBG009812.

InParanoid

Q16769.

OMA

GYRSFSN.

OrthoDB

EOG4XSKQ7.

PhylomeDB

Q16769.

Gene expression databases

ArrayExpress

Q16769.

Bgee

Q16769.

CleanEx

HS_QPCT.

Genevestigator

Q16769.

GermOnline

ENSG00000115828. Homo sapiens.

Family and domain databases

InterPro

IPR007484. Peptidase_M28.
[Graphical view]

KO

K00683.

Pfam

PF04389. Peptidase_M28. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

46985.

SOURCE

Search...

Entry information

Entry name

QPCT_HUMAN

Accession

Primary (citable) accession number: Q16769
Secondary accession number(s): Q16770, Q3KRG6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 96 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.