Q99895 (CTRC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Chymotrypsin-C
EC=3.4.21.2

Alternative name(s):
Caldecrin

Gene names

Name:	CTRC
Synonyms:	CLCR

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	268 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	Has chymotrypsin-type protease activity and hypocalcemic activity.
Catalytic activity	Preferential cleavage: Leu-|-Xaa, Tyr-|-Xaa, Phe-|-Xaa, Met-|-Xaa, Trp-|-Xaa, Gln-|-Xaa, Asn-|-Xaa.
Tissue specificity	Pancreas.
Involvement in disease	Genetic variations in CTRC can predispose to chronic pancreatitis by diminishing its protective trypsin-degrading activity.
Sequence similarities	Belongs to the peptidase S1 family. Elastase subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Traceable author statement Ref.1. Source: ProtInc
Molecular_function	peptidase activity Traceable author statement Ref.1. Source: ProtInc serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 16	16	Potential
	Propeptide	17 – 29	13	Activation peptide		PRO_0000027713
	Chain	30 – 268	239	Chymotrypsin-C		PRO_0000027714
Regions
	Domain	30 – 267	238	Peptidase S1
Sites
	Active site	74	1	Charge relay system By similarity
	Active site	121	1	Charge relay system By similarity
	Active site	216	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	25	1	N-linked (GlcNAc...) Potential
	Glycosylation	52	1	N-linked (GlcNAc...) Potential
	Glycosylation	226	1	N-linked (GlcNAc...) Potential
	Disulfide bond	17 ↔ 141		By similarity
	Disulfide bond	59 ↔ 75		By similarity
	Disulfide bond	155 ↔ 222		By similarity
	Disulfide bond	186 ↔ 202		By similarity
	Disulfide bond	212 ↔ 243		By similarity
Natural variations
	Natural variant	35	1	D → H. Ref.8		VAR_043516
	Natural variant	35	1	D → N. Ref.8		VAR_043517
	Natural variant	37	1	R → Q Normal secretion and activity. Ref.8		VAR_043518
	Natural variant	48	1	Q → R Reduced secretion and activity. Ref.8		VAR_043519
	Natural variant	73	1	A → T Reduced secretion; abolishes activity. Ref.8		VAR_043520
	Natural variant	80	1	R → W. Ref.1		VAR_010928
	Natural variant	172	1	K → E. Ref.8 Corresponds to variant rs34949635 [ dbSNP | Ensembl ].		VAR_043521
	Natural variant	217	1	G → R. Ref.8		VAR_043522
	Natural variant	217	1	G → S Reduced secretion and activity. Ref.8		VAR_043523
	Natural variant	218	1	G → S. Ref.8		VAR_043524
	Natural variant	220	1	L → R. Ref.8		VAR_043525
	Natural variant	225	1	E → A. Ref.8		VAR_043526
	Natural variant	235	1	V → I Slightly reduced secretion and activity. Ref.8		VAR_043527
	Natural variant	249	1	P → L. Ref.8		VAR_043528
	Natural variant	254	1	R → W Reduced secretion; normal activity. Ref.8		VAR_043529
	Natural variant	260	1	D → N. Ref.8		VAR_043530
Experimental info
	Sequence conflict	16	1	S → T in AAB47104. Ref.1
	Sequence conflict	52	1	N → D in CAA74031. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q99895 [UniParc]. Last modified June 1, 2001. Version 2. Checksum: 460BF33B4A96516F	FASTA	268	29,484
	10 20 30 40 50 60 MLGITVLAAL LACASSCGVP SFPPNLSARV VGGEDARPHS WPWQISLQYL KNDTWRHTCG 70 80 90 100 110 120 GTLIASNFVL TAAHCISNTR TYRVAVGKNN LEVEDEEGSL FVGVDTIHVH KRWNALLLRN 130 140 150 160 170 180 DIALIKLAEH VELSDTIQVA CLPEKDSLLP KDYPCYVTGW GRLWTNGPIA DKLQQGLQPV 190 200 210 220 230 240 VDHATCSRID WWGFRVKKTM VCAGGDGVIS ACNGDSGGPL NCQLENGSWE VFGIVSFGSR 250 260 RGCNTRKKPV VYTRVSAYID WINEKMQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of human caldecrin." Tomomura A., Akiyama M., Itoh H., Yoshino I., Tomomura M., Nishii Y., Noikura T., Saheki T. FEBS Lett. 386:26-28(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TRP-80. Tissue: Pancreas.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[6]	"A human pancreatic chymotrypsin: biochemical and molecular characterization." Sziegoleit A. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-268. Tissue: Pancreas.
[7]	"Caldecrin is a novel-type serine protease expressed in pancreas, but its homologue, elastase IV, is an artifact during cloning derived from caldecrin gene." Yoshino-Yasuda I., Kobayashi K., Akiyama M., Itoh H., Tomomura A., Saheki T. J. Biochem. 123:546-554(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis." Rosendahl J., Witt H., Szmola R., Bhatia E., Ozsvari B., Landt O., Schulz H.-U., Gress T.M., Pfuetzer R., Loehr M., Kovacs P., Blueher M., Stumvoll M., Choudhuri G., Hegyi P., te Morsche R.H.M., Drenth J.P.H., Truninger K. , Macek M. Jr., Puhl G., Witt U., Schmidt H., Buening C., Ockenga J., Kage A., Groneberg D.A., Nickel R., Berg T., Wiedenmann B., Boedeker H., Keim V., Moessner J., Teich N., Sahin-Toth M. Nat. Genet. 40:78-82(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HIS-35; ASN-35; GLN-37; ARG-48; THR-73; GLU-172; SER-217; ARG-217; SER-218; ARG-220; ALA-225; ILE-235; LEU-249; TRP-254 AND ASN-260, CHARACTERIZATION OF VARIANTS GLN-37; ARG-48; THR-73; SER-217; ILE-235 AND TRP-254, INVOLVEMENT IN CHRONIC PANCREATITIS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S82198 mRNA. Translation: AAB47104.2. Sequence problems.
AK289447 mRNA. Translation: BAF82136.1.
AL031283 Genomic DNA. Translation: CAB77355.1.
CH471167 Genomic DNA. Translation: EAW51726.1.
BC015118 mRNA. Translation: AAH15118.1.
Y13697 mRNA. Translation: CAA74031.1.

IPI

IPI00018553.

PIR

S68825.
S68826.

RefSeq

NP_009203.2. NM_007272.2.

UniGene

Hs.631869.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4H4F	X-ray	1.90	A	30-268	[»]
			Q	17-26	[»]

ProteinModelPortal

Q99895.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000365116.

Protein family/group databases

MEROPS

S01.157.

Polymorphism databases

DMDM

14194504.

Proteomic databases

PaxDb

Q99895.

PRIDE

Q99895.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375949; ENSP00000365116; ENSG00000162438.

GeneID

11330.

KEGG

hsa:11330.

UCSC

uc001awi.1. human.

Organism-specific databases

CTD

11330.

GeneCards

GC01P015764.

HGNC

HGNC:2523. CTRC.

HPA

HPA046920.

MIM

601405. gene.

neXtProt

NX_Q99895.

Orphanet

676. Hereditary chronic pancreatitis.

PharmGKB

PA27024.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

Q99895.

KO

K01311.

OMA

AHCISNT.

OrthoDB

EOG4XPQGN.

PhylomeDB

Q99895.

Enzyme and pathway databases

BRENDA

3.4.21.2. 2681.

Gene expression databases

ArrayExpress

Q99895.

Bgee

Q99895.

CleanEx

HS_CTRC.

Genevestigator

Q99895.

GermOnline

ENSG00000162438. Homo sapiens.

Family and domain databases

InterPro

IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q99895.

ChEMBL

CHEMBL2386.

GenomeRNAi

11330.

NextBio

43039.

SOURCE

Search...

Entry information

Entry name

CTRC_HUMAN

Accession

Primary (citable) accession number: Q99895
Secondary accession number(s): A8K082, O00765, Q9NUH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 114 of the entry and version 2 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.