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Protein

Chymotrypsin-C

Gene

CTRC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. Has chymotrypsin-type protease activity and hypocalcemic activity.1 Publication

Catalytic activityi

Preferential cleavage: Leu-|-Xaa, Tyr-|-Xaa, Phe-|-Xaa, Met-|-Xaa, Trp-|-Xaa, Gln-|-Xaa, Asn-|-Xaa.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei74Charge relay systemBy similarity1
Active sitei121Charge relay systemBy similarity1
Active sitei216Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cobalamin metabolic process Source: Reactome
  • proteolysis Source: ProtInc

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.2 2681
ReactomeiR-HSA-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism

Protein family/group databases

MEROPSiS01.157

Names & Taxonomyi

Protein namesi
Recommended name:
Chymotrypsin-C (EC:3.4.21.2)
Alternative name(s):
Caldecrin
Gene namesi
Name:CTRC
Synonyms:CLCR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000162438.11
HGNCiHGNC:2523 CTRC
MIMi601405 gene
neXtProtiNX_Q99895

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Pancreatitis, hereditary (PCTT)4 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. Loss-of-function CTRC variants predispose to pancreatitis by diminishing its protective trypsin-degrading activity (PubMed:18059268). They cause loss of function by one or more of three mechanisms: reduced secretion, catalytic defect and increased degradation by trypsin (PubMed:22942235).2 Publications
Disease descriptionA disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks.
See also OMIM:167800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07052232G → V in PCTT; associated with disease susceptibility; highly reduced catalytic efficiency. 1 Publication1
Natural variantiVAR_04352073A → T in PCTT; associated with susceptibility to disease; results in markedly reduced protein secretion. 4 PublicationsCorresponds to variant dbSNP:rs515726209EnsemblClinVar.1
Natural variantiVAR_070526155C → Y in PCTT; associated with susceptibility to disease; the mutant is not secreted. 2 Publications1
Natural variantiVAR_070528178Q → R in PCTT; associated with disease susceptibility; impaired catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs200678111EnsemblClinVar.1
Natural variantiVAR_043522217G → R in PCTT; associated with susceptibility to disease; results in markedly reduced protein secretion and loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs202058123EnsemblClinVar.1
Natural variantiVAR_043523217G → S in PCTT; associated with susceptibility to disease; reduced protein secretion; impaired catalytic activity. 3 PublicationsCorresponds to variant dbSNP:rs202058123EnsemblClinVar.1
Natural variantiVAR_043527235V → I in PCTT; associated with susceptibility to disease; slightly reduced activity. 4 PublicationsCorresponds to variant dbSNP:rs140993290EnsemblClinVar.1
Natural variantiVAR_070536247 – 254Missing in PCTT; associated with disease susceptibility; results in reduced protein secretion and loss of activity. 2 Publications8
Natural variantiVAR_043528249P → L in PCTT; associated with disease susceptibility; results in reduced protein secretion and loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs142560329Ensembl.1
Natural variantiVAR_070538250V → E in PCTT; associated with disease susceptibility; results in altered enzyme specificity and loss of activity. 1 Publication1
Natural variantiVAR_043529254R → W in PCTT; associated with susceptibility to disease; results in reduced secretion; normal activity; the mutant undergoes proteolytic degradation during trypsin-mediated activation. 5 PublicationsCorresponds to variant dbSNP:rs121909293EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi11330
MalaCardsiCTRC
MIMi167800 phenotype
OpenTargetsiENSG00000162438
Orphaneti676 Hereditary chronic pancreatitis
103918 Tropical pancreatitis
PharmGKBiPA27024

Chemistry databases

ChEMBLiCHEMBL2386
GuidetoPHARMACOLOGYi2341

Polymorphism and mutation databases

BioMutaiCTRC
DMDMi14194504

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
PropeptideiPRO_000002771317 – 29Activation peptideAdd BLAST13
ChainiPRO_000002771430 – 268Chymotrypsin-CAdd BLAST239

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi17 ↔ 141PROSITE-ProRule annotation1 Publication
Glycosylationi25N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi52N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi59 ↔ 75PROSITE-ProRule annotation1 Publication
Disulfide bondi155 ↔ 222PROSITE-ProRule annotation1 Publication
Disulfide bondi186 ↔ 202PROSITE-ProRule annotation1 Publication
Disulfide bondi212 ↔ 243PROSITE-ProRule annotation1 Publication
Glycosylationi226N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ99895
PeptideAtlasiQ99895
PRIDEiQ99895
ProteomicsDBi78519

Expressioni

Tissue specificityi

Pancreas.

Gene expression databases

BgeeiENSG00000162438
CleanExiHS_CTRC
ExpressionAtlasiQ99895 baseline and differential
GenevisibleiQ99895 HS

Organism-specific databases

HPAiHPA046920

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
KRTAP10-7P604093EBI-10295404,EBI-10172290

Protein-protein interaction databases

BioGridi116458, 6 interactors
IntActiQ99895, 13 interactors
STRINGi9606.ENSP00000365116

Chemistry databases

BindingDBiQ99895

Structurei

Secondary structure

1268
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi44 – 51Combined sources8
Beta strandi54 – 65Combined sources12
Beta strandi68 – 71Combined sources4
Helixi73 – 75Combined sources3
Beta strandi82 – 87Combined sources6
Beta strandi100 – 102Combined sources3
Beta strandi104 – 109Combined sources6
Turni115 – 117Combined sources3
Beta strandi123 – 129Combined sources7
Beta strandi155 – 160Combined sources6
Beta strandi162 – 164Combined sources3
Beta strandi174 – 177Combined sources4
Helixi183 – 186Combined sources4
Turni189 – 192Combined sources4
Helixi193 – 195Combined sources3
Beta strandi200 – 203Combined sources4
Beta strandi206 – 210Combined sources5
Beta strandi219 – 223Combined sources5
Beta strandi229 – 239Combined sources11
Beta strandi242 – 245Combined sources4
Beta strandi250 – 254Combined sources5
Helixi255 – 257Combined sources3
Helixi259 – 265Combined sources7

3D structure databases

ProteinModelPortaliQ99895
SMRiQ99895
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 267Peptidase S1PROSITE-ProRule annotationAdd BLAST238

Sequence similaritiesi

Belongs to the peptidase S1 family. Elastase subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000119027
HOGENOMiHOG000251820
HOVERGENiHBG013304
InParanoidiQ99895
KOiK01311
OMAiDTWRHTC
OrthoDBiEOG091G0DF7
PhylomeDBiQ99895
TreeFamiTF330455

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99895-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGITVLAAL LACASSCGVP SFPPNLSARV VGGEDARPHS WPWQISLQYL
60 70 80 90 100
KNDTWRHTCG GTLIASNFVL TAAHCISNTR TYRVAVGKNN LEVEDEEGSL
110 120 130 140 150
FVGVDTIHVH KRWNALLLRN DIALIKLAEH VELSDTIQVA CLPEKDSLLP
160 170 180 190 200
KDYPCYVTGW GRLWTNGPIA DKLQQGLQPV VDHATCSRID WWGFRVKKTM
210 220 230 240 250
VCAGGDGVIS ACNGDSGGPL NCQLENGSWE VFGIVSFGSR RGCNTRKKPV
260
VYTRVSAYID WINEKMQL
Length:268
Mass (Da):29,484
Last modified:June 1, 2001 - v2
Checksum:i460BF33B4A96516F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16S → T in AAB47104 (PubMed:8635596).Curated1
Sequence conflicti52N → D in CAA74031 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07052018G → R Found in a patient with chronic pancreatitis; unknown pathological significance; catalytic activity comparable to that of wild type; the mutant undergoes proteolytic degradation during trypsin-mediated activation. 1 PublicationCorresponds to variant dbSNP:rs200576965Ensembl.1
Natural variantiVAR_07052129R → Q Found in patients with chronic pancreatitis; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs772024986Ensembl.1
Natural variantiVAR_07052232G → V in PCTT; associated with disease susceptibility; highly reduced catalytic efficiency. 1 Publication1
Natural variantiVAR_04351635D → H1 Publication1
Natural variantiVAR_04351735D → N1 PublicationCorresponds to variant dbSNP:rs184977421Ensembl.1
Natural variantiVAR_07052335D → Y Found in a patient with chronic pancreatitis; unknown pathological significance; catalytic activity comparable to that of wild type. 1 Publication1
Natural variantiVAR_04351837R → Q Rare variant; results in normal secretion and activity. 1 PublicationCorresponds to variant dbSNP:rs145868278EnsemblClinVar.1
Natural variantiVAR_04351948Q → R Rare variant that may be associated with susceptibility to pancreatitis; results in markedly reduced protein secretion. 3 PublicationsCorresponds to variant dbSNP:rs536812916Ensembl.1
Natural variantiVAR_07052461G → R Found in a patient with chronic pancreatitis; unknown pathological significance; the mutant is not secreted. 1 PublicationCorresponds to variant dbSNP:rs769482036Ensembl.1
Natural variantiVAR_04352073A → T in PCTT; associated with susceptibility to disease; results in markedly reduced protein secretion. 4 PublicationsCorresponds to variant dbSNP:rs515726209EnsemblClinVar.1
Natural variantiVAR_01092880R → W1 PublicationCorresponds to variant dbSNP:rs779643710Ensembl.1
Natural variantiVAR_070525151K → N Found in a patient with chronic pancreatitis; unknown pathological significance. 1
Natural variantiVAR_070526155C → Y in PCTT; associated with susceptibility to disease; the mutant is not secreted. 2 Publications1
Natural variantiVAR_070527162R → H Rare variant; found in a patient with chronic pancreatitis; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs775404479Ensembl.1
Natural variantiVAR_043521172K → E3 PublicationsCorresponds to variant dbSNP:rs34949635EnsemblClinVar.1
Natural variantiVAR_070528178Q → R in PCTT; associated with disease susceptibility; impaired catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs200678111EnsemblClinVar.1
Natural variantiVAR_070529200M → V Rare variant; found in a patient with chronic pancreatitis; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs146235499Ensembl.1
Natural variantiVAR_070530209I → M1 Publication1
Natural variantiVAR_043522217G → R in PCTT; associated with susceptibility to disease; results in markedly reduced protein secretion and loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs202058123EnsemblClinVar.1
Natural variantiVAR_043523217G → S in PCTT; associated with susceptibility to disease; reduced protein secretion; impaired catalytic activity. 3 PublicationsCorresponds to variant dbSNP:rs202058123EnsemblClinVar.1
Natural variantiVAR_043524218G → S1 Publication1
Natural variantiVAR_043525220L → R Rare variant; results in impaired protein secretion. 2 Publications1
Natural variantiVAR_043526225E → A1 PublicationCorresponds to variant dbSNP:rs201486613EnsemblClinVar.1
Natural variantiVAR_070531225E → K Found in a patient with chronic pancreatitis; unknown pathological significance. 1 Publication1
Natural variantiVAR_070532227G → S1 PublicationCorresponds to variant dbSNP:rs567745213Ensembl.1
Natural variantiVAR_043527235V → I in PCTT; associated with susceptibility to disease; slightly reduced activity. 4 PublicationsCorresponds to variant dbSNP:rs140993290EnsemblClinVar.1
Natural variantiVAR_070533239S → A Found in patients with chronic pancreatitis; unknown pathological significance. 1 Publication1
Natural variantiVAR_070534239S → C Found in patients with chronic pancreatitis; unknown pathological significance. 1 Publication1
Natural variantiVAR_070535246R → C1 PublicationCorresponds to variant dbSNP:rs200412314EnsemblClinVar.1
Natural variantiVAR_070536247 – 254Missing in PCTT; associated with disease susceptibility; results in reduced protein secretion and loss of activity. 2 Publications8
Natural variantiVAR_070537247K → E Found in patients with chronic pancreatitis; unknown pathological significance. 1 Publication1
Natural variantiVAR_043528249P → L in PCTT; associated with disease susceptibility; results in reduced protein secretion and loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs142560329Ensembl.1
Natural variantiVAR_070538250V → E in PCTT; associated with disease susceptibility; results in altered enzyme specificity and loss of activity. 1 Publication1
Natural variantiVAR_070539254R → Q Found in a patient with chronic pancreatitis; unknown pathological significance; mutant protein secretion, activity and trypsin-mediated degradation are comparable to those of wild-type. 2 PublicationsCorresponds to variant dbSNP:rs755811899Ensembl.1
Natural variantiVAR_043529254R → W in PCTT; associated with susceptibility to disease; results in reduced secretion; normal activity; the mutant undergoes proteolytic degradation during trypsin-mediated activation. 5 PublicationsCorresponds to variant dbSNP:rs121909293EnsemblClinVar.1
Natural variantiVAR_070540257A → T Found in patients with chronic pancreatitis; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs200406696Ensembl.1
Natural variantiVAR_043530260D → N1 PublicationCorresponds to variant dbSNP:rs540753875Ensembl.1
Natural variantiVAR_070541263N → S Found in a patient with chronic pancreatitis; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs769975164Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S82198 mRNA Translation: AAB47104.2 Sequence problems.
AK289447 mRNA Translation: BAF82136.1
AL031283 Genomic DNA No translation available.
CH471167 Genomic DNA Translation: EAW51726.1
BC015118 mRNA Translation: AAH15118.1
Y13697 mRNA Translation: CAA74031.1
CCDSiCCDS156.1
PIRiS68825
S68826
RefSeqiNP_009203.2, NM_007272.2
UniGeneiHs.631869

Genome annotation databases

EnsembliENST00000375949; ENSP00000365116; ENSG00000162438
GeneIDi11330
KEGGihsa:11330
UCSCiuc001awi.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCTRC_HUMAN
AccessioniPrimary (citable) accession number: Q99895
Secondary accession number(s): A8K082, O00765, Q9NUH5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: June 1, 2001
Last modified: July 18, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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