Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

A disintegrin and metalloproteinase with thrombospondin motifs 18

Gene

ADAMTS18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi254Zinc; in inhibited formBy similarity1
Metal bindingi436Zinc; catalyticPROSITE-ProRule annotation1
Active sitei437PROSITE-ProRule annotation1
Metal bindingi440Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi446Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • eye development Source: UniProtKB
  • negative regulation of platelet aggregation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140873-MONOMER.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Protein family/group databases

MEROPSiM12.028.

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 18 (EC:3.4.24.-)
Short name:
ADAM-TS 18
Short name:
ADAM-TS18
Short name:
ADAMTS-18
Gene namesi
Name:ADAMTS18
Synonyms:ADAMTS21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:17110. ADAMTS18.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA ocular syndrome characterized by microcornea and myopic chorioretinal atrophy. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye. In addition to ocular findings, some patients have telecanthus and posteriorly rotated ears.
See also OMIM:615458
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070849202L → P in MMCAT. 1 PublicationCorresponds to variant rs397515468dbSNPEnsembl.1
Natural variantiVAR_070850577C → W in MMCAT. 1 PublicationCorresponds to variant rs148319220dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi170692.
MalaCardsiADAMTS18.
MIMi615458. phenotype.
OpenTargetsiENSG00000140873.
Orphaneti369970. Microcornea-myopic chorioretinal atrophy-telecanthus syndrome.
PharmGKBiPA24544.

Polymorphism and mutation databases

BioMutaiADAMTS18.
DMDMi296439427.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 47Sequence analysisAdd BLAST47
PropeptideiPRO_000002920048 – 284By similarityAdd BLAST237
ChainiPRO_0000042163285 – 1221A disintegrin and metalloproteinase with thrombospondin motifs 18Add BLAST937

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi151N-linked (GlcNAc...)Sequence analysis1
Glycosylationi190N-linked (GlcNAc...)Sequence analysis1
Glycosylationi313N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi369 ↔ 420By similarity
Disulfide bondi395 ↔ 402By similarity
Disulfide bondi414 ↔ 493By similarity
Disulfide bondi453 ↔ 477By similarity
Disulfide bondi521 ↔ 546By similarity
Disulfide bondi532 ↔ 553By similarity
Disulfide bondi541 ↔ 572By similarity
Disulfide bondi566 ↔ 577By similarity
Disulfide bondi601 ↔ 638By similarity
Disulfide bondi605 ↔ 643By similarity
Disulfide bondi616 ↔ 628By similarity
Glycosylationi745N-linked (GlcNAc...)Sequence analysis1
Glycosylationi838N-linked (GlcNAc...)Sequence analysis1
Glycosylationi909N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity
Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ8TE60.
PeptideAtlasiQ8TE60.
PRIDEiQ8TE60.

PTM databases

iPTMnetiQ8TE60.
PhosphoSitePlusiQ8TE60.

Expressioni

Tissue specificityi

Expressed in fetal lung, liver, and kidney and in adult brain, prostate, submaxillary gland, and endothelium.

Gene expression databases

BgeeiENSG00000140873.
CleanExiHS_ADAMTS18.
ExpressionAtlasiQ8TE60. baseline and differential.
GenevisibleiQ8TE60. HS.

Organism-specific databases

HPAiHPA044326.

Interactioni

Protein-protein interaction databases

BioGridi128084. 5 interactors.
STRINGi9606.ENSP00000282849.

Structurei

3D structure databases

ProteinModelPortaliQ8TE60.
SMRiQ8TE60.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini293 – 498Peptidase M12BPROSITE-ProRule annotationAdd BLAST206
Domaini498 – 577DisintegrinAdd BLAST80
Domaini589 – 644TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini931 – 990TSP type-1 2PROSITE-ProRule annotationAdd BLAST60
Domaini991 – 1049TSP type-1 3PROSITE-ProRule annotationAdd BLAST59
Domaini1052 – 1116TSP type-1 4PROSITE-ProRule annotationAdd BLAST65
Domaini1123 – 1178TSP type-1 5PROSITE-ProRule annotationAdd BLAST56
Domaini1184 – 1221PLACPROSITE-ProRule annotationAdd BLAST38

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni750 – 876SpacerAdd BLAST127

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi252 – 259Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi644 – 749Cys-richAdd BLAST106

Domaini

The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Sequence similaritiesi

Contains 1 disintegrin domain.Curated
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation
Contains 1 PLAC domain.PROSITE-ProRule annotation
Contains 5 TSP type-1 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000004800.
HOVERGENiHBG004315.
InParanoidiQ8TE60.
KOiK08632.
OMAiGCLVDEP.
OrthoDBiEOG091G14M8.
PhylomeDBiQ8TE60.
TreeFamiTF313537.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR010909. PLAC.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF08686. PLAC. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 5 hits.
[Graphical view]
PRINTSiPR01857. ADAMTSFAMILY.
SMARTiSM00209. TSP1. 6 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 5 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 5 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TE60-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MECALLLACA FPAAGSGPPR GLAGLGRVAK ALQLCCLCCA SVAAALASDS
60 70 80 90 100
SSGASGLNDD YVFVTPVEVD SAGSYISHDI LHNGRKKRSA QNARSSLHYR
110 120 130 140 150
FSAFGQELHL ELKPSAILSS HFIVQVLGKD GASETQKPEV QQCFYQGFIR
160 170 180 190 200
NDSSSSVAVS TCAGLSGLIR TRKNEFLISP LPQLLAQEHN YSSPAGHHPH
210 220 230 240 250
VLYKRTAEEK IQRYRGYPGS GRNYPGYSPS HIPHASQSRE TEYHHRRLQK
260 270 280 290 300
QHFCGRRKKY APKPPTEDTY LRFDEYGSSG RPRRSAGKSQ KGLNVETLVV
310 320 330 340 350
ADKKMVEKHG KGNVTTYILT VMNMVSGLFK DGTIGSDINV VVVSLILLEQ
360 370 380 390 400
EPGGLLINHH ADQSLNSFCQ WQSALIGKNG KRHDHAILLT GFDICSWKNE
410 420 430 440 450
PCDTLGFAPI SGMCSKYRSC TINEDTGLGL AFTIAHESGH NFGMIHDGEG
460 470 480 490 500
NPCRKAEGNI MSPTLTGNNG VFSWSSCSRQ YLKKFLSTPQ AGCLVDEPKQ
510 520 530 540 550
AGQYKYPDKL PGQIYDADTQ CKWQFGAKAK LCSLGFVKDI CKSLWCHRVG
560 570 580 590 600
HRCETKFMPA AEGTVCGLSM WCRQGQCVKF GELGPRPIHG QWSAWSKWSE
610 620 630 640 650
CSRTCGGGVK FQERHCNNPK PQYGGLFCPG SSRIYQLCNI NPCNENSLDF
660 670 680 690 700
RAQQCAEYNS KPFRGWFYQW KPYTKVEEED RCKLYCKAEN FEFFFAMSGK
710 720 730 740 750
VKDGTPCSPN KNDVCIDGVC ELVGCDHELG SKAVSDACGV CKGDNSTCKF
760 770 780 790 800
YKGLYLNQHK ANEYYPVVLI PAGARSIEIQ ELQVSSSYLA VRSLSQKYYL
810 820 830 840 850
TGGWSIDWPG EFPFAGTTFE YQRSFNRPER LYAPGPTNET LVFEILMQGK
860 870 880 890 900
NPGIAWKYAL PKVMNGTPPA TKRPAYTWSI VQSECSVSCG GGYINVKAIC
910 920 930 940 950
LRDQNTQVNS SFCSAKTKPV TEPKICNAFS CPAYWMPGEW STCSKACAGG
960 970 980 990 1000
QQSRKIQCVQ KKPFQKEEAV LHSLCPVSTP TQVQACNSHA CPPQWSLGPW
1010 1020 1030 1040 1050
SQCSKTCGRG VRKRELLCKG SAAETLPESQ CTSLPRPELQ EGCVLGRCPK
1060 1070 1080 1090 1100
NSRLQWVASS WSECSATCGL GVRKREMKCS EKGFQGKLIT FPERRCRNIK
1110 1120 1130 1140 1150
KPNLDLEETC NRRACPAHPV YNMVAGWYSL PWQQCTVTCG GGVQTRSVHC
1160 1170 1180 1190 1200
VQQGRPSSSC LLHQKPPVLR ACNTNFCPAP EKREDPSCVD FFNWCHLVPQ
1210 1220
HGVCNHKFYG KQCCKSCTRK I
Length:1,221
Mass (Da):135,167
Last modified:May 18, 2010 - v3
Checksum:i4F662B2D2ABF5CA3
GO
Isoform 2 (identifier: Q8TE60-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1064-1082: CSATCGLGVRKREMKCSEK → VWIRSHCWVRRLRPSWLTQ
     1083-1221: Missing.

Note: No experimental confirmation available.
Show »
Length:1,082
Mass (Da):119,768
Checksum:i5620CE80BDFEEA8E
GO

Sequence cautioni

The sequence BAC85503 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAC83612 differs from that shown. Probable intron retention.Curated
The sequence CAC83612 differs from that shown. Aberrant splicing.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti410I → T in CAC83612 (PubMed:11867212).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066554179S → L.2 PublicationsCorresponds to variant rs387906972dbSNPEnsembl.1
Natural variantiVAR_060231191Y → H.1 PublicationCorresponds to variant rs11643211dbSNPEnsembl.1
Natural variantiVAR_070849202L → P in MMCAT. 1 PublicationCorresponds to variant rs397515468dbSNPEnsembl.1
Natural variantiVAR_036152382R → K in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs368783738dbSNPEnsembl.1
Natural variantiVAR_036153455K → T in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs776584074dbSNPEnsembl.1
Natural variantiVAR_070850577C → W in MMCAT. 1 PublicationCorresponds to variant rs148319220dbSNPEnsembl.1
Natural variantiVAR_060232626L → I.2 PublicationsCorresponds to variant rs11640912dbSNPEnsembl.1
Natural variantiVAR_057083769L → I.1 PublicationCorresponds to variant rs9930984dbSNPEnsembl.1
Natural variantiVAR_057084946A → S.1 PublicationCorresponds to variant rs12935394dbSNPEnsembl.1
Natural variantiVAR_0570851080S → R.1 PublicationCorresponds to variant rs35478105dbSNPEnsembl.1
Natural variantiVAR_0570861159S → T.Corresponds to variant rs3743749dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0157761064 – 1082CSATC…KCSEK → VWIRSHCWVRRLRPSWLTQ in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_0157771083 – 1221Missing in isoform 2. 1 PublicationAdd BLAST139

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ311903 mRNA. Translation: CAC83612.1. Sequence problems.
AC009139 Genomic DNA. No translation available.
AC010548 Genomic DNA. No translation available.
AC025284 Genomic DNA. No translation available.
BC063283 mRNA. Translation: AAH63283.1.
AK122677 mRNA. Translation: BAC85503.1. Different initiation.
CCDSiCCDS10926.1. [Q8TE60-1]
RefSeqiNP_955387.1. NM_199355.3. [Q8TE60-1]
UniGeneiHs.188746.

Genome annotation databases

EnsembliENST00000282849; ENSP00000282849; ENSG00000140873. [Q8TE60-1]
GeneIDi170692.
KEGGihsa:170692.
UCSCiuc002ffc.4. human. [Q8TE60-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ311903 mRNA. Translation: CAC83612.1. Sequence problems.
AC009139 Genomic DNA. No translation available.
AC010548 Genomic DNA. No translation available.
AC025284 Genomic DNA. No translation available.
BC063283 mRNA. Translation: AAH63283.1.
AK122677 mRNA. Translation: BAC85503.1. Different initiation.
CCDSiCCDS10926.1. [Q8TE60-1]
RefSeqiNP_955387.1. NM_199355.3. [Q8TE60-1]
UniGeneiHs.188746.

3D structure databases

ProteinModelPortaliQ8TE60.
SMRiQ8TE60.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128084. 5 interactors.
STRINGi9606.ENSP00000282849.

Protein family/group databases

MEROPSiM12.028.

PTM databases

iPTMnetiQ8TE60.
PhosphoSitePlusiQ8TE60.

Polymorphism and mutation databases

BioMutaiADAMTS18.
DMDMi296439427.

Proteomic databases

PaxDbiQ8TE60.
PeptideAtlasiQ8TE60.
PRIDEiQ8TE60.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282849; ENSP00000282849; ENSG00000140873. [Q8TE60-1]
GeneIDi170692.
KEGGihsa:170692.
UCSCiuc002ffc.4. human. [Q8TE60-1]

Organism-specific databases

CTDi170692.
DisGeNETi170692.
GeneCardsiADAMTS18.
H-InvDBHIX0026938.
HGNCiHGNC:17110. ADAMTS18.
HPAiHPA044326.
MalaCardsiADAMTS18.
MIMi607512. gene.
615458. phenotype.
neXtProtiNX_Q8TE60.
OpenTargetsiENSG00000140873.
Orphaneti369970. Microcornea-myopic chorioretinal atrophy-telecanthus syndrome.
PharmGKBiPA24544.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000004800.
HOVERGENiHBG004315.
InParanoidiQ8TE60.
KOiK08632.
OMAiGCLVDEP.
OrthoDBiEOG091G14M8.
PhylomeDBiQ8TE60.
TreeFamiTF313537.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140873-MONOMER.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Miscellaneous databases

GenomeRNAii170692.
PROiQ8TE60.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140873.
CleanExiHS_ADAMTS18.
ExpressionAtlasiQ8TE60. baseline and differential.
GenevisibleiQ8TE60. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR010909. PLAC.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF08686. PLAC. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 5 hits.
[Graphical view]
PRINTSiPR01857. ADAMTSFAMILY.
SMARTiSM00209. TSP1. 6 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 5 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 5 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATS18_HUMAN
AccessioniPrimary (citable) accession number: Q8TE60
Secondary accession number(s): Q6P4R5, Q6ZWJ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 25, 2003
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 138 of the entry and version 3 of the sequence. [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

Caution

Variant Leu-179 has been originally reported as disease-causing mutation in a patient with Knobloch syndrome (PubMed:21862674). It has been subsequently shown that Knobloch syndrome in the patient was due to an intronic mutation in COL18A1. Variant Leu-179 is, therefore, not responsible for the disease phenotype (PubMed:23667181).2 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.