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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 6

Gene

ADAMTS6

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

Functioni

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi403Zinc; catalyticBy similarity1
Active sitei404PROSITE-ProRule annotation1
Metal bindingi407Zinc; catalyticBy similarity1
Metal bindingi413Zinc; catalyticBy similarity1

GO - Molecular functioni

  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000049192-MONOMER.
ReactomeiR-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Protein family/group databases

MEROPSiM12.230.

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 6 (EC:3.4.24.-)
Short name:
ADAM-TS 6
Short name:
ADAM-TS6
Short name:
ADAMTS-6
Gene namesi
Name:ADAMTS6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:222. ADAMTS6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi11174.
OpenTargetsiENSG00000049192.
PharmGKBiPA24550.

Polymorphism and mutation databases

BioMutaiADAMTS6.
DMDMi229462816.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
PropeptideiPRO_000002917422 – 244By similarityAdd BLAST223
ChainiPRO_0000029175245 – 1117A disintegrin and metalloproteinase with thrombospondin motifs 6Add BLAST873

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi99N-linked (GlcNAc...)Sequence analysis1
Glycosylationi172N-linked (GlcNAc...)Sequence analysis1
Glycosylationi222N-linked (GlcNAc...)Sequence analysis1
Glycosylationi234N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi326 ↔ 387By similarity
Disulfide bondi362 ↔ 369By similarity
Disulfide bondi381 ↔ 463By similarity
Disulfide bondi420 ↔ 447By similarity
Disulfide bondi490 ↔ 512By similarity
Disulfide bondi501 ↔ 519By similarity
Disulfide bondi507 ↔ 542By similarity
Disulfide bondi532 ↔ 547By similarity
Disulfide bondi570 ↔ 607By similarity
Disulfide bondi574 ↔ 612By similarity
Disulfide bondi585 ↔ 597By similarity
Glycosylationi724N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi911 ↔ 954By similarity
Disulfide bondi915 ↔ 959By similarity
Disulfide bondi926 ↔ 943By similarity
Glycosylationi956N-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

PaxDbiQ9UKP5.
PeptideAtlasiQ9UKP5.
PRIDEiQ9UKP5.

PTM databases

iPTMnetiQ9UKP5.
PhosphoSitePlusiQ9UKP5.

Expressioni

Tissue specificityi

Expressed at low levels in placenta and barely detectable in a number of other tissues.

Inductioni

Isoform 1 and isoform 2 expressions are up-regulated by TNF in retinal pigment epithelial cells.2 Publications

Gene expression databases

BgeeiENSG00000049192.
CleanExiHS_ADAMTS6.
GenevisibleiQ9UKP5. HS.

Organism-specific databases

HPAiHPA043441.

Interactioni

Protein-protein interaction databases

BioGridi116345. 2 interactors.
STRINGi9606.ENSP00000370443.

Structurei

3D structure databases

ProteinModelPortaliQ9UKP5.
SMRiQ9UKP5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini250 – 468Peptidase M12BPROSITE-ProRule annotationAdd BLAST219
Domaini495 – 557DisintegrinAdd BLAST63
Domaini558 – 613TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini840 – 900TSP type-1 2PROSITE-ProRule annotationAdd BLAST61
Domaini902 – 960TSP type-1 3PROSITE-ProRule annotationAdd BLAST59
Domaini962 – 1007TSP type-1 4PROSITE-ProRule annotationAdd BLAST46
Domaini1018 – 1073TSP type-1 5PROSITE-ProRule annotationAdd BLAST56
Domaini1079 – 1117PLACPROSITE-ProRule annotationAdd BLAST39

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni717 – 843SpacerAdd BLAST127

Domaini

The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.

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.
KOG4597. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000004800.
HOVERGENiHBG004315.
InParanoidiQ9UKP5.
KOiK08621.
OMAiDNEVGFM.
OrthoDBiEOG091G14M8.
PhylomeDBiQ9UKP5.
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. 5 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 5 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UKP5-1) [UniParc]FASTAAdd to basket
Also known as: Variant 2

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
MEILWKTLTW ILSLIMASSE FHSDHRLSYS SQEEFLTYLE HYQLTIPIRV
60 70 80 90 100
DQNGAFLSFT VKNDKHSRRR RSMDPIDPQQ AVSKLFFKLS AYGKHFHLNL
110 120 130 140 150
TLNTDFVSKH FTVEYWGKDG PQWKHDFLDN CHYTGYLQDQ RSTTKVALSN
160 170 180 190 200
CVGLHGVIAT EDEEYFIEPL KNTTEDSKHF SYENGHPHVI YKKSALQQRH
210 220 230 240 250
LYDHSHCGVS DFTRSGKPWW LNDTSTVSYS LPINNTHIHH RQKRSVSIER
260 270 280 290 300
FVETLVVADK MMVGYHGRKD IEHYILSVMN IVAKLYRDSS LGNVVNIIVA
310 320 330 340 350
RLIVLTEDQP NLEINHHADK SLDSFCKWQK SILSHQSDGN TIPENGIAHH
360 370 380 390 400
DNAVLITRYD ICTYKNKPCG TLGLASVAGM CEPERSCSIN EDIGLGSAFT
410 420 430 440 450
IAHEIGHNFG MNHDGIGNSC GTKGHEAAKL MAAHITANTN PFSWSACSRD
460 470 480 490 500
YITSFLDSGR GTCLDNEPPK RDFLYPAVAP GQVYDADEQC RFQYGATSRQ
510 520 530 540 550
CKYGEVCREL WCLSKSNRCV TNSIPAAEGT LCQTGNIEKG WCYQGDCVPF
560 570 580 590 600
GTWPQSIDGG WGPWSLWGEC SRTCGGGVSS SLRHCDSPAP SGGGKYCLGE
610 620 630 640 650
RKRYRSCNTD PCPLGSRDFR EKQCADFDNM PFRGKYYNWK PYTGGGVKPC
660 670 680 690 700
ALNCLAEGYN FYTERAPAVI DGTQCNADSL DICINGECKH VGCDNILGSD
710 720 730 740 750
AREDRCRVCG GDGSTCDAIE GFFNDSLPRG GYMEVVQIPR GSVHIEVREV
760 770 780 790 800
AMSKNYIALK SEGDDYYING AWTIDWPRKF DVAGTAFHYK RPTDEPESLE
810 820 830 840 850
ALGPTSENLI VMVLLQEQNL GIRYKFNVPI TRTGSGDNEV GFTWNHQPWS
860 870 880 890 900
ECSATCAGGV QRQEVVCKRL DDNSIVQNNY CDPDSKPPEN QRACNTEPCP
910 920 930 940 950
PEWFIGDWLE CSKTCDGGMR TRAVLCIRKI GPSEEETLDY SGCLTHRPVE
960 970 980 990 1000
KEPCNNQSCP PQWVALDWSE CTPKCGPGFK HRIVLCKSSD LSKTFPAAQC
1010 1020 1030 1040 1050
PEESKPPVRI RCSLGRCPPP RWVTGDWGQC SAQCGLGQQM RTVQCLSYTG
1060 1070 1080 1090 1100
QASSDCLETV RPPSMQQCES KCDSTPISNT EECKDVNKVA YCPLVLKFKF
1110
CSRAYFRQMC CKTCQGH
Length:1,117
Mass (Da):125,273
Last modified:May 5, 2009 - v2
Checksum:i5901E86BC82A9A87
GO
Isoform 2 (identifier: Q9UKP5-2) [UniParc]FASTAAdd to basket
Also known as: Variant 1

The sequence of this isoform differs from the canonical sequence as follows:
     422-504: TKGHEAAKLM...GATSRQCKYG → RKVMKQQNYGSSHYCEYQSFFLVCLQSRFHHQLFR
     860-908: VQRQEVVCKR...CPPEWFIGDW → KMPTRQPTQR...SCNLAKETLL
     909-1117: Missing.

Note: Contains critical point mutations in the region encoding the catalytic domain as well as 2 point mutations compared with genomic sequence. May either be a rare polymorphism or may have arisen through a combination of aberrant RNA editing and point mutation/sequencing error.
Show »
Length:860
Mass (Da):97,152
Checksum:iEA137275B9A465C2
GO
Isoform 3 (identifier: Q9UKP5-3) [UniParc]FASTAAdd to basket
Also known as: Variant 3

The sequence of this isoform differs from the canonical sequence as follows:
     457-468: DSGRGTCLDNEP → EFLKLGDSISGS
     469-1117: Missing.

Show »
Length:468
Mass (Da):53,165
Checksum:iE8D2E75EF8A1C468
GO
Isoform 4 (identifier: Q9UKP5-4) [UniParc]FASTAAdd to basket
Also known as: Variant 4

The sequence of this isoform differs from the canonical sequence as follows:
     283-292: AKLYRDSSLG → RLPNFTVIPA
     293-1117: Missing.

Show »
Length:292
Mass (Da):34,189
Checksum:i01A54680DCEFABD7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4L → S in AAW47399 (PubMed:16129570).Curated1
Sequence conflicti24D → G in AAW47398 (PubMed:16129570).Curated1
Sequence conflicti83S → P in AAW47398 (PubMed:16129570).Curated1
Sequence conflicti229Y → H in AAW47397 (PubMed:16129570).Curated1
Sequence conflicti406G → V in AAD56357 (PubMed:10464288).Curated1
Sequence conflicti426E → G in AAD56357 (PubMed:10464288).Curated1
Sequence conflicti426E → G in AAW47397 (PubMed:16129570).Curated1
Sequence conflicti588 – 589PA → LK in BAD92922 (Ref. 4) Curated2
Sequence conflicti712D → G in AAD56357 (PubMed:10464288).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_037093283 – 292AKLYRDSSLG → RLPNFTVIPA in isoform 4. 1 Publication10
Alternative sequenceiVSP_037094293 – 1117Missing in isoform 4. 1 PublicationAdd BLAST825
Alternative sequenceiVSP_037095422 – 504TKGHE…QCKYG → RKVMKQQNYGSSHYCEYQSF FLVCLQSRFHHQLFR in isoform 2. 1 PublicationAdd BLAST83
Alternative sequenceiVSP_037096457 – 468DSGRG…LDNEP → EFLKLGDSISGS in isoform 3. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_037097469 – 1117Missing in isoform 3. 1 PublicationAdd BLAST649
Alternative sequenceiVSP_037098860 – 908VQRQE…FIGDW → KMPTRQPTQRARWRTKHILS YALCLLKKLIGNISCRFASS CNLAKETLL in isoform 2. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_037099909 – 1117Missing in isoform 2. 1 PublicationAdd BLAST209

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF140674 mRNA. Translation: AAD56357.1.
AY692424 mRNA. Translation: AAW47397.1.
AY692425 mRNA. Translation: AAW47398.1.
AY692426 mRNA. Translation: AAW47399.1.
AC008847 Genomic DNA. No translation available.
AC008868 Genomic DNA. No translation available.
AC025176 Genomic DNA. No translation available.
AC025186 Genomic DNA. No translation available.
AC099505 Genomic DNA. No translation available.
AB209685 mRNA. Translation: BAD92922.1.
CR749356 mRNA. Translation: CAH18209.1.
CCDSiCCDS3983.2. [Q9UKP5-1]
RefSeqiNP_922932.2. NM_197941.3. [Q9UKP5-1]
XP_011541415.1. XM_011543113.2. [Q9UKP5-1]
XP_011541416.1. XM_011543114.2. [Q9UKP5-1]
UniGeneiHs.482291.

Genome annotation databases

EnsembliENST00000381052; ENSP00000424377; ENSG00000049192. [Q9UKP5-4]
ENST00000381055; ENSP00000370443; ENSG00000049192. [Q9UKP5-1]
GeneIDi11174.
KEGGihsa:11174.
UCSCiuc003jtp.4. human. [Q9UKP5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF140674 mRNA. Translation: AAD56357.1.
AY692424 mRNA. Translation: AAW47397.1.
AY692425 mRNA. Translation: AAW47398.1.
AY692426 mRNA. Translation: AAW47399.1.
AC008847 Genomic DNA. No translation available.
AC008868 Genomic DNA. No translation available.
AC025176 Genomic DNA. No translation available.
AC025186 Genomic DNA. No translation available.
AC099505 Genomic DNA. No translation available.
AB209685 mRNA. Translation: BAD92922.1.
CR749356 mRNA. Translation: CAH18209.1.
CCDSiCCDS3983.2. [Q9UKP5-1]
RefSeqiNP_922932.2. NM_197941.3. [Q9UKP5-1]
XP_011541415.1. XM_011543113.2. [Q9UKP5-1]
XP_011541416.1. XM_011543114.2. [Q9UKP5-1]
UniGeneiHs.482291.

3D structure databases

ProteinModelPortaliQ9UKP5.
SMRiQ9UKP5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116345. 2 interactors.
STRINGi9606.ENSP00000370443.

Protein family/group databases

MEROPSiM12.230.

PTM databases

iPTMnetiQ9UKP5.
PhosphoSitePlusiQ9UKP5.

Polymorphism and mutation databases

BioMutaiADAMTS6.
DMDMi229462816.

Proteomic databases

PaxDbiQ9UKP5.
PeptideAtlasiQ9UKP5.
PRIDEiQ9UKP5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381052; ENSP00000424377; ENSG00000049192. [Q9UKP5-4]
ENST00000381055; ENSP00000370443; ENSG00000049192. [Q9UKP5-1]
GeneIDi11174.
KEGGihsa:11174.
UCSCiuc003jtp.4. human. [Q9UKP5-1]

Organism-specific databases

CTDi11174.
DisGeNETi11174.
GeneCardsiADAMTS6.
HGNCiHGNC:222. ADAMTS6.
HPAiHPA043441.
MIMi605008. gene.
neXtProtiNX_Q9UKP5.
OpenTargetsiENSG00000049192.
PharmGKBiPA24550.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
KOG4597. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000004800.
HOVERGENiHBG004315.
InParanoidiQ9UKP5.
KOiK08621.
OMAiDNEVGFM.
OrthoDBiEOG091G14M8.
PhylomeDBiQ9UKP5.
TreeFamiTF313537.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000049192-MONOMER.
ReactomeiR-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Miscellaneous databases

GenomeRNAii11174.
PROiQ9UKP5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000049192.
CleanExiHS_ADAMTS6.
GenevisibleiQ9UKP5. 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. 5 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 5 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATS6_HUMAN
AccessioniPrimary (citable) accession number: Q9UKP5
Secondary accession number(s): Q59EX6
, Q5IR87, Q5IR88, Q5IR89, Q68DL1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 5, 2009
Last modified: November 2, 2016
This is version 154 of the entry and version 2 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. 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.