Reviewed, UniProtKB/Swiss-Prot Q9UKP5 (ATS6_HUMAN)

Names and origin

Protein names

Recommended name:
    A disintegrin and metalloproteinase with thrombospondin motifs 6
      Short name=ADAMTS-6
      Short name=ADAM-TS 6
      Short name=ADAM-TS6
    EC=3.4.24.-

Gene names

Name:

ADAMTS6

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1117 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Expressed at low levels in placenta and barely detectable in a number of other tissues.
Induction	Isoform 1 and isoform 2 expressions are up-regulated by TNF-alpha in retinal pigment epithelial cells.
Domain	The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
Post-translational modification	The precursor is cleaved by a furin endopeptidase By similarity.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 peptidase M12B domain. Contains 1 PLAC domain. Contains 5 TSP type-1 domains.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UKP5-1)

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.

Isoform 2 (identifier: Q9UKP5-2)

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.

Isoform 3 (identifier: Q9UKP5-3)

Also known as: Variant 3;

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

Isoform 4 (identifier: Q9UKP5-4)

Also known as: Variant 4;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Propeptide	22 – 244	223	By similarity		PRO_0000029174
	Chain	245 – 1117	873	A disintegrin and metalloproteinase with thrombospondin motifs 6		PRO_0000029175
Regions
	Domain	250 – 468	219	Peptidase M12B
	Domain	495 – 557	63	Disintegrin
	Domain	558 – 613	56	TSP type-1 1
	Domain	840 – 900	61	TSP type-1 2
	Domain	902 – 960	59	TSP type-1 3
	Domain	962 – 1007	46	TSP type-1 4
	Domain	1018 – 1073	56	TSP type-1 5
	Domain	1079 – 1117	39	PLAC
	Region	717 – 843	127	Spacer
Sites
	Active site	404	1	By similarity
	Metal binding	403	1	Zinc; catalytic By similarity
	Metal binding	407	1	Zinc; catalytic By similarity
	Metal binding	413	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	99	1	N-linked (GlcNAc...) Potential
	Glycosylation	172	1	N-linked (GlcNAc...) Potential
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
	Glycosylation	234	1	N-linked (GlcNAc...) Potential
	Glycosylation	724	1	N-linked (GlcNAc...) Potential
	Glycosylation	956	1	N-linked (GlcNAc...) Potential
	Disulfide bond	381 ↔ 463		By similarity
	Disulfide bond	420 ↔ 447		By similarity
	Disulfide bond	570 ↔ 607		By similarity
	Disulfide bond	574 ↔ 612		By similarity
	Disulfide bond	585 ↔ 597		By similarity
	Disulfide bond	911 ↔ 954		By similarity
	Disulfide bond	915 ↔ 959		By similarity
	Disulfide bond	926 ↔ 943		By similarity
Natural variations
	Alternative sequence	283 – 292	10	AKLYRDSSLG → RLPNFTVIPA in isoform 4.		VSP_037093
	Alternative sequence	293 – 1117	825	Missing in isoform 4.		VSP_037094
	Alternative sequence	422 – 504	83	TKGHE…QCKYG → RKVMKQQNYGSSHYCEYQSF FLVCLQSRFHHQLFR in isoform 2.		VSP_037095
	Alternative sequence	457 – 468	12	DSGRG…LDNEP → EFLKLGDSISGS in isoform 3.		VSP_037096
	Alternative sequence	469 – 1117	649	Missing in isoform 3.		VSP_037097
	Alternative sequence	860 – 908	49	VQRQE…FIGDW → KMPTRQPTQRARWRTKHILS YALCLLKKLIGNISCRFASS CNLAKETLL in isoform 2.		VSP_037098
	Alternative sequence	909 – 1117	209	Missing in isoform 2.		VSP_037099
Experimental info
	Sequence conflict	4	1	L → S in AAW47399. Ref.2
	Sequence conflict	24	1	D → G in AAW47398. Ref.2
	Sequence conflict	83	1	S → P in AAW47398. Ref.2
	Sequence conflict	229	1	Y → H in AAW47397. Ref.2
	Sequence conflict	406	1	G → V in AAD56357. Ref.1
	Sequence conflict	426	1	E → G in AAD56357. Ref.1
	Sequence conflict	426	1	E → G in AAW47397. Ref.2
	Sequence conflict	588 – 589	2	PA → LK in BAD92922. Ref.4
	Sequence conflict	712	1	D → G in AAD56357. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Variant 2) [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 5901E86BC82A9A87	FASTA	1,117	125,273
	10 20 30 40 50 60 MEILWKTLTW ILSLIMASSE FHSDHRLSYS SQEEFLTYLE HYQLTIPIRV DQNGAFLSFT 70 80 90 100 110 120 VKNDKHSRRR RSMDPIDPQQ AVSKLFFKLS AYGKHFHLNL TLNTDFVSKH FTVEYWGKDG 130 140 150 160 170 180 PQWKHDFLDN CHYTGYLQDQ RSTTKVALSN CVGLHGVIAT EDEEYFIEPL KNTTEDSKHF 190 200 210 220 230 240 SYENGHPHVI YKKSALQQRH LYDHSHCGVS DFTRSGKPWW LNDTSTVSYS LPINNTHIHH 250 260 270 280 290 300 RQKRSVSIER FVETLVVADK MMVGYHGRKD IEHYILSVMN IVAKLYRDSS LGNVVNIIVA 310 320 330 340 350 360 RLIVLTEDQP NLEINHHADK SLDSFCKWQK SILSHQSDGN TIPENGIAHH DNAVLITRYD 370 380 390 400 410 420 ICTYKNKPCG TLGLASVAGM CEPERSCSIN EDIGLGSAFT IAHEIGHNFG MNHDGIGNSC 430 440 450 460 470 480 GTKGHEAAKL MAAHITANTN PFSWSACSRD YITSFLDSGR GTCLDNEPPK RDFLYPAVAP 490 500 510 520 530 540 GQVYDADEQC RFQYGATSRQ CKYGEVCREL WCLSKSNRCV TNSIPAAEGT LCQTGNIEKG 550 560 570 580 590 600 WCYQGDCVPF GTWPQSIDGG WGPWSLWGEC SRTCGGGVSS SLRHCDSPAP SGGGKYCLGE 610 620 630 640 650 660 RKRYRSCNTD PCPLGSRDFR EKQCADFDNM PFRGKYYNWK PYTGGGVKPC ALNCLAEGYN 670 680 690 700 710 720 FYTERAPAVI DGTQCNADSL DICINGECKH VGCDNILGSD AREDRCRVCG GDGSTCDAIE 730 740 750 760 770 780 GFFNDSLPRG GYMEVVQIPR GSVHIEVREV AMSKNYIALK SEGDDYYING AWTIDWPRKF 790 800 810 820 830 840 DVAGTAFHYK RPTDEPESLE ALGPTSENLI VMVLLQEQNL GIRYKFNVPI TRTGSGDNEV 850 860 870 880 890 900 GFTWNHQPWS ECSATCAGGV QRQEVVCKRL DDNSIVQNNY CDPDSKPPEN QRACNTEPCP 910 920 930 940 950 960 PEWFIGDWLE CSKTCDGGMR TRAVLCIRKI GPSEEETLDY SGCLTHRPVE KEPCNNQSCP 970 980 990 1000 1010 1020 PQWVALDWSE CTPKCGPGFK HRIVLCKSSD LSKTFPAAQC PEESKPPVRI RCSLGRCPPP 1030 1040 1050 1060 1070 1080 RWVTGDWGQC SAQCGLGQQM RTVQCLSYTG QASSDCLETV RPPSMQQCES KCDSTPISNT 1090 1100 1110 EECKDVNKVA YCPLVLKFKF CSRAYFRQMC CKTCQGH
	Isoform 2 (Variant 1). Checksum: EA137275B9A465C2	FASTA	860	97,152
	10 20 30 40 50 60 MEILWKTLTW ILSLIMASSE FHSDHRLSYS SQEEFLTYLE HYQLTIPIRV DQNGAFLSFT 70 80 90 100 110 120 VKNDKHSRRR RSMDPIDPQQ AVSKLFFKLS AYGKHFHLNL TLNTDFVSKH FTVEYWGKDG 130 140 150 160 170 180 PQWKHDFLDN CHYTGYLQDQ RSTTKVALSN CVGLHGVIAT EDEEYFIEPL KNTTEDSKHF 190 200 210 220 230 240 SYENGHPHVI YKKSALQQRH LYDHSHCGVS DFTRSGKPWW LNDTSTVSYS LPINNTHIHH 250 260 270 280 290 300 RQKRSVSIER FVETLVVADK MMVGYHGRKD IEHYILSVMN IVAKLYRDSS LGNVVNIIVA 310 320 330 340 350 360 RLIVLTEDQP NLEINHHADK SLDSFCKWQK SILSHQSDGN TIPENGIAHH DNAVLITRYD 370 380 390 400 410 420 ICTYKNKPCG TLGLASVAGM CEPERSCSIN EDIGLGSAFT IAHEIGHNFG MNHDGIGNSC 430 440 450 460 470 480 GRKVMKQQNY GSSHYCEYQS FFLVCLQSRF HHQLFREVCR ELWCLSKSNR CVTNSIPAAE 490 500 510 520 530 540 GTLCQTGNIE KGWCYQGDCV PFGTWPQSID GGWGPWSLWG ECSRTCGGGV SSSLRHCDSP 550 560 570 580 590 600 APSGGGKYCL GERKRYRSCN TDPCPLGSRD FREKQCADFD NMPFRGKYYN WKPYTGGGVK 610 620 630 640 650 660 PCALNCLAEG YNFYTERAPA VIDGTQCNAD SLDICINGEC KHVGCDNILG SDAREDRCRV 670 680 690 700 710 720 CGGDGSTCDA IEGFFNDSLP RGGYMEVVQI PRGSVHIEVR EVAMSKNYIA LKSEGDDYYI 730 740 750 760 770 780 NGAWTIDWPR KFDVAGTAFH YKRPTDEPES LEALGPTSEN LIVMVLLQEQ NLGIRYKFNV 790 800 810 820 830 840 PITRTGSGDN EVGFTWNHQP WSECSATCAG GKMPTRQPTQ RARWRTKHIL SYALCLLKKL 850 860 IGNISCRFAS SCNLAKETLL
	Isoform 3 (Variant 3). Checksum: E8D2E75EF8A1C468	FASTA	468	53,165
	10 20 30 40 50 60 MEILWKTLTW ILSLIMASSE FHSDHRLSYS SQEEFLTYLE HYQLTIPIRV DQNGAFLSFT 70 80 90 100 110 120 VKNDKHSRRR RSMDPIDPQQ AVSKLFFKLS AYGKHFHLNL TLNTDFVSKH FTVEYWGKDG 130 140 150 160 170 180 PQWKHDFLDN CHYTGYLQDQ RSTTKVALSN CVGLHGVIAT EDEEYFIEPL KNTTEDSKHF 190 200 210 220 230 240 SYENGHPHVI YKKSALQQRH LYDHSHCGVS DFTRSGKPWW LNDTSTVSYS LPINNTHIHH 250 260 270 280 290 300 RQKRSVSIER FVETLVVADK MMVGYHGRKD IEHYILSVMN IVAKLYRDSS LGNVVNIIVA 310 320 330 340 350 360 RLIVLTEDQP NLEINHHADK SLDSFCKWQK SILSHQSDGN TIPENGIAHH DNAVLITRYD 370 380 390 400 410 420 ICTYKNKPCG TLGLASVAGM CEPERSCSIN EDIGLGSAFT IAHEIGHNFG MNHDGIGNSC 430 440 450 460 GTKGHEAAKL MAAHITANTN PFSWSACSRD YITSFLEFLK LGDSISGS
	Isoform 4 (Variant 4). Checksum: 01A54680DCEFABD7	FASTA	292	34,189
	10 20 30 40 50 60 MEILWKTLTW ILSLIMASSE FHSDHRLSYS SQEEFLTYLE HYQLTIPIRV DQNGAFLSFT 70 80 90 100 110 120 VKNDKHSRRR RSMDPIDPQQ AVSKLFFKLS AYGKHFHLNL TLNTDFVSKH FTVEYWGKDG 130 140 150 160 170 180 PQWKHDFLDN CHYTGYLQDQ RSTTKVALSN CVGLHGVIAT EDEEYFIEPL KNTTEDSKHF 190 200 210 220 230 240 SYENGHPHVI YKKSALQQRH LYDHSHCGVS DFTRSGKPWW LNDTSTVSYS LPINNTHIHH 250 260 270 280 290 RQKRSVSIER FVETLVVADK MMVGYHGRKD IEHYILSVMN IVRLPNFTVI PA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases." Hurskainen T.L., Hirohata S., Seldin M.F., Apte S.S. J. Biol. Chem. 274:25555-25563(1999) [PubMed: 10464288] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Analysis of full length ADAMTS6 transcript reveals alternative splicing and a role for the 5' untranslated region in translational control." Bevitt D.J., Li Z., Lindrop J.L., Barker M.D., Clarke M.P., McKie N. Gene 359:99-110(2005) [PubMed: 16129570] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), INDUCTION.
[3]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 588-1117 (ISOFORM 1). Tissue: Brain.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 804-1117 (ISOFORM 1). Tissue: Uterus.
[6]	"Expression of ADAMTS metalloproteinases in the retinal pigment epithelium derived cell line ARPE-19: transcriptional regulation by TNFalpha." Bevitt D.J., Mohamed J., Catterall J.B., Li Z., Arris C.E., Hiscott P., Sheridan C., Langton K.P., Barker M.D., Clarke M.P., McKie N. Biochim. Biophys. Acta 1626:83-91(2003) [PubMed: 12697333] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00296965. IPI00658047. IPI00929414. IPI00929566.
RefSeq	NP_922932.2.
UniGene	Hs.482291
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9UKP5.
Protein family/group databases
MEROPS	M12.230.
Genome annotation databases
Ensembl	ENST00000381055; ENSP00000370443; ENSG00000049192; Homo sapiens. [Genome view]
GeneID	11174.
KEGG	hsa:11174.
Organism-specific databases
CTD	11174.
GeneCards	GC05M064545.
H-InvDB	HIX0024828.
HGNC	HGNC:222. ADAMTS6.
HPA	HPA027216.
MIM	605008. gene.
PharmGKB	PA24550.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9UKP5.
OMA	SDFTRSG
OrthoDB	EOG9PG8KG
Gene expression databases
ArrayExpress	Q9UKP5.
Bgee	Q9UKP5.
CleanEx	HS_ADAMTS6.
Genevestigator	Q9UKP5.
GermOnline	ENSG00000049192. Homo sapiens.
Family and domain databases
InterPro	IPR010294. ADAM_spacer1. IPR001590. Peptidase_M12B. IPR013273. Peptidase_M12B_ADAM-TS. IPR002870. Peptidase_M12B_N. IPR010909. PLAC. IPR000884. Thrombospondin_1_rpt. [Graphical view]
Pfam	PF05986. ADAM_spacer1. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF08686. PLAC. 1 hit. PF00090. TSP_1. 4 hits. [Graphical view]
PRINTS	PR01857. ADAMTSFAMILY.
SMART	SM00209. TSP1. 5 hits. [Graphical view]
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. False negative. PS50900. PLAC. 1 hit. PS50092. TSP1. 4 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

ATS6_HUMAN

Accession

Primary (citable) accession number: Q9UKP5
Secondary accession number(s): Q59EX6 , Q5IR87, Q5IR88, Q5IR89, Q68DL1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 5, 2009
Last modified:	November 24, 2009
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.