Reviewed, UniProtKB/Swiss-Prot Q9UKP4 (ATS7_HUMAN)

Names and origin

Protein names

Recommended name:
    A disintegrin and metalloproteinase with thrombospondin motifs 7
      Short name=ADAMTS-7
      Short name=ADAM-TS 7
      Short name=ADAM-TS7
    EC=3.4.24.-
Alternative name(s):
    COMPase

Gene names

Name:

ADAMTS7

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1686 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	Metalloprotease that may play a role in the degradation of COMP.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Interacts with COMP.
Subcellular location	Secreted › extracellular space › extracellular matrixBy similarity. Note= Also found associated with the external cell surface By similarity.
Tissue specificity	Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Detected in meniscus, bone, tendon, cartilage, synovium, fat and ligaments.
Induction	Up-regulated in articular cartilage and synovium from arthritis patients.
Domain	The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix. 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.
Post-translational modification	N-glycosylated. O-glycosylated proteoglycan. Contains chondroitin sulfate By similarity. May be cleaved by a furin endopeptidase By similarity. The precursor is sequentially processed.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 peptidase M12B domain. Contains 1 PLAC domain. Contains 8 TSP type-1 domains.
Biophysicochemical properties	pH dependence: Optimum pH is between 7.5 and 9.5.
Sequence caution	The sequence AAD56358.1 differs from that shown. Reason: Frameshift at position 863.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Glycoprotein Proteoglycan Zymogen
Technical term	Direct protein sequencing
Gene Ontology (GO)
Molecular function	metallopeptidase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UKP4-1)

Also known as: ADAMTS7B;

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: Q9UKP4-2)

Also known as: ADAMTS7A;

The sequence of this isoform differs from the canonical sequence as follows:
     793-864: LLFQESNPGV...PVDEEHCDPL → VPASRGPGGG...VHRGGWGQLL
     865-1686: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Propeptide	28 – 236	209
	Chain	237 – 1686	1450	A disintegrin and metalloproteinase with thrombospondin motifs 7
Regions
	Domain	242 – 452	211	Peptidase M12B
	Domain	462 – 537	76	Disintegrin
	Domain	538 – 593	56	TSP type-1 1
	Domain	821 – 880	60	TSP type-1 2
	Domain	881 – 940	60	TSP type-1 3
	Domain	942 – 995	54	TSP type-1 4
	Domain	1411 – 1459	49	TSP type-1 5
	Domain	1462 – 1522	61	TSP type-1 6
	Domain	1523 – 1567	45	TSP type-1 7
	Domain	1569 – 1629	61	TSP type-1 8
	Domain	1632 – 1672	41	PLAC
	Region	698 – 809	112	Spacer
	Motif	202 – 209	8	Cysteine switch By similarity
	Compositional bias	595 – 697	103	Cys-rich
Sites
	Active site	389	1	By similarity
	Metal binding	204	1	Zinc; in inhibited form By similarity
	Metal binding	388	1	Zinc; catalytic By similarity
	Metal binding	392	1	Zinc; catalytic By similarity
	Metal binding	398	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	94	1	N-linked (GlcNAc...) Potential
	Glycosylation	693	1	N-linked (GlcNAc...) Potential
	Glycosylation	778	1	N-linked (GlcNAc...) Potential
	Disulfide bond	366 ↔ 447		By similarity
	Disulfide bond	405 ↔ 431		By similarity
	Disulfide bond	550 ↔ 587		By similarity
	Disulfide bond	554 ↔ 592		By similarity
	Disulfide bond	565 ↔ 577		By similarity
Natural variations
	Alternative sequence	793 – 864	72	LLFQE…HCDPL → VPASRGPGGGSRGGVPRPST LHGRSGGVSPGSVTEPGSEP GPPAAASTSVSPSLKWPNLV AAVHRGGWGQLL in isoform 2.
	Alternative sequence	865 – 1686	822	Missing in isoform 2.
	Natural variant	214	1	S → P: dbSNP rs3825807.
	Natural variant	307	1	T → M: dbSNP rs2127898.
	Natural variant	1319	1	T → A: dbSNP rs11630236.
	Natural variant	1414	1	G → S: dbSNP rs2929155.
	Natural variant	1583	1	G → A: dbSNP rs7495616.
Experimental info
	Sequence conflict	642	1	E → K in AAD56358. Ref.1
	Sequence conflict	1101	1	H → R in AAQ94616. Ref.2
	Sequence conflict	1364	1	S → T in AAQ94616. Ref.2
	Sequence conflict	1479	1	G → D in AAQ94616. Ref.2
	Sequence conflict	1511	1	P → H in AAQ94616. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ADAMTS7B) [UniParc]. Last modified September 2, 2008. Version 2. Checksum: AB38264B8E8DB740	FASTA	1,686	184,095
	10 20 30 40 50 60 MPGGPSPRSP APLLRPLLLL LCALAPGAPG PAPGRATEGR AALDIVHPVR VDAGGSFLSY 70 80 90 100 110 120 ELWPRALRKR DVSVRRDAPA FYELQYRGRE LRFNLTANQH LLAPGFVSET RRRGGLGRAH 130 140 150 160 170 180 IRAHTPACHL LGEVQDPELE GGLAAISACD GLKGVFQLSN EDYFIEPLDS APARPGHAQP 190 200 210 220 230 240 HVVYKRQAPE RLAQRGDSSA PSTCGVQVYP ELESRRERWE QRQQWRRPRL RRLHQRSVSK 250 260 270 280 290 300 EKWVETLVVA DAKMVEYHGQ PQVESYVLTI MNMVAGLFHD PSIGNPIHIT IVRLVLLEDE 310 320 330 340 350 360 EEDLKITHHA DNTLKSFCKW QKSINMKGDA HPLHHDTAIL LTRKDLCAAM NRPCETLGLS 370 380 390 400 410 420 HVAGMCQPHR SCSINEDTGL PLAFTVAHEL GHSFGIQHDG SGNDCEPVGK RPFIMSPQLL 430 440 450 460 470 480 YDAAPLTWSR CSRQYITRFL DRGWGLCLDD PPAKDIIDFP SVPPGVLYDV SHQCRLQYGA 490 500 510 520 530 540 YSAFCEDMDN VCHTLWCSVG TTCHSKLDAA VDGTRCGENK WCLSGECVPV GFRPEAVDGG 550 560 570 580 590 600 WSGWSAWSIC SRSCGMGVQS AERQCTQPTP KYKGRYCVGE RKRFRLCNLQ ACPAGRPSFR 610 620 630 640 650 660 HVQCSHFDAM LYKGQLHTWV PVVNDVNPCE LHCRPANEYF AEKLRDAVVD GTPCYQVRAS 670 680 690 700 710 720 RDLCINGICK NVGCDFEIDS GAMEDRCGVC HGNGSTCHTV SGTFEEAEGL GYVDVGLIPA 730 740 750 760 770 780 GAREIRIQEV AEAANFLALR SEDPEKYFLN GGWTIQWNGD YQVAGTTFTY ARRGNWENLT 790 800 810 820 830 840 SPGPTKEPVW IQLLFQESNP GVHYEYTIHR EAGGHDEVPP PVFSWHYGPW TKCTVTCGRG 850 860 870 880 890 900 VQRQNVYCLE RQAGPVDEEH CDPLGRPDDQ QRKCSEQPCP ARWWAGEWQL CSSSCGPGGL 910 920 930 940 950 960 SRRAVLCIRS VGLDEQSALE PPACEHLPRP PTETPCNRHV PCPATWAVGN WSQCSVTCGE 970 980 990 1000 1010 1020 GTQRRNVLCT NDTGVPCDEA QQPASEVTCS LPLCRWPLGT LGPEGSGSGS SSHELFNEAD 1030 1040 1050 1060 1070 1080 FIPHHLAPRP SPASSPKPGT MGNAIEEEAP ELDLPGPVFV DDFYYDYNFI NFHEDLSYGP 1090 1100 1110 1120 1130 1140 SEEPDLDLAG TGDRTPPPHS HPAAPSTGSP VPATEPPAAK EEGVLGPWSP SPWPSQAGRS 1150 1160 1170 1180 1190 1200 PPPPSEQTPG NPLINFLPEE DTPIGAPDLG LPSLSWPRVS TDGLQTPATP ESQNDFPVGK 1210 1220 1230 1240 1250 1260 DSQSQLPPPW RDRTNEVFKD DEEPKGRGAP HLPPRPSSTL PPLSPVGSTH SSPSPDVAEL 1270 1280 1290 1300 1310 1320 WTGGTVAWEP ALEGGLGPVD SELWPTVGVA SLLPPPIAPL PEMKVRDSSL EPGTPSFPTP 1330 1340 1350 1360 1370 1380 GPGSWDLQTV AVWGTFLPTT LTGLGHMPEP ALNPGPKGQP ESLSPEVPLS SRLLSTPAWD 1390 1400 1410 1420 1430 1440 SPANSHRVPE TQPLAPSLAE AGPPADPLVV RNAGWQAGNW SECSTTCGLG AVWRPVRCSS 1450 1460 1470 1480 1490 1500 GRDEDCAPAG RPQPARRCHL RPCATWHSGN WSKCSRSCGG GSSVRDVQCV DTRDLRPLRP 1510 1520 1530 1540 1550 1560 FHCQPGPAKP PAHRPCGAQP CLSWYTSSWR ECSEACGGGE QQRLVTCPEP GLCEEALRPN 1570 1580 1590 1600 1610 1620 TTRPCNTHPC TQWVVGPWGQ CSGPCGGGVQ RRLVKCVNTQ TGLPEEDSDQ CGHEAWPESS 1630 1640 1650 1660 1670 1680 RPCGTEDCEP VEPPRCERDR LSFGFCETLR LLGRCQLPTI RTQCCRSCSP PSHGAPSRGH QRVARR
	Isoform 2 (ADAMTS7A) [UniParc]. Checksum: BA0B3C573164B385		864	94,868
	10 20 30 40 50 60 MPGGPSPRSP APLLRPLLLL LCALAPGAPG PAPGRATEGR AALDIVHPVR VDAGGSFLSY 70 80 90 100 110 120 ELWPRALRKR DVSVRRDAPA FYELQYRGRE LRFNLTANQH LLAPGFVSET RRRGGLGRAH 130 140 150 160 170 180 IRAHTPACHL LGEVQDPELE GGLAAISACD GLKGVFQLSN EDYFIEPLDS APARPGHAQP 190 200 210 220 230 240 HVVYKRQAPE RLAQRGDSSA PSTCGVQVYP ELESRRERWE QRQQWRRPRL RRLHQRSVSK 250 260 270 280 290 300 EKWVETLVVA DAKMVEYHGQ PQVESYVLTI MNMVAGLFHD PSIGNPIHIT IVRLVLLEDE 310 320 330 340 350 360 EEDLKITHHA DNTLKSFCKW QKSINMKGDA HPLHHDTAIL LTRKDLCAAM NRPCETLGLS 370 380 390 400 410 420 HVAGMCQPHR SCSINEDTGL PLAFTVAHEL GHSFGIQHDG SGNDCEPVGK RPFIMSPQLL 430 440 450 460 470 480 YDAAPLTWSR CSRQYITRFL DRGWGLCLDD PPAKDIIDFP SVPPGVLYDV SHQCRLQYGA 490 500 510 520 530 540 YSAFCEDMDN VCHTLWCSVG TTCHSKLDAA VDGTRCGENK WCLSGECVPV GFRPEAVDGG 550 560 570 580 590 600 WSGWSAWSIC SRSCGMGVQS AERQCTQPTP KYKGRYCVGE RKRFRLCNLQ ACPAGRPSFR 610 620 630 640 650 660 HVQCSHFDAM LYKGQLHTWV PVVNDVNPCE LHCRPANEYF AEKLRDAVVD GTPCYQVRAS 670 680 690 700 710 720 RDLCINGICK NVGCDFEIDS GAMEDRCGVC HGNGSTCHTV SGTFEEAEGL GYVDVGLIPA 730 740 750 760 770 780 GAREIRIQEV AEAANFLALR SEDPEKYFLN GGWTIQWNGD YQVAGTTFTY ARRGNWENLT 790 800 810 820 830 840 SPGPTKEPVW IQVPASRGPG GGSRGGVPRP STLHGRSGGV SPGSVTEPGS EPGPPAAAST 850 860 SVSPSLKWPN LVAAVHRGGW GQLL

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]	"ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein." Liu C.-J., Kong W., Ilalov K., Yu S., Xu K., Prazak L., Fajardo M., Sehgal B., Di Cesare P.E. FASEB J. 20:988-990(2006) [PubMed: 16585064] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, COFACTOR, PH DEPENDENCE, INTERACTION WITH COMP, INDUCTION, TISSUE SPECIFICITY, VARIANTS ALA-1319; SER-1414 AND ALA-1583.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT MET-307. Tissue: Ovary.
[4]	"ADAMTS7B, the full-length product of the ADAMTS7 gene, is a chondroitin sulfate proteoglycan containing a mucin domain." Somerville R.P.T., Longpre J.-M., Apel E.D., Lewis R.M., Wang L.W., Sanes J.R., Leduc R., Apte S.S. J. Biol. Chem. 279:35159-35175(2004) [PubMed: 15192113] [Abstract] Cited for: PROTEIN SEQUENCE OF 237-243, IDENTIFICATION, GLYCOSYLATION, PROTEOLYTIC PROCESSING, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF140675 mRNA. Translation: AAD56358.1. Frameshift. AY327122 mRNA. Translation: AAQ94616.1. BC061631 mRNA. Translation: AAH61631.1.
RefSeq	NP_055087.2.
UniGene	Hs.16441
3D structure databases
HSSP	HSSP built from PDB template 1ATL based on UniProtKB P15167.
ModBase	Search...
Protein family/group databases
MEROPS	M12.231.
Genome annotation databases
Ensembl	ENSG00000136378. Homo sapiens. [Contig view]
GeneID	11173.
Organism-specific databases
H-InvDB	HIX0012467.
HGNC	HGNC:223. ADAMTS7.
MIM	605009. gene.
PharmGKB	PA24551.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q9UKP4.
Gene expression databases
CleanEx	HS_ADAMTS7.
Family and domain databases
InterPro	IPR010294. ADAM_spacer1. IPR001762. Blood-coag_inhib_Disintegrin. IPR001818. Pept_M10A_M12B. IPR006025. Pept_M_Zn_BS. IPR001590. Peptidase_M12B. IPR013273. Peptidase_M12B_ADAM-TS. IPR002870. Peptidase_M12B_N. IPR000884. TSP1. IPR008085. TSP_1. [Graphical view]
Pfam	PF05986. ADAM_spacer1. 2 hits. PF01562. Pep_M12B_propep. 1 hit. PF01421. Reprolysin. 1 hit. PF00090. TSP_1. 1 hit. [Graphical view]
PRINTS	PR01857. ADAMTSFAMILY. PR01705. TSP1REPEAT.
SMART	SM00209. TSP1. 2 hits. [Graphical view]
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00546. CYSTEINE_SWITCH. False negative. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. False negative. PS50900. PLAC. 1 hit. PS50092. TSP1. 7 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ATS7_HUMAN

Accession

Primary (citable) accession number: Q9UKP4
Secondary accession number(s): Q14F51, Q6P7J9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	September 2, 2008
Last modified:	September 23, 2008
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)