Q769J6

SS
Gene name
Adamts13 (Gm710)
Protein name
A disintegrin and metalloproteinase with thrombospondin motifs 13
Names
ADAM-TS 13 , ADAM-TS13 , ADAMTS-13 , EC 3.4.24.87 , von Willebrand factor-cleaving protease , vWF-CP , vWF-cleaving protease
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:279028
EC number
3.4.24.87: Metalloendopeptidases
Protein Class

Descriptions

ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats, member 13) is a member of the ADAMTS type 1 repeats family of metalloproteases and a multidomain protein with Ca2+ and Zn2+-dependent metalloprotease (M), disintegrin-like (D), thrombospondin-1 repeat (TSP1), Cys-rich (C), and Spacer (S) domains, followed by 7 TSP domains and 2 CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains. ADAMTS13 specifically cleaves VWF (von Willebrand Factor) to prevent excessive platelet aggregation and thrombus formation at the sites of vascular injury. To avoid non-specific cleavage, ADAMTS13 has the autoinhibition effect in which the Spacer domain in N-terminal interacts with the TSP8-CUB2 domains in C-terminal, resulting in decreased proteolytic activity. The autoinhibition of ADAMTS13 is relieved by the binding of the VWF D4-CK region to the C-terminal regions of ADAMTS13. The binding facilitates the exosites on the Spacer, Cys, and Dis domains to interact with the discrete binding sites on the unfolded VWF A2 domain, and then the metalloprotease domain is allosterically activated and cleaves the VWF scissile bond.

Autoinhibitory domains (AIDs)

563-685 (Spacer domain) SS

Target domain

82-291 (Peptidase domain)

Relief mechanism

Partner binding

Assay

1078-1137 (TSP8 domain) SS

Target domain

82-291 (Peptidase domain)

Relief mechanism

Partner binding

Assay

1138-1192 (TSP8-CUB1 linker) SS

Target domain

82-291 (Peptidase domain)

Relief mechanism

Partner binding

Assay

1193-1278 (CUB1 domain) SS

Target domain

82-291 (Peptidase domain)

Relief mechanism

Partner binding

Assay

1299-1409 (CUB2 domain) SS

Target domain

82-291 (Peptidase domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q769J6

Entry ID Method Resolution Chain Position Source
AF-Q769J6-F1 Predicted AlphaFoldDB

97 variants for Q769J6

Variant ID(s) Position Change Description Diseaes Association Provenance
rs263828935 12 P>S No EVA
rs3388532247 15 A>V No EVA
rs3388537882 29 L>M No EVA
rs238416287 50 V>M No EVA
rs3388537922 53 Y>* No EVA
rs3388540409 78 L>V No EVA
rs250306637 96 R>Q No EVA
rs3388533833 113 G>V No EVA
rs257546780 213 T>A No EVA
rs27185300 259 T>A No EVA
rs27185297 299 R>Q No EVA
rs242107170 347 L>S No EVA
rs3388539500 372 S>P No EVA
rs3388536847 396 G>D No EVA
rs3391404406 397 P>L No EVA
rs3391308049 398 H>Y No EVA
rs3388539509 400 P>S No EVA
rs3388535167 414 R>Q No EVA
rs3388536126 421 P>H No EVA
rs27185272 445 K>T No EVA
rs3388533886 498 S>I No EVA
rs263319830 520 D>E No EVA
rs3388537921 534 T>I No EVA
rs3388539508 539 G>D No EVA
rs3388539855 551 Q>H No EVA
rs27226451 563 R>Q No EVA
rs3388535122 576 V>I No EVA
rs3388540483 586 T>S No EVA
rs27226445 587 N>S No EVA
rs3391405452 602 V>L No EVA
rs3388537958 626 L>P No EVA
rs3388535117 651 R>Q No EVA
rs1134853936 654 V>I No EVA
rs27226441 657 D>N No EVA
rs3391436301 666 Y>* No EVA
rs27226433 681 S>T No EVA
rs214610167 727 A>S No EVA
rs3388540525 728 Q>H No EVA
rs3388533870 737 A>T No EVA
rs242765264 753 A>V No EVA
rs3391363918 763 C>LYTAQ* No EVA
rs216879630 788 A>G No EVA
rs27226424 825 A>T No EVA
rs586585724 831 D>V No EVA
rs582711840 831 D>Y No EVA
rs3388535108 841 A>T No EVA
rs1132555597 853 C>* No EVA
rs257903852 858 M>K No EVA
rs257903852 858 M>T No EVA
rs3388540494 860 A>V No EVA
rs228811604 866 S>F No EVA
rs235420775 880 T>I No EVA
rs3388536041 881 M>L No EVA
rs27226416 889 S>A No EVA
rs3388535627 909 G>R No EVA
rs3388536870 911 C>S No EVA
rs3388532204 912 S>F No EVA
rs254473185 947 P>Q No EVA
rs3391401026 970 C>G No EVA
rs3391404392 971 P>T No EVA
rs3388538198 972 V>E No EVA
rs3391257757 973 T>P No EVA
rs232478251 982 S>A No EVA
rs248221005 990 R>H No EVA
rs262869391 994 I>V No EVA
rs3388539484 1015 P>H No EVA
rs3388536978 1017 P>S No EVA
rs3388536895 1018 C>Y No EVA
1022 W>ALVWEAAPTFAVTRWR Adamts13S [UniProt] No
rs27226393 1038 T>A No EVA
1038 T>del Adamts13S [UniProt] No
rs27226390 1081 R>Q No EVA
rs3388540418 1095 G>R No EVA
rs3388536872 1099 Q>P No EVA
rs3388532268 1125 P>Q No EVA
rs27226382 1126 M>V No EVA
rs3388538197 1129 R>I No EVA
rs27226381 1146 P>L No EVA
rs3388532188 1154 S>T No EVA
rs3388532253 1157 Q>H No EVA
rs3388536834 1170 P>L No EVA
rs3388540427 1173 R>L No EVA
rs236991608 1173 R>W No EVA
rs236291021 1181 S>F No EVA
rs3388540476 1213 G>* No EVA
rs3388535083 1284 G>D No EVA
rs1132522660 1312 G>S No EVA
rs1133810719 1317 P>L No EVA
rs238970071 1323 G>R No EVA
rs3388532178 1334 S>R No EVA
rs3388538608 1376 W>G No EVA
rs237588031 1380 V>L No EVA
rs3388540428 1389 E>* No EVA
rs3388536912 1392 L>M No EVA
rs227797047 1402 H>P No EVA
rs260244705 1408 E>Q No EVA
rs3388534763 1413 S>* No EVA

No associated diseases with Q769J6

11 regional properties for Q769J6

Type Name Position InterPro Accession
repeat Thrombospondin type-1 (TSP1) repeat 389 - 444 IPR000884-1
repeat Thrombospondin type-1 (TSP1) repeat 693 - 748 IPR000884-2
repeat Thrombospondin type-1 (TSP1) repeat 747 - 810 IPR000884-3
repeat Thrombospondin type-1 (TSP1) repeat 904 - 959 IPR000884-4
repeat Thrombospondin type-1 (TSP1) repeat 958 - 1019 IPR000884-5
repeat Thrombospondin type-1 (TSP1) repeat 1078 - 1137 IPR000884-6
domain Peptidase M12B, ADAM/reprolysin 74 - 291 IPR001590
domain ADAM, cysteine-rich domain 305 - 379 IPR006586
domain ADAMTS/ADAMTS-like, Spacer 1 563 - 684 IPR010294
domain ADAMTS, cysteine-rich domain 2 306 - 376 IPR041645
domain ADAMTS/ADAMTS-like, cysteine-rich domain 3 446 - 560 IPR045371

Functions

Description
EC Number 3.4.24.87 Metalloendopeptidases
Subcellular Localization
  • Secreted
  • Secretion enhanced by O-fucosylation of TSP type-1 repeats
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
extracellular matrix A structure lying external to one or more cells, which provides structural support, biochemical or biomechanical cues for cells or tissues.
extracellular space That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.

4 GO annotations of molecular function

Name Definition
endopeptidase activity Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain.
metal ion binding Binding to a metal ion.
metalloendopeptidase activity Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which water acts as a nucleophile, one or two metal ions hold the water molecule in place, and charged amino acid side chains are ligands for the metal ions.
peptidase activity Catalysis of the hydrolysis of a peptide bond. A peptide bond is a covalent bond formed when the carbon atom from the carboxyl group of one amino acid shares electrons with the nitrogen atom from the amino group of a second amino acid.

12 GO annotations of biological process

Name Definition
blood coagulation The sequential process in which the multiple coagulation factors of the blood interact, ultimately resulting in the formation of an insoluble fibrin clot; it may be divided into three stages
cellular response to interleukin-4 Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-4 stimulus.
cellular response to lipopolysaccharide Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
cellular response to tumor necrosis factor Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus.
cellular response to type II interferon Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far.
extracellular matrix organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an extracellular matrix.
peptide catabolic process The chemical reactions and pathways resulting in the breakdown of peptides, compounds of 2 or more (but usually less than 100) amino acids where the alpha carboxyl group of one is bound to the alpha amino group of another.
protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
proteolysis The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds.
response to amine Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amine stimulus. An amine is a compound formally derived from ammonia by replacing one, two or three hydrogen atoms by hydrocarbyl groups.
response to potassium ion Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a potassium ion stimulus.
response to toxic substance Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a toxic stimulus.

1 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q76LX8 ADAMTS13 A disintegrin and metalloproteinase with thrombospondin motifs 13 Homo sapiens (Human) EV
10 20 30 40 50 60
MSQLCLWLTC QPCYAVSVRG ILTGAIFILG CWGLSDFQKS LLQDLEPKDV SSYFGHHAAP
70 80 90 100 110 120
FTGHPPSHLQ RLRRRRTLED ILHLELLVAV GPDVSRAHQE DTERYVLTNL NIGSELLRNP
130 140 150 160 170 180
SLGVQFQVHL VKLITLSDSE STPNITANIT SSLMSVCEWS QTINPHDDRD PSHADLILYI
190 200 210 220 230 240
TRFDLELPDG NQQVRGVTQL GGACSLSWSC LITEDTGFDL GVTIAHEIGH SFGLDHDGAP
250 260 270 280 290 300
GSGSTCKASG HVMAADGATP TGGTLEWSAC SQRQLQHLLS TGQMHCFQDP PGLQSGLTRH
310 320 330 340 350 360
QLMAQPGLYY SADDQCRVAF GSGAVACTFS REGLDVCQAL SCHTDPLDQS SCSRLLVPLL
370 380 390 400 410 420
DGTECGVEKW CSKARCRSLA ELAPVAAVHG HWSSWGPHSP CSRSCGGGVI TRRRWCNNPR
430 440 450 460 470 480
PAFGGRACVG EDLQAKMCNT QACEKTQLEF MSEQCAQTDR QPLQLSQGTA SFYHWDAAVQ
490 500 510 520 530 540
YSQGDTLCRH MCWAVGESFI VSRGDRFLDG TRCVPSGPQD DGTLSLCLLG SCRTFGCDGR
550 560 570 580 590 600
MDSQKVWDAC QVCGGDNSTC SSRNGSFTAG RAREYVTFLI VTPNMTNAHI VNRRPLFTHL
610 620 630 640 650 660
AVRIQGHYIV AGKTSISPNT TYPSLLEDYR VEYRVTLTED QLPHLEEIHI RGPVRDDIEI
670 680 690 700 710 720
QVYRRYGGEY GDLTHPDITF SYFQLKQQAA WVWTAKRGPC SVSCGAGLRW VTYSCQDQAQ
730 740 750 760 770 780
DKWVKNAQCQ GSPQPPAWQE PCVSAPCSPY WVAGDFSPCS VSCGGGLRER SLRCVETQDG
790 800 810 820 830 840
FLKTLPPARC RAVAQQPAAE VENCNSQPCP TRWEVSDPGP CMSSACEAGL DSRNVTCVSR
850 860 870 880 890 900
AGDPEKPETA GPCRTDEMSA MLEPCSRSLC SPGLGQVDNT MSLGEEAPSP VGSDKPGAQA
910 920 930 940 950 960
EHVWTPLVGL CSISCGRGLK ELYFLCMDSV LKMPVQEELC GLASKPPSRW EVCRARPCPA
970 980 990 1000 1010 1020
RWETQVLAPC PVTCGGGRVP LSVRCVQLDR GHPISVPHSK CSPVPKPGSF EDCSPEPCPA
1030 1040 1050 1060 1070 1080
RWKVLSLGPC SASCGLGTAT QMVACMQLDQ GHDNEVNETF CKALVRPQAS VPCLIADCAF
1090 1100 1110 1120 1130 1140
RWHISAWTEC SVSCGDGIQR RHDTCLGPQA QVPVPANFCQ HLPKPMTVRG CWAGPCAGQE
1150 1160 1170 1180 1190 1200
TSSSLPHKEA TLPSQTQAAA TVASLQWSQP RARTPTLFSA SQSLGLQENL EEHGACGRQY
1210 1220 1230 1240 1250 1260
LEPTGTIHMR DQGRLDCVVA IGRPLGEVVT LQILESSLKC SAGEQLLLWG RFTWRKTCRK
1270 1280 1290 1300 1310 1320
MPGMTFSTKT NTVVVKQHRV LPGGGVLLRY WSQPAPGTFY KECDRQLFGP RGEIVSPSLS
1330 1340 1350 1360 1370 1380
PDGRKAGTCR VFISVAPQAR IAIRALASDM GTASEGTNAN YVSIRDIHSL RTTTFWGQQV
1390 1400 1410 1420
LYWESEGSEA ELEFSPGFLE AHASLQGEYW TISPRTSEQD DSLALS