ADAMs y ADAMTS

ADAMs
Estructura esquemática de las familias de proteínas ADAM y ADAMTS

La familia ADAM (“A Disintegrin And Metalloprotease”) está formada por proteínas con dominios similares a desintegrina y metaloproteasa, que desempeñan funciones en el desarrollo, las interacciones celulares y la eliminación de ectodominios. En a familia se han identificado distintos miembros (40), cada uno de ellos nombrado con el nombre del gen. Estos nombres reflejan el orden de descubrimiento, ADAM1 y ADAM2 fueron el primero y el segundo miembro de la familia. Algunos ADAM tienen repeticiones del dominio trombospondina (TS) y se denominan proteínas ADAMTSx, pueden tener algunos alias cuando existen diferentes nombres para el mismo gen. Cada ADAM tiene características únicas, incluidas sus funciones fisiológicas, pero algunas características pueden ser específicas de cada especie.

Organización y Dominos

Todas las ADAM se caracterizan por una organización de dominios muy particular:

Prodominio cadena larga de unos 200 AA.:Una cisteína de este dominio actúa sobre el átomo de Zinc- - interruptor de Cisteína- -bloqueando el centro activo de la metaloproteinasa. Una escisión por proteasas tipo Furina produce la activación del complejo.

Metaloproteinasa: Incluye una secuencia HExxHxxGxxH, como el resto de las metaloproteinasas (M).

Desintegrina: Este dominio afecta la adhesión celular y las interacciones con otras células a través de su unión con integrinas. (D)

Dominio rico en cisteínas: Esta región proporciona posibilidades de adhesión adicionales a las del dominio desintegrina. En concreto, se descrito su capacidad para interaccionar con proteoglicanos del tipo sindecano y con componentes de la matriz como la fibronectina. (C)

Dominio EGF: o dominio similar al del factor de crecimiento epidérmico. Su función no es aun bien comprendida

Dominio transmembrana:Dispuesto a continuación del dominio rico en cisteínas, es el responsable del anclaje a la membrana. Este domino no está presente en las ADAMTSx. (TM)

Cola citoplásmica C-terminal:responsable de interaccionar con el citoesqueleto. (CT)

ADAMTSx tiene una estructura similar a ADAMs pero incluyendo 1 o más copias de trombospondina (TS). Estructuralmente ADAMTS están organizados en un domino proteinasa y un dominio auxiliar. El dominio proteinasa comprende los dominios señal, pro, metaloproteinasa y desintegrina. La mayor variabilidad entre los miembros de ADAMTS se encuentra en el dominio auxiliar, que se compone de una o más repeticiones de secuencia de trombospondina tipo 1 (TSR), un dominio rico en cisteína y un dominio espaciador. Los ADAMTS no poseen un dominio transmembrana (TM).

ADAMS participa en procesos celulares como adhesión celular gracias a su domino desintegrina y en procesos como el procesamiento de otras proteinas gracias su dominio metaloproteinasa. Esto da como resultado participaciones en procesos inflamatorios, angiogeneis y cancer gracias a sus actividades Adhesión-Fusión, señalización y “protein Sheeding” ADAMTS esta asociado a la rotura del Agrecano.

La gran mayoria de miembros de este grupo contiene la secuencia HEXGHXXGXXHD, lo que las catacteriza lo que es indicativo de una auténtica capacidad proteolítica. Otras sin embargo como por ejemplo ADAM2 o ADAM11, no parecen tener esta acividad proteolitica

Para la mayoria de miembros de ADAM la activación implica el recorte del predominio n terminal por la acción de convertasas, como por ejemplo La Furina. Prodominios aislados pueden actuar como inhibidores de las formas activas. Los TIMPs tambien participan de la regulacion de ADAMs y ADAMTSs.

ADAMTSs juegan un papel importante en el recambio de proteínas de la matriz extracelular en multiples tejidos y se las ha implicado en enfermedades como el cáncer, la artritis y aterosclerosis. A diferencia de otras metaloproteinasas, los miembros de ADAMTSs demuestran una alta especificad, por sus subtratos, lo que resulta en un limitado numero de porteinas afectadas, por su activacion o inhibición. Esta caracteristica las posiciona como buenos candidatos a farmacos.

Clasificación

FAMILIAALIAS
ADAM1ADAM Metallopeptidase Domain 1Fertilin α,fertilin alpha,FTNAP; PH-30a; Ftna; ADAM1P,ADAM-1
ADAM2ADAM Metallopeptidase Domain 2fertilin β, fertilin beta,PH30,CT15 ,CRYN1,CRYN2,ADAM-2
ADAM5ADAM Metallopeptidase Domain 5ADAM5P,TMDC2,Rich Protein II,TMDc II,ADAM-5
ADAM6ADAM Metallopeptidase Domain 6TMDCIV,C14orf96.ADAM-6
ADAM7ADAM Metallopeptidase Domain 7EAPI, GP83,ADAM-7
ADAM8ADAM Metallopeptidase Domain 8ADAM Metallopeptidase Domain 8
ADAM9ADAM Metallopeptidase Domain 9MDC9,MCMP,KIAA0021 ,CORD9,Meltrin Gamma
ADAM10ADAM Metallopeptidase Domain 10MADM, HsT18717,Kuz ,CD156d,AD10,AD18,RAK,KUZ,ADAM-10
ADAM11ADAM Metallopeptidase Domain 11MDC,ADAM-11
ADAM12ADAM Metallopeptidase Domain 12ADAM Metallopeptidase Domain 12
ADAM15ADAM Metallopeptidase Domain 15MDC15,MDC-15,Metargidin,ADAM-15
ADAM17ADAM Metallopeptidase Domain 17CSVP, CD156B, TACE,TNF-Alpha Convertase,TNF-Alpha Converting enzyme,adam-17
ADAM18ADAM Metallopeptidase Domain 18TMDCIII, ADAM27,Cysteine-Rich Protein III,adam-18
ADAM19ADAM Metallopeptidase Domain 19MLTNB, MADDAM,Meltrin Beta,FKSG34,adam-19
ADAM20ADAM Metallopeptidase Domain 20EC 3.4.24.58, EC 3.4.24,A Disintegrin And Metalloproteinase Domain 20,adam-20
ADAM21ADAM Metallopeptidase Domain 21ADAM31, EC 3.4.24,A Disintegrin And Metalloproteinase Domain 21,adam-21
ADAM22ADAM Metallopeptidase Domain 22MDC2,Disintegrin And Metalloproteinase Domain-Containing Protein 22,DEE61,EIEE61,adam-22
ADAM23ADAM Metallopeptidase Domain 23MDC3,A Disintegrin And Metalloproteinase Domain 23,adam-23
ADAM24ADAM Metallopeptidase Domain 24ADAM24P,A Disintegrin And Metalloproteinase Domain 24,adam24,adam-24
ADAM25ADAM Metallopeptidase Domain 25adam-25
ADAM26AADAM Metallopeptidase Domain 26Aadam-26A
ADAM28ADAM Metallopeptidase Domain 28EMDCII, MDC-Lm, MDC-Ls,Cysteine-Rich Protein II,MDCL,adam-28
ADAM29ADAM Metallopeptidase Domain 29CT73, Svph1,adam-29,Testis Antigen 73
ADAM30ADAM Metallopeptidase Domain 30Svph4, EC 3.4.24,A Disintegrin And Metalloproteinase Domain 30,adam-30
ADAM32ADAM Metallopeptidase Domain 32A Disintegrin And Metalloproteinase Domain 32,Testicular Tissue Protein Li,adam-32
ADAM33ADAM Metallopeptidase Domain 33C20orf153,A Disintegrin And Metalloprotease 33 ,adam-33
ADAMTS1ADAM Metallopeptidase With Thrombospondin Type 1 MotifMETH1, KIAA1346, C3-C5,Metalloprotease And Thrombospondin-1,ADAM-TS1,ADAMTS-1
ADAMTS2ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2PCINP,NPI,ADAM-TS2,Procollagen N-Endopeptidase,ADAMTS-2
ADAMTS3ADAM Metallopeptidase With Thrombospondin Type 1 Motif 3KIAA0366, Type 1 Motif 3,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 3,ADAM-TS3,adamts-3
ADAMTS4ADAM Metallopeptidase With Thrombospondin Type 1 Motif 4KIAA0688, Type 1 Motif 4,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 4 ,Aggrecanase-1,ADAM-TS4,ADAMTS-4
ADAMTS5ADAM Metallopeptidase With Thrombospondin Type 1 Motif 5ADMP-2, Type 1 Motif 5,Aggrecanase-2,ADAMTS-5,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 5,ADAM-TS5
ADAMTS6ADAM Metallopeptidase With Thrombospondin Type 1 Motif 6A Disintegrin And Metalloproteinase With Thrombospondin Motifs 6,ADAM-TS 6,ADAMTS-6
ADAMTS7ADAM Metallopeptidase With Thrombospondin Type 1 Motif 7COMPase, Type 1 Motif 7,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 7,ADAMTS-7,ADAM-TS 7
ADAMTS8ADAM Metallopeptidase With Thrombospondin Type 1 Motif 8METH2,Type 1 Motif 8,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 8,ADAM-TS 8,ADAM-TS8
ADAMTS9ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9KIAA1312, Type 1 Motif 9,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 9,ADAMTS-9,ADAM-TS9
ADAMTS10ADAM Metallopeptidase With Thrombospondin Type 1 Motif 10Type 1 Motif 10,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 10,WMS,WMS1,ADAMTS-10,ADAM-TS10
ADAMTS12ADAM Metallopeptidase With Thrombospondin Type 1 Motif 12Type 1 Motif 12,PRO4389,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 12,ADAMTS-12,ADAM-TS12
ADAMTS13ADAM Metallopeptidase With Thrombospondin Type 1 Motif 13VWF-CP,VWFCP,Von Willebrand Factor-Cleaving Protease,ADAM-TS13,ADAMTS-13,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 13
ADAMTS14ADAM Metallopeptidase With Thrombospondin Type 1 Motif 14Type 1 Motif 14,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 14,ADAMTS-14,ADAM-TS14
ADAMTS15ADAM Metallopeptidase With Thrombospondin Type 1 Motif 15A Disintegrin-Like And Metalloprotease (Reprolysin Type) With Thrombospondin Type 1 Motif 15,ADAMTS-15,ADAM-TS15
ADAMTS16ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16Type 1 Motif 16,ADAMTS16s,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 16,ADAMTS-16,ADAM-TS16
ADAMTS17ADAM Metallopeptidase With Thrombospondin Type 1 Motif 17Type 1 Motif 17,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 17,WMS4,ADAMTS-17,ADAM-TS17
ADAMTS18ADAM Metallopeptidase With Thrombospondin Type 1 Motif 18KNO2, MMCAT,ADAMTS21,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 18,ADAMTS-18,ADAM-TS18
ADAMTS19ADAM Metallopeptidase With Thrombospondin Type 1 Motif 19CVDP2,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 19,CVDP2,ADAMTS-19,ADAM-TS19
ADAMTS20ADAM Metallopeptidase With Thrombospondin Type 1 Motif 20GON-1,A Disintegrin And Metalloproteinase With Thrombospondin Motifs 20,ADAMTS-20,ADAM-TS20

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Human ADAM12(Disintegrin and metalloproteinase domain-containing protein 12) ELISA KitHuman ADAMTS8(A disintegrin and metalloproteinase with thrombospondin motifs 8) ELISA KitHuman ADAMTS6(A disintegrin and metalloproteinase with thrombospondin motifs 6) ELISA KitHuman ADAMTS20(A disintegrin and metalloproteinase with thrombospondin motifs 20) ELISA KitHuman ADAMTS18(A disintegrin and metalloproteinase with thrombospondin motifs 18) ELISA KitHuman ADAM29(Disintegrin and metalloproteinase domain-containing protein 29) ELISA KitHuman ADAMTS12(A Disintegrin And Metalloproteinase With Thrombospondin 12) ELISA KitHuman ADAMTS10(A disintegrin and metalloproteinase with thrombospondin motifs 10) ELISA KitMouse ADAM10(Disintegrin and metalloproteinase domain-containing protein 10) ELISA Kitanti- ADAM5 antibodyRecombinant Human ADAM17Recombinant Human ADAM12Recombinant Human ADAMTSL3Recombinant Human ADAM21ADAM Metallopeptidase With Thrombospondin Type 1 Motif 4 (ADAMTS4) AntibodyADAMTS-Like Protein 4 (ADAMTSL4) AntibodyADAM Metallopeptidase Domain 33 (ADAM33) AntibodyADAM Metallopeptidase With Thrombospondin Type 1 Motif 13 / vWFCP (ADAMTS13) AntibodyADAM Metallopeptidase Domain 12 (ADAM12) AntibodyA Disintegrin And Metalloprotease 15 (ADAM15) AntibodyADAM Metallopeptidase With Thrombospondin Type 1 Motif 18 (ADAMTS18) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 10 (ADAMTS10) AntibodyADAM Metallopeptidase Domain 8 (ADAM8) AntibodyDisintegrin And Metalloproteinase Domain-Containing Protein 32 (ADAM32) AntibodyDisintegrin And Metalloproteinase Domain-Containing Protein 23 (ADAM23) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 19 (ADAMTS19) AntibodyADAM Like Decysin 1 (ADAMDEC1) AntibodyADAMTS-Like Protein 3 (ADAMTSL3) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin Motifs 3 (ADAMTS3) AntibodyADAM Metallopeptidase Domain 19 (ADAM19) AntibodyDisintegrin And Metalloproteinase Domain-Containing Protein 21 (ADAM21) AntibodyDisintegrin And Metalloproteinase Domain-Containing Protein 18 (ADAM18) AntibodyADAM Metallopeptidase Domain 29 (ADAM29) AntibodyA Disintegrin And Metalloprotease 20 (ADAM20) AntibodyRat ADAM Metallopeptidase Domain 9 (ADAM9) ELISA KitRat ADAM Metallopeptidase With Thrombospondin Type 1 Motif 4 (ADAMTS4) ELISA KitHuman A Disintegrin And Metalloprotease 20 (ADAM20) ProteinRat A Disintegrin And Metalloprotease 5 (ADAM5) ProteinRat A Disintegrin And Metalloprotease 6 (ADAM6) ProteinHuman A Disintegrin And Metalloprotease 9 (ADAM9) ProteinHuman A Disintegrin And Metalloproteinase With Thrombospondin 1 (ADAMTS1) ProteinRat A Disintegrin And Metalloproteinase With Thrombospondin 1 (ADAMTS1) ProteinMouse A Disintegrin And Metalloproteinase With Thrombospondin 12 (ADAMTS12) ProteinHuman A Disintegrin And Metalloproteinase With Thrombospondin 12 (ADAMTS12) ProteinCow A Disintegrin And Metalloproteinase With Thrombospondin 2 (ADAMTS2) ProteinHuman A Disintegrin And Metalloproteinase With Thrombospondin 7 (ADAMTS7) ProteinRat A Disintegrin And Metalloproteinase With Thrombospondin 7 (ADAMTS7) ProteinA Disintegrin And Metalloprotease 6 (ADAM6) AntibodyA Disintegrin And Metalloprotease 9 (ADAM9) AntibodyA Disintegrin And Metalloprotease 17 (ADAM17) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 1 (ADAMTS1) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 2 (ADAMTS2) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 7 (ADAMTS7) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 8 (ADAMTS8) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 12 (ADAMTS12) AntibodyDisintegrin And Metalloproteinase Domain-Containing Protein 30 (ADAM30) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 5 (ADAMTS5) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 16 (ADAMTS16) AntibodyA Disintegrin And Metalloproteinase With Thrombospondin 9 (ADAMTS9) AntibodyADAM Metallopeptidase With Thrombospondin Type 1 Motif 20 (ADAMTS20) AntibodyDisintegrin And Metalloproteinase Domain-Containing Protein 30 (ADAM30) AntibodyHuman ADAM Metallopeptidase Domain 12 (ADAM12) ELISA KitHuman ADAM Metallopeptidase Domain 15 (ADAM15) ELISA KitHuman ADAM Metallopeptidase Domain 19 (ADAM19) ELISA KitHuman ADAM Metallopeptidase Domain 22 (ADAM22) ELISA KitHuman ADAM Metallopeptidase Domain 28 (ADAM28) ELISA KitHuman ADAM Metallopeptidase Domain 33 (ADAM33) ELISA KitHuman ADAM Metallopeptidase Domain 8 (ADAM8) ELISA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 4 (ADAMTS4) ELISA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 5 (ADAMTS5) ELISA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9 (ADAMTS9) ELISA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 13 / vWFCP (ADAMTS13) ELISA KitRat ADAM Metallopeptidase With Thrombospondin Type 1 Motif 5 (ADAMTS5) ELISA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 8 (ADAMTS8) ELISA KitHuman A Disintegrin And Metalloproteinase With Thrombospondin 16 (ADAMTS16) ProteinHuman A Disintegrin And Metalloproteinase With Thrombospondin 19 (ADAMTS19) ProteinHuman A Disintegrin And Metalloprotease 33 (ADAM33) ProteinA Disintegrin And Metalloprotease 10 (ADAM10) AntibodyRat ADAM Metallopeptidase Domain 10 (ADAM10) CLIA KitHuman ADAM Metallopeptidase Domain 10 (ADAM10) CLIA KitRat ADAM Metallopeptidase With Thrombospondin Type 1 Motif 13 / vWFCP (ADAMTS13) CLIA KitA Disintegrin And Metalloprotease 28 (ADAM28) AntibodyADAM Metallopeptidase With Thrombospondin Type 1 Motif 14 (ADAMTS14) AntibodyADAMTS Like 1 (ADAMTSL1) AntibodyADAM Metallopeptidase Domain 11 (ADAM11) AntibodyADAMTS Like 2 (ADAMTSL2) AntibodyADAM Metallopeptidase With Thrombospondin Type 1 Motif 15 (ADAMTS15) AntibodyADAM Metallopeptidase With Thrombospondin Type 1 Motif 17 (ADAMTS17) AntibodyADAM Metallopeptidase Domain 2 (ADAM2) AntibodyADAM Metallopeptidase Domain 28 (ADAM28) AntibodyHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 1 (ADAMTS1) ELISA KitHuman ADAM Metallopeptidase Domain 10 (ADAM10) ELISA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 12 (ADAMTS12) ELISA KitMouse ADAM Metallopeptidase Domain 28 (ADAM28) ELISA KitRat ADAM Metallopeptidase With Thrombospondin Type 1 Motif 13 / vWFCP (ADAMTS13) ELISA KitMouse ADAM Metallopeptidase With Thrombospondin Type 1 Motif 5 (ADAMTS5) ELISA KitMouse ADAM Metallopeptidase Domain 17 (ADAM17) ELISA KitADAM12 ProteinADAM Metallopeptidase Domain 10 (ADAM10) AntibodyADAM Metallopeptidase Domain 32 (ADAM32) AntibodyADAM Metallopeptidase Domain 21 (ADAM21) AntibodyADAM Metallopeptidase Domain 7 (ADAM7) AntibodyADAM Metallopeptidase With Thrombospondin Type 1 Motif 6 (ADAMTS6) AntibodyChicken ADAM Metallopeptidase Domain 17 (ADAM17) ELISA KitChicken ADAM Metallopeptidase Domain 10 (ADAM10) ELISA KitPig ADAM Metallopeptidase Domain 9 (ADAM9) ELISA KitHuman A Disintegrin And Metalloprotease 5 (ADAM5) ELISA KitHuman ADAM Like Decysin 1 (ADAMDEC1) ELISA KitHuman ADAMTS-Like Protein 4 (ADAMTSL4) ELISA KitHuman ADAM Metallopeptidase Domain 8 (ADAM8) CLIA KitMouse ADAM Metallopeptidase Domain 8 (ADAM8) CLIA KitHuman ADAM Metallopeptidase Domain 17 (ADAM17) CLIA KitMouse ADAM Metallopeptidase Domain 17 (ADAM17) CLIA KitHuman ADAM Metallopeptidase Domain 9 (ADAM9) CLIA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 1 (ADAMTS1) CLIA KitRat ADAM Metallopeptidase With Thrombospondin Type 1 Motif 1 (ADAMTS1) CLIA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 7 (ADAMTS7) CLIA KitRat ADAM Metallopeptidase With Thrombospondin Type 1 Motif 7 (ADAMTS7) CLIA KitHuman ADAM Metallopeptidase Domain 15 (ADAM15) CLIA KitHuman ADAM Metallopeptidase Domain 22 (ADAM22) CLIA KitHuman ADAM Metallopeptidase Domain 28 (ADAM28) CLIA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 4 (ADAMTS4) CLIA KitRat ADAM Metallopeptidase With Thrombospondin Type 1 Motif 4 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KitHuman Disintegrin and metalloproteinase domain-containing protein 20 (ADAM20) ELISA KitHuman Disintegrin and metalloproteinase domain-containing protein 21 (ADAM21) ELISA KitMouse Disintegrin and metalloproteinase domain-containing protein 21 (ADAM21) ELISA KitMouse Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) ELISA KitMouse Disintegrin and metalloproteinase domain-containing protein 24 (ADAM24) ELISA KitMouse Disintegrin and metalloproteinase domain-containing protein 25 (ADAM25) ELISA KitHuman Disintegrin and metalloproteinase domain-containing protein 32 (ADAM32) ELISA KitMouse Disintegrin and metalloproteinase domain-containing protein 32 (ADAM32) ELISA KitRat A Disintegrin And Metalloprotease 1 (ADAM1) ELISA KitRat ADAM Metallopeptidase Domain 5, Pseudogene (ADAM5) ELISA KitHuman Disintegrin and metalloproteinase domain-containing protein 7 (ADAM7) ELISA KitMouse ADAM DEC1 (ADAMDEC1) ELISA KitMouse Disintegrin and metalloproteinase domain-containing 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Metallopeptidase Domain 29 (ADAM29) ELISA KitHuman ADAM Metallopeptidase With Thrombospondin Type 1 Motif 6 (ADAMTS6) ELISA KitRat A Disintegrin And Metalloproteinase With Thrombospondin 4 (ADAMTS4) ProteinRabbit A Disintegrin And Metalloproteinase With Thrombospondin 4 (ADAMTS4) Protein