Reviewed, UniProtKB/Swiss-Prot Q76LX8 (ATS13_HUMAN)

Names and origin

Protein names

Recommended name:
    A disintegrin and metalloproteinase with thrombospondin motifs 13
      Short name=ADAMTS-13
      Short name=ADAM-TS 13
      Short name=ADAM-TS13
    EC=3.4.24.-
Alternative name(s):
    von Willebrand factor-cleaving protease
      Short name=vWF-cleaving protease
      Short name=vWF-CP

Gene names

Name:	ADAMTS13
Synonyms:	C9orf8
ORF Names:	UNQ6102/PRO20085

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	1427 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	Cleaves the vWF multimers in plasma into smaller forms.
Catalytic activity	Cleaves the vWF at the 842-Tyr-|-Met-843 in the A2 domain of the vWF subunit.
Cofactor	Binds 1 zinc ion per subunit By similarity. Binds 4 calcium ions Potential.
Enzyme regulation	Zinc and calcium ions cooperatively modulate enzyme activity. The cleavage of the pro-domain is not required for protease activity. Ref.12 Ref.14
Subcellular location	Secreted.
Tissue specificity	Plasma. Expressed primarily in liver. Ref.1
Domain	The pro-domain is not required for folding or secretion and does not perform the common function of maintening enzyme latency. The spacer domain is necessary to recognize and cleave vWF. The C-terminal TSP type-1 and CUB domains may modulate this interaction.
Post-translational modification	May contain a C-mannosylation site and O-fucosylation sites in the TSP type-1 domains. The precursor is processed by a furin endopeptidase which cleaves off the pro-domain.
Polymorphism	Genetic variations in ADAMTS13 coding region influence plasmatic ADAMTS13 activity levels. Dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression, thereby altering the phenotype of ADAMTS13 deficiency.
Involvement in disease	Defects in ADAMTS13 are the cause of congenital thrombotic thrombocytopenic purpura (TTP) [MIM:274150]; also known as Upshaw-Schulman syndrome (USS). Congenital TTP is a life-threatening systemic disorder due to constitutional deficiency of vWF-cleaving protease. Typical features are hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and nonfocal neurologic findings, decreased renal function and fever. Congenital TTP is characterized by neonatal onset, response to fresh plasma infusion and frequent relapses. Inheritance pattern is autosomal recessive. In sporadic cases, TTP is associated with deficiency of vWF-cleaving protease due to the presence of inhibiting autoantibodies (acquired TTP or autoimmune TTP). Acquired TTP is characterized by adult-onset. TTP shares overlapping clinical features with hemolytic-uremic syndrome (HUS) [MIM:235400], a disease characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia associated with distorted erythrocytes. Ref.3 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24
Sequence similarities	Contains 2 CUB domains. Contains 1 disintegrin domain. Contains 1 peptidase M12B domain. Contains 8 TSP type-1 domains.

Ontologies

Keywords
Biological process	Blood coagulation Hemostasis
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell-matrix adhesion Ref.2 Non-traceable author statement. Source: UniProtKB glycoprotein metabolic process Ref.2 Non-traceable author statement. Source: UniProtKB integrin-mediated signaling pathway Ref.2 Non-traceable author statement. Source: UniProtKB peptide catabolic process Ref.10 Inferred from direct assay. Source: UniProtKB platelet activation Ref.2 Non-traceable author statement. Source: UniProtKB protein processing Ref.2 Traceable author statement. Source: UniProtKB proteolysis Ref.10 Inferred from direct assay. Source: UniProtKB
Cellular component	cell surface Ref.2 Non-traceable author statement. Source: UniProtKB proteinaceous extracellular matrix Ref.2 Traceable author statement. Source: UniProtKB
Molecular function	calcium ion binding Ref.2 Traceable author statement. Source: UniProtKB integrin binding Ref.2 Traceable author statement. Source: UniProtKB metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Ref.2 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VWF	P04275	2	EBI-981764,EBI-981819

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q76LX8-1)

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: Q76LX8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1135-1190: Missing.

Isoform 3 (identifier: Q76LX8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     275-305: Missing.
     1135-1190: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Propeptide	30 – 74	45			PRO_0000247510
	Chain	75 – 1427	1353	A disintegrin and metalloproteinase with thrombospondin motifs 13		PRO_0000247511
Regions
	Domain	80 – 286	207	Peptidase M12B
	Domain	287 – 383	97	Disintegrin
	Domain	384 – 439	56	TSP type-1 1
	Domain	682 – 730	49	TSP type-1 2
	Domain	742 – 805	64	TSP type-1 3
	Domain	808 – 859	52	TSP type-1 4
	Domain	896 – 950	55	TSP type-1 5
	Domain	951 – 1011	61	TSP type-1 6
	Domain	1012 – 1068	57	TSP type-1 7
	Domain	1072 – 1131	60	TSP type-1 8
	Domain	1192 – 1298	107	CUB 1
	Domain	1299 – 1427	129	CUB 2
	Region	300 – 374	75	Cysteine-rich
	Region	556 – 685	130	Spacer
	Motif	498 – 500	3	Cell attachment site Potential
Sites
	Active site	225	1	By similarity
	Metal binding	83	1	Calcium Potential
	Metal binding	173	1	Calcium Potential
	Metal binding	224	1	Zinc; catalytic By similarity
	Metal binding	228	1	Zinc; catalytic By similarity
	Metal binding	234	1	Zinc; catalytic By similarity
	Metal binding	281	1	Calcium Potential
	Metal binding	284	1	Calcium Potential
Amino acid modifications
	Glycosylation	142	1	N-linked (GlcNAc...) Potential
	Glycosylation	146	1	N-linked (GlcNAc...) Potential
	Glycosylation	552	1	N-linked (GlcNAc...) Potential
	Glycosylation	579	1	N-linked (GlcNAc...) Potential
	Glycosylation	614	1	N-linked (GlcNAc...) Ref.13
	Glycosylation	667	1	N-linked (GlcNAc...) Ref.13
	Glycosylation	707	1	N-linked (GlcNAc...) Potential
	Glycosylation	828	1	N-linked (GlcNAc...) Potential
	Glycosylation	1235	1	N-linked (GlcNAc...) Potential
	Glycosylation	1354	1	N-linked (GlcNAc...) Ref.13
	Disulfide bond	202 ↔ 281		By similarity
	Disulfide bond	242 ↔ 265		By similarity
	Disulfide bond	396 ↔ 433		By similarity
	Disulfide bond	400 ↔ 438		By similarity
	Disulfide bond	411 ↔ 423		By similarity
Natural variations
	Alternative sequence	275 – 305	31	Missing in isoform 3.		VSP_020002
	Alternative sequence	1135 – 1190	56	Missing in isoform 2 and isoform 3.		VSP_020003
	Natural variant	7	1	R → W Does not affect protein secretion. dbSNP rs34024143. Ref.3 Ref.22 Ref.5		VAR_027109
	Natural variant	88	1	V → M in TTP; reduces protein secretion and proteolytic activity. Ref.23		VAR_027110
	Natural variant	96	1	H → D in TTP. Ref.3		VAR_027111
	Natural variant	102	1	R → C in TTP. Ref.3		VAR_027112
	Natural variant	193	1	R → W in TTP; low activity. Ref.18		VAR_027113
	Natural variant	196	1	T → I in TTP. Ref.3 Ref.17		VAR_027114
	Natural variant	234	1	H → Q in TTP. Ref.24		VAR_027115
	Natural variant	250	1	A → V in TTP; mild effect on protein secretion; strong reduction of proteolytic activity. Ref.19		VAR_027116
	Natural variant	268	1	R → P in TTP; affects protein secretion. Ref.15		VAR_027117
	Natural variant	390	1	W → C in TTP. Ref.20		VAR_027118
	Natural variant	398	1	R → H in TTP. Ref.3		VAR_027119
	Natural variant	448	1	Q → E Does not affect protein secretion; normal proteolytic activity. dbSNP rs2301612. Ref.3 Ref.15 Ref.17 Ref.18 Ref.22 Ref.5 Ref.7		VAR_027120
	Natural variant	456	1	Q → H: dbSNP rs36220239. Ref.5		VAR_027162
	Natural variant	457	1	P → L: dbSNP rs36220240.		VAR_027163
	Natural variant	475	1	P → S: dbSNP rs11575933.		VAR_027121
	Natural variant	508	1	C → Y in TTP; impairs protein secretion. Ref.15		VAR_027122
	Natural variant	528	1	R → G in TTP. Ref.3		VAR_027123
	Natural variant	618	1	P → A: dbSNP rs28647808.		VAR_027124
	Natural variant	625	1	R → H: dbSNP rs36090624. Ref.3 Ref.5		VAR_027125
	Natural variant	673	1	I → F in TTP; impairs protein secretion. Ref.18		VAR_027126
	Natural variant	692	1	R → C in TTP. Ref.3		VAR_027127
	Natural variant	732	1	A → V: dbSNP rs41314453.		VAR_027128
	Natural variant	740	1	E → K: dbSNP rs36221451. Ref.5		VAR_027164
	Natural variant	900	1	A → V: dbSNP rs685523. Ref.3 Ref.5 Ref.2		VAR_027129
	Natural variant	903	1	S → L in a patient with thrombotic thrombocytopenic purpura; probable polymorphism. Ref.24 Ref.21		VAR_027130
	Natural variant	908	1	C → Y in TTP; impairs protein secretion. Ref.18		VAR_027131
	Natural variant	951	1	C → G in TTP. Ref.3		VAR_027132
	Natural variant	982	1	G → R: dbSNP rs36222275.		VAR_027165
	Natural variant	1024	1	C → G in TTP. Ref.3		VAR_027133
	Natural variant	1033	1	A → T: dbSNP rs28503257. Ref.3 Ref.5		VAR_027134
	Natural variant	1095	1	R → W in a patient with thrombotic thrombocytopenic purpura. Ref.21		VAR_027135
	Natural variant	1123	1	R → C in TTP; impairs protein secretion. Ref.18		VAR_027136
	Natural variant	1213	1	C → Y in TTP. Ref.3		VAR_027137
	Natural variant	1226	1	T → I: dbSNP rs36222894.		VAR_027166
	Natural variant	1239	1	G → V in TTP; impairs protein secretion. Ref.23		VAR_027138
	Natural variant	1336	1	R → W in TTP; impairs protein secretion and proteolytic activity. Ref.16 Ref.22		VAR_027139
Experimental info
	Mutagenesis	71	1	R → K: Abolishes pro-domain removal but no loss of proteolytic activity; when associated with D-73. Ref.12
	Mutagenesis	73	1	R → D: Abolishes pro-domain removal but no loss of proteolytic activity; when associated with K-71. Ref.12
	Sequence conflict	101	1	E → R AA sequence Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 19, 2004. Version 1. Checksum: A2103AFABC1A4445	FASTA	1,427	153,604
	10 20 30 40 50 60 MHQRHPRARC PPLCVAGILA CGFLLGCWGP SHFQQSCLQA LEPQAVSSYL SPGAPLKGRP 70 80 90 100 110 120 PSPGFQRQRQ RQRRAAGGIL HLELLVAVGP DVFQAHQEDT ERYVLTNLNI GAELLRDPSL 130 140 150 160 170 180 GAQFRVHLVK MVILTEPEGA PNITANLTSS LLSVCGWSQT INPEDDTDPG HADLVLYITR 190 200 210 220 230 240 FDLELPDGNR QVRGVTQLGG ACSPTWSCLI TEDTGFDLGV TIAHEIGHSF GLEHDGAPGS 250 260 270 280 290 300 GCGPSGHVMA SDGAAPRAGL AWSPCSRRQL LSLLSAGRAR CVWDPPRPQP GSAGHPPDAQ 310 320 330 340 350 360 PGLYYSANEQ CRVAFGPKAV ACTFAREHLD MCQALSCHTD PLDQSSCSRL LVPLLDGTEC 370 380 390 400 410 420 GVEKWCSKGR CRSLVELTPI AAVHGRWSSW GPRSPCSRSC GGGVVTRRRQ CNNPRPAFGG 430 440 450 460 470 480 RACVGADLQA EMCNTQACEK TQLEFMSQQC ARTDGQPLRS SPGGASFYHW GAAVPHSQGD 490 500 510 520 530 540 ALCRHMCRAI GESFIMKRGD SFLDGTRCMP SGPREDGTLS LCVSGSCRTF GCDGRMDSQQ 550 560 570 580 590 600 VWDRCQVCGG DNSTCSPRKG SFTAGRAREY VTFLTVTPNL TSVYIANHRP LFTHLAVRIG 610 620 630 640 650 660 GRYVVAGKMS ISPNTTYPSL LEDGRVEYRV ALTEDRLPRL EEIRIWGPLQ EDADIQVYRR 670 680 690 700 710 720 YGEEYGNLTR PDITFTYFQP KPRQAWVWAA VRGPCSVSCG AGLRWVNYSC LDQARKELVE 730 740 750 760 770 780 TVQCQGSQQP PAWPEACVLE PCPPYWAVGD FGPCSASCGG GLRERPVRCV EAQGSLLKTL 790 800 810 820 830 840 PPARCRAGAQ QPAVALETCN PQPCPARWEV SEPSSCTSAG GAGLALENET CVPGADGLEA 850 860 870 880 890 900 PVTEGPGSVD EKLPAPEPCV GMSCPPGWGH LDATSAGEKA PSPWGSIRTG AQAAHVWTPA 910 920 930 940 950 960 AGSCSVSCGR GLMELRFLCM DSALRVPVQE ELCGLASKPG SRREVCQAVP CPARWQYKLA 970 980 990 1000 1010 1020 ACSVSCGRGV VRRILYCARA HGEDDGEEIL LDTQCQGLPR PEPQEACSLE PCPPRWKVMS 1030 1040 1050 1060 1070 1080 LGPCSASCGL GTARRSVACV QLDQGQDVEV DEAACAALVR PEASVPCLIA DCTYRWHVGT 1090 1100 1110 1120 1130 1140 WMECSVSCGD GIQRRRDTCL GPQAQAPVPA DFCQHLPKPV TVRGCWAGPC VGQGTPSLVP 1150 1160 1170 1180 1190 1200 HEEAAAPGRT TATPAGASLE WSQARGLLFS PAPQPRRLLP GPQENSVQSS ACGRQHLEPT 1210 1220 1230 1240 1250 1260 GTIDMRGPGQ ADCAVAIGRP LGEVVTLRVL ESSLNCSAGD MLLLWGRLTW RKMCRKLLDM 1270 1280 1290 1300 1310 1320 TFSSKTNTLV VRQRCGRPGG GVLLRYGSQL APETFYRECD MQLFGPWGEI VSPSLSPATS 1330 1340 1350 1360 1370 1380 NAGGCRLFIN VAPHARIAIH ALATNMGAGT EGANASYILI RDTHSLRTTA FHGQQVLYWE 1390 1400 1410 1420 SESSQAEMEF SEGFLKAQAS LRGQYWTLQS WVPEMQDPQS WKGKEGT
	Isoform 2. Checksum: AE4C713AE5B64DFC	FASTA	1,371	147,804
	10 20 30 40 50 60 MHQRHPRARC PPLCVAGILA CGFLLGCWGP SHFQQSCLQA LEPQAVSSYL SPGAPLKGRP 70 80 90 100 110 120 PSPGFQRQRQ RQRRAAGGIL HLELLVAVGP DVFQAHQEDT ERYVLTNLNI GAELLRDPSL 130 140 150 160 170 180 GAQFRVHLVK MVILTEPEGA PNITANLTSS LLSVCGWSQT INPEDDTDPG HADLVLYITR 190 200 210 220 230 240 FDLELPDGNR QVRGVTQLGG ACSPTWSCLI TEDTGFDLGV TIAHEIGHSF GLEHDGAPGS 250 260 270 280 290 300 GCGPSGHVMA SDGAAPRAGL AWSPCSRRQL LSLLSAGRAR CVWDPPRPQP GSAGHPPDAQ 310 320 330 340 350 360 PGLYYSANEQ CRVAFGPKAV ACTFAREHLD MCQALSCHTD PLDQSSCSRL LVPLLDGTEC 370 380 390 400 410 420 GVEKWCSKGR CRSLVELTPI AAVHGRWSSW GPRSPCSRSC GGGVVTRRRQ CNNPRPAFGG 430 440 450 460 470 480 RACVGADLQA EMCNTQACEK TQLEFMSQQC ARTDGQPLRS SPGGASFYHW GAAVPHSQGD 490 500 510 520 530 540 ALCRHMCRAI GESFIMKRGD SFLDGTRCMP SGPREDGTLS LCVSGSCRTF GCDGRMDSQQ 550 560 570 580 590 600 VWDRCQVCGG DNSTCSPRKG SFTAGRAREY VTFLTVTPNL TSVYIANHRP LFTHLAVRIG 610 620 630 640 650 660 GRYVVAGKMS ISPNTTYPSL LEDGRVEYRV ALTEDRLPRL EEIRIWGPLQ EDADIQVYRR 670 680 690 700 710 720 YGEEYGNLTR PDITFTYFQP KPRQAWVWAA VRGPCSVSCG AGLRWVNYSC LDQARKELVE 730 740 750 760 770 780 TVQCQGSQQP PAWPEACVLE PCPPYWAVGD FGPCSASCGG GLRERPVRCV EAQGSLLKTL 790 800 810 820 830 840 PPARCRAGAQ QPAVALETCN PQPCPARWEV SEPSSCTSAG GAGLALENET CVPGADGLEA 850 860 870 880 890 900 PVTEGPGSVD EKLPAPEPCV GMSCPPGWGH LDATSAGEKA PSPWGSIRTG AQAAHVWTPA 910 920 930 940 950 960 AGSCSVSCGR GLMELRFLCM DSALRVPVQE ELCGLASKPG SRREVCQAVP CPARWQYKLA 970 980 990 1000 1010 1020 ACSVSCGRGV VRRILYCARA HGEDDGEEIL LDTQCQGLPR PEPQEACSLE PCPPRWKVMS 1030 1040 1050 1060 1070 1080 LGPCSASCGL GTARRSVACV QLDQGQDVEV DEAACAALVR PEASVPCLIA DCTYRWHVGT 1090 1100 1110 1120 1130 1140 WMECSVSCGD GIQRRRDTCL GPQAQAPVPA DFCQHLPKPV TVRGCWAGPC VGQGACGRQH 1150 1160 1170 1180 1190 1200 LEPTGTIDMR GPGQADCAVA IGRPLGEVVT LRVLESSLNC SAGDMLLLWG RLTWRKMCRK 1210 1220 1230 1240 1250 1260 LLDMTFSSKT NTLVVRQRCG RPGGGVLLRY GSQLAPETFY RECDMQLFGP WGEIVSPSLS 1270 1280 1290 1300 1310 1320 PATSNAGGCR LFINVAPHAR IAIHALATNM GAGTEGANAS YILIRDTHSL RTTAFHGQQV 1330 1340 1350 1360 1370 LYWESESSQA EMEFSEGFLK AQASLRGQYW TLQSWVPEMQ DPQSWKGKEG T
	Isoform 3. Checksum: 0BFBEF4C3D58B2C2	FASTA	1,340	144,517
	10 20 30 40 50 60 MHQRHPRARC PPLCVAGILA CGFLLGCWGP SHFQQSCLQA LEPQAVSSYL SPGAPLKGRP 70 80 90 100 110 120 PSPGFQRQRQ RQRRAAGGIL HLELLVAVGP DVFQAHQEDT ERYVLTNLNI GAELLRDPSL 130 140 150 160 170 180 GAQFRVHLVK MVILTEPEGA PNITANLTSS LLSVCGWSQT INPEDDTDPG HADLVLYITR 190 200 210 220 230 240 FDLELPDGNR QVRGVTQLGG ACSPTWSCLI TEDTGFDLGV TIAHEIGHSF GLEHDGAPGS 250 260 270 280 290 300 GCGPSGHVMA SDGAAPRAGL AWSPCSRRQL LSLLSANEQC RVAFGPKAVA CTFAREHLDM 310 320 330 340 350 360 CQALSCHTDP LDQSSCSRLL VPLLDGTECG VEKWCSKGRC RSLVELTPIA AVHGRWSSWG 370 380 390 400 410 420 PRSPCSRSCG GGVVTRRRQC NNPRPAFGGR ACVGADLQAE MCNTQACEKT QLEFMSQQCA 430 440 450 460 470 480 RTDGQPLRSS PGGASFYHWG AAVPHSQGDA LCRHMCRAIG ESFIMKRGDS FLDGTRCMPS 490 500 510 520 530 540 GPREDGTLSL CVSGSCRTFG CDGRMDSQQV WDRCQVCGGD NSTCSPRKGS FTAGRAREYV 550 560 570 580 590 600 TFLTVTPNLT SVYIANHRPL FTHLAVRIGG RYVVAGKMSI SPNTTYPSLL EDGRVEYRVA 610 620 630 640 650 660 LTEDRLPRLE EIRIWGPLQE DADIQVYRRY GEEYGNLTRP DITFTYFQPK PRQAWVWAAV 670 680 690 700 710 720 RGPCSVSCGA GLRWVNYSCL DQARKELVET VQCQGSQQPP AWPEACVLEP CPPYWAVGDF 730 740 750 760 770 780 GPCSASCGGG LRERPVRCVE AQGSLLKTLP PARCRAGAQQ PAVALETCNP QPCPARWEVS 790 800 810 820 830 840 EPSSCTSAGG AGLALENETC VPGADGLEAP VTEGPGSVDE KLPAPEPCVG MSCPPGWGHL 850 860 870 880 890 900 DATSAGEKAP SPWGSIRTGA QAAHVWTPAA GSCSVSCGRG LMELRFLCMD SALRVPVQEE 910 920 930 940 950 960 LCGLASKPGS RREVCQAVPC PARWQYKLAA CSVSCGRGVV RRILYCARAH GEDDGEEILL 970 980 990 1000 1010 1020 DTQCQGLPRP EPQEACSLEP CPPRWKVMSL GPCSASCGLG TARRSVACVQ LDQGQDVEVD 1030 1040 1050 1060 1070 1080 EAACAALVRP EASVPCLIAD CTYRWHVGTW MECSVSCGDG IQRRRDTCLG PQAQAPVPAD 1090 1100 1110 1120 1130 1140 FCQHLPKPVT VRGCWAGPCV GQGACGRQHL EPTGTIDMRG PGQADCAVAI GRPLGEVVTL 1150 1160 1170 1180 1190 1200 RVLESSLNCS AGDMLLLWGR LTWRKMCRKL LDMTFSSKTN TLVVRQRCGR PGGGVLLRYG 1210 1220 1230 1240 1250 1260 SQLAPETFYR ECDMQLFGPW GEIVSPSLSP ATSNAGGCRL FINVAPHARI AIHALATNMG 1270 1280 1290 1300 1310 1320 AGTEGANASY ILIRDTHSLR TTAFHGQQVL YWESESSQAE MEFSEGFLKA QASLRGQYWT 1330 1340 LQSWVPEMQD PQSWKGKEGT

References

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[1]	"A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease?" Soejima K., Mimura N., Hirashima M., Maeda H., Hamamoto T., Nakagaki T., Nozaki C. J. Biochem. 130:475-480(2001) [PubMed: 11574066] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 75-103, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura." Zheng X., Chung D., Takayama T.K., Majerus E.M., Sadler J.E., Fujikawa K. J. Biol. Chem. 276:41059-41063(2001) [PubMed: 11557746] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, VARIANT VAL-900. Tissue: Liver.
[3]	"Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura." Levy G.G., Nichols W.C., Lian E.C., Foroud T., McClintick J.N., McGee B.M., Yang A.Y., Siemieniak D.R., Stark K.R., Gruppo R., Sarode R., Shurin S.B., Chandrasekaran V., Stabler S.P., Sabio H., Bouhassira E.E., Upshaw J.D. Jr., Ginsburg D., Tsai H.-M. Nature 413:488-494(2001) [PubMed: 11586351] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN THROMBOTIC THROMBOCYTOPENIC PURPURA, VARIANTS TTP ASP-96; CYS-102; ILE-196; HIS-398; GLY-528; CYS-692; GLY-951; GLY-1024 AND TYR-1213, VARIANTS TRP-7; GLU-448; ALA-618; HIS-625; VAL-732; VAL-900 AND THR-1033. Tissue: Liver.
[4]	"Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains." Cal S., Obaya A.J., Llamazares M., Garabaya C., Quesada V., Lopez-Otin C. Gene 283:49-62(2002) [PubMed: 11867212] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3). Tissue: Liver.
[5]	SeattleSNPs variation discovery resource Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TRP-7; GLU-448; HIS-456; LEU-457; ALA-618; HIS-625; LYS-740; VAL-900; ARG-982; THR-1033 AND ILE-1226.
[6]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 275-1427, VARIANT GLU-448.
[8]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1191-1427. Tissue: Testis.
[9]	"Partial amino acid sequence of purified von Willebrand factor-cleaving protease." Gerritsen H.E., Robles R., Laemmle B., Furlan M. Blood 98:1654-1661(2001) [PubMed: 11535494] [Abstract] Cited for: PROTEIN SEQUENCE OF 75-89.
[10]	"Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family." Fujikawa K., Suzuki H., McMullen B., Chung D. Blood 98:1662-1666(2001) [PubMed: 11535495] [Abstract] Cited for: PROTEIN SEQUENCE OF 75-94.
[11]	"Cleavage of von Willebrand factor requires the spacer domain of the metalloprotease ADAMTS13." Zheng X., Nishio K., Majerus E.M., Sadler J.E. J. Biol. Chem. 278:30136-30141(2003) [PubMed: 12791682] [Abstract] Cited for: CHARACTERIZATION, SUBCELLULAR LOCATION.
[12]	"Cleavage of the ADAMTS13 propeptide is not required for protease activity." Majerus E.M., Zheng X., Tuley E.A., Sadler J.E. J. Biol. Chem. 278:46643-46648(2003) [PubMed: 12975358] [Abstract] Cited for: ENZYME REGULATION, MUTAGENESIS OF ARG-71 AND ARG-73.
[13]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-614; ASN-667 AND ASN-1354, MASS SPECTROMETRY. Tissue: Plasma.
[14]	"Zinc and calcium ions cooperatively modulate ADAMTS13 activity." Anderson P.J., Kokame K., Sadler J.E. J. Biol. Chem. 281:850-857(2006) [PubMed: 16286459] [Abstract] Cited for: ENZYME REGULATION.
[15]	"Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity." Kokame K., Matsumoto M., Soejima K., Yagi H., Ishizashi H., Funato M., Tamai H., Konno M., Kamide K., Kawano Y., Miyata T., Fujimura Y. Proc. Natl. Acad. Sci. U.S.A. 99:11902-11907(2002) [PubMed: 12181489] [Abstract] Cited for: VARIANTS TTP PRO-268 AND TYR-508, VARIANTS GLU-448 AND SER-475, CHARACTERIZATION OF VARIANTS TTP PRO-268 AND TYR-508, CHARACTERIZATION OF VARIANTS GLU-448 AND SER-475.
[16]	"ADAMTS13 gene defects in two brothers with constitutional thrombotic thrombocytopenic purpura and normalization of von Willebrand factor-cleaving protease activity by recombinant human ADAMTS13." Antoine G., Zimmermann K., Plaimauer B., Grillowitzer M., Studt J.D., Lammle B., Scheiflinger F. Br. J. Haematol. 120:821-824(2003) [PubMed: 12614216] [Abstract] Cited for: VARIANT TTP TRP-1336, VARIANT VAL-732.
[17]	"Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13." Pimanda J.E., Maekawa A., Wind T., Paxton J., Chesterman C.N., Hogg P.J. Blood 103:627-629(2004) [PubMed: 14512317] [Abstract] Cited for: VARIANT TTP ILE-196, VARIANT GLU-448.
[18]	"Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome." Matsumoto M., Kokame K., Soejima K., Miura M., Hayashi S., Fujii Y., Iwai A., Ito E., Tsuji Y., Takeda-Shitaka M., Iwadate M., Umeyama H., Yagi H., Ishizashi H., Banno F., Nakagaki T., Miyata T., Fujimura Y. Blood 103:1305-1310(2004) [PubMed: 14563640] [Abstract] Cited for: VARIANTS TTP TRP-193; PHE-673; TYR-908 AND CYS-1123, VARIANT GLU-448, CHARACTERIZATION OF VARIANTS TTP TRP-193; PHE-673; TYR-908 AND CYS-1123.
[19]	"Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura." Uchida T., Wada H., Mizutani M., Iwashita M., Ishihara H., Shibano T., Suzuki M., Matsubara Y., Soejima K., Matsumoto M., Fujimura Y., Ikeda Y., Murata M. Blood 104:2081-2083(2004) [PubMed: 15126318] [Abstract] Cited for: VARIANT TTP VAL-250, CHARACTERIZATION OF VARIANT TTP VAL-250.
[20]	"Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS)." Licht C., Stapenhorst L., Simon T., Budde U., Schneppenheim R., Hoppe B. Kidney Int. 66:955-958(2004) [PubMed: 15327386] [Abstract] Cited for: VARIANT TTP CYS-390.
[21]	"Identification of two novel mutations in ADAMTS13 gene in a patient with hereditary thrombotic thrombocytopenic purpura." Liu F., Jin J., Dong N.Z., Wang Y.G., Ruan C.G. Zhonghua Xue Ye Xue Za Zhi 26:521-524(2005) [PubMed: 16468327] [Abstract] Cited for: VARIANTS LEU-903 AND TRP-1095.
[22]	"Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation." Plaimauer B., Fuhrmann J., Mohr G., Wernhart W., Bruno K., Ferrari S., Konetschny C., Antoine G., Rieger M., Scheiflinger F. Blood 107:118-125(2006) [PubMed: 16160007] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS TRP-7; GLU-448; ALA-618 AND VAL-732, CHARACTERIZATION OF VARIANT TTP TRP-1336, DISCUSSION ON MUTUAL MODULATORY EFFECTS OF POLYMORPHISMS.
[23]	"Mechanisms of the interaction between two ADAMTS13 gene mutations leading to severe deficiency of enzymatic activity." Peyvandi F., Lavoretano S., Palla R., Valsecchi C., Merati G., De Cristofaro R., Rossi E., Mannuccio Mannucci P. Hum. Mutat. 27:330-336(2006) [PubMed: 16453338] [Abstract] Cited for: VARIANTS TTP MET-88 AND VAL-1239, CHARACTERIZATION OF VARIANTS TTP MET-88 AND VAL-1239.
[24]	"Novel compound heterozygote mutations (H234Q/R1206X) of the ADAMTS13 gene in an adult patient with Upshaw-Schulman syndrome showing predominant episodes of repeated acute renal failure." Shibagaki Y., Matsumoto M., Kokame K., Ohba S., Miyata T., Fujimura Y., Fujita T. Nephrol. Dial. Transplant. 21:1289-1292(2006) [PubMed: 16449289] [Abstract] Cited for: VARIANT TTP GLN-234, VARIANT LEU-903.
+	Additional computationally mapped references.

Web resources

Wikipedia

ADAMTS13 entry

GeneReviews

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB069698 mRNA. Translation: BAB69487.2. AY055376 mRNA. Translation: AAL17652.1. AF414401 mRNA. Translation: AAL11095.1. AJ305314 mRNA. Translation: CAC83682.1. AJ420810 mRNA. Translation: CAD12729.1. DQ422807 Genomic DNA. Translation: ABD72606.1. AL158826, AL593848 Genomic DNA. Translation: CAI12850.1. AL158826, AL593848 Genomic DNA. Translation: CAI12851.1. AL158826, AL593848 Genomic DNA. Translation: CAI12852.1. AL593848 Genomic DNA. Translation: CAI17248.1. AL593848, AL158826 Genomic DNA. Translation: CAI17256.1. AL593848, AL158826 Genomic DNA. Translation: CAI17257.1. AL593848, AL158826 Genomic DNA. Translation: CAI17258.1. AY358118 mRNA. Translation: AAQ88485.1. Different initiation. AL136809 mRNA. Translation: CAB66743.1. Different initiation.
IPI	IPI00427822. IPI00449028. IPI00453457.
RefSeq	NP_620594.1. NP_620595.1. NP_620596.2.
UniGene	Hs.131433
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q76LX8. 1 interaction.
STRING	Q76LX8.
Protein family/group databases
MEROPS	M12.241.
Proteomic databases
PRIDE	Q76LX8.
Genome annotation databases
Ensembl	ENST00000371929; ENSP00000360997; ENSG00000160323; Homo sapiens. [Genome view]
GeneID	11093.
KEGG	hsa:11093.
UCSC	uc004cdt.1. human. uc004cdu.1. human. uc004cdv.2. human.
Organism-specific databases
CTD	11093.
GeneCards	GC09P135276.
HGNC	HGNC:1366. ADAMTS13.
MIM	235400. phenotype. 274150. phenotype. 604134. gene.
Orphanet	54057. Thrombotic thrombocytopenic purpura. 93583. Thrombotic thrombocytopenic purpura, congenital, due to ADAMTS-13 deficiency.
PharmGKB	PA24539.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q76LX8.
HOVERGEN	Q76LX8.
OMA	AQPGLYY
OrthoDB	EOG9B2WGX
Gene expression databases
ArrayExpress	Q76LX8.
Bgee	Q76LX8.
CleanEx	HS_ADAMTS13.
Genevestigator	Q76LX8.
GermOnline	ENSG00000160323. Homo sapiens.
Family and domain databases
InterPro	IPR000859. CUB. IPR001590. Peptidase_M12B. IPR013273. Peptidase_M12B_ADAM-TS. IPR000884. Thrombospondin_1_rpt. [Graphical view]
Pfam	PF01421. Reprolysin. 1 hit. PF00090. TSP_1. 3 hits. [Graphical view]
PRINTS	PR01857. ADAMTSFAMILY.
SMART	SM00209. TSP1. 7 hits. [Graphical view]
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS01180. CUB. False negative. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. False negative. PS50092. TSP1. 4 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	42166.
SOURCE	Search...

Entry information

Entry name

ATS13_HUMAN

Accession

Primary (citable) accession number: Q76LX8
Secondary accession number(s): Q6UY16 , Q710F6, Q711T8, Q96L37, Q9H0G3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	July 19, 2004
Last modified:	November 24, 2009
This is version 64 of the entry and version 1 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.