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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 13

Gene

ADAMTS13

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.1 Publication

Catalytic activityi

Cleaves the vWF at the 842-Tyr-|-Met-843 in the A2 domain of the vWF subunit.
The enzyme cleaves the von Willebrand factor at bond Tyr(842)-|-Met(843) within the A2 domain.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
  • Ca2+1 PublicationNote: Binds 4 Ca2+ ions.1 Publication

Enzyme regulationi

Zinc and calcium ions cooperatively modulate enzyme activity. The cleavage of the pro-domain is not required for protease activity. Dependence on calcium for proteolytic activity is mediated by the high affinity site.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi83CalciumSequence analysis1
Metal bindingi173CalciumSequence analysis1
Metal bindingi182Calcium; high affinity1 Publication1
Metal bindingi184Calcium; high affinity1 Publication1
Metal bindingi187Calcium; high affinity1 Publication1
Metal bindingi212Calcium; high affinity1 Publication1
Metal bindingi224Zinc; catalyticBy similarity1
Active sitei225PROSITE-ProRule annotation1
Metal bindingi228Zinc; catalyticBy similarity1
Metal bindingi234Zinc; catalyticBy similarity1
Metal bindingi281CalciumSequence analysis1
Metal bindingi284CalciumSequence analysis1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • integrin binding Source: UniProtKB
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • cell-matrix adhesion Source: UniProtKB
  • cellular response to interferon-gamma Source: Ensembl
  • cellular response to interleukin-4 Source: Ensembl
  • cellular response to lipopolysaccharide Source: Ensembl
  • cellular response to tumor necrosis factor Source: Ensembl
  • glycoprotein metabolic process Source: UniProtKB
  • integrin-mediated signaling pathway Source: UniProtKB
  • peptide catabolic process Source: UniProtKB
  • platelet activation Source: UniProtKB
  • protein O-linked fucosylation Source: Reactome
  • protein processing Source: UniProtKB
  • proteolysis Source: UniProtKB
  • response to amine Source: Ensembl
  • response to potassium ion Source: Ensembl
  • response to toxic substance Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Blood coagulation, Hemostasis

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.87. 2681.
ReactomeiR-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Protein family/group databases

MEROPSiM12.241.

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 13 (EC:3.4.24.87)
Short name:
ADAM-TS 13
Short name:
ADAM-TS13
Short name:
ADAMTS-13
Alternative name(s):
von Willebrand factor-cleaving protease
Short name:
vWF-CP
Short name:
vWF-cleaving protease
Gene namesi
Name:ADAMTS13
Synonyms:C9orf8
ORF Names:UNQ6102/PRO20085
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:1366. ADAMTS13.

Subcellular locationi

  • Secreted 1 Publication

  • Note: Secretion enhanced by O-fucosylation of TSP type-1 repeats.

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • endoplasmic reticulum lumen Source: Reactome
  • extracellular space Source: Ensembl
  • proteinaceous extracellular matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Thrombotic thrombocytopenic purpura congenital (TTP)19 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever. recessive.
See also OMIM:274150
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06777079I → M in TTP. 1 PublicationCorresponds to variant rs281875297dbSNPEnsembl.1
Natural variantiVAR_02711088V → M in TTP; reduces protein secretion and proteolytic activity. 1 PublicationCorresponds to variant rs281875302dbSNPEnsembl.1
Natural variantiVAR_02711196H → D in TTP. 1 PublicationCorresponds to variant rs121908467dbSNPEnsembl.1
Natural variantiVAR_027112102R → C in TTP. 1 PublicationCorresponds to variant rs121908469dbSNPEnsembl.1
Natural variantiVAR_067771119S → F in TTP. 1 PublicationCorresponds to variant rs281875291dbSNPEnsembl.1
Natural variantiVAR_067772178I → T in TTP. 1 PublicationCorresponds to variant rs281875289dbSNPEnsembl.1
Natural variantiVAR_027113193R → W in TTP; low activity. 2 PublicationsCorresponds to variant rs281875287dbSNPEnsembl.1
Natural variantiVAR_027114196T → I in TTP. 3 PublicationsCorresponds to variant rs121908470dbSNPEnsembl.1
Natural variantiVAR_067773203S → P in TTP. 1 PublicationCorresponds to variant rs281875298dbSNPEnsembl.1
Natural variantiVAR_067774232L → Q in TTP. 1 PublicationCorresponds to variant rs281875292dbSNPEnsembl.1
Natural variantiVAR_027115234H → Q in TTP. 1 PublicationCorresponds to variant rs281875304dbSNPEnsembl.1
Natural variantiVAR_067775235D → H in TTP. 1 PublicationCorresponds to variant rs281875337dbSNPEnsembl.1
Natural variantiVAR_027116250A → V in TTP; mild effect on protein secretion; strong reduction of proteolytic activity. 1 PublicationCorresponds to variant rs121908478dbSNPEnsembl.1
Natural variantiVAR_067776263S → C in TTP. 2 PublicationsCorresponds to variant rs281875293dbSNPEnsembl.1
Natural variantiVAR_027117268R → P in TTP; affects protein secretion. 2 PublicationsCorresponds to variant rs121908477dbSNPEnsembl.1
Natural variantiVAR_067777304Y → C in TTP. 1 PublicationCorresponds to variant rs281875285dbSNPEnsembl.1
Natural variantiVAR_067778311C → Y in TTP. 1 PublicationCorresponds to variant rs281875336dbSNPEnsembl.1
Natural variantiVAR_067780347C → S in TTP. 1 PublicationCorresponds to variant rs281875294dbSNPEnsembl.1
Natural variantiVAR_067781349R → C in TTP. 1 PublicationCorresponds to variant rs281875288dbSNPEnsembl.1
Natural variantiVAR_067782353P → L in TTP. 3 PublicationsCorresponds to variant rs281875338dbSNPEnsembl.1
Natural variantiVAR_027118390W → C in TTP. 1 PublicationCorresponds to variant rs281875306dbSNPEnsembl.1
Natural variantiVAR_027119398R → H in TTP. 1 PublicationCorresponds to variant rs121908471dbSNPEnsembl.1
Natural variantiVAR_067783507R → Q in TTP. 2 PublicationsCorresponds to variant rs281875296dbSNPEnsembl.1
Natural variantiVAR_027122508C → Y in TTP; impairs protein secretion. 1 PublicationCorresponds to variant rs281875305dbSNPEnsembl.1
Natural variantiVAR_067784525G → D in TTP. 1 PublicationCorresponds to variant rs281875286dbSNPEnsembl.1
Natural variantiVAR_027123528R → G in TTP. 1 PublicationCorresponds to variant rs121908473dbSNPEnsembl.1
Natural variantiVAR_067785596A → V in TTP. 1 PublicationCorresponds to variant rs281875299dbSNPEnsembl.1
Natural variantiVAR_067786606A → P in TTP. 1 PublicationCorresponds to variant rs281875290dbSNPEnsembl.1
Natural variantiVAR_067787658Y → C in TTP. 1 PublicationCorresponds to variant rs281875335dbSNPEnsembl.1
Natural variantiVAR_067788671P → L in TTP. 1 PublicationCorresponds to variant rs281875295dbSNPEnsembl.1
Natural variantiVAR_027126673I → F in TTP; impairs protein secretion. 1 PublicationCorresponds to variant rs281875307dbSNPEnsembl.1
Natural variantiVAR_027127692R → C in TTP. 1 PublicationCorresponds to variant rs121908475dbSNPEnsembl.1
Natural variantiVAR_067789758C → R in TTP. 1 PublicationCorresponds to variant rs281875300dbSNPEnsembl.1
Natural variantiVAR_067790908C → S in TTP. 1 PublicationCorresponds to variant rs281875301dbSNPEnsembl.1
Natural variantiVAR_027131908C → Y in TTP; impairs protein secretion. 1 PublicationCorresponds to variant rs281875301dbSNPEnsembl.1
Natural variantiVAR_027132951C → G in TTP. 1 PublicationCorresponds to variant rs121908468dbSNPEnsembl.1
Natural variantiVAR_067791977 – 979CAR → W in TTP. 1 Publication3
Natural variantiVAR_0271331024C → G in TTP. 1 PublicationCorresponds to variant rs121908472dbSNPEnsembl.1
Natural variantiVAR_0677921060R → W in TTP; affects protein secretion; the mutant protein has reduced protease activity. 3 PublicationsCorresponds to variant rs142572218dbSNPEnsembl.1
Natural variantiVAR_0271361123R → C in TTP; impairs protein secretion; the mutant protein has reduced protease activity. 2 PublicationsCorresponds to variant rs281875340dbSNPEnsembl.1
Natural variantiVAR_0271371213C → Y in TTP. 1 PublicationCorresponds to variant rs121908474dbSNPEnsembl.1
Natural variantiVAR_0677931219R → W in TTP; affects protein secretion; the mutant protein has reduced protease activity. 1 PublicationCorresponds to variant rs281875339dbSNPEnsembl.1
Natural variantiVAR_0271381239G → V in TTP; impairs protein secretion. 1 PublicationCorresponds to variant rs281875303dbSNPEnsembl.1
Natural variantiVAR_0271391336R → W in TTP; impairs protein secretion and proteolytic activity. 2 PublicationsCorresponds to variant rs281875308dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi71R → K: Abolishes pro-domain removal but no loss of proteolytic activity; when associated with D-73. 1 Publication1
Mutagenesisi73R → D: Abolishes pro-domain removal but no loss of proteolytic activity; when associated with K-71. 1 Publication1
Mutagenesisi83E → A: No change in calcium dependence for proteolysis. 1 Publication1
Mutagenesisi173D → A: No change in calcium dependence for proteolysis. 1 Publication1
Mutagenesisi184E → A: Dramatically reduced affinity for calcium. 1 Publication1
Mutagenesisi187D → A: Dramatically reduced affinity for calcium. 1 Publication1
Mutagenesisi212E → A: Dramatically reduced affinity for calcium. 1 Publication1
Mutagenesisi399S → A: No effect on cleavage of VWF and little change in secretion of ADAMTS13. Abolishes secretion of ADAMTS13; when associated with A-698. 1 Publication1
Mutagenesisi698S → A: No effect on cleavage of VWF and greatly reduced secretion of ADAMTS13. Abolishes secretion of ADAMTS13; when associated with A-399. 1 Publication1
Mutagenesisi757S → A: No effect on cleavage of VWF and little change in secretion of ADAMTS13. 1 Publication1
Mutagenesisi907S → A: No effect on cleavage of VWF and greatly reduced secretion of ADAMTS13. Abolishes most of the secretion of ADAMTS13; when associated with A-965. 1 Publication1
Mutagenesisi965S → A: No effect on cleavage of VWF and little change in secretion of ADAMTS13. Abolishes most of the secretion of ADAMTS13; when associated with A-907. 1 Publication1
Mutagenesisi1027S → A: No effect on cleavage of VWF and little change in secretion of ADAMTS13. Abolishes most of the secretion of ADAMTS13; when associated with A-1087. 1 Publication1
Mutagenesisi1087S → A: No effect on cleavage of VWF and little change in secretion of ADAMTS13. Abolishes most of the secretion of ADAMTS13; when associated with A-1027. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi11093.
MalaCardsiADAMTS13.
MIMi274150. phenotype.
OpenTargetsiENSG00000160323.
ENSG00000281244.
Orphaneti93583. Congenital thrombotic thrombocytopenic purpura due to ADAMTS-13 deficiency.
PharmGKBiPA24539.

Chemistry databases

ChEMBLiCHEMBL2346492.

Polymorphism and mutation databases

BioMutaiADAMTS13.
DMDMi74749836.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
PropeptideiPRO_000024751030 – 743 PublicationsAdd BLAST45
ChainiPRO_000024751175 – 1427A disintegrin and metalloproteinase with thrombospondin motifs 13Add BLAST1353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi142N-linked (GlcNAc...)Sequence analysis1
Glycosylationi146N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi155 ↔ 208By similarity
Disulfide bondi202 ↔ 281By similarity
Disulfide bondi242 ↔ 265By similarity
Disulfide bondi311 ↔ 337Combined sources1 Publication
Disulfide bondi322 ↔ 347Combined sources1 Publication
Disulfide bondi332 ↔ 366Combined sources1 Publication
Disulfide bondi360 ↔ 371Combined sources1 Publication
Glycosylationi387C-linked (Man)Combined sources1
Disulfide bondi396 ↔ 433Combined sources1 Publication
Glycosylationi399O-linked (Fuc...)Combined sources1
Disulfide bondi400 ↔ 438Combined sources1 Publication
Disulfide bondi411 ↔ 423Combined sources1 Publication
Disulfide bondi450 ↔ 487Combined sources
Disulfide bondi483 ↔ 522Combined sources1 Publication
Disulfide bondi508 ↔ 527Combined sources1 Publication
Disulfide bondi532 ↔ 548Combined sources1 Publication
Disulfide bondi545 ↔ 555Combined sources1 Publication
Glycosylationi552N-linked (GlcNAc...)Combined sources1 Publication1
Glycosylationi579N-linked (GlcNAc...)Sequence analysis1
Glycosylationi614N-linked (GlcNAc...)Combined sources2 Publications1
Glycosylationi667N-linked (GlcNAc...) (complex)2 Publications1
Glycosylationi698O-linked (Fuc...)1 Publication1
Glycosylationi707N-linked (GlcNAc...) (complex)1 Publication1
Glycosylationi757O-linked (Fuc...)1 Publication1
Glycosylationi828N-linked (GlcNAc...)Sequence analysis1
Glycosylationi907O-linked (Fuc...)1 Publication1
Glycosylationi965O-linked (Fuc...)1 Publication1
Glycosylationi1027O-linked (Fuc...)1 Publication1
Glycosylationi1087O-linked (Fuc...)1 Publication1
Glycosylationi1235N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1354N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

Glycosylated. O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS13. May also be C-glycosylated on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and also N-glycosylated. These other glycosylations can also facilitate secretion.5 Publications
The precursor is processed by a furin endopeptidase which cleaves off the pro-domain.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ76LX8.
PeptideAtlasiQ76LX8.
PRIDEiQ76LX8.

PTM databases

iPTMnetiQ76LX8.
PhosphoSitePlusiQ76LX8.

Expressioni

Tissue specificityi

Plasma. Expressed primarily in liver.1 Publication

Gene expression databases

BgeeiENSG00000160323.
CleanExiHS_ADAMTS13.
ExpressionAtlasiQ76LX8. baseline and differential.
GenevisibleiQ76LX8. HS.

Organism-specific databases

HPAiHPA042014.
HPA042844.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
VWFP042755EBI-981764,EBI-981819

GO - Molecular functioni

  • integrin binding Source: UniProtKB

Protein-protein interaction databases

DIPiDIP-36050N.
IntActiQ76LX8. 1 interactor.
MINTiMINT-4713142.
STRINGi9606.ENSP00000360997.

Chemistry databases

BindingDBiQ76LX8.

Structurei

Secondary structure

11427
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi301 – 303Combined sources3
Helixi307 – 314Combined sources8
Helixi331 – 334Combined sources4
Beta strandi337 – 340Combined sources4
Beta strandi348 – 351Combined sources4
Beta strandi359 – 361Combined sources3
Beta strandi364 – 367Combined sources4
Beta strandi370 – 373Combined sources4
Helixi374 – 377Combined sources4
Beta strandi399 – 401Combined sources3
Beta strandi403 – 406Combined sources4
Beta strandi417 – 419Combined sources3
Beta strandi430 – 433Combined sources4
Helixi442 – 451Combined sources10
Turni452 – 455Combined sources4
Beta strandi470 – 472Combined sources3
Turni474 – 476Combined sources3
Helixi479 – 483Combined sources5
Beta strandi486 – 489Combined sources4
Beta strandi495 – 497Combined sources3
Beta strandi519 – 523Combined sources5
Beta strandi526 – 530Combined sources5
Beta strandi534 – 536Combined sources3
Beta strandi554 – 562Combined sources9
Beta strandi569 – 576Combined sources8
Beta strandi581 – 588Combined sources8
Beta strandi592 – 599Combined sources8
Beta strandi602 – 605Combined sources4
Beta strandi608 – 610Combined sources3
Beta strandi614 – 618Combined sources5
Beta strandi623 – 632Combined sources10
Beta strandi634 – 636Combined sources3
Beta strandi638 – 647Combined sources10
Beta strandi653 – 661Combined sources9
Helixi663 – 665Combined sources3
Helixi667 – 669Combined sources3
Beta strandi673 – 680Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GHMX-ray2.60A287-685[»]
3GHNX-ray2.80A287-685[»]
3VN4X-ray2.80A287-685[»]
ProteinModelPortaliQ76LX8.
SMRiQ76LX8.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ76LX8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini80 – 286Peptidase M12BPROSITE-ProRule annotationAdd BLAST207
Domaini287 – 383DisintegrinAdd BLAST97
Domaini384 – 439TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini682 – 730TSP type-1 2PROSITE-ProRule annotationAdd BLAST49
Domaini742 – 805TSP type-1 3PROSITE-ProRule annotationAdd BLAST64
Domaini808 – 859TSP type-1 4PROSITE-ProRule annotationAdd BLAST52
Domaini896 – 950TSP type-1 5PROSITE-ProRule annotationAdd BLAST55
Domaini951 – 1011TSP type-1 6PROSITE-ProRule annotationAdd BLAST61
Domaini1012 – 1068TSP type-1 7PROSITE-ProRule annotationAdd BLAST57
Domaini1072 – 1131TSP type-1 8PROSITE-ProRule annotationAdd BLAST60
Domaini1192 – 1298CUB 1Add BLAST107
Domaini1299 – 1427CUB 2Add BLAST129

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni440 – 556Cysteine-richAdd BLAST117
Regioni556 – 685SpacerAdd BLAST130

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi498 – 500Cell attachment siteSequence analysis3

Domaini

The pro-domain is not required for folding or secretion and does not perform the common function of maintening enzyme latency.
The globular cysteineless spacer domain adopts a jelly-roll topology, and is necessary to recognize and cleave vWF. The C-terminal TSP type-1 and CUB domains may modulate this interaction.

Sequence similaritiesi

Contains 2 CUB domains.Curated
Contains 1 disintegrin domain.Curated
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation
Contains 8 TSP type-1 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118885.
HOGENOMiHOG000231627.
HOVERGENiHBG080358.
InParanoidiQ76LX8.
KOiK08627.
OMAiQCRVAFG.
OrthoDBiEOG091G14M8.
PhylomeDBiQ76LX8.
TreeFamiTF313537.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR000859. CUB_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 4 hits.
[Graphical view]
PRINTSiPR01857. ADAMTSFAMILY.
SMARTiSM00608. ACR. 1 hit.
SM00209. TSP1. 7 hits.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 2 hits.
SSF82895. SSF82895. 5 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q76LX8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MHQRHPRARC PPLCVAGILA CGFLLGCWGP SHFQQSCLQA LEPQAVSSYL
60 70 80 90 100
SPGAPLKGRP PSPGFQRQRQ RQRRAAGGIL HLELLVAVGP DVFQAHQEDT
110 120 130 140 150
ERYVLTNLNI GAELLRDPSL GAQFRVHLVK MVILTEPEGA PNITANLTSS
160 170 180 190 200
LLSVCGWSQT INPEDDTDPG HADLVLYITR FDLELPDGNR QVRGVTQLGG
210 220 230 240 250
ACSPTWSCLI TEDTGFDLGV TIAHEIGHSF GLEHDGAPGS GCGPSGHVMA
260 270 280 290 300
SDGAAPRAGL AWSPCSRRQL LSLLSAGRAR CVWDPPRPQP GSAGHPPDAQ
310 320 330 340 350
PGLYYSANEQ CRVAFGPKAV ACTFAREHLD MCQALSCHTD PLDQSSCSRL
360 370 380 390 400
LVPLLDGTEC GVEKWCSKGR CRSLVELTPI AAVHGRWSSW GPRSPCSRSC
410 420 430 440 450
GGGVVTRRRQ CNNPRPAFGG RACVGADLQA EMCNTQACEK TQLEFMSQQC
460 470 480 490 500
ARTDGQPLRS SPGGASFYHW GAAVPHSQGD ALCRHMCRAI GESFIMKRGD
510 520 530 540 550
SFLDGTRCMP SGPREDGTLS LCVSGSCRTF GCDGRMDSQQ VWDRCQVCGG
560 570 580 590 600
DNSTCSPRKG SFTAGRAREY VTFLTVTPNL TSVYIANHRP LFTHLAVRIG
610 620 630 640 650
GRYVVAGKMS ISPNTTYPSL LEDGRVEYRV ALTEDRLPRL EEIRIWGPLQ
660 670 680 690 700
EDADIQVYRR YGEEYGNLTR PDITFTYFQP KPRQAWVWAA VRGPCSVSCG
710 720 730 740 750
AGLRWVNYSC LDQARKELVE TVQCQGSQQP PAWPEACVLE PCPPYWAVGD
760 770 780 790 800
FGPCSASCGG GLRERPVRCV EAQGSLLKTL PPARCRAGAQ QPAVALETCN
810 820 830 840 850
PQPCPARWEV SEPSSCTSAG GAGLALENET CVPGADGLEA PVTEGPGSVD
860 870 880 890 900
EKLPAPEPCV GMSCPPGWGH LDATSAGEKA PSPWGSIRTG AQAAHVWTPA
910 920 930 940 950
AGSCSVSCGR GLMELRFLCM DSALRVPVQE ELCGLASKPG SRREVCQAVP
960 970 980 990 1000
CPARWQYKLA ACSVSCGRGV VRRILYCARA HGEDDGEEIL LDTQCQGLPR
1010 1020 1030 1040 1050
PEPQEACSLE PCPPRWKVMS LGPCSASCGL GTARRSVACV QLDQGQDVEV
1060 1070 1080 1090 1100
DEAACAALVR PEASVPCLIA DCTYRWHVGT WMECSVSCGD GIQRRRDTCL
1110 1120 1130 1140 1150
GPQAQAPVPA DFCQHLPKPV TVRGCWAGPC VGQGTPSLVP HEEAAAPGRT
1160 1170 1180 1190 1200
TATPAGASLE WSQARGLLFS PAPQPRRLLP GPQENSVQSS ACGRQHLEPT
1210 1220 1230 1240 1250
GTIDMRGPGQ ADCAVAIGRP LGEVVTLRVL ESSLNCSAGD MLLLWGRLTW
1260 1270 1280 1290 1300
RKMCRKLLDM TFSSKTNTLV VRQRCGRPGG GVLLRYGSQL APETFYRECD
1310 1320 1330 1340 1350
MQLFGPWGEI VSPSLSPATS NAGGCRLFIN VAPHARIAIH ALATNMGAGT
1360 1370 1380 1390 1400
EGANASYILI RDTHSLRTTA FHGQQVLYWE SESSQAEMEF SEGFLKAQAS
1410 1420
LRGQYWTLQS WVPEMQDPQS WKGKEGT
Length:1,427
Mass (Da):153,604
Last modified:July 19, 2004 - v1
Checksum:iA2103AFABC1A4445
GO
Isoform 2 (identifier: Q76LX8-2) [UniParc]FASTAAdd to basket

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

Show »
Length:1,371
Mass (Da):147,804
Checksum:iAE4C713AE5B64DFC
GO
Isoform 3 (identifier: Q76LX8-3) [UniParc]FASTAAdd to basket

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

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Length:1,340
Mass (Da):144,517
Checksum:i0BFBEF4C3D58B2C2
GO
Isoform 4 (identifier: Q76LX8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-329: Missing.
     658-692: YRRYGEEYGNLTRPDITFTYFQPKPRQAWVWAAVR → GGVRAQLMHISWWSRPGLGERDLCARGRWPGGSSD
     693-1427: Missing.

Show »
Length:364
Mass (Da):39,864
Checksum:iDA42FC5F5345F3A0
GO

Sequence cautioni

The sequence AAQ88485 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAB66743 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti101E → R AA sequence (PubMed:11574066).Curated1

Polymorphismi

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.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0271097R → W Does not affect protein secretion. 3 PublicationsCorresponds to variant rs34024143dbSNPEnsembl.1
Natural variantiVAR_06777079I → M in TTP. 1 PublicationCorresponds to variant rs281875297dbSNPEnsembl.1
Natural variantiVAR_02711088V → M in TTP; reduces protein secretion and proteolytic activity. 1 PublicationCorresponds to variant rs281875302dbSNPEnsembl.1
Natural variantiVAR_02711196H → D in TTP. 1 PublicationCorresponds to variant rs121908467dbSNPEnsembl.1
Natural variantiVAR_027112102R → C in TTP. 1 PublicationCorresponds to variant rs121908469dbSNPEnsembl.1
Natural variantiVAR_067771119S → F in TTP. 1 PublicationCorresponds to variant rs281875291dbSNPEnsembl.1
Natural variantiVAR_067772178I → T in TTP. 1 PublicationCorresponds to variant rs281875289dbSNPEnsembl.1
Natural variantiVAR_027113193R → W in TTP; low activity. 2 PublicationsCorresponds to variant rs281875287dbSNPEnsembl.1
Natural variantiVAR_027114196T → I in TTP. 3 PublicationsCorresponds to variant rs121908470dbSNPEnsembl.1
Natural variantiVAR_067773203S → P in TTP. 1 PublicationCorresponds to variant rs281875298dbSNPEnsembl.1
Natural variantiVAR_067774232L → Q in TTP. 1 PublicationCorresponds to variant rs281875292dbSNPEnsembl.1
Natural variantiVAR_027115234H → Q in TTP. 1 PublicationCorresponds to variant rs281875304dbSNPEnsembl.1
Natural variantiVAR_067775235D → H in TTP. 1 PublicationCorresponds to variant rs281875337dbSNPEnsembl.1
Natural variantiVAR_027116250A → V in TTP; mild effect on protein secretion; strong reduction of proteolytic activity. 1 PublicationCorresponds to variant rs121908478dbSNPEnsembl.1
Natural variantiVAR_067776263S → C in TTP. 2 PublicationsCorresponds to variant rs281875293dbSNPEnsembl.1
Natural variantiVAR_027117268R → P in TTP; affects protein secretion. 2 PublicationsCorresponds to variant rs121908477dbSNPEnsembl.1
Natural variantiVAR_067777304Y → C in TTP. 1 PublicationCorresponds to variant rs281875285dbSNPEnsembl.1
Natural variantiVAR_067778311C → Y in TTP. 1 PublicationCorresponds to variant rs281875336dbSNPEnsembl.1
Natural variantiVAR_067779339T → R.1 PublicationCorresponds to variant rs149517360dbSNPEnsembl.1
Natural variantiVAR_067780347C → S in TTP. 1 PublicationCorresponds to variant rs281875294dbSNPEnsembl.1
Natural variantiVAR_067781349R → C in TTP. 1 PublicationCorresponds to variant rs281875288dbSNPEnsembl.1
Natural variantiVAR_067782353P → L in TTP. 3 PublicationsCorresponds to variant rs281875338dbSNPEnsembl.1
Natural variantiVAR_027118390W → C in TTP. 1 PublicationCorresponds to variant rs281875306dbSNPEnsembl.1
Natural variantiVAR_027119398R → H in TTP. 1 PublicationCorresponds to variant rs121908471dbSNPEnsembl.1
Natural variantiVAR_027120448Q → E Does not affect protein secretion; normal proteolytic activity. 9 PublicationsCorresponds to variant rs2301612dbSNPEnsembl.1
Natural variantiVAR_027162456Q → H.1 PublicationCorresponds to variant rs36220239dbSNPEnsembl.1
Natural variantiVAR_027163457P → L.2 PublicationsCorresponds to variant rs36220240dbSNPEnsembl.1
Natural variantiVAR_027121475P → S.1 PublicationCorresponds to variant rs11575933dbSNPEnsembl.1
Natural variantiVAR_067783507R → Q in TTP. 2 PublicationsCorresponds to variant rs281875296dbSNPEnsembl.1
Natural variantiVAR_027122508C → Y in TTP; impairs protein secretion. 1 PublicationCorresponds to variant rs281875305dbSNPEnsembl.1
Natural variantiVAR_067784525G → D in TTP. 1 PublicationCorresponds to variant rs281875286dbSNPEnsembl.1
Natural variantiVAR_027123528R → G in TTP. 1 PublicationCorresponds to variant rs121908473dbSNPEnsembl.1
Natural variantiVAR_067785596A → V in TTP. 1 PublicationCorresponds to variant rs281875299dbSNPEnsembl.1
Natural variantiVAR_067786606A → P in TTP. 1 PublicationCorresponds to variant rs281875290dbSNPEnsembl.1
Natural variantiVAR_027124618P → A.4 PublicationsCorresponds to variant rs28647808dbSNPEnsembl.1
Natural variantiVAR_027125625R → H.2 PublicationsCorresponds to variant rs36090624dbSNPEnsembl.1
Natural variantiVAR_067787658Y → C in TTP. 1 PublicationCorresponds to variant rs281875335dbSNPEnsembl.1
Natural variantiVAR_067788671P → L in TTP. 1 PublicationCorresponds to variant rs281875295dbSNPEnsembl.1
Natural variantiVAR_027126673I → F in TTP; impairs protein secretion. 1 PublicationCorresponds to variant rs281875307dbSNPEnsembl.1
Natural variantiVAR_027127692R → C in TTP. 1 PublicationCorresponds to variant rs121908475dbSNPEnsembl.1
Natural variantiVAR_027128732A → V.3 PublicationsCorresponds to variant rs41314453dbSNPEnsembl.1
Natural variantiVAR_027164740E → K.1 PublicationCorresponds to variant rs36221451dbSNPEnsembl.1
Natural variantiVAR_067789758C → R in TTP. 1 PublicationCorresponds to variant rs281875300dbSNPEnsembl.1
Natural variantiVAR_027129900A → V.3 PublicationsCorresponds to variant rs685523dbSNPEnsembl.1
Natural variantiVAR_027130903S → L.2 PublicationsCorresponds to variant rs78977446dbSNPEnsembl.1
Natural variantiVAR_067790908C → S in TTP. 1 PublicationCorresponds to variant rs281875301dbSNPEnsembl.1
Natural variantiVAR_027131908C → Y in TTP; impairs protein secretion. 1 PublicationCorresponds to variant rs281875301dbSNPEnsembl.1
Natural variantiVAR_027132951C → G in TTP. 1 PublicationCorresponds to variant rs121908468dbSNPEnsembl.1
Natural variantiVAR_067791977 – 979CAR → W in TTP. 1 Publication3
Natural variantiVAR_027165982G → R.1 PublicationCorresponds to variant rs36222275dbSNPEnsembl.1
Natural variantiVAR_0271331024C → G in TTP. 1 PublicationCorresponds to variant rs121908472dbSNPEnsembl.1
Natural variantiVAR_0271341033A → T.2 PublicationsCorresponds to variant rs28503257dbSNPEnsembl.1
Natural variantiVAR_0677921060R → W in TTP; affects protein secretion; the mutant protein has reduced protease activity. 3 PublicationsCorresponds to variant rs142572218dbSNPEnsembl.1
Natural variantiVAR_0271351095R → W in a patient with thrombotic thrombocytopenic purpura. 1 PublicationCorresponds to variant rs782383410dbSNPEnsembl.1
Natural variantiVAR_0271361123R → C in TTP; impairs protein secretion; the mutant protein has reduced protease activity. 2 PublicationsCorresponds to variant rs281875340dbSNPEnsembl.1
Natural variantiVAR_0271371213C → Y in TTP. 1 PublicationCorresponds to variant rs121908474dbSNPEnsembl.1
Natural variantiVAR_0677931219R → W in TTP; affects protein secretion; the mutant protein has reduced protease activity. 1 PublicationCorresponds to variant rs281875339dbSNPEnsembl.1
Natural variantiVAR_0271661226T → I.1 PublicationCorresponds to variant rs36222894dbSNPEnsembl.1
Natural variantiVAR_0271381239G → V in TTP; impairs protein secretion. 1 PublicationCorresponds to variant rs281875303dbSNPEnsembl.1
Natural variantiVAR_0677941314S → L Found in a patient with hemolytic uremic syndrome. 1 PublicationCorresponds to variant rs142060916dbSNPEnsembl.1
Natural variantiVAR_0271391336R → W in TTP; impairs protein secretion and proteolytic activity. 2 PublicationsCorresponds to variant rs281875308dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0555372 – 329Missing in isoform 4. 1 PublicationAdd BLAST328
Alternative sequenceiVSP_020002275 – 305Missing in isoform 3. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_055538658 – 692YRRYG…WAAVR → GGVRAQLMHISWWSRPGLGE RDLCARGRWPGGSSD in isoform 4. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_055539693 – 1427Missing in isoform 4. 1 PublicationAdd BLAST735
Alternative sequenceiVSP_0200031135 – 1190Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AJ011374 mRNA. Translation: CAB66157.1.
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.
CH471090 Genomic DNA. Translation: EAW88086.1.
AY358118 mRNA. Translation: AAQ88485.1. Different initiation.
AL136809 mRNA. Translation: CAB66743.1. Different initiation.
CCDSiCCDS6970.1. [Q76LX8-1]
CCDS6971.1. [Q76LX8-3]
CCDS6972.1. [Q76LX8-2]
RefSeqiNP_620594.1. NM_139025.4. [Q76LX8-1]
NP_620595.1. NM_139026.4. [Q76LX8-3]
NP_620596.2. NM_139027.4. [Q76LX8-2]
UniGeneiHs.131433.

Genome annotation databases

EnsembliENST00000355699; ENSP00000347927; ENSG00000160323. [Q76LX8-2]
ENST00000356589; ENSP00000348997; ENSG00000160323. [Q76LX8-3]
ENST00000371929; ENSP00000360997; ENSG00000160323. [Q76LX8-1]
ENST00000626597; ENSP00000486201; ENSG00000281244. [Q76LX8-1]
ENST00000626744; ENSP00000486734; ENSG00000281244. [Q76LX8-2]
ENST00000630465; ENSP00000485989; ENSG00000281244. [Q76LX8-3]
GeneIDi11093.
KEGGihsa:11093.
UCSCiuc004cdv.6. human. [Q76LX8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

ADAMTS13 entry

SeattleSNPs
Mendelian genes ADAM metallopeptidase with thrombospondin type 1 motif, 13 (ADAMTS13)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AJ011374 mRNA. Translation: CAB66157.1.
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.
CH471090 Genomic DNA. Translation: EAW88086.1.
AY358118 mRNA. Translation: AAQ88485.1. Different initiation.
AL136809 mRNA. Translation: CAB66743.1. Different initiation.
CCDSiCCDS6970.1. [Q76LX8-1]
CCDS6971.1. [Q76LX8-3]
CCDS6972.1. [Q76LX8-2]
RefSeqiNP_620594.1. NM_139025.4. [Q76LX8-1]
NP_620595.1. NM_139026.4. [Q76LX8-3]
NP_620596.2. NM_139027.4. [Q76LX8-2]
UniGeneiHs.131433.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GHMX-ray2.60A287-685[»]
3GHNX-ray2.80A287-685[»]
3VN4X-ray2.80A287-685[»]
ProteinModelPortaliQ76LX8.
SMRiQ76LX8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-36050N.
IntActiQ76LX8. 1 interactor.
MINTiMINT-4713142.
STRINGi9606.ENSP00000360997.

Chemistry databases

BindingDBiQ76LX8.
ChEMBLiCHEMBL2346492.

Protein family/group databases

MEROPSiM12.241.

PTM databases

iPTMnetiQ76LX8.
PhosphoSitePlusiQ76LX8.

Polymorphism and mutation databases

BioMutaiADAMTS13.
DMDMi74749836.

Proteomic databases

PaxDbiQ76LX8.
PeptideAtlasiQ76LX8.
PRIDEiQ76LX8.

Protocols and materials databases

DNASUi11093.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355699; ENSP00000347927; ENSG00000160323. [Q76LX8-2]
ENST00000356589; ENSP00000348997; ENSG00000160323. [Q76LX8-3]
ENST00000371929; ENSP00000360997; ENSG00000160323. [Q76LX8-1]
ENST00000626597; ENSP00000486201; ENSG00000281244. [Q76LX8-1]
ENST00000626744; ENSP00000486734; ENSG00000281244. [Q76LX8-2]
ENST00000630465; ENSP00000485989; ENSG00000281244. [Q76LX8-3]
GeneIDi11093.
KEGGihsa:11093.
UCSCiuc004cdv.6. human. [Q76LX8-1]

Organism-specific databases

CTDi11093.
DisGeNETi11093.
GeneCardsiADAMTS13.
HGNCiHGNC:1366. ADAMTS13.
HPAiHPA042014.
HPA042844.
MalaCardsiADAMTS13.
MIMi274150. phenotype.
604134. gene.
neXtProtiNX_Q76LX8.
OpenTargetsiENSG00000160323.
ENSG00000281244.
Orphaneti93583. Congenital thrombotic thrombocytopenic purpura due to ADAMTS-13 deficiency.
PharmGKBiPA24539.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118885.
HOGENOMiHOG000231627.
HOVERGENiHBG080358.
InParanoidiQ76LX8.
KOiK08627.
OMAiQCRVAFG.
OrthoDBiEOG091G14M8.
PhylomeDBiQ76LX8.
TreeFamiTF313537.

Enzyme and pathway databases

BRENDAi3.4.24.87. 2681.
ReactomeiR-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Miscellaneous databases

EvolutionaryTraceiQ76LX8.
GeneWikiiADAMTS13.
GenomeRNAii11093.
PROiQ76LX8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160323.
CleanExiHS_ADAMTS13.
ExpressionAtlasiQ76LX8. baseline and differential.
GenevisibleiQ76LX8. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR000859. CUB_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 4 hits.
[Graphical view]
PRINTSiPR01857. ADAMTSFAMILY.
SMARTiSM00608. ACR. 1 hit.
SM00209. TSP1. 7 hits.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 2 hits.
SSF82895. SSF82895. 5 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATS13_HUMAN
Accessioni