Seroatlas · Human Serome Atlas

ADAMTS8

A disintegrin and metalloproteinase with thrombospondin motifs 8

Also known as: ADAM-TS8, ATS8_HUMAN, FLJ41712, METH2

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9UP79
Gene: ADAMTS8
Ensembl: ENSG00000134917
Chromosome: 11
Canonical length: 889 aa
Protein class: Cancer-related genes, Plasma proteins, Predicted secreted proteins
Secretome location: Secreted to extracellular matrix

OverviewNCBI Gene

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs, and disrupts angiogenesis in vivo. A number of disorders have been mapped in the vicinity of this gene, most notably lung neoplasms. Reduced expression of this gene has been observed in multiple human cancers and this gene has been proposed as a potential tumor suppressor. [provided by RefSeq, Feb 2016]

Canonical amino-acid sequenceUniProt

889 residues, UniProt reviewed canonical sequence.

>Q9UP79|ADAMTS8
     1  MLPAPAAPRW PPLLLLLLLL LPLARGAPAR PAAGGQASEL VVPTRLPGSA GELALHLSAF
    61  GKGFVLRLAP DDSFLAPEFK IERLGGSGRA TGGERGLRGC FFSGTVNGEP ESLAAVSLCR
   121  GLSGSFLLDG EEFTIQPQGA GGSLAQPHRL QRWGPAGARP LPRGPEWEVE TGEGQRQERG
   181  DHQEDSEEES QEEEAEGASE PPPPLGATSR TKRFVSEARF VETLLVADAS MAAFYGADLQ
   241  NHILTLMSVA ARIYKHPSIK NSINLMVVKV LIVEDEKWGP EVSDNGGLTL RNFCNWQRRF
   301  NQPSDRHPEH YDTAILLTRQ NFCGQEGLCD TLGVADIGTI CDPNKSCSVI EDEGLQAAHT
   361  LAHELGHVLS MPHDDSKPCT RLFGPMGKHH VMAPLFVHLN QTLPWSPCSA MYLTELLDGG
   421  HGDCLLDAPA AALPLPTGLP GRMALYQLDQ QCRQIFGPDF RHCPNTSAQD VCAQLWCHTD
   481  GAEPLCHTKN GSLPWADGTP CGPGHLCSEG SCLPEEEVER PKPVADGGWA PWGPWGECSR
   541  TCGGGVQFSH RECKDPEPQN GGRYCLGRRA KYQSCHTEEC PPDGKSFREQ QCEKYNAYNY
   601  TDMDGNLLQW VPKYAGVSPR DRCKLFCRAR GRSEFKVFEA KVIDGTLCGP ETLAICVRGQ
   661  CVKAGCDHVV DSPRKLDKCG VCGGKGNSCR KVSGSLTPTN YGYNDIVTIP AGATNIDVKQ
   721  RSHPGVQNDG NYLALKTADG QYLLNGNLAI SAIEQDILVK GTILKYSGSI ATLERLQSFR
   781  PLPEPLTVQL LTVPGEVFPP KVKYTFFVPN DVDFSMQSSK ERATTNIIQP LLHAQWVLGD
   841  WSECSSTCGA GWQRRTVECR DPSGQASATC NKALKPEDAK PCESQLCPL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADAMTS8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.34
Highest tissue expression: 33 nTPM

Expression across tissuesHPA

Tissue

lung: 33 nTPM
blood vessel: 13 nTPM
appendix: 9.5 nTPM
colon: 8.1 nTPM
stomach: 6.5 nTPM
seminal vesicle: 4.6 nTPM

Single-cell type

endometrial glandular cells: 41 nCPM
decidual stromal cells: 37 nCPM
vascular smooth muscle cells: 35 nCPM
endometrial stromal cells: 31 nCPM
epididymal basal cells: 30 nCPM
endometrial luminal cells: 30 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

cerebral cortex: 13 nTPM
basal ganglia: 9 nTPM
hippocampal formation: 9 nTPM
white matter: 8.7 nTPM
amygdala: 8.1 nTPM
thalamus: 5.7 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.91
gnomAD pLI: 0
gnomAD missense Z: 0.52
DepMap mean gene effect: 0.06
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

heparin binding
integrin binding
metalloendopeptidase activity
metallopeptidase activity
zinc ion binding
low-affinity phosphate transmembrane transporter activity

Cellular components

extracellular matrix

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ADAMTS8 as an antibody target. Whether an autoantibody or antibody against ADAMTS8 could matter depends on whether native ADAMTS8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ADAMTS8 is annotated as secreted, so native ADAMTS8 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label ADAMTS8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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