ATS4_HUMAN
ID ATS4_HUMAN Reviewed; 837 AA.
AC O75173; Q2HYD0; Q5VTW2; Q6P4Q8; Q6UWA8; Q9UN83;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 4;
DE Short=ADAM-TS 4;
DE Short=ADAM-TS4;
DE Short=ADAMTS-4;
DE EC=3.4.24.82;
DE AltName: Full=ADMP-1;
DE AltName: Full=Aggrecanase-1;
DE Flags: Precursor;
GN Name=ADAMTS4; Synonyms=KIAA0688; ORFNames=UNQ769/PRO1563;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-626.
RX PubMed=10356395; DOI=10.1126/science.284.5420.1664;
RA Tortorella M.D., Burn T.C., Pratta M.A., Abbaszade I., Hollis J.M.,
RA Liu R.-Q., Rosenfeld S.A., Copeland R.A., Decicco C.P., Wynn R.,
RA Rockwell A., Yang F., Duke J.L., Solomon K., George H., Bruckner R.,
RA Nagase H., Itoh Y., Ellis D.M., Ross H., Wiswall B.H., Murphy K.,
RA Hillman M.C. Jr., Hollis G.F., Newton R.C., Magolda R.L., Trzaskos J.M.,
RA Arner E.C.;
RT "Purification and cloning of aggrecanase-1: a member of the ADAMTS family
RT of proteins.";
RL Science 284:1664-1666(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 651-837 (ISOFORM 2), AND TISSUE SPECIFICITY
RP (ISOFORM 2).
RC TISSUE=Synovium;
RX PubMed=16723216; DOI=10.1016/j.matbio.2006.03.006;
RA Wainwright S.D., Bondeson J., Hughes C.E.;
RT "An alternative spliced transcript of ADAMTS4 is present in human synovium
RT from OA patients.";
RL Matrix Biol. 25:317-320(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Sawaji Y., Nagase H., Saklatvala J., Clark A.R.;
RT "ADAMTS-4 genomic locus.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS THR-77 AND
RP ARG-626.
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-626.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ILE-4;
RP ASN-304; VAL-369; THR-552 AND ALA-564.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RX PubMed=10827174; DOI=10.1074/jbc.m001065200;
RA Tortorella M.D., Pratta M.A., Liu R.-Q., Abbaszade I., Ross H., Burn T.C.,
RA Arner E.C.;
RT "The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for
RT aggrecan substrate recognition and cleavage.";
RL J. Biol. Chem. 275:25791-25797(2000).
RN [9]
RP INTERACTION WITH SRPX2.
RX PubMed=18718938; DOI=10.1093/hmg/ddn256;
RA Royer-Zemmour B., Ponsole-Lenfant M., Gara H., Roll P., Leveque C.,
RA Massacrier A., Ferracci G., Cillario J., Robaglia-Schlupp A.,
RA Vincentelli R., Cau P., Szepetowski P.;
RT "Epileptic and developmental disorders of the speech cortex:
RT ligand/receptor interaction of wild-type and mutant SRPX2 with the
RT plasminogen activator receptor uPAR.";
RL Hum. Mol. Genet. 17:3617-3630(2008).
RN [10]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY (ISOFORM 2).
RX PubMed=23897278; DOI=10.1002/art.38102;
RA Wainwright S.D., Bondeson J., Caterson B., Hughes C.E.;
RT "ADAMTS-4_v1 is a splice variant of ADAMTS-4 that is expressed as a protein
RT in human synovium and cleaves aggrecan at the interglobular domain.";
RL Arthritis Rheum. 65:2866-2875(2013).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 213-520 ALONE AND IN COMPLEX WITH
RP INHIBITOR, ACTIVE SITE, COFACTOR, ZINC-BINDING SITES, AND DISULFIDE BONDS.
RX PubMed=18042673; DOI=10.1110/ps.073287008;
RA Mosyak L., Georgiadis K., Shane T., Svenson K., Hebert T., McDonagh T.,
RA Mackie S., Olland S., Lin L., Zhong X., Kriz R., Reifenberg E.L.,
RA Collins-Racie L.A., Corcoran C., Freeman B., Zollner R., Marvell T.,
RA Vera M., Sum P.E., Lavallie E.R., Stahl M., Somers W.;
RT "Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4
RT and ADAMTS5.";
RL Protein Sci. 17:16-21(2008).
CC -!- FUNCTION: Cleaves aggrecan, a cartilage proteoglycan, and may be
CC involved in its turnover. May play an important role in the destruction
CC of aggrecan in arthritic diseases. Could also be a critical factor in
CC the exacerbation of neurodegeneration in Alzheimer disease. Cleaves
CC aggrecan at the '392-Glu-|-Ala-393' site.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Glutamyl endopeptidase. Bonds cleaved include 370-Thr-Glu-Gly-
CC Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian
CC aggrecan.; EC=3.4.24.82;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18042673};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18042673};
CC -!- SUBUNIT: Interacts with SRPX2. {ECO:0000269|PubMed:18042673,
CC ECO:0000269|PubMed:18718938}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75173-1; Sequence=Displayed;
CC Name=2; Synonyms=ADAMTS4_v1;
CC IsoId=O75173-2; Sequence=VSP_057293;
CC -!- TISSUE SPECIFICITY: Expressed in brain, lung and heart
CC (PubMed:23897278). Expressed at very low level in placenta and skeletal
CC muscles (PubMed:23897278). Isoform 2: Detected in osteoarthritic
CC synovium (PubMed:16723216, PubMed:23897278).
CC {ECO:0000269|PubMed:16723216, ECO:0000269|PubMed:23897278}.
CC -!- INDUCTION: By IL1/interleukin-1.
CC -!- DOMAIN: The spacer domain and the TSP type-1 domains are important for
CC a tight interaction with the extracellular matrix.
CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC dissociation of the cysteine from the zinc ion upon the activation-
CC peptide release activates the enzyme.
CC -!- PTM: The precursor is cleaved by a furin endopeptidase.
CC -!- PTM: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a
CC threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-
CC G of the TSP type-1 repeat domains where C1 and C2 are the first and
CC second cysteine residue of the repeat, respectively. Fucosylated
CC repeats can then be further glycosylated by the addition of a beta-1,3-
CC glucose residue by the glucosyltransferase, B3GALTL. Fucosylation
CC mediates the efficient secretion of ADAMTS family members. Can also be
CC C-glycosylated with one or two mannose molecules on tryptophan residues
CC within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated.
CC These other glycosylations can also facilitate secretion (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: Functional aggrecanase.
CC {ECO:0000269|PubMed:23897278}.
CC -!- CAUTION: Has sometimes been referred to as ADAMTS2. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABC88384.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA31663.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF148213; AAD41494.1; -; mRNA.
DR EMBL; DQ364570; ABC88384.1; ALT_FRAME; mRNA.
DR EMBL; AY044847; AAL02262.1; -; Genomic_DNA.
DR EMBL; AB014588; BAA31663.2; ALT_INIT; mRNA.
DR EMBL; AY358886; AAQ89245.1; -; mRNA.
DR EMBL; AL590714; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063293; AAH63293.1; -; mRNA.
DR CCDS; CCDS1223.1; -. [O75173-1]
DR PIR; T00355; T00355.
DR RefSeq; NP_001307265.1; NM_001320336.1. [O75173-2]
DR RefSeq; NP_005090.3; NM_005099.5. [O75173-1]
DR PDB; 2RJP; X-ray; 2.80 A; A/B/C/D=213-520.
DR PDB; 3B2Z; X-ray; 2.80 A; A/B/C/D/E/F/G/H=213-520.
DR PDB; 4WK7; X-ray; 1.24 A; A=213-439.
DR PDB; 4WKE; X-ray; 1.62 A; A=213-439.
DR PDB; 4WKI; X-ray; 1.60 A; A=213-439.
DR PDBsum; 2RJP; -.
DR PDBsum; 3B2Z; -.
DR PDBsum; 4WK7; -.
DR PDBsum; 4WKE; -.
DR PDBsum; 4WKI; -.
DR AlphaFoldDB; O75173; -.
DR SMR; O75173; -.
DR BioGRID; 114885; 71.
DR IntAct; O75173; 25.
DR STRING; 9606.ENSP00000356975; -.
DR BindingDB; O75173; -.
DR ChEMBL; CHEMBL2318; -.
DR DrugBank; DB06822; Tinzaparin.
DR GuidetoPHARMACOLOGY; 1677; -.
DR MEROPS; M12.221; -.
DR TCDB; 8.A.77.1.7; the sheddase (sheddase) family.
DR GlyGen; O75173; 2 sites, 2 O-linked glycans (1 site).
DR iPTMnet; O75173; -.
DR PhosphoSitePlus; O75173; -.
DR BioMuta; ADAMTS4; -.
DR EPD; O75173; -.
DR jPOST; O75173; -.
DR MassIVE; O75173; -.
DR PaxDb; O75173; -.
DR PeptideAtlas; O75173; -.
DR PRIDE; O75173; -.
DR ProteomicsDB; 49841; -. [O75173-1]
DR ABCD; O75173; 1 sequenced antibody.
DR Antibodypedia; 20503; 567 antibodies from 36 providers.
DR DNASU; 9507; -.
DR Ensembl; ENST00000367996.6; ENSP00000356975.4; ENSG00000158859.10. [O75173-1]
DR GeneID; 9507; -.
DR KEGG; hsa:9507; -.
DR MANE-Select; ENST00000367996.6; ENSP00000356975.4; NM_005099.6; NP_005090.3.
DR UCSC; uc001fyt.5; human. [O75173-1]
DR CTD; 9507; -.
DR DisGeNET; 9507; -.
DR GeneCards; ADAMTS4; -.
DR HGNC; HGNC:220; ADAMTS4.
DR HPA; ENSG00000158859; Tissue enhanced (ovary).
DR MIM; 603876; gene.
DR neXtProt; NX_O75173; -.
DR OpenTargets; ENSG00000158859; -.
DR PharmGKB; PA24548; -.
DR VEuPathDB; HostDB:ENSG00000158859; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000160966; -.
DR HOGENOM; CLU_000660_3_0_1; -.
DR InParanoid; O75173; -.
DR OMA; CGPSQAC; -.
DR OrthoDB; 125522at2759; -.
DR PhylomeDB; O75173; -.
DR TreeFam; TF331949; -.
DR BioCyc; MetaCyc:ENSG00000158859-MON; -.
DR PathwayCommons; O75173; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR SignaLink; O75173; -.
DR SIGNOR; O75173; -.
DR BioGRID-ORCS; 9507; 11 hits in 1070 CRISPR screens.
DR ChiTaRS; ADAMTS4; human.
DR EvolutionaryTrace; O75173; -.
DR GeneWiki; ADAMTS4; -.
DR GenomeRNAi; 9507; -.
DR Pharos; O75173; Tchem.
DR PRO; PR:O75173; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75173; protein.
DR Bgee; ENSG00000158859; Expressed in left uterine tube and 95 other tissues.
DR ExpressionAtlas; O75173; baseline and differential.
DR Genevisible; O75173; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR Gene3D; 2.20.100.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR006586; ADAM_Cys-rich.
DR InterPro; IPR013273; ADAMTS/ADAMTS-like.
DR InterPro; IPR041645; ADAMTS_CR_2.
DR InterPro; IPR045371; ADAMTS_CR_3.
DR InterPro; IPR010294; ADAMTS_spacer1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF17771; ADAM_CR_2; 1.
DR Pfam; PF19236; ADAM_CR_3; 1.
DR Pfam; PF05986; ADAM_spacer1; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR Pfam; PF00090; TSP_1; 1.
DR PRINTS; PR01857; ADAMTSFAMILY.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50092; TSP1; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..51
FT /evidence="ECO:0000255"
FT PROPEP 52..212
FT /id="PRO_0000029164"
FT CHAIN 213..837
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 4"
FT /id="PRO_0000029165"
FT DOMAIN 218..428
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 437..519
FT /note="Disintegrin"
FT DOMAIN 520..575
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 686..837
FT /note="Spacer"
FT MOTIF 192..199
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 362
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:18042673"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 361
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18042673"
FT BINDING 365
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18042673"
FT BINDING 371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18042673"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 293..345
FT /evidence="ECO:0000269|PubMed:18042673"
FT DISULFID 322..327
FT /evidence="ECO:0000269|PubMed:18042673"
FT DISULFID 339..423
FT /evidence="ECO:0000269|PubMed:18042673"
FT DISULFID 377..407
FT /evidence="ECO:0000269|PubMed:18042673"
FT DISULFID 449..472
FT /evidence="ECO:0000269|PubMed:18042673"
FT DISULFID 460..482
FT /evidence="ECO:0000269|PubMed:18042673"
FT DISULFID 467..501
FT /evidence="ECO:0000269|PubMed:18042673"
FT DISULFID 495..506
FT /evidence="ECO:0000269|PubMed:18042673"
FT DISULFID 532..569
FT /evidence="ECO:0000250"
FT DISULFID 536..574
FT /evidence="ECO:0000250"
FT DISULFID 547..559
FT /evidence="ECO:0000250"
FT VAR_SEQ 697..837
FT /note="YGYNNVVTIPAGATHILVRQQGNPGHRSIYLALKLPDGSYALNGEYTLMPSP
FT TDVVLPGAVSLRYSGATAASETLSGHGPLAQPLTLQVLVAGNPQDTRLRYSFFVPRPTP
FT STPRPTPQDWLHRRAQILEILRRRPWAGRK -> CGTAWGSQLALQRGHCSLRDTVRPW
FT ATGPAFDTASPSGWQPPGHTPPIQLLRAPADPFNATPHSPGLAAPKSTDSGDPSAAPLG
FT GQEITSLSRLPFLGTGASDLAGRKRELLLLPHAKTQWGGAVGVRPAPPLCPNAQAGPAL
FT VSCPGRQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16723216"
FT /id="VSP_057293"
FT VARIANT 4
FT /note="T -> I (in dbSNP:rs17855814)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030636"
FT VARIANT 77
FT /note="A -> T (in dbSNP:rs34448954)"
FT /evidence="ECO:0000269|PubMed:9734811"
FT /id="VAR_057073"
FT VARIANT 304
FT /note="D -> N (in dbSNP:rs17855813)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030637"
FT VARIANT 369
FT /note="M -> V (in dbSNP:rs17855812)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030638"
FT VARIANT 552
FT /note="P -> T (in dbSNP:rs17855815)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030639"
FT VARIANT 564
FT /note="T -> A (in dbSNP:rs17855816)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030640"
FT VARIANT 626
FT /note="Q -> R (in dbSNP:rs4233367)"
FT /evidence="ECO:0000269|PubMed:10356395,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9734811"
FT /id="VAR_022450"
FT VARIANT 836
FT /note="R -> K (in dbSNP:rs11807350)"
FT /id="VAR_030641"
FT CONFLICT 306
FT /note="D -> G (in Ref. 5; AAQ89245)"
FT /evidence="ECO:0000305"
FT CONFLICT 682
FT /note="G -> R (in Ref. 3; AAL02262)"
FT /evidence="ECO:0000305"
FT STRAND 219..226
FT /evidence="ECO:0007829|PDB:4WK7"
FT HELIX 228..234
FT /evidence="ECO:0007829|PDB:4WK7"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:4WK7"
FT HELIX 238..254
FT /evidence="ECO:0007829|PDB:4WK7"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:4WK7"
FT STRAND 263..271
FT /evidence="ECO:0007829|PDB:4WK7"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:3B2Z"
FT HELIX 285..297
FT /evidence="ECO:0007829|PDB:4WK7"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:2RJP"
FT STRAND 311..317
FT /evidence="ECO:0007829|PDB:4WK7"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:3B2Z"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:4WK7"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:4WK7"
FT STRAND 345..349
FT /evidence="ECO:0007829|PDB:4WK7"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:4WK7"
FT HELIX 355..366
FT /evidence="ECO:0007829|PDB:4WK7"
FT HELIX 375..381
FT /evidence="ECO:0007829|PDB:4WK7"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:4WK7"
FT HELIX 406..417
FT /evidence="ECO:0007829|PDB:4WK7"
FT TURN 418..423
FT /evidence="ECO:0007829|PDB:4WK7"
FT HELIX 439..442
FT /evidence="ECO:0007829|PDB:2RJP"
FT HELIX 445..453
FT /evidence="ECO:0007829|PDB:2RJP"
FT STRAND 463..465
FT /evidence="ECO:0007829|PDB:3B2Z"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:3B2Z"
FT STRAND 472..476
FT /evidence="ECO:0007829|PDB:2RJP"
FT STRAND 479..483
FT /evidence="ECO:0007829|PDB:2RJP"
FT STRAND 494..496
FT /evidence="ECO:0007829|PDB:2RJP"
FT STRAND 499..502
FT /evidence="ECO:0007829|PDB:2RJP"
FT STRAND 505..507
FT /evidence="ECO:0007829|PDB:2RJP"
SQ SEQUENCE 837 AA; 90197 MW; 0C05299D7FB23A8D CRC64;
MSQTGSHPGR GLAGRWLWGA QPCLLLPIVP LSWLVWLLLL LLASLLPSAR LASPLPREEE
IVFPEKLNGS VLPGSGAPAR LLCRLQAFGE TLLLELEQDS GVQVEGLTVQ YLGQAPELLG
GAEPGTYLTG TINGDPESVA SLHWDGGALL GVLQYRGAEL HLQPLEGGTP NSAGGPGAHI
LRRKSPASGQ GPMCNVKAPL GSPSPRPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR
YLLTVMAAAA KAFKHPSIRN PVSLVVTRLV ILGSGEEGPQ VGPSAAQTLR SFCAWQRGLN
TPEDSDPDHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED DGLQSAFTAA
HELGHVFNML HDNSKPCISL NGPLSTSRHV MAPVMAHVDP EEPWSPCSAR FITDFLDNGY
GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA
MCQTKHSPWA DGTPCGPAQA CMGGRCLHMD QLQDFNIPQA GGWGPWGPWG DCSRTCGGGV
QFSSRDCTRP VPRNGGKYCE GRRTRFRSCN TEDCPTGSAL TFREEQCAAY NHRTDLFKSF
PGPMDWVPRY TGVAPQDQCK LTCQAQALGY YYVLEPRVVD GTPCSPDSSS VCVQGRCIHA
GCDRIIGSKK KFDKCMVCGG DGSGCSKQSG SFRKFRYGYN NVVTIPAGAT HILVRQQGNP
GHRSIYLALK LPDGSYALNG EYTLMPSPTD VVLPGAVSLR YSGATAASET LSGHGPLAQP
LTLQVLVAGN PQDTRLRYSF FVPRPTPSTP RPTPQDWLHR RAQILEILRR RPWAGRK
