GenomeNet

Database: UniProt
Entry: ATS4_HUMAN
LinkDB: ATS4_HUMAN
Original site: 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   08-MAY-2019, entry version 193.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Trzaskos J.M., Arner E.C.;
RT   "Purification and cloning of aggrecanase-1: a member of the ADAMTS
RT   family of proteins.";
RL   Science 284:1664-1666(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 651-837 (ISOFORM 2), AND TISSUE
RP   SPECIFICITY (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
RT   synovium 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
RP   THR-77 AND 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.
RT   The complete sequences of 100 new cDNA clones from brain which can
RT   code for large proteins in vitro.";
RL   DNA Res. 5:169-176(1998).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP   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.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics 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.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   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.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   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.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   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
RP   ILE-4; 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
RT   project: 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.,
RA   Burn T.C., 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
RT   protein in human synovium and cleaves aggrecan at the interglobular
RT   domain.";
RL   Arthritis Rheum. 65:2866-2875(2013).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 213-520 ALONE AND IN COMPLEX
RP   WITH INHIBITOR, ACTIVE SITE, COFACTOR, ZINC-BINDING SITES, AND
RP   DISULFIDE BONDS.
RX   PubMed=18042673; DOI=10.1110/ps.073287008;
RA   Mosyak L., Georgiadis K., Shane T., Svenson K., Hebert T.,
RA   McDonagh T., Mackie S., Olland S., Lin L., Zhong X., Kriz R.,
RA   Reifenberg E.L., Collins-Racie L.A., Corcoran C., Freeman B.,
RA   Zollner R., Marvell T., Vera M., Sum P.E., Lavallie E.R., Stahl M.,
RA   Somers W.;
RT   "Crystal structures of the two major aggrecan degrading enzymes,
RT   ADAMTS4 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
CC       destruction of aggrecan in arthritic diseases. Could also be a
CC       critical factor in the exacerbation of neurodegeneration in
CC       Alzheimer disease. Cleaves aggrecan at the '392-Glu-|-Ala-393'
CC       site.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Glutamyl endopeptidase. Bonds cleaved include 370-Thr-
CC         Glu-Gly-Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of
CC         mammalian 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         Note=Functional aggrecanase. {ECO:0000269|PubMed:23897278};
CC   -!- TISSUE SPECIFICITY: Expressed in brain, lung and heart
CC       (PubMed:23897278). Expressed at very low level in placenta and
CC       skeletal muscles (PubMed:23897278). Isoform 2: Detected in
CC       osteoarthritic 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
CC       for a tight interaction with the extracellular matrix.
CC   -!- DOMAIN: The conserved cysteine present in the cysteine-switch
CC       motif binds the catalytic zinc ion, thus inhibiting the enzyme.
CC       The dissociation of the cysteine from the zinc ion upon the
CC       activation-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)-
CC       (S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are
CC       the first and second cysteine residue of the repeat, respectively.
CC       Fucosylated repeats can then be further glycosylated by the
CC       addition of a beta-1,3-glucose residue by the glucosyltransferase,
CC       B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS
CC       family members. Also can be C-glycosylated with one or two mannose
CC       molecules on tryptophan residues within the consensus sequence W-
CC       X-X-W of the TPRs, and N-glycosylated. These other glycosylations
CC       can also facilitate secretion (By similarity). {ECO:0000250}.
CC   -!- CAUTION: Has sometimes been referred to as ADAMTS2. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=ABC88384.1; Type=Frameshift; Positions=697; Evidence={ECO:0000305};
CC       Sequence=BAA31663.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
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   SMR; O75173; -.
DR   BioGrid; 114885; 29.
DR   IntAct; O75173; 2.
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   iPTMnet; O75173; -.
DR   PhosphoSitePlus; O75173; -.
DR   BioMuta; ADAMTS4; -.
DR   EPD; O75173; -.
DR   jPOST; O75173; -.
DR   PaxDb; O75173; -.
DR   PeptideAtlas; O75173; -.
DR   PRIDE; O75173; -.
DR   ProteomicsDB; 49841; -.
DR   Ensembl; ENST00000367996; ENSP00000356975; ENSG00000158859. [O75173-1]
DR   GeneID; 9507; -.
DR   KEGG; hsa:9507; -.
DR   UCSC; uc001fyt.5; human. [O75173-1]
DR   CTD; 9507; -.
DR   DisGeNET; 9507; -.
DR   GeneCards; ADAMTS4; -.
DR   H-InvDB; HIX0001237; -.
DR   HGNC; HGNC:220; ADAMTS4.
DR   HPA; CAB025876; -.
DR   HPA; HPA051296; -.
DR   HPA; HPA068374; -.
DR   MIM; 603876; gene.
DR   neXtProt; NX_O75173; -.
DR   OpenTargets; ENSG00000158859; -.
DR   PharmGKB; PA24548; -.
DR   eggNOG; KOG3538; Eukaryota.
DR   eggNOG; ENOG410XPKZ; LUCA.
DR   GeneTree; ENSGT00940000160966; -.
DR   HOGENOM; HOG000004799; -.
DR   InParanoid; O75173; -.
DR   KO; K07764; -.
DR   OMA; QYRGTEL; -.
DR   OrthoDB; 949920at2759; -.
DR   PhylomeDB; O75173; -.
DR   TreeFam; TF331949; -.
DR   BioCyc; MetaCyc:ENSG00000158859-MONOMER; -.
DR   Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-HSA-5083635; Defective B3GALTL causes Peters-plus syndrome (PpS).
DR   Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR   ChiTaRS; ADAMTS4; human.
DR   EvolutionaryTrace; O75173; -.
DR   GeneWiki; ADAMTS4; -.
DR   GenomeRNAi; 9507; -.
DR   PMAP-CutDB; O75173; -.
DR   PRO; PR:O75173; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000158859; Expressed in 86 organ(s), highest expression level in left coronary artery.
DR   ExpressionAtlas; O75173; baseline and differential.
DR   Genevisible; O75173; HS.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
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; IEA:InterPro.
DR   GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR   GO; GO:0008233; F:peptidase activity; TAS:ProtInc.
DR   GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR   GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
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; IPR041645; ADAM_CR_2.
DR   InterPro; IPR006586; ADAM_Cys-rich.
DR   InterPro; IPR010294; ADAM_spacer1.
DR   InterPro; IPR013273; ADAMTS/ADAMTS-like.
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; 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;
KW   Cleavage on pair of basic residues; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; Extracellular matrix;
KW   Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Polymorphism;
KW   Protease; Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL        1     51       {ECO:0000255}.
FT   PROPEP       52    212
FT                                /FTId=PRO_0000029164.
FT   CHAIN       213    837       A disintegrin and metalloproteinase with
FT                                thrombospondin motifs 4.
FT                                /FTId=PRO_0000029165.
FT   DOMAIN      218    428       Peptidase M12B. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   DOMAIN      437    519       Disintegrin.
FT   DOMAIN      520    575       TSP type-1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   REGION      686    837       Spacer.
FT   MOTIF       192    199       Cysteine switch. {ECO:0000250}.
FT   COMPBIAS    247    252       Poly-Ala.
FT   COMPBIAS    577    685       Cys-rich.
FT   ACT_SITE    362    362       {ECO:0000255|PROSITE-ProRule:PRU00276,
FT                                ECO:0000255|PROSITE-ProRule:PRU10095,
FT                                ECO:0000269|PubMed:18042673}.
FT   METAL       194    194       Zinc; in inhibited form. {ECO:0000250}.
FT   METAL       361    361       Zinc; catalytic.
FT                                {ECO:0000269|PubMed:18042673}.
FT   METAL       365    365       Zinc; catalytic.
FT                                {ECO:0000269|PubMed:18042673}.
FT   METAL       371    371       Zinc; catalytic.
FT                                {ECO:0000269|PubMed:18042673}.
FT   CARBOHYD     68     68       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    293    345       {ECO:0000269|PubMed:18042673}.
FT   DISULFID    322    327       {ECO:0000269|PubMed:18042673}.
FT   DISULFID    339    423       {ECO:0000269|PubMed:18042673}.
FT   DISULFID    377    407       {ECO:0000269|PubMed:18042673}.
FT   DISULFID    449    472       {ECO:0000269|PubMed:18042673}.
FT   DISULFID    460    482       {ECO:0000269|PubMed:18042673}.
FT   DISULFID    467    501       {ECO:0000269|PubMed:18042673}.
FT   DISULFID    495    506       {ECO:0000269|PubMed:18042673}.
FT   DISULFID    532    569       {ECO:0000250}.
FT   DISULFID    536    574       {ECO:0000250}.
FT   DISULFID    547    559       {ECO:0000250}.
FT   VAR_SEQ     697    837       YGYNNVVTIPAGATHILVRQQGNPGHRSIYLALKLPDGSYA
FT                                LNGEYTLMPSPTDVVLPGAVSLRYSGATAASETLSGHGPLA
FT                                QPLTLQVLVAGNPQDTRLRYSFFVPRPTPSTPRPTPQDWLH
FT                                RRAQILEILRRRPWAGRK -> CGTAWGSQLALQRGHCSLR
FT                                DTVRPWATGPAFDTASPSGWQPPGHTPPIQLLRAPADPFNA
FT                                TPHSPGLAAPKSTDSGDPSAAPLGGQEITSLSRLPFLGTGA
FT                                SDLAGRKRELLLLPHAKTQWGGAVGVRPAPPLCPNAQAGPA
FT                                LVSCPGRQ (in isoform 2).
FT                                {ECO:0000303|PubMed:16723216}.
FT                                /FTId=VSP_057293.
FT   VARIANT       4      4       T -> I (in dbSNP:rs17855814).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_030636.
FT   VARIANT      77     77       A -> T (in dbSNP:rs34448954).
FT                                {ECO:0000269|PubMed:9734811}.
FT                                /FTId=VAR_057073.
FT   VARIANT     304    304       D -> N (in dbSNP:rs17855813).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_030637.
FT   VARIANT     369    369       M -> V (in dbSNP:rs17855812).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_030638.
FT   VARIANT     552    552       P -> T (in dbSNP:rs17855815).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_030639.
FT   VARIANT     564    564       T -> A (in dbSNP:rs17855816).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_030640.
FT   VARIANT     626    626       Q -> R (in dbSNP:rs4233367).
FT                                {ECO:0000269|PubMed:10356395,
FT                                ECO:0000269|PubMed:12975309,
FT                                ECO:0000269|PubMed:9734811}.
FT                                /FTId=VAR_022450.
FT   VARIANT     836    836       R -> K (in dbSNP:rs11807350).
FT                                /FTId=VAR_030641.
FT   CONFLICT    306    306       D -> G (in Ref. 5; AAQ89245).
FT                                {ECO:0000305}.
FT   CONFLICT    682    682       G -> R (in Ref. 3; AAL02262).
FT                                {ECO:0000305}.
FT   STRAND      219    226       {ECO:0000244|PDB:4WK7}.
FT   HELIX       228    234       {ECO:0000244|PDB:4WK7}.
FT   HELIX       235    237       {ECO:0000244|PDB:4WK7}.
FT   HELIX       238    254       {ECO:0000244|PDB:4WK7}.
FT   HELIX       256    258       {ECO:0000244|PDB:4WK7}.
FT   STRAND      263    271       {ECO:0000244|PDB:4WK7}.
FT   STRAND      274    276       {ECO:0000244|PDB:3B2Z}.
FT   HELIX       285    297       {ECO:0000244|PDB:4WK7}.
FT   STRAND      304    306       {ECO:0000244|PDB:2RJP}.
FT   STRAND      311    317       {ECO:0000244|PDB:4WK7}.
FT   TURN        322    324       {ECO:0000244|PDB:3B2Z}.
FT   STRAND      331    333       {ECO:0000244|PDB:4WK7}.
FT   TURN        341    343       {ECO:0000244|PDB:4WK7}.
FT   STRAND      345    349       {ECO:0000244|PDB:4WK7}.
FT   STRAND      352    354       {ECO:0000244|PDB:4WK7}.
FT   HELIX       355    366       {ECO:0000244|PDB:4WK7}.
FT   HELIX       375    381       {ECO:0000244|PDB:4WK7}.
FT   STRAND      392    394       {ECO:0000244|PDB:4WK7}.
FT   HELIX       406    417       {ECO:0000244|PDB:4WK7}.
FT   TURN        418    423       {ECO:0000244|PDB:4WK7}.
FT   HELIX       439    442       {ECO:0000244|PDB:2RJP}.
FT   HELIX       445    453       {ECO:0000244|PDB:2RJP}.
FT   STRAND      463    465       {ECO:0000244|PDB:3B2Z}.
FT   TURN        466    468       {ECO:0000244|PDB:3B2Z}.
FT   STRAND      472    476       {ECO:0000244|PDB:2RJP}.
FT   STRAND      479    483       {ECO:0000244|PDB:2RJP}.
FT   STRAND      494    496       {ECO:0000244|PDB:2RJP}.
FT   STRAND      499    502       {ECO:0000244|PDB:2RJP}.
FT   STRAND      505    507       {ECO:0000244|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
//
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