TINAG_HUMAN
ID TINAG_HUMAN Reviewed; 476 AA.
AC Q9UJW2; Q5T467; Q9UJW1; Q9ULZ4;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Tubulointerstitial nephritis antigen;
DE Short=TIN-Ag;
GN Name=TINAG;
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 {ECO:0000312|EMBL:AAF08931.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP PRO-158.
RC TISSUE=Kidney {ECO:0000269|PubMed:10652240};
RX PubMed=10652240; DOI=10.1006/bbrc.2000.2103;
RA Ikeda M., Takemura T., Hino S., Yoshioka K.;
RT "Molecular cloning, expression, and chromosomal localization of a human
RT tubulointerstitial nephritis antigen.";
RL Biochem. Biophys. Res. Commun. 268:225-230(2000).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND VARIANT PRO-158.
RC TISSUE=Kidney {ECO:0000269|PubMed:10752525};
RX PubMed=10752525; DOI=10.1681/asn.v114658;
RA Zhou B., Nelson T.R., Kashtan C., Gleason B., Michael A.F., Vlassi M.,
RA Charonis A.S.;
RT "Identification of two alternatively spliced forms of human
RT tubulointerstitial nephritis antigen (TIN-Ag).";
RL J. Am. Soc. Nephrol. 11:658-668(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305}
RP IDENTIFICATION, AND INVOLVEMENT IN TUBULOINTERSTITIAL NEPHRITIS.
RC TISSUE=Kidney {ECO:0000269|PubMed:3553704};
RX PubMed=3553704; DOI=10.1038/ki.1987.69;
RA Fliger F.D., Wieslander J., Brentjens J.R., Andres G.A., Butkowski R.J.;
RT "Identification of a target antigen in human anti-tubular basement membrane
RT nephritis.";
RL Kidney Int. 31:800-807(1987).
RN [7] {ECO:0000305}
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=1762287; DOI=10.1038/ki.1991.283;
RA Butkowski R.J., Kleppel M.M., Katz A., Michael A.F., Fish A.J.;
RT "Distribution of tubulointerstitial nephritis antigen and evidence for
RT multiple forms.";
RL Kidney Int. 40:838-846(1991).
RN [8] {ECO:0000305}
RP DISEASE.
RX PubMed=1466368; DOI=10.1016/0002-9343(92)90205-p;
RA Katz A., Fish A.J., Santamaria P., Nevins T.E., Kim Y., Butkowski R.J.;
RT "Role of antibodies to tubulointerstitial nephritis antigen in human anti-
RT tubular basement membrane nephritis associated with membranous
RT nephropathy.";
RL Am. J. Med. 93:691-698(1992).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=8770961; DOI=10.1038/ki.1996.20;
RA Chen Y., Krishnamurti U., Wayner E.A., Michael A.F., Charonis A.S.;
RT "Receptors in proximal tubular epithelial cells for tubulointerstitial
RT nephritis antigen.";
RL Kidney Int. 49:153-157(1996).
RN [10] {ECO:0000305}
RP DEVELOPMENTAL STAGE.
RX PubMed=9643646; DOI=10.3109/03008209809028899;
RA Nelson T.R., Kim Y., Michael A.F., Butkowski R.J., Charonis A.S.;
RT "Tubulointerstitial nephritis antigen (TIN-ag) is expressed in distinct
RT segments of the developing human nephron.";
RL Connect. Tissue Res. 37:53-60(1998).
CC -!- FUNCTION: Mediates adhesion of proximal tubule epithelial cells via
CC integrins alpha3-beta1 and alphaV-beta3. This is a non catalytic
CC peptidase C1 family protein. {ECO:0000269|PubMed:8770961}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000269|PubMed:10752525,
CC ECO:0000269|PubMed:1762287}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=TIN1 {ECO:0000269|PubMed:10752525};
CC IsoId=Q9UJW2-1; Sequence=Displayed;
CC Name=2; Synonyms=TIN2 {ECO:0000269|PubMed:10752525};
CC IsoId=Q9UJW2-2; Sequence=VSP_050567, VSP_050568;
CC -!- TISSUE SPECIFICITY: Expressed in the kidney cortex, small intestine and
CC cornea. {ECO:0000269|PubMed:10652240, ECO:0000269|PubMed:10752525,
CC ECO:0000269|PubMed:1762287}.
CC -!- DEVELOPMENTAL STAGE: Initially observed in the Bowman capsule during
CC early glomerular capillary loop formation in the kidney. In more
CC developmentally mature glomeruli, following transition from early to
CC mid-capillary loop stage, expression is higher in the proximal tubular
CC basement membrane than in the distal basement membrane and Bowman
CC capsule. {ECO:0000269|PubMed:9643646}.
CC -!- PTM: It has been suggested that the active SMB domain may be permitted
CC considerable disulfide bond heterogeneity or variability, thus 2
CC alternate disulfide patterns based on 3D structures are described with
CC 1 disulfide bond conserved in both.
CC -!- MISCELLANEOUS: Antibodies against TINAG are found in sera of patients
CC with tubulointerstitial nephritis, a rare autoimmune disorder that
CC causes acute and chronic renal injury.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10090}.
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DR EMBL; AB022277; BAA84949.1; -; mRNA.
DR EMBL; AF195116; AAF08931.1; -; mRNA.
DR EMBL; AF195117; AAF08932.1; -; mRNA.
DR EMBL; AK312918; BAG35763.1; -; mRNA.
DR EMBL; AL359380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL589946; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04437.1; -; Genomic_DNA.
DR CCDS; CCDS4955.1; -. [Q9UJW2-1]
DR PIR; JC7189; JC7189.
DR RefSeq; NP_055279.3; NM_014464.3. [Q9UJW2-1]
DR AlphaFoldDB; Q9UJW2; -.
DR SMR; Q9UJW2; -.
DR BioGRID; 118107; 75.
DR IntAct; Q9UJW2; 24.
DR STRING; 9606.ENSP00000259782; -.
DR MEROPS; C01.973; -.
DR GlyGen; Q9UJW2; 6 sites, 2 O-linked glycans (1 site).
DR iPTMnet; Q9UJW2; -.
DR PhosphoSitePlus; Q9UJW2; -.
DR BioMuta; TINAG; -.
DR DMDM; 317373501; -.
DR EPD; Q9UJW2; -.
DR jPOST; Q9UJW2; -.
DR MassIVE; Q9UJW2; -.
DR PaxDb; Q9UJW2; -.
DR PeptideAtlas; Q9UJW2; -.
DR PRIDE; Q9UJW2; -.
DR ProteomicsDB; 84670; -. [Q9UJW2-1]
DR ProteomicsDB; 84671; -. [Q9UJW2-2]
DR ABCD; Q9UJW2; 4 sequenced antibodies.
DR Antibodypedia; 31018; 75 antibodies from 20 providers.
DR DNASU; 27283; -.
DR Ensembl; ENST00000259782.9; ENSP00000259782.4; ENSG00000137251.16. [Q9UJW2-1]
DR GeneID; 27283; -.
DR KEGG; hsa:27283; -.
DR MANE-Select; ENST00000259782.9; ENSP00000259782.4; NM_014464.4; NP_055279.3.
DR UCSC; uc003pcj.3; human. [Q9UJW2-1]
DR CTD; 27283; -.
DR DisGeNET; 27283; -.
DR GeneCards; TINAG; -.
DR HGNC; HGNC:14599; TINAG.
DR HPA; ENSG00000137251; Tissue enriched (kidney).
DR MIM; 606749; gene.
DR neXtProt; NX_Q9UJW2; -.
DR OpenTargets; ENSG00000137251; -.
DR PharmGKB; PA37905; -.
DR VEuPathDB; HostDB:ENSG00000137251; -.
DR eggNOG; KOG1544; Eukaryota.
DR GeneTree; ENSGT00940000161065; -.
DR HOGENOM; CLU_012184_3_2_1; -.
DR InParanoid; Q9UJW2; -.
DR OMA; HTNGPCP; -.
DR PhylomeDB; Q9UJW2; -.
DR TreeFam; TF313765; -.
DR PathwayCommons; Q9UJW2; -.
DR SignaLink; Q9UJW2; -.
DR BioGRID-ORCS; 27283; 16 hits in 1068 CRISPR screens.
DR GeneWiki; TINAG; -.
DR GenomeRNAi; 27283; -.
DR Pharos; Q9UJW2; Tbio.
DR PRO; PR:Q9UJW2; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9UJW2; protein.
DR Bgee; ENSG00000137251; Expressed in kidney epithelium and 52 other tissues.
DR ExpressionAtlas; Q9UJW2; baseline and differential.
DR Genevisible; Q9UJW2; HS.
DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0000166; F:nucleotide binding; TAS:ProtInc.
DR GO; GO:0007155; P:cell adhesion; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR001212; Somatomedin_B_dom.
DR InterPro; IPR033164; TINAG.
DR PANTHER; PTHR12411:SF274; PTHR12411:SF274; 1.
DR Pfam; PF00112; Peptidase_C1; 1.
DR Pfam; PF01033; Somatomedin_B; 1.
DR SMART; SM00645; Pept_C1; 1.
DR SMART; SM00201; SO; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00524; SMB_1; 1.
DR PROSITE; PS50958; SMB_2; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Basement membrane; Cell adhesion; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Reference proteome; Secreted.
FT CHAIN 1..476
FT /note="Tubulointerstitial nephritis antigen"
FT /id="PRO_0000050600"
FT DOMAIN 59..107
FT /note="SMB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT SITE 49..50
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000255"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 63..70
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 70..102
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 81..95
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 81..83
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 87..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 95..102
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT VAR_SEQ 119..169
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10752525"
FT /id="VSP_050567"
FT VAR_SEQ 209..300
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10752525"
FT /id="VSP_050568"
FT VARIANT 3
FT /note="T -> A (in dbSNP:rs16885197)"
FT /id="VAR_047091"
FT VARIANT 22
FT /note="Q -> R (in dbSNP:rs2297980)"
FT /id="VAR_047092"
FT VARIANT 158
FT /note="S -> P (in dbSNP:rs1058768)"
FT /evidence="ECO:0000269|PubMed:10652240,
FT ECO:0000269|PubMed:10752525"
FT /id="VAR_047093"
FT VARIANT 413
FT /note="V -> I (in dbSNP:rs34011963)"
FT /id="VAR_047094"
FT VARIANT 433
FT /note="I -> L (in dbSNP:rs3736352)"
FT /id="VAR_047095"
FT CONFLICT 7..8
FT /note="IL -> FS (in Ref. 2; AAF08931/AAF08932)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="N -> I (in Ref. 2; AAF08932)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="P -> L (in Ref. 1; BAA84949)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="H -> D (in Ref. 2; AAF08931/AAF08932)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="R -> H (in Ref. 1; BAA84949)"
FT /evidence="ECO:0000305"
FT CONFLICT 421
FT /note="L -> R (in Ref. 2; AAF08932)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="S -> F (in Ref. 2; AAF08931/AAF08932)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="I -> V (in Ref. 2; AAF08931/AAF08932)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 476 AA; 54605 MW; 6D90C734DAC3A5AE CRC64;
MWTGYKILIF SYLTTEIWME KQYLSQREVD LEAYFTRNHT VLQGTRFKRA IFQGQYCRNF
GCCEDRDDGC VTEFYAANAL CYCDKFCDRE NSDCCPDYKS FCREEKEWPP HTQPWYPEGC
FKDGQHYEEG SVIKENCNSC TCSGQQWKCS QHVCLVRSEL IEQVNKGDYG WTAQNYSQFW
GMTLEDGFKF RLGTLPPSPM LLSMNEMTAS LPATTDLPEF FVASYKWPGW THGPLDQKNC
AASWAFSTAS VAADRIAIQS KGRYTANLSP QNLISCCAKN RHGCNSGSID RAWWYLRKRG
LVSHACYPLF KDQNATNNGC AMASRSDGRG KRHATKPCPN NVEKSNRIYQ CSPPYRVSSN
ETEIMKEIMQ NGPVQAIMQV REDFFHYKTG IYRHVTSTNK ESEKYRKLQT HAVKLTGWGT
LRGAQGQKEK FWIAANSWGK SWGENGYFRI LRGVNESDIE KLIIAAWGQL TSSDEP
