THSD4_MOUSE
ID THSD4_MOUSE Reviewed; 1018 AA.
AC Q3UTY6; Q8BLE5;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Thrombospondin type-1 domain-containing protein 4;
DE AltName: Full=A disintegrin and metalloproteinase with thrombospondin motifs-like protein 6;
DE Short=ADAMTS-like protein 6;
DE Short=ADAMTSL-6;
DE AltName: Full=ADAMTS-like protein 4;
DE Short=ADAMTSL-4;
DE Flags: Precursor;
GN Name=Thsd4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Blood vessel, and Corpora quadrigemina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=18757743; DOI=10.1073/pnas.0803640105;
RA Manabe R., Tsutsui K., Yamada T., Kimura M., Nakano I., Shimono C.,
RA Sanzen N., Furutani Y., Fukuda T., Oguri Y., Shimamoto K., Kiyozumi D.,
RA Sato Y., Sado Y., Senoo H., Yamashina S., Fukuda S., Kawai J., Sugiura N.,
RA Kimata K., Hayashizaki Y., Sekiguchi K.;
RT "Transcriptome-based systematic identification of extracellular matrix
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12849-12854(2008).
RN [3]
RP FUNCTION, INTERACTION WITH FBN1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND ALTERNATIVE PROMOTER USAGE.
RX PubMed=19940141; DOI=10.1074/jbc.m109.076919;
RA Tsutsui K., Manabe R., Yamada T., Nakano I., Oguri Y., Keene D.R.,
RA Sengle G., Sakai L.Y., Sekiguchi K.;
RT "ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-
RT 1 and promotes fibrillin-1 fibril formation.";
RL J. Biol. Chem. 285:4870-4882(2010).
RN [4]
RP FUNCTION, INTERACTION WITH TGFB1, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=21880733; DOI=10.1074/jbc.m111.243451;
RA Saito M., Kurokawa M., Oda M., Oshima M., Tsutsui K., Kosaka K., Nakao K.,
RA Ogawa M., Manabe R., Suda N., Ganjargal G., Hada Y., Noguchi T.,
RA Teranaka T., Sekiguchi K., Yoneda T., Tsuji T.;
RT "ADAMTSL6beta protein rescues fibrillin-1 microfibril disorder in a Marfan
RT syndrome mouse model through the promotion of fibrillin-1 assembly.";
RL J. Biol. Chem. 286:38602-38613(2011).
CC -!- FUNCTION: Promotes FBN1 matrix assembly. Attenuates TGFB signaling,
CC possibly by accelerating the sequestration of large latent complexes of
CC TGFB or active TGFB by FBN1 microfibril assembly, thereby negatively
CC regulating the expression of TGFB regulatory targets, such as POSTN.
CC {ECO:0000269|PubMed:18757743, ECO:0000269|PubMed:19940141,
CC ECO:0000269|PubMed:21880733}.
CC -!- SUBUNIT: Isoform 2 interacts with FBN1. Isoform 2 may interact with
CC TGFB1. {ECO:0000269|PubMed:19940141, ECO:0000269|PubMed:21880733}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted, extracellular space,
CC extracellular matrix {ECO:0000269|PubMed:18757743,
CC ECO:0000269|PubMed:19940141}. Note=Mostly deposited into pericellular
CC fibrillar matrices (PubMed:19940141). Colocalizes with FBN1
CC (PubMed:19940141). {ECO:0000269|PubMed:19940141}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted
CC {ECO:0000269|PubMed:19940141}. Secreted, extracellular space,
CC extracellular matrix {ECO:0000269|PubMed:18757743,
CC ECO:0000269|PubMed:19940141}. Note=Mostly secreted in the extracellular
CC milieu (PubMed:19940141). In the pericellular fibrillar matrix,
CC colocalizes with FBN1 (PubMed:19940141) (PubMed:21880733).
CC {ECO:0000269|PubMed:19940141, ECO:0000269|PubMed:21880733}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=ADAMTSL6-alpha;
CC IsoId=Q3UTY6-1; Sequence=Displayed;
CC Name=2; Synonyms=ADAMTSL6-beta;
CC IsoId=Q3UTY6-2; Sequence=VSP_030042, VSP_030043;
CC -!- TISSUE SPECIFICITY: Both isoforms are expressed in the embryo from 7
CC dpc through 17. Isoform 1 is widely expressed in adult tissues. Isoform
CC 2 is detected in brain, spinal cord, eye, kidney, stomach and uterus.
CC Mainly observed in fibrillar extracellular matrices in elastic tissues
CC (at protein level). {ECO:0000269|PubMed:19940141}.
CC -!- DEVELOPMENTAL STAGE: At 16.5 dpc, detected in fibrillar structures in
CC various elastic tissues, including developing dermis, perichondria
CC surrounding cartilages and the vessel walls of aortae (at protein
CC level). At postnatal day 7 (P7), weakly expressed in the early stage
CC dental follicle, but becomes readily detectable in assembled
CC microfibril-like structures during the periodontal ligament-forming
CC stage of the dental follicle and in organized microfibrils in the adult
CC periodontal ligament (P35) (at protein level). Up-regulated in the
CC periodontal ligament during wound healing (at protein level).
CC {ECO:0000269|PubMed:18757743, ECO:0000269|PubMed:21880733}.
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DR EMBL; AK045414; BAC32352.1; -; mRNA.
DR EMBL; AK138976; BAE23844.1; -; mRNA.
DR CCDS; CCDS23256.1; -. [Q3UTY6-2]
DR CCDS; CCDS40661.1; -. [Q3UTY6-1]
DR RefSeq; NP_001035516.2; NM_001040426.3. [Q3UTY6-1]
DR RefSeq; NP_766032.1; NM_172444.4. [Q3UTY6-2]
DR RefSeq; XP_006510969.1; XM_006510906.3. [Q3UTY6-1]
DR RefSeq; XP_006510970.1; XM_006510907.3. [Q3UTY6-1]
DR AlphaFoldDB; Q3UTY6; -.
DR SMR; Q3UTY6; -.
DR STRING; 10090.ENSMUSP00000096257; -.
DR GlyConnect; 2766; 2 N-Linked glycans (1 site).
DR GlyGen; Q3UTY6; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q3UTY6; -.
DR PhosphoSitePlus; Q3UTY6; -.
DR MaxQB; Q3UTY6; -.
DR PaxDb; Q3UTY6; -.
DR PRIDE; Q3UTY6; -.
DR ProteomicsDB; 262818; -. [Q3UTY6-1]
DR ProteomicsDB; 262819; -. [Q3UTY6-2]
DR Antibodypedia; 26512; 9 antibodies from 7 providers.
DR DNASU; 207596; -.
DR Ensembl; ENSMUST00000034829; ENSMUSP00000034829; ENSMUSG00000032289. [Q3UTY6-2]
DR Ensembl; ENSMUST00000098660; ENSMUSP00000096257; ENSMUSG00000032289. [Q3UTY6-1]
DR Ensembl; ENSMUST00000171654; ENSMUSP00000131418; ENSMUSG00000032289. [Q3UTY6-1]
DR GeneID; 207596; -.
DR KEGG; mmu:207596; -.
DR UCSC; uc009pyx.2; mouse. [Q3UTY6-2]
DR UCSC; uc009pyy.2; mouse. [Q3UTY6-1]
DR CTD; 79875; -.
DR MGI; MGI:2672033; Thsd4.
DR VEuPathDB; HostDB:ENSMUSG00000032289; -.
DR eggNOG; KOG3538; Eukaryota.
DR eggNOG; KOG4597; Eukaryota.
DR GeneTree; ENSGT00940000156594; -.
DR HOGENOM; CLU_000660_6_0_1; -.
DR InParanoid; Q3UTY6; -.
DR OMA; EGIFMEP; -.
DR OrthoDB; 414258at2759; -.
DR PhylomeDB; Q3UTY6; -.
DR TreeFam; TF316874; -.
DR Reactome; R-MMU-5173214; O-glycosylation of TSR domain-containing proteins.
DR BioGRID-ORCS; 207596; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Thsd4; mouse.
DR PRO; PR:Q3UTY6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q3UTY6; protein.
DR Bgee; ENSMUSG00000032289; Expressed in ascending aorta and 149 other tissues.
DR ExpressionAtlas; Q3UTY6; baseline and differential.
DR Genevisible; Q3UTY6; MM.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0001527; C:microfibril; IDA:MGI.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0048251; P:elastic fiber assembly; IDA:MGI.
DR Gene3D; 2.20.100.10; -; 7.
DR InterPro; IPR045371; ADAMTS_CR_3.
DR InterPro; IPR010294; ADAMTS_spacer1.
DR InterPro; IPR010909; PLAC.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF19236; ADAM_CR_3; 1.
DR Pfam; PF05986; ADAM_spacer1; 1.
DR Pfam; PF08686; PLAC; 1.
DR Pfam; PF00090; TSP_1; 1.
DR SMART; SM00209; TSP1; 7.
DR SUPFAM; SSF82895; SSF82895; 7.
DR PROSITE; PS50900; PLAC; 1.
DR PROSITE; PS50092; TSP1; 6.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Extracellular matrix; Hydrolase;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1018
FT /note="Thrombospondin type-1 domain-containing protein 4"
FT /id="PRO_0000313584"
FT DOMAIN 54..307
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 676..737
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 739..792
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 793..851
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 852..911
FT /note="TSP type-1 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 912..968
FT /note="TSP type-1 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 971..1008
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 34..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 116..240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..160
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..234
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 546..577
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..592
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..360
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030042"
FT VAR_SEQ 361..384
FT /note="AEKVIDGTPCDQNGTAICVSGQCK -> MFVSYLLLTLFHTETAMLARPGGE
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030043"
FT CONFLICT 486
FT /note="R -> Q (in Ref. 1; BAE23844)"
FT /evidence="ECO:0000305"
FT CONFLICT 571
FT /note="E -> K (in Ref. 1; BAE23844)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1018 AA; 113243 MW; B066DE8A9F7EEC71 CRC64;
MVSYLTSCLS ALSTLLLLLG SQLVCPQPST EHRKVPQRMA VTEGTPEDSG SGSPGVWGSW
GPWSACSRSC SGGVMEQTRP CLPSSYRARG GSRPNGRALS ITGHVVSAVR TSVPLHRSQE
DQRALAGSNA SRQGPAVVRG SRHPQARGRE PSERRSRTRG PIGPGKYGYG KAPYILPLQT
DTTHTPQRLR RQRPSSRHSR SQEASASKQG YRPPTHQFSH SQPLYQSDSG PRSGLPPSEA
SIYQLPLTHD QSYPAASSLF HRPELSSHHG ARPHGAAQAF PQHLRSTAIS CIGAYRQYKL
CNTNACPESG RSIREVQCAS YNNKPFMGRF YEWEPFAEVK GNRKCELNCQ ATGYRFYVRQ
AEKVIDGTPC DQNGTAICVS GQCKSIGCDD FLGSDKVLDK CGVCGGDNTG CQVVSGVFKH
ALTSLGYHRV VEIPQGATKI NITEMHKSNN YLALRSRSGR SIINGNWAID RPGKYEGGGT
MFTYKRPNEV SSTAGESFLA EGPTNEILDV YMIHQQPNPG VHYEYVIMRN NAISPQVPPH
RRPGEPFNGQ LEEEDRGQED REEREKNQEK EDSQVEAPEV FTSESTQTFP VRHPERFPSH
RPDNLVPPAP QPPRRSRDHN WKQLGTTECS TTCGKGSQYP IFRCVHRNTH EEVPESYCDS
SMKPTPEEEP CNLFPCPAFW DIGEWSECSK TCGLGMQHRQ VLCRQVYANR SLTVQPYRCQ
HLEKPETTST CQLKICSEWQ IRTDWTSCSV PCGVGQRTRD VKCVSNIGDM VHDEECNMKL
RPNDIENCDM GPCAKSWFLT EWSERCSAEC GAGVRTRSVV CMTNHVSSLP LEGCGNNRPV
EATPCDNGPC TGKVEWFTGS WSQCSIECGS GTQQREVICV RKNADTFEVL DPYECSFLEK
PPSQQACHLK PCGAKWFSTE WSMCSKSCQG GFRVREVRCL SDDMTPSSLC DPQLKPEERE
SCNTQDCVPE VDENCKDKYY NCNVVVQARL CVYNYYKTAC CASCTRVANR HVGFLGSR
