LOCUS       NM_000362               4597 bp    mRNA    linear   PRI 20-AUG-2024
DEFINITION  Homo sapiens TIMP metallopeptidase inhibitor 3 (TIMP3), mRNA.
ACCESSION   NM_000362
VERSION     NM_000362.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4597)
  AUTHORS   Li,Y., Wang,X., Zhang,X., Chen,Q., Shi,X., Zhang,B., Xu,J. and
            Han,B.
  TITLE     Associations between genetically predicted TIMP-3 levels and risk
            of venous thromboembolism: A two sample Mendelian randomization
            study
  JOURNAL   J Pharm Biomed Anal 248, 116290 (2024)
   PUBMED   38878456
  REMARK    GeneRIF: Associations between genetically predicted TIMP-3 levels
            and risk of venous thromboembolism: A two sample Mendelian
            randomization study.
REFERENCE   2  (bases 1 to 4597)
  AUTHORS   Yang,Y., Huang,F., Wu,X., Huang,C. and Li,Y.
  TITLE     Demethylation of TIMP2 and TIMP3 Inhibits Cell Proliferation,
            Migration, and Invasion in Pituitary Adenomas
  JOURNAL   Discov Med 36 (184), 971-980 (2024)
   PUBMED   38798256
  REMARK    GeneRIF: Demethylation of TIMP2 and TIMP3 Inhibits Cell
            Proliferation, Migration, and Invasion in Pituitary Adenomas.
REFERENCE   3  (bases 1 to 4597)
  AUTHORS   Hung,J.H., Tsai,P.H., Aala,W.J.F., Chen,C.C., Chiou,S.H.,
            Wong,T.W., Tsai,K.J., Hsu,S.M. and Wu,L.W.
  TITLE     TIMP3/Wnt axis regulates gliosis of Muller glia
  JOURNAL   Biochim Biophys Acta Mol Basis Dis 1870 (4), 167087 (2024)
   PUBMED   38369214
  REMARK    GeneRIF: TIMP3/Wnt axis regulates gliosis of Muller glia.
REFERENCE   4  (bases 1 to 4597)
  AUTHORS   Vergaro,A., Pankievic,M., Jedlickova,J., Dudakova,L., Vajter,M.,
            Michaelides,M., Meliska,M., Nemec,P., Babincova,D., Kousal,B. and
            Liskova,P.
  TITLE     Disease-Causing TIMP3 Variants and Deep Phenotyping of Two Czech
            Families with Sorsby Fundus Dystrophy Associated with Novel
            p.(Tyr152Cys) Mutation
  JOURNAL   Int J Mol Sci 25 (7), 3744 (2024)
   PUBMED   38612555
  REMARK    GeneRIF: Disease-Causing TIMP3 Variants and Deep Phenotyping of Two
            Czech Families with Sorsby Fundus Dystrophy Associated with Novel
            p.(Tyr152Cys) Mutation.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4597)
  AUTHORS   Betts,J.H.J. and Troeberg,L.
  TITLE     Review: Mechanisms of TIMP-3 accumulation and pathogenesis in
            Sorsby fundus dystrophy
  JOURNAL   Mol Vis 30, 74-91 (2024)
   PUBMED   38601018
  REMARK    GeneRIF: Review: Mechanisms of TIMP-3 accumulation and pathogenesis
            in Sorsby fundus dystrophy.
            Review article
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4597)
  AUTHORS   Higuchi,T., Kanzaki,H., Nakayama,H., Fujimoto,M., Hatayama,H.,
            Kojima,K., Iwai,M., Mori,T. and Fujita,J.
  TITLE     Induction of tissue inhibitor of metalloproteinase 3 gene
            expression during in vitro decidualization of human endometrial
            stromal cells
  JOURNAL   Endocrinology 136 (11), 4973-4981 (1995)
   PUBMED   7588231
REFERENCE   7  (bases 1 to 4597)
  AUTHORS   Wick,M., Haronen,R., Mumberg,D., Burger,C., Olsen,B.R.,
            Budarf,M.L., Apte,S.S. and Muller,R.
  TITLE     Structure of the human TIMP-3 gene and its cell cycle-regulated
            promoter
  JOURNAL   Biochem J 311 (Pt 2) (Pt 2), 549-554 (1995)
   PUBMED   7487894
REFERENCE   8  (bases 1 to 4597)
  AUTHORS   Jacobson,S.G., Cideciyan,A.V., Regunath,G., Rodriguez,F.J.,
            Vandenburgh,K., Sheffield,V.C. and Stone,E.M.
  TITLE     Night blindness in Sorsby's fundus dystrophy reversed by vitamin A
  JOURNAL   Nat Genet 11 (1), 27-32 (1995)
   PUBMED   7550309
REFERENCE   9  (bases 1 to 4597)
  AUTHORS   Docherty,A.J., Lyons,A., Smith,B.J., Wright,E.M., Stephens,P.E.,
            Harris,T.J., Murphy,G. and Reynolds,J.J.
  TITLE     Sequence of human tissue inhibitor of metalloproteinases and its
            identity to erythroid-potentiating activity
  JOURNAL   Nature 318 (6041), 66-69 (1985)
   PUBMED   3903517
REFERENCE   10 (bases 1 to 4597)
  AUTHORS   Forsius,H.R., Eriksson,A.W., Suvanto,E.A. and Alanko,H.I.
  TITLE     Pseudoinflammatory fundus dystrophy with autosomal recessive
            inheritance
  JOURNAL   Am J Ophthalmol 94 (5), 634-649 (1982)
   PUBMED   7148944
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL023282.1, BC014277.2,
            Z98256.1 and AF035289.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Dec 23, 2019 this sequence version replaced NM_000362.4.
            
            Summary: This gene belongs to the TIMP gene family. The proteins
            encoded by this gene family are inhibitors of the matrix
            metalloproteinases, a group of peptidases involved in degradation
            of the extracellular matrix (ECM). Expression of this gene is
            induced in response to mitogenic stimulation and this netrin
            domain-containing protein is localized to the ECM. Mutations in
            this gene have been associated with the autosomal dominant disorder
            Sorsby's fundus dystrophy. [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR11853562.22363.1, U14394.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000266085.7/ ENSP00000266085.5
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-54                AL023282.1         5259-5312
            55-2549             BC014277.2         1-2495
            2550-3201           Z98256.1           14844-15495
            3202-4597           AF035289.1         53-1448
FEATURES             Location/Qualifiers
     source          1..4597
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q12.3"
     gene            1..4597
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /note="TIMP metallopeptidase inhibitor 3"
                     /db_xref="GeneID:7078"
                     /db_xref="HGNC:HGNC:11822"
                     /db_xref="MIM:188826"
     exon            1..418
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /inference="alignment:Splign:2.1.0"
     CDS             298..933
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /note="MIG-5 protein; metalloproteinase inhibitor 3;
                     protein MIG-5; tissue inhibitor of metalloproteinases 3;
                     TIMP-3"
                     /codon_start=1
                     /product="metalloproteinase inhibitor 3 precursor"
                     /protein_id="NP_000353.1"
                     /db_xref="CCDS:CCDS13911.1"
                     /db_xref="GeneID:7078"
                     /db_xref="HGNC:HGNC:11822"
                     /db_xref="MIM:188826"
                     /translation="MTPWLGLIVLLGSWSLGDWGAEACTCSPSHPQDAFCNSDIVIRA
                     KVVGKKLVKEGPFGTLVYTIKQMKMYRGFTKMPHVQYIHTEASESLCGLKLEVNKYQY
                     LLTGRVYDGKMYTGLCNFVERWDQLTLSQRKGLNYRYHLGCNCKIKSCYYLPCFVTSK
                     NECLWTDMLSNFGYPGYQSKHYACIRQKGGYCSWYRGWAPPDKSIINATDP"
     exon            419..501
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /inference="alignment:Splign:2.1.0"
     exon            502..613
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /inference="alignment:Splign:2.1.0"
     exon            614..735
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /inference="alignment:Splign:2.1.0"
     exon            736..4597
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2105..2110
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /note="hexamer: ATTAAA"
     polyA_site      2125
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /note="major polyA site"
     regulatory      4572..4577
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /note="hexamer: AGTAAA"
     polyA_site      4597
                     /gene="TIMP3"
                     /gene_synonym="HSMRK222; K222; K222TA2; SFD"
                     /note="major polyA site"
ORIGIN      
        1 agagcgggca gcaggcaggc ggcgggcgct cagacggctt ctcctcctcc tcttgctcct
       61 ccagctcctg ctccttcgcc gggaggccgc ccgccgagtc ctgcgccagc gccgaggcag
      121 cctcgctgcg ccccatcccg tcccgccggg cactcggagg gcagcgcgcc ggaggccaag
      181 gttgccccgc acggcccggc gggcgagcga gctcgggctg cagcagcccc gccggcggcg
      241 cgcacggcaa ctttggagag gcgagcagca gccccggcag cggcggcagc agcggcaatg
      301 accccttggc tcgggctcat cgtgctcctg ggcagctgga gcctggggga ctggggcgcc
      361 gaggcgtgca catgctcgcc cagccacccc caggacgcct tctgcaactc cgacatcgtg
      421 atccgggcca aggtggtggg gaagaagctg gtaaaggagg ggcccttcgg cacgctggtc
      481 tacaccatca agcagatgaa gatgtaccga ggcttcacca agatgcccca tgtgcagtac
      541 atccatacgg aagcttccga gagtctctgt ggccttaagc tggaggtcaa caagtaccag
      601 tacctgctga caggtcgcgt ctatgatggc aagatgtaca cggggctgtg caacttcgtg
      661 gagaggtggg accagctcac cctctcccag cgcaaggggc tgaactatcg gtatcacctg
      721 ggttgtaact gcaagatcaa gtcctgctac tacctgcctt gctttgtgac ttccaagaac
      781 gagtgtctct ggaccgacat gctctccaat ttcggttacc ctggctacca gtccaaacac
      841 tacgcctgca tccggcagaa gggcggctac tgcagctggt accgaggatg ggcccccccg
      901 gataaaagca tcatcaatgc cacagacccc tgagcgccag accctgcccc acctcacttc
      961 cctcccttcc cgctgagctt cccttggaca ctaactcttc ccagatgatg acaatgaaat
     1021 tagtgcctgt tttcttgcaa atttagcact tggaacattt aaagaaaggt ctatgctgtc
     1081 atatggggtt tattgggaac tatcctcctg gccccaccct gccccttctt tttggttttg
     1141 acatcattca tttccacctg ggaatttctg gtgccatgcc agaaagaatg aggaacctgt
     1201 attcctcttc ttcgtgataa tataatctct atttttttag gaaaacaaaa atgaaaaact
     1261 actccatttg aggattgtaa ttcccacccc tcttgcttct tccccacctc accatctccc
     1321 agaccctctt ccctttgccc ttctcctcca atacataaag gacacagaca aggaacttgc
     1381 tgaaaggcca accatttcag gatcagtcaa aggcagcaag cagatagact caaggtgtgt
     1441 gaaagatgtt atacaccagg agctgccact gcatgtccca accagactgt gtctgtctgt
     1501 gtctgcatgt aagagtgagg gagggaagga aggaactaca agagagtcgg agatgatgca
     1561 gcacacacac aattccccag cccagtgatg cttgtgttga ccagatgttc ctgagtctgg
     1621 agcaagcacc caggccagaa taacagagct ttcttagttg gtgaagactt aaacatctgc
     1681 ctgaggtcag gaggcaattt gcctgccttg tacaaaagct caggtgaaag actgagatga
     1741 atgtctttcc tctccctgcc tcccaccaga cttcctcctg gaaaacgctt tggtagattt
     1801 ggccaggagc tttcttttat gtaaattgga taaatacaca caccatacac tatccacaga
     1861 tatagccaag tagatttggg tagaggatac tatttccaga atagtgttta gctcacctag
     1921 ggggatatgt ttgtatacac atttgcatat acccacatgg ggacataagc taattttttt
     1981 acaggacaca gaattctgtt caatgctgtt aaatatgcca atagtttaat ctcttctatt
     2041 ttgttgtcgt tgcttgtttg aagaaaatca tgacattcca agttgacatt tttttttcat
     2101 tttaattaaa atttgaaatt ctgaacaccg tcagcaccct ctcttcccta tcatgggtca
     2161 tctgacccct gtccgtctcc ttgtccctgc ttcatgtttg ggggcctttc tttaactgcc
     2221 ttcctggctt agctcagatg gcagatgaga gtgtagtcaa gggcctgggc acaggaggga
     2281 gagctgcaga gtgtcctgcc tgccttggct ggagggacac ctctcctggg tgtggagaca
     2341 gcttggttcc ctttccctag ctccctggtg ggtgaatgcc acctcctgag atcctcacct
     2401 cttggaatta aaattgttgg tcactgggga aagcctgagt ttgcaaccag ttgtagggtt
     2461 tctgttgtgt tttttttttt ttttttgaaa taaaactata atataaattc tcctattaaa
     2521 taaaattatt ttaagtttta gtgtcaaaag tgagatgctg agagtaggtg ataatgtata
     2581 ttttacagag tgggggttgg caggatggtg acattgaaca tgattgctct ctgtctcttt
     2641 tttcagctta tgggtattta tcttctatta gtatttgtat cttcagttca ttccacttta
     2701 ggaaacagag ctgccaattg aaacagaaga agaaaaaaaa aaaaagcagc agacaacaca
     2761 ctgtagagtc ttgcacacac acaagtgccc aggcaaggtg cttggcagaa ccgcagagtg
     2821 ggaagagagt accggcatcg ggtttccttg ggatcaattt cattaccgtg tacctttccc
     2881 attgtggtca tgccatttgg cagggggaga atgggaggct tggccttctt tgtgaggcag
     2941 tgtgagcaga agctgatgcc agcatgtcac tggttttgaa gggatgagcc cagacttgat
     3001 gttttgggat tgtccttatt ttaacctcaa ggtctcgcat ggtggggccc ctgaccaacc
     3061 tacacaagtt ccctcccaca agtggacatc agtgtcttct ctgtgaggca tctggccatt
     3121 cgcactccct ggtgtggtca gcctctctca cacaaggagg aacttgggtg aaggctgagt
     3181 gtgaggcacc tgaagtttcc ctgcggagtc gataaattag cagaaccaca tccccatctg
     3241 ttaggccttg gtgaggaggc cctgggcaaa gaagggtctt tcgcaaagcg atgtcagagg
     3301 gcggttttga gctttctata agctatagct ttgtttattt cacccgttca cttactgtat
     3361 aatttaaaat catttatgta gctgagacac ttctgtattt caatcatatc atgaacattt
     3421 tattttgcta aatcttgtgt catgtgtagg ctgtaatatg tgtacattgt gtttaagaga
     3481 aaaatgaaac ccacatgccg ccattttcct gaatcaaatt ctgcagtgga atggagagga
     3541 aaatacttct aggcaagcag ctagactggt gaattggggg aaatagaagg aactagtaac
     3601 tgagactcct ccagcctcct ccctattgga atcccaatgg ctcctggagt aggaaaaaag
     3661 tttaaactac attcatgttc ttgttctgtg tcactcggcc ctgggtagtc taccatttac
     3721 ttcaccccaa gtcctgctgc ccatccagtt gggaagccat gattttccta agaatccagg
     3781 gccatgggag atacaattcc aagttctcgc ttcctccttt gggcatctct tctgcctccc
     3841 aatcaaggaa gctccatgct caggctctca gctctcgggc cagtgctctg ctctgtccag
     3901 ggtaggtaat actgggagac tcctgtcttt taccctcccc tcgttccaga cctgcctcat
     3961 ggtggcaaca tggttcttga acaattaaag aaacaaatga ctttttggaa tagccctgtc
     4021 tagggcaaac tgtggccccc aggagacact acccttccat gccccagacc tctgtcttgc
     4081 atgtgacaat tgacaatctg gactacccca agatggcacc caagtgtttg gcttctggct
     4141 acctaaggtt aacatgtcac tagagtattt ttatgagaga caaacattat aaaaatctga
     4201 tggcaaaagc aaaacaaaat ggaaagtagg ggaggtggat gtgacaacaa cttccaaatt
     4261 ggctctttgg aggcgagagg aaggggagaa cttggagaat agtttttgct ttgggggtag
     4321 aggcttctta gattctccca gcatccgcct ttccctttag ccagtctgct gtcctgaaac
     4381 ccagaagtga tggagagaaa ccaacaagag atctcgaacc ctgtctagaa ggaatgtatt
     4441 tgttgctaaa tttcgtagca ctgtttacag ttttcctcca tgttatttat gaattttata
     4501 ttccgtgaat gtatattgtc ttgtaatgtt gcataatgtt cactttttat agtgtgtcct
     4561 ttattctaaa cagtaaagtg gttttatttc tatcaca
//
