Full text data of SERPINB5
SERPINB5
(PI5)
[Confidence: low (only semi-automatic identification from reviews)]
Serpin B5 (Maspin; Peptidase inhibitor 5; PI-5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serpin B5 (Maspin; Peptidase inhibitor 5; PI-5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P36952
ID SPB5_HUMAN Reviewed; 375 AA.
AC P36952; B2R6Y4; Q6N0B4; Q8WW89;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 2.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Serpin B5;
DE AltName: Full=Maspin;
DE AltName: Full=Peptidase inhibitor 5;
DE Short=PI-5;
GN Name=SERPINB5; Synonyms=PI5;
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 VARIANTS PRO-176 AND
RP LEU-187.
RC TISSUE=Mammary gland;
RX PubMed=8290962; DOI=10.1126/science.8290962;
RA Zou Z., Anisowicz A., Hendrix M.J.C., Thor A., Neveu M., Sheng S.,
RA Rafidi K., Seftor E., Sager R.;
RT "Maspin, a serpin with tumor-suppressing activity in human mammary
RT epithelial cells.";
RL Science 263:526-529(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP PRO-176.
RC TISSUE=Esophagus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP PRO-176.
RC TISSUE=Prostate;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 245-375 (ISOFORM 1), AND
RP VARIANT VAL-319.
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP PROTEIN SEQUENCE OF 341-360, AND CHARACTERIZATION.
RX PubMed=7797587; DOI=10.1074/jbc.270.26.15832;
RA Pemberton P.A., Wong D.T., Gibson H.L., Kiefer M.C., Fitzpatrick P.A.,
RA Sager R., Barr P.J.;
RT "The tumor suppressor maspin does not undergo the stressed to relaxed
RT transition or inhibit trypsin-like serine proteases. Evidence that
RT maspin is not a protease inhibitory serpin.";
RL J. Biol. Chem. 270:15832-15837(1995).
RN [7]
RP INTERACTION WITH IRF6.
RX PubMed=16049006; DOI=10.1074/jbc.M503523200;
RA Bailey C.M., Khalkhali-Ellis Z., Kondo S., Margaryan N.V.,
RA Seftor R.E.B., Wheaton W.W., Amir S., Pins M.R., Schutte B.C.,
RA Hendrix M.J.C.;
RT "Mammary serine protease inhibitor (Maspin) binds directly to
RT interferon regulatory factor 6: identification of a novel serpin
RT partnership.";
RL J. Biol. Chem. 280:34210-34217(2005).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=15760906; DOI=10.1074/jbc.M412043200;
RA Law R.H., Irving J.A., Buckle A.M., Ruzyla K., Buzza M.,
RA Bashtannyk-Puhalovich T.A., Beddoe T.C., Nguyen K., Worrall D.M.,
RA Bottomley S.P., Bird P.I., Rossjohn J., Whisstock J.C.;
RT "The high resolution crystal structure of the human tumor suppressor
RT maspin reveals a novel conformational switch in the G-helix.";
RL J. Biol. Chem. 280:22356-22364(2005).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] PRO-176, AND MASS SPECTROMETRY.
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Tumor suppressor. It blocks the growth, invasion, and
CC metastatic properties of mammary tumors. As it does not undergo
CC the S (stressed) to R (relaxed) conformational transition
CC characteristic of active serpins, it exhibits no serine protease
CC inhibitory activity.
CC -!- SUBUNIT: Interacts with IRF6.
CC -!- INTERACTION:
CC Q9Y6M0:PRSS21; NbExp=7; IntAct=EBI-2371394, EBI-7054564;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P36952-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P36952-2; Sequence=VSP_037145, VSP_037146;
CC -!- TISSUE SPECIFICITY: Normal mammary epithelial cells.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SerpinB5ID42267.html";
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DR EMBL; U04313; AAA18957.1; -; mRNA.
DR EMBL; AK312765; BAG35631.1; -; mRNA.
DR EMBL; AC036176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020713; AAH20713.1; -; mRNA.
DR EMBL; BX640597; CAE45703.1; -; mRNA.
DR PIR; A36898; A36898.
DR RefSeq; NP_002630.2; NM_002639.4.
DR UniGene; Hs.55279; -.
DR PDB; 1WZ9; X-ray; 2.10 A; A/B=1-375.
DR PDB; 1XQG; X-ray; 3.10 A; A/B=1-375.
DR PDB; 1XQJ; X-ray; 3.10 A; A=1-375.
DR PDB; 1XU8; X-ray; 2.80 A; A/B=1-375.
DR PDBsum; 1WZ9; -.
DR PDBsum; 1XQG; -.
DR PDBsum; 1XQJ; -.
DR PDBsum; 1XU8; -.
DR ProteinModelPortal; P36952; -.
DR SMR; P36952; 1-375.
DR IntAct; P36952; 3.
DR MINT; MINT-7712082; -.
DR STRING; 9606.ENSP00000372221; -.
DR MEROPS; I04.980; -.
DR PhosphoSite; P36952; -.
DR DMDM; 229462757; -.
DR PaxDb; P36952; -.
DR PRIDE; P36952; -.
DR DNASU; 5268; -.
DR Ensembl; ENST00000382771; ENSP00000372221; ENSG00000206075.
DR Ensembl; ENST00000489441; ENSP00000467158; ENSG00000206075.
DR GeneID; 5268; -.
DR KEGG; hsa:5268; -.
DR UCSC; uc002liz.4; human.
DR CTD; 5268; -.
DR GeneCards; GC18P061117; -.
DR H-InvDB; HIX0014501; -.
DR HGNC; HGNC:8949; SERPINB5.
DR HPA; CAB009570; -.
DR HPA; HPA019025; -.
DR HPA; HPA019132; -.
DR HPA; HPA020136; -.
DR MIM; 154790; gene.
DR neXtProt; NX_P36952; -.
DR PharmGKB; PA35515; -.
DR eggNOG; COG4826; -.
DR HOGENOM; HOG000238519; -.
DR HOVERGEN; HBG005957; -.
DR InParanoid; P36952; -.
DR KO; K10139; -.
DR OMA; XEFISST; -.
DR OrthoDB; EOG7327PB; -.
DR ChiTaRS; SERPINB5; human.
DR EvolutionaryTrace; P36952; -.
DR GeneWiki; Maspin; -.
DR GenomeRNAi; 5268; -.
DR NextBio; 20352; -.
DR PRO; PR:P36952; -.
DR ArrayExpress; P36952; -.
DR Bgee; P36952; -.
DR CleanEx; HS_SERPINB5; -.
DR Genevestigator; P36952; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:RefGenome.
DR GO; GO:0006928; P:cellular component movement; TAS:ProtInc.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IEA:Ensembl.
DR GO; GO:0060512; P:prostate gland morphogenesis; IEA:Ensembl.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0030162; P:regulation of proteolysis; IBA:RefGenome.
DR InterPro; IPR000240; Serpin_B9/Maspin.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR PRINTS; PR00676; MASPIN.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Glycoprotein; Polymorphism;
KW Reference proteome; Secreted.
FT CHAIN 1 375 Serpin B5.
FT /FTId=PRO_0000032486.
FT SITE 340 341 Reactive bond homolog (By similarity).
FT CARBOHYD 99 99 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 133 133 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 188 188 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 361 361 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 190 231 TDTKPVQMMNMEATFCMGNIDSINCKIIELPFQNKHLSMFI
FT L -> VCGAACSSKRSPIIDVKNDRDRVGHKSIPMRNLRAR
FT PAKCLS (in isoform 2).
FT /FTId=VSP_037145.
FT VAR_SEQ 232 375 Missing (in isoform 2).
FT /FTId=VSP_037146.
FT VARIANT 176 176 S -> P (in dbSNP:rs2289519).
FT /FTId=VAR_055223.
FT VARIANT 187 187 V -> L (in dbSNP:rs2289520).
FT /FTId=VAR_055224.
FT VARIANT 319 319 I -> V (in dbSNP:rs1455555).
FT /FTId=VAR_022115.
FT CONFLICT 66 66 V -> I (in Ref. 1; AAA18957).
FT CONFLICT 245 245 K -> Q (in Ref. 5; CAE45703).
FT HELIX 2 22
FT STRAND 28 30
FT HELIX 32 45
FT HELIX 48 57
FT HELIX 60 62
FT HELIX 66 80
FT TURN 81 83
FT STRAND 84 95
FT HELIX 96 98
FT HELIX 102 108
FT TURN 109 115
FT STRAND 116 119
FT TURN 121 123
FT HELIX 125 139
FT TURN 140 142
FT TURN 147 150
FT STRAND 159 168
FT STRAND 171 173
FT HELIX 177 179
FT STRAND 181 190
FT STRAND 192 209
FT TURN 210 213
FT STRAND 214 221
FT HELIX 222 224
FT STRAND 225 235
FT HELIX 239 249
FT HELIX 252 258
FT HELIX 261 263
FT STRAND 265 274
FT STRAND 276 282
FT HELIX 284 291
FT TURN 295 297
FT TURN 299 301
FT TURN 305 307
FT STRAND 315 326
FT TURN 337 341
FT STRAND 344 349
FT STRAND 354 360
FT TURN 361 364
FT STRAND 365 372
SQ SEQUENCE 375 AA; 42100 MW; 9F24E18505912804 CRC64;
MDALQLANSA FAVDLFKQLC EKEPLGNVLF SPICLSTSLS LAQVGAKGDT ANEIGQVLHF
ENVKDVPFGF QTVTSDVNKL SSFYSLKLIK RLYVDKSLNL STEFISSTKR PYAKELETVD
FKDKLEETKG QINNSIKDLT DGHFENILAD NSVNDQTKIL VVNAAYFVGK WMKKFSESET
KECPFRVNKT DTKPVQMMNM EATFCMGNID SINCKIIELP FQNKHLSMFI LLPKDVEDES
TGLEKIEKQL NSESLSQWTN PSTMANAKVK LSIPKFKVEK MIDPKACLEN LGLKHIFSED
TSDFSGMSET KGVALSNVIH KVCLEITEDG GDSIEVPGAR ILQHKDELNA DHPFIYIIRH
NKTRNIIFFG KFCSP
//
ID SPB5_HUMAN Reviewed; 375 AA.
AC P36952; B2R6Y4; Q6N0B4; Q8WW89;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 2.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Serpin B5;
DE AltName: Full=Maspin;
DE AltName: Full=Peptidase inhibitor 5;
DE Short=PI-5;
GN Name=SERPINB5; Synonyms=PI5;
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 VARIANTS PRO-176 AND
RP LEU-187.
RC TISSUE=Mammary gland;
RX PubMed=8290962; DOI=10.1126/science.8290962;
RA Zou Z., Anisowicz A., Hendrix M.J.C., Thor A., Neveu M., Sheng S.,
RA Rafidi K., Seftor E., Sager R.;
RT "Maspin, a serpin with tumor-suppressing activity in human mammary
RT epithelial cells.";
RL Science 263:526-529(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP PRO-176.
RC TISSUE=Esophagus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP PRO-176.
RC TISSUE=Prostate;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 245-375 (ISOFORM 1), AND
RP VARIANT VAL-319.
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP PROTEIN SEQUENCE OF 341-360, AND CHARACTERIZATION.
RX PubMed=7797587; DOI=10.1074/jbc.270.26.15832;
RA Pemberton P.A., Wong D.T., Gibson H.L., Kiefer M.C., Fitzpatrick P.A.,
RA Sager R., Barr P.J.;
RT "The tumor suppressor maspin does not undergo the stressed to relaxed
RT transition or inhibit trypsin-like serine proteases. Evidence that
RT maspin is not a protease inhibitory serpin.";
RL J. Biol. Chem. 270:15832-15837(1995).
RN [7]
RP INTERACTION WITH IRF6.
RX PubMed=16049006; DOI=10.1074/jbc.M503523200;
RA Bailey C.M., Khalkhali-Ellis Z., Kondo S., Margaryan N.V.,
RA Seftor R.E.B., Wheaton W.W., Amir S., Pins M.R., Schutte B.C.,
RA Hendrix M.J.C.;
RT "Mammary serine protease inhibitor (Maspin) binds directly to
RT interferon regulatory factor 6: identification of a novel serpin
RT partnership.";
RL J. Biol. Chem. 280:34210-34217(2005).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=15760906; DOI=10.1074/jbc.M412043200;
RA Law R.H., Irving J.A., Buckle A.M., Ruzyla K., Buzza M.,
RA Bashtannyk-Puhalovich T.A., Beddoe T.C., Nguyen K., Worrall D.M.,
RA Bottomley S.P., Bird P.I., Rossjohn J., Whisstock J.C.;
RT "The high resolution crystal structure of the human tumor suppressor
RT maspin reveals a novel conformational switch in the G-helix.";
RL J. Biol. Chem. 280:22356-22364(2005).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] PRO-176, AND MASS SPECTROMETRY.
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Tumor suppressor. It blocks the growth, invasion, and
CC metastatic properties of mammary tumors. As it does not undergo
CC the S (stressed) to R (relaxed) conformational transition
CC characteristic of active serpins, it exhibits no serine protease
CC inhibitory activity.
CC -!- SUBUNIT: Interacts with IRF6.
CC -!- INTERACTION:
CC Q9Y6M0:PRSS21; NbExp=7; IntAct=EBI-2371394, EBI-7054564;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P36952-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P36952-2; Sequence=VSP_037145, VSP_037146;
CC -!- TISSUE SPECIFICITY: Normal mammary epithelial cells.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SerpinB5ID42267.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U04313; AAA18957.1; -; mRNA.
DR EMBL; AK312765; BAG35631.1; -; mRNA.
DR EMBL; AC036176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020713; AAH20713.1; -; mRNA.
DR EMBL; BX640597; CAE45703.1; -; mRNA.
DR PIR; A36898; A36898.
DR RefSeq; NP_002630.2; NM_002639.4.
DR UniGene; Hs.55279; -.
DR PDB; 1WZ9; X-ray; 2.10 A; A/B=1-375.
DR PDB; 1XQG; X-ray; 3.10 A; A/B=1-375.
DR PDB; 1XQJ; X-ray; 3.10 A; A=1-375.
DR PDB; 1XU8; X-ray; 2.80 A; A/B=1-375.
DR PDBsum; 1WZ9; -.
DR PDBsum; 1XQG; -.
DR PDBsum; 1XQJ; -.
DR PDBsum; 1XU8; -.
DR ProteinModelPortal; P36952; -.
DR SMR; P36952; 1-375.
DR IntAct; P36952; 3.
DR MINT; MINT-7712082; -.
DR STRING; 9606.ENSP00000372221; -.
DR MEROPS; I04.980; -.
DR PhosphoSite; P36952; -.
DR DMDM; 229462757; -.
DR PaxDb; P36952; -.
DR PRIDE; P36952; -.
DR DNASU; 5268; -.
DR Ensembl; ENST00000382771; ENSP00000372221; ENSG00000206075.
DR Ensembl; ENST00000489441; ENSP00000467158; ENSG00000206075.
DR GeneID; 5268; -.
DR KEGG; hsa:5268; -.
DR UCSC; uc002liz.4; human.
DR CTD; 5268; -.
DR GeneCards; GC18P061117; -.
DR H-InvDB; HIX0014501; -.
DR HGNC; HGNC:8949; SERPINB5.
DR HPA; CAB009570; -.
DR HPA; HPA019025; -.
DR HPA; HPA019132; -.
DR HPA; HPA020136; -.
DR MIM; 154790; gene.
DR neXtProt; NX_P36952; -.
DR PharmGKB; PA35515; -.
DR eggNOG; COG4826; -.
DR HOGENOM; HOG000238519; -.
DR HOVERGEN; HBG005957; -.
DR InParanoid; P36952; -.
DR KO; K10139; -.
DR OMA; XEFISST; -.
DR OrthoDB; EOG7327PB; -.
DR ChiTaRS; SERPINB5; human.
DR EvolutionaryTrace; P36952; -.
DR GeneWiki; Maspin; -.
DR GenomeRNAi; 5268; -.
DR NextBio; 20352; -.
DR PRO; PR:P36952; -.
DR ArrayExpress; P36952; -.
DR Bgee; P36952; -.
DR CleanEx; HS_SERPINB5; -.
DR Genevestigator; P36952; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:RefGenome.
DR GO; GO:0006928; P:cellular component movement; TAS:ProtInc.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IEA:Ensembl.
DR GO; GO:0060512; P:prostate gland morphogenesis; IEA:Ensembl.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0030162; P:regulation of proteolysis; IBA:RefGenome.
DR InterPro; IPR000240; Serpin_B9/Maspin.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR PRINTS; PR00676; MASPIN.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Glycoprotein; Polymorphism;
KW Reference proteome; Secreted.
FT CHAIN 1 375 Serpin B5.
FT /FTId=PRO_0000032486.
FT SITE 340 341 Reactive bond homolog (By similarity).
FT CARBOHYD 99 99 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 133 133 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 188 188 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 361 361 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 190 231 TDTKPVQMMNMEATFCMGNIDSINCKIIELPFQNKHLSMFI
FT L -> VCGAACSSKRSPIIDVKNDRDRVGHKSIPMRNLRAR
FT PAKCLS (in isoform 2).
FT /FTId=VSP_037145.
FT VAR_SEQ 232 375 Missing (in isoform 2).
FT /FTId=VSP_037146.
FT VARIANT 176 176 S -> P (in dbSNP:rs2289519).
FT /FTId=VAR_055223.
FT VARIANT 187 187 V -> L (in dbSNP:rs2289520).
FT /FTId=VAR_055224.
FT VARIANT 319 319 I -> V (in dbSNP:rs1455555).
FT /FTId=VAR_022115.
FT CONFLICT 66 66 V -> I (in Ref. 1; AAA18957).
FT CONFLICT 245 245 K -> Q (in Ref. 5; CAE45703).
FT HELIX 2 22
FT STRAND 28 30
FT HELIX 32 45
FT HELIX 48 57
FT HELIX 60 62
FT HELIX 66 80
FT TURN 81 83
FT STRAND 84 95
FT HELIX 96 98
FT HELIX 102 108
FT TURN 109 115
FT STRAND 116 119
FT TURN 121 123
FT HELIX 125 139
FT TURN 140 142
FT TURN 147 150
FT STRAND 159 168
FT STRAND 171 173
FT HELIX 177 179
FT STRAND 181 190
FT STRAND 192 209
FT TURN 210 213
FT STRAND 214 221
FT HELIX 222 224
FT STRAND 225 235
FT HELIX 239 249
FT HELIX 252 258
FT HELIX 261 263
FT STRAND 265 274
FT STRAND 276 282
FT HELIX 284 291
FT TURN 295 297
FT TURN 299 301
FT TURN 305 307
FT STRAND 315 326
FT TURN 337 341
FT STRAND 344 349
FT STRAND 354 360
FT TURN 361 364
FT STRAND 365 372
SQ SEQUENCE 375 AA; 42100 MW; 9F24E18505912804 CRC64;
MDALQLANSA FAVDLFKQLC EKEPLGNVLF SPICLSTSLS LAQVGAKGDT ANEIGQVLHF
ENVKDVPFGF QTVTSDVNKL SSFYSLKLIK RLYVDKSLNL STEFISSTKR PYAKELETVD
FKDKLEETKG QINNSIKDLT DGHFENILAD NSVNDQTKIL VVNAAYFVGK WMKKFSESET
KECPFRVNKT DTKPVQMMNM EATFCMGNID SINCKIIELP FQNKHLSMFI LLPKDVEDES
TGLEKIEKQL NSESLSQWTN PSTMANAKVK LSIPKFKVEK MIDPKACLEN LGLKHIFSED
TSDFSGMSET KGVALSNVIH KVCLEITEDG GDSIEVPGAR ILQHKDELNA DHPFIYIIRH
NKTRNIIFFG KFCSP
//
MIM
154790
*RECORD*
*FIELD* NO
154790
*FIELD* TI
*154790 PROTEASE INHIBITOR 5; PI5
;;MASPIN;;
SERPINB5
*FIELD* TX
CLONING
Zou et al. (1994) used subtractive hybridization and the 'differential
read moredisplay' method to identify candidate tumor suppressor genes that are
defective in human breast carcinoma cells. These genes were identified
initially by searching for mRNAs whose expression is reduced or absent
in tumor cells compared with normal cells grown under similar
conditions. Zou et al. (1994) reported the characteristics of one of the
more than 30 genes so identified, a member of the serpin family of
protease inhibitors which they termed maspin. A single 3.0-kb maspin
mRNA was expressed in normal mammary epithelial cell strains, but not in
most mammary tumor cell lines examined. Southern blot analysis of
XbaI-restricted DNA from normal and tumor cells with a maspin cDNA probe
revealed no gross structural alterations of the maspin gene in the tumor
cells. This result suggested that the maspin gene is downregulated but
not mutated in cancer cells. Transfection of mammary carcinoma cells
with the maspin gene did not alter the growth properties of the cells in
vitro, but reduced their ability to induce tumors and metastasize in
nude mice and to invade through a basement membrane matrix in vitro.
Analysis of human breast cancer specimens demonstrated that loss of
maspin expression occurred most frequently in advanced cancers. These
results supported the hypothesis that maspin functions as a tumor
suppressor.
Ngamkitidechakul et al. (2001) determined that human corneal cells in
the epithelium, endothelium, and stroma express maspin. They stated that
corneal stromal cells are the first nonepithelial cells shown to
synthesize maspin. They hypothesized that maspin might function within
the cornea to regulate cell adhesion to extracellular matrix molecules
and perhaps to regulate the migration of activated fibroblasts during
corneal stromal wound healing.
MAPPING
Schneider et al. (1995) demonstrated that the maspin gene is located at
18q21.3 in a cluster of genes encoding members of the ovalbumin family
of serine proteinase inhibitors. The others are plasminogen activator
inhibitor type 2 (PAI2; 173390) and squamous cell carcinoma antigen-1
(SCCA1; 600517) and -2 (SCCA2; 600518). The 4 ovalbumin serine protease
inhibitors (Ov-serpins) reside within a 300-kb region of 18q21.3. Their
telomere-to-centromere order was PAI2--SCCA1--SCCA2--PI5. The
transcriptional orientation of SCCA1 and SCCA2 was telomere to
centromere and opposite to that of PAI2 and PI5. Schneider et al. (1995)
localized maspin to band 18q21.3 using DNA from a chromosome 18 deletion
panel of somatic cell hybrids and sublocalized the gene to the same YAC
clone that contained SCCA1 and SCCA2 by PCR and pulsed field gel
electrophoresis.
GENE FUNCTION
The nucleotide 5-methylcytosine is involved in processes crucial to
mammalian development, such as X-chromosome inactivation and gene
imprinting. In addition, cytosine methylation may be involved in the
establishment and maintenance of cell type-specific expression of
developmentally regulated genes; however, it is difficult to identify
clear examples of such genes, particularly in humans. Futscher et al.
(2002) provided evidence that cytosine methylation of the maspin gene
promoter controls, in part, normal cell type-specific SERPINB5
expression. In normal cells expressing SERPINB5, the SERPINB5 promoter
is unmethylated and the promoter region has acetylated histones and an
accessible chromatin structure. In contrast, normal cells that do not
express SERPINB5 have a completely methylated SERPINB5 promoter with
hypoacetylated histones, an inaccessible chromatin structure, and a
transcriptional repression that is relieved by inhibition of DNA
methylation. These findings indicated that cytosine methylation is
important in the establishment and maintenance of cell type-restricted
gene expression.
Bass et al. (2002) characterized eukaryotic maspin and found that it had
no protease inhibitory effect against any of the proteolytic systems
tested. It did, however, inhibit the migration of both tumor and
vascular smooth muscle cells. Bass et al. (2002) concluded that maspin
is a noninhibitory serpin and that protease inhibition does not account
for its activity as a tumor suppressor.
Maspin specifically inhibits prostate cancer-associated PLAU (191840)
and prostate cancer cell invasion and motility in vitro. Cher et al.
(2003) showed that maspin-expressing transfectant cells derived from a
prostate cancer cell line were inhibited in in vitro extracellular
matrix and collagen degradation assays. To test the effect of
tumor-associated maspin on prostate cancer-induced bone matrix
remodeling and tumor growth, Cher et al. (2003) injected
maspin-transfected prostate cancer cells into human fetal bone fragments
which were previously implanted in immunodeficient mice. These studies
showed that maspin expression decreased tumor growth, reduced
osteolysis, and decreased angiogenesis. The maspin-expressing tumors
contained significant fibrosis and collagen staining, and exhibited a
more glandular organization. These data represented evidence that maspin
inhibits prostate cancer-induced bone matrix remodeling and induces
prostate cancer glandular redifferentiation. These results support the
working hypothesis that maspin exerts its tumor suppressive role, at
least in part, by blocking the pericellular uPA system and suggest that
maspin may offer an opportunity to improve therapeutic intervention of
bone metastases.
Luo et al. (2007) examined IKK-alpha (CHUK; 600664) involvement in
prostate cancer and its progression. They demonstrated that a mutation
that prevents IKK-alpha activation slowed down prostate cancer growth
and inhibited metastatogenesis in TRAMP mice, which express SV40 T
antigen in the prostate epithelium. Decreased metastasis correlated with
elevated expression of the metastasis suppressor Maspin, the ablation of
which restored metastatic activity. IKK-alpha activation by RANK ligand
(RANKL; 602642) inhibited Maspin expression in prostate epithelial
cells, whereas repression of Maspin transcription required nuclear
translocation of active IKK-alpha. The amount of active nuclear
IKK-alpha in mouse and human prostate cancer correlated with metastatic
progression, reduced Maspin expression, and infiltration of prostate
tumors with RANKL-expressing inflammatory cells. Luo et al. (2007)
proposed that tumor-infiltrating RANKL-expressing cells leads to nuclear
IKK-alpha activation and inhibition of Maspin transcription, thereby
promoting the metastatic phenotype.
*FIELD* SA
Miyake et al. (1999)
*FIELD* RF
1. Bass, R.; Fernandez, A.-M. M.; Ellis, V.: Maspin inhibits cell
migration in the absence of protease inhibitory activity. J. Biol.
Chem. 277: 46845-46848, 2002.
2. Cher, M. L.; Biliran, H. R., Jr.; Bhagat, S.; Meng, Y.; Che, M.;
Lockett, J.; Abrams, J.; Fridman, R.; Zachareas, M.; Sheng, S.: Maspin
expression inhibits osteolysis, tumor growth, and angiogenesis in
a model of prostate cancer bone metastasis. Proc. Nat. Acad. Sci. 100:
7847-7852, 2003.
3. Futscher, B. W.; Oshiro, M. M.; Wozniak, R. J.; Holtan, N.; Hanigan,
C. L.; Duan, H.; Domann, F. E.: Role for DNA methylation in the control
of cell type-specific maspin expression. Nature Genet. 31: 175-179,
2002.
4. Luo, J.-L.; Tan, W.; Ricono, J. M.; Korchynskyi, O.; Zhang, M.;
Gonias, S. L.; Cheresh, D. A.; Karin, M.: Nuclear cytokine-activated
IKK-alpha controls prostate cancer metastasis by repressing Maspin. Nature 446:
690-694, 2007. Note: Erratum: Nature 457: 920 only, 2009.
5. Miyake, H.; Hara, I.; Yamanaka, K.; Arakawa, S.; Kamidono, S.:
Elevation of urokinase-type plasminogen activator and its receptor
densities as new predictors of disease progression and prognosis in
men with prostate cancer. Int. J. Oncol. 14: 535-541, 1999.
6. Ngamkitidechakul, C.; Burke, J. M.; O'Brien, W. J.; Twining, S.
S.: Maspin: synthesis by human cornea and regulation of in vitro
stromal cell adhesion to extracellular matrix. Invest. Ophthal. Vis.
Sci. 42: 3135-3141, 2001.
7. Schneider, S. S.; Schick, C.; Fish, K. E.; Miller, E.; Pena, J.
C.; Treter, S. D.; Hui, S. M.; Silverman, G. A.: A serine proteinase
inhibitor locus at 18q21.3 contains a tandem duplication of the human
squamous cell carcinoma antigen gene. Proc. Nat. Acad. Sci. 92:
3147-3151, 1995.
8. Zou, Z.; Anisowicz, A.; Hendrix, M. J. C.; Thor, A.; Neveu, M.;
Sheng, S.; Rafidi, K.; Seftor, E.; Sager, R.: Maspin, a serpin with
tumor-suppressing activity in human mammary epithelial cells. Science 263:
526-529, 1994.
*FIELD* CN
Ada Hamosh - updated: 4/27/2007
Victor A. McKusick - updated: 7/16/2003
Patricia A. Hartz - updated: 1/30/2003
Jane Kelly - updated: 6/21/2002
Victor A. McKusick - updated: 5/30/2002
*FIELD* CD
Victor A. McKusick: 3/3/1994
*FIELD* ED
alopez: 03/11/2009
alopez: 5/11/2007
terry: 4/27/2007
tkritzer: 7/30/2003
cwells: 7/23/2003
terry: 7/16/2003
mgross: 2/3/2003
terry: 1/30/2003
carol: 6/24/2002
terry: 6/21/2002
alopez: 6/5/2002
terry: 5/30/2002
terry: 3/13/2002
mark: 10/14/1997
mark: 5/7/1995
jason: 7/29/1994
carol: 3/3/1994
*RECORD*
*FIELD* NO
154790
*FIELD* TI
*154790 PROTEASE INHIBITOR 5; PI5
;;MASPIN;;
SERPINB5
*FIELD* TX
CLONING
Zou et al. (1994) used subtractive hybridization and the 'differential
read moredisplay' method to identify candidate tumor suppressor genes that are
defective in human breast carcinoma cells. These genes were identified
initially by searching for mRNAs whose expression is reduced or absent
in tumor cells compared with normal cells grown under similar
conditions. Zou et al. (1994) reported the characteristics of one of the
more than 30 genes so identified, a member of the serpin family of
protease inhibitors which they termed maspin. A single 3.0-kb maspin
mRNA was expressed in normal mammary epithelial cell strains, but not in
most mammary tumor cell lines examined. Southern blot analysis of
XbaI-restricted DNA from normal and tumor cells with a maspin cDNA probe
revealed no gross structural alterations of the maspin gene in the tumor
cells. This result suggested that the maspin gene is downregulated but
not mutated in cancer cells. Transfection of mammary carcinoma cells
with the maspin gene did not alter the growth properties of the cells in
vitro, but reduced their ability to induce tumors and metastasize in
nude mice and to invade through a basement membrane matrix in vitro.
Analysis of human breast cancer specimens demonstrated that loss of
maspin expression occurred most frequently in advanced cancers. These
results supported the hypothesis that maspin functions as a tumor
suppressor.
Ngamkitidechakul et al. (2001) determined that human corneal cells in
the epithelium, endothelium, and stroma express maspin. They stated that
corneal stromal cells are the first nonepithelial cells shown to
synthesize maspin. They hypothesized that maspin might function within
the cornea to regulate cell adhesion to extracellular matrix molecules
and perhaps to regulate the migration of activated fibroblasts during
corneal stromal wound healing.
MAPPING
Schneider et al. (1995) demonstrated that the maspin gene is located at
18q21.3 in a cluster of genes encoding members of the ovalbumin family
of serine proteinase inhibitors. The others are plasminogen activator
inhibitor type 2 (PAI2; 173390) and squamous cell carcinoma antigen-1
(SCCA1; 600517) and -2 (SCCA2; 600518). The 4 ovalbumin serine protease
inhibitors (Ov-serpins) reside within a 300-kb region of 18q21.3. Their
telomere-to-centromere order was PAI2--SCCA1--SCCA2--PI5. The
transcriptional orientation of SCCA1 and SCCA2 was telomere to
centromere and opposite to that of PAI2 and PI5. Schneider et al. (1995)
localized maspin to band 18q21.3 using DNA from a chromosome 18 deletion
panel of somatic cell hybrids and sublocalized the gene to the same YAC
clone that contained SCCA1 and SCCA2 by PCR and pulsed field gel
electrophoresis.
GENE FUNCTION
The nucleotide 5-methylcytosine is involved in processes crucial to
mammalian development, such as X-chromosome inactivation and gene
imprinting. In addition, cytosine methylation may be involved in the
establishment and maintenance of cell type-specific expression of
developmentally regulated genes; however, it is difficult to identify
clear examples of such genes, particularly in humans. Futscher et al.
(2002) provided evidence that cytosine methylation of the maspin gene
promoter controls, in part, normal cell type-specific SERPINB5
expression. In normal cells expressing SERPINB5, the SERPINB5 promoter
is unmethylated and the promoter region has acetylated histones and an
accessible chromatin structure. In contrast, normal cells that do not
express SERPINB5 have a completely methylated SERPINB5 promoter with
hypoacetylated histones, an inaccessible chromatin structure, and a
transcriptional repression that is relieved by inhibition of DNA
methylation. These findings indicated that cytosine methylation is
important in the establishment and maintenance of cell type-restricted
gene expression.
Bass et al. (2002) characterized eukaryotic maspin and found that it had
no protease inhibitory effect against any of the proteolytic systems
tested. It did, however, inhibit the migration of both tumor and
vascular smooth muscle cells. Bass et al. (2002) concluded that maspin
is a noninhibitory serpin and that protease inhibition does not account
for its activity as a tumor suppressor.
Maspin specifically inhibits prostate cancer-associated PLAU (191840)
and prostate cancer cell invasion and motility in vitro. Cher et al.
(2003) showed that maspin-expressing transfectant cells derived from a
prostate cancer cell line were inhibited in in vitro extracellular
matrix and collagen degradation assays. To test the effect of
tumor-associated maspin on prostate cancer-induced bone matrix
remodeling and tumor growth, Cher et al. (2003) injected
maspin-transfected prostate cancer cells into human fetal bone fragments
which were previously implanted in immunodeficient mice. These studies
showed that maspin expression decreased tumor growth, reduced
osteolysis, and decreased angiogenesis. The maspin-expressing tumors
contained significant fibrosis and collagen staining, and exhibited a
more glandular organization. These data represented evidence that maspin
inhibits prostate cancer-induced bone matrix remodeling and induces
prostate cancer glandular redifferentiation. These results support the
working hypothesis that maspin exerts its tumor suppressive role, at
least in part, by blocking the pericellular uPA system and suggest that
maspin may offer an opportunity to improve therapeutic intervention of
bone metastases.
Luo et al. (2007) examined IKK-alpha (CHUK; 600664) involvement in
prostate cancer and its progression. They demonstrated that a mutation
that prevents IKK-alpha activation slowed down prostate cancer growth
and inhibited metastatogenesis in TRAMP mice, which express SV40 T
antigen in the prostate epithelium. Decreased metastasis correlated with
elevated expression of the metastasis suppressor Maspin, the ablation of
which restored metastatic activity. IKK-alpha activation by RANK ligand
(RANKL; 602642) inhibited Maspin expression in prostate epithelial
cells, whereas repression of Maspin transcription required nuclear
translocation of active IKK-alpha. The amount of active nuclear
IKK-alpha in mouse and human prostate cancer correlated with metastatic
progression, reduced Maspin expression, and infiltration of prostate
tumors with RANKL-expressing inflammatory cells. Luo et al. (2007)
proposed that tumor-infiltrating RANKL-expressing cells leads to nuclear
IKK-alpha activation and inhibition of Maspin transcription, thereby
promoting the metastatic phenotype.
*FIELD* SA
Miyake et al. (1999)
*FIELD* RF
1. Bass, R.; Fernandez, A.-M. M.; Ellis, V.: Maspin inhibits cell
migration in the absence of protease inhibitory activity. J. Biol.
Chem. 277: 46845-46848, 2002.
2. Cher, M. L.; Biliran, H. R., Jr.; Bhagat, S.; Meng, Y.; Che, M.;
Lockett, J.; Abrams, J.; Fridman, R.; Zachareas, M.; Sheng, S.: Maspin
expression inhibits osteolysis, tumor growth, and angiogenesis in
a model of prostate cancer bone metastasis. Proc. Nat. Acad. Sci. 100:
7847-7852, 2003.
3. Futscher, B. W.; Oshiro, M. M.; Wozniak, R. J.; Holtan, N.; Hanigan,
C. L.; Duan, H.; Domann, F. E.: Role for DNA methylation in the control
of cell type-specific maspin expression. Nature Genet. 31: 175-179,
2002.
4. Luo, J.-L.; Tan, W.; Ricono, J. M.; Korchynskyi, O.; Zhang, M.;
Gonias, S. L.; Cheresh, D. A.; Karin, M.: Nuclear cytokine-activated
IKK-alpha controls prostate cancer metastasis by repressing Maspin. Nature 446:
690-694, 2007. Note: Erratum: Nature 457: 920 only, 2009.
5. Miyake, H.; Hara, I.; Yamanaka, K.; Arakawa, S.; Kamidono, S.:
Elevation of urokinase-type plasminogen activator and its receptor
densities as new predictors of disease progression and prognosis in
men with prostate cancer. Int. J. Oncol. 14: 535-541, 1999.
6. Ngamkitidechakul, C.; Burke, J. M.; O'Brien, W. J.; Twining, S.
S.: Maspin: synthesis by human cornea and regulation of in vitro
stromal cell adhesion to extracellular matrix. Invest. Ophthal. Vis.
Sci. 42: 3135-3141, 2001.
7. Schneider, S. S.; Schick, C.; Fish, K. E.; Miller, E.; Pena, J.
C.; Treter, S. D.; Hui, S. M.; Silverman, G. A.: A serine proteinase
inhibitor locus at 18q21.3 contains a tandem duplication of the human
squamous cell carcinoma antigen gene. Proc. Nat. Acad. Sci. 92:
3147-3151, 1995.
8. Zou, Z.; Anisowicz, A.; Hendrix, M. J. C.; Thor, A.; Neveu, M.;
Sheng, S.; Rafidi, K.; Seftor, E.; Sager, R.: Maspin, a serpin with
tumor-suppressing activity in human mammary epithelial cells. Science 263:
526-529, 1994.
*FIELD* CN
Ada Hamosh - updated: 4/27/2007
Victor A. McKusick - updated: 7/16/2003
Patricia A. Hartz - updated: 1/30/2003
Jane Kelly - updated: 6/21/2002
Victor A. McKusick - updated: 5/30/2002
*FIELD* CD
Victor A. McKusick: 3/3/1994
*FIELD* ED
alopez: 03/11/2009
alopez: 5/11/2007
terry: 4/27/2007
tkritzer: 7/30/2003
cwells: 7/23/2003
terry: 7/16/2003
mgross: 2/3/2003
terry: 1/30/2003
carol: 6/24/2002
terry: 6/21/2002
alopez: 6/5/2002
terry: 5/30/2002
terry: 3/13/2002
mark: 10/14/1997
mark: 5/7/1995
jason: 7/29/1994
carol: 3/3/1994