ID MMP10_HUMAN Reviewed; 476 AA. AC P09238; B2R9X9; Q53HH9; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 27-MAR-2024, entry version 216. DE RecName: Full=Stromelysin-2; DE Short=SL-2; DE EC=3.4.24.22; DE AltName: Full=Matrix metalloproteinase-10; DE Short=MMP-10; DE AltName: Full=Transin-2; DE Flags: Precursor; GN Name=MMP10; Synonyms=STMY2; 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; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2844164; DOI=10.1042/bj2530187; RA Muller D., Quantin B., Gesnel M.-C., Millon-Collard R., Abecassis J., RA Breathnach R.; RT "The collagenase gene family in humans consists of at least four members."; RL Biochem. J. 253:187-192(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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., 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 MRNA], AND VARIANT LYS-53. RC TISSUE=Coronary artery; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-4; LYS-53; ARG-65; RP LEU-226; GLU-282; PHE-440 AND LEU-475. RG NIEHS SNPs program; RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases. RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 99-263, CATALYTIC ACTIVITY, ACTIVE RP SITE, COFACTOR, CALCIUM-BINDING, AND ZINC-BINDING SITES. RX PubMed=15095982; DOI=10.1016/j.jmb.2003.12.033; RA Bertini I., Calderone V., Fragai M., Luchinat C., Mangani S., Terni B.; RT "Crystal structure of the catalytic domain of human matrix RT metalloproteinase 10."; RL J. Mol. Biol. 336:707-716(2004). RN [9] RP VARIANT [LARGE SCALE ANALYSIS] GLN-142. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Can degrade fibronectin, gelatins of type I, III, IV, and V; CC weakly collagens III, IV, and V. Activates procollagenase. CC -!- CATALYTIC ACTIVITY: CC Reaction=Similar to stromelysin 1, but action on collagen types III, IV CC and V is weak.; EC=3.4.24.22; Evidence={ECO:0000269|PubMed:15095982}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:15095982}; CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:15095982}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:15095982}; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000305}. CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif CC binds the catalytic zinc ion, thus inhibiting the enzyme. The CC dissociation of the cysteine from the zinc ion upon the activation- CC peptide release activates the enzyme. CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mmp10/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X07820; CAA30679.1; -; mRNA. DR EMBL; BT007442; AAP36110.1; -; mRNA. DR EMBL; AK222601; BAD96321.1; -; mRNA. DR EMBL; AK313960; BAG36676.1; -; mRNA. DR EMBL; AY744675; AAU21039.1; -; Genomic_DNA. DR EMBL; CH471065; EAW67029.1; -; Genomic_DNA. DR EMBL; BC002591; AAH02591.1; -; mRNA. DR CCDS; CCDS8321.1; -. DR PIR; A28816; KCHUS2. DR RefSeq; NP_002416.1; NM_002425.2. DR PDB; 1Q3A; X-ray; 2.10 A; A/B/C=99-263. DR PDB; 3V96; X-ray; 1.90 A; B=99-263. DR PDB; 4ILW; X-ray; 2.10 A; D/F=99-263. DR PDBsum; 1Q3A; -. DR PDBsum; 3V96; -. DR PDBsum; 4ILW; -. DR AlphaFoldDB; P09238; -. DR SMR; P09238; -. DR BioGRID; 110462; 29. DR IntAct; P09238; 14. DR STRING; 9606.ENSP00000279441; -. DR BindingDB; P09238; -. DR ChEMBL; CHEMBL4270; -. DR DrugBank; DB00786; Marimastat. DR DrugBank; DB08271; N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID. DR GuidetoPHARMACOLOGY; 1634; -. DR MEROPS; M10.006; -. DR iPTMnet; P09238; -. DR PhosphoSitePlus; P09238; -. DR BioMuta; MMP10; -. DR DMDM; 116869; -. DR jPOST; P09238; -. DR MassIVE; P09238; -. DR PaxDb; 9606-ENSP00000279441; -. DR PeptideAtlas; P09238; -. DR ProteomicsDB; 52211; -. DR TopDownProteomics; P09238; -. DR Antibodypedia; 3688; 671 antibodies from 36 providers. DR DNASU; 4319; -. DR Ensembl; ENST00000279441.9; ENSP00000279441.4; ENSG00000166670.10. DR GeneID; 4319; -. DR KEGG; hsa:4319; -. DR MANE-Select; ENST00000279441.9; ENSP00000279441.4; NM_002425.3; NP_002416.1. DR UCSC; uc001phg.3; human. DR AGR; HGNC:7156; -. DR CTD; 4319; -. DR DisGeNET; 4319; -. DR GeneCards; MMP10; -. DR HGNC; HGNC:7156; MMP10. DR HPA; ENSG00000166670; Tissue enriched (endometrium). DR MIM; 185260; gene. DR neXtProt; NX_P09238; -. DR OpenTargets; ENSG00000166670; -. DR PharmGKB; PA30868; -. DR VEuPathDB; HostDB:ENSG00000166670; -. DR eggNOG; KOG1565; Eukaryota. DR GeneTree; ENSGT00940000163375; -. DR HOGENOM; CLU_015489_6_0_1; -. DR InParanoid; P09238; -. DR OMA; NLEPEFH; -. DR OrthoDB; 391167at2759; -. DR PhylomeDB; P09238; -. DR TreeFam; TF315428; -. DR BRENDA; 3.4.24.22; 2681. DR PathwayCommons; P09238; -. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases. DR SignaLink; P09238; -. DR SIGNOR; P09238; -. DR BioGRID-ORCS; 4319; 13 hits in 1162 CRISPR screens. DR ChiTaRS; MMP10; human. DR EvolutionaryTrace; P09238; -. DR GeneWiki; MMP10; -. DR GenomeRNAi; 4319; -. DR Pharos; P09238; Tchem. DR PRO; PR:P09238; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P09238; Protein. DR Bgee; ENSG00000166670; Expressed in mucosa of paranasal sinus and 87 other cell types or tissues. DR ExpressionAtlas; P09238; baseline and differential. DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. DR CDD; cd00094; HX; 1. DR CDD; cd04278; ZnMc_MMP; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 2.110.10.10; Hemopexin-like domain; 1. DR InterPro; IPR000585; Hemopexin-like_dom. DR InterPro; IPR036375; Hemopexin-like_dom_sf. DR InterPro; IPR018487; Hemopexin-like_repeat. DR InterPro; IPR018486; Hemopexin_CS. DR InterPro; IPR033739; M10A_MMP. DR InterPro; IPR024079; MetalloPept_cat_dom_sf. DR InterPro; IPR001818; Pept_M10_metallopeptidase. DR InterPro; IPR021190; Pept_M10A. DR InterPro; IPR021158; Pept_M10A_Zn_BS. DR InterPro; IPR006026; Peptidase_Metallo. DR InterPro; IPR002477; Peptidoglycan-bd-like. DR InterPro; IPR036365; PGBD-like_sf. DR PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1. DR PANTHER; PTHR10201:SF270; STROMELYSIN-2; 1. DR Pfam; PF00045; Hemopexin; 4. DR Pfam; PF00413; Peptidase_M10; 1. DR Pfam; PF01471; PG_binding_1; 1. DR PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1. DR PRINTS; PR00138; MATRIXIN. DR SMART; SM00120; HX; 4. DR SMART; SM00235; ZnMc; 1. DR SUPFAM; SSF50923; Hemopexin-like domain; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR SUPFAM; SSF47090; PGBD-like; 1. DR PROSITE; PS00546; CYSTEINE_SWITCH; 1. DR PROSITE; PS00024; HEMOPEXIN; 1. DR PROSITE; PS51642; HEMOPEXIN_2; 4. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; P09238; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Collagen degradation; Disulfide bond; KW Extracellular matrix; Hydrolase; Metal-binding; Metalloprotease; Protease; KW Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen. FT SIGNAL 1..17 FT /evidence="ECO:0000305" FT PROPEP 18..98 FT /note="Activation peptide" FT /id="PRO_0000028764" FT CHAIN 99..476 FT /note="Stromelysin-2" FT /id="PRO_0000028765" FT REPEAT 286..335 FT /note="Hemopexin 1" FT REPEAT 336..382 FT /note="Hemopexin 2" FT REPEAT 384..432 FT /note="Hemopexin 3" FT REPEAT 433..476 FT /note="Hemopexin 4" FT MOTIF 89..96 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT ACT_SITE 218 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, FT ECO:0000269|PubMed:15095982" FT BINDING 91 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /note="in inhibited form" FT /evidence="ECO:0000250" FT BINDING 167 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 169 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 182 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 195 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 217 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT BINDING 221 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT BINDING 227 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT DISULFID 289..476 FT /evidence="ECO:0000250" FT VARIANT 4 FT /note="L -> V (in dbSNP:rs17435959)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_020949" FT VARIANT 53 FT /note="R -> K (in dbSNP:rs486055)" FT /evidence="ECO:0000269|Ref.4, ECO:0000269|Ref.5" FT /id="VAR_020950" FT VARIANT 65 FT /note="G -> R (in dbSNP:rs17293607)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_020951" FT VARIANT 142 FT /note="E -> Q (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036139" FT VARIANT 226 FT /note="F -> L (in dbSNP:rs17860971)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_020952" FT VARIANT 282 FT /note="G -> E (in dbSNP:rs17860973)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_020953" FT VARIANT 440 FT /note="L -> F (in dbSNP:rs17860996)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_020954" FT VARIANT 475 FT /note="H -> L (in dbSNP:rs17861009)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_020955" FT STRAND 111..117 FT /evidence="ECO:0007829|PDB:3V96" FT HELIX 126..141 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 147..150 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 157..163 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 168..171 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 175..183 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 186..188 FT /evidence="ECO:0007829|PDB:3V96" FT TURN 189..192 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 194..197 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 202..210 FT /evidence="ECO:0007829|PDB:3V96" FT HELIX 211..223 FT /evidence="ECO:0007829|PDB:3V96" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:1Q3A" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:3V96" FT HELIX 242..247 FT /evidence="ECO:0007829|PDB:3V96" FT HELIX 252..262 FT /evidence="ECO:0007829|PDB:3V96" SQ SEQUENCE 476 AA; 54151 MW; 516DCDDFEF92A0D6 CRC64; MMHLAFLVLL CLPVCSAYPL SGAAKEEDSN KDLAQQYLEK YYNLEKDVKQ FRRKDSNLIV KKIQGMQKFL GLEVTGKLDT DTLEVMRKPR CGVPDVGHFS SFPGMPKWRK THLTYRIVNY TPDLPRDAVD SAIEKALKVW EEVTPLTFSR LYEGEADIMI SFAVKEHGDF YSFDGPGHSL AHAYPPGPGL YGDIHFDDDE KWTEDASGTN LFLVAAHELG HSLGLFHSAN TEALMYPLYN SFTELAQFRL SQDDVNGIQS LYGPPPASTE EPLVPTKSVP SGSEMPAKCD PALSFDAIST LRGEYLFFKD RYFWRRSHWN PEPEFHLISA FWPSLPSYLD AAYEVNSRDT VFIFKGNEFW AIRGNEVQAG YPRGIHTLGF PPTIRKIDAA VSDKEKKKTY FFAADKYWRF DENSQSMEQG FPRLIADDFP GVEPKVDAVL QAFGFFYFFS GSSQFEFDPN ARMVTHILKS NSWLHC //