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Q14703 (MBTP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Membrane-bound transcription factor site-1 protease

EC=3.4.21.112
Alternative name(s):
Endopeptidase S1P
Subtilisin/kexin-isozyme 1
Short name=SKI-1
Gene names
Name:MBTPS1
Synonyms:KIAA0091, S1P, SKI1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1052 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine protease that catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs). Other known substrates are BDNF, GNPTAB and ATF6. Cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4. Cleaves known substrates after Arg-Ser-Val-Leu (SERBP-2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. Ref.9

Catalytic activity

Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3.

Cofactor

Calcium.

Enzyme regulation

Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments thereof.

Subcellular location

Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Note: May sort to other organelles, including lysosomal and/or endosomal compartments. Ref.8

Tissue specificity

Widely expressed.

Induction

Down-regulated by sterols.

Post-translational modification

The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and late into a secreted 98 kDa form. The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates.

Sequence similarities

Belongs to the peptidase S8 family.

Sequence caution

The sequence BAA07653.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processCholesterol metabolism
Lipid metabolism
Steroid metabolism
Sterol metabolism
   Cellular componentEndoplasmic reticulum
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionHydrolase
Protease
Serine protease
   PTMAutocatalytic cleavage
Glycoprotein
Zymogen
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of signaling protein activity involved in unfolded protein response

Traceable author statement. Source: Reactome

cellular protein metabolic process

Traceable author statement. Source: Reactome

cholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

endoplasmic reticulum unfolded protein response

Traceable author statement. Source: Reactome

lipid metabolic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

lysosome organization

Inferred from mutant phenotype Ref.9. Source: UniProtKB

proteolysis

Inferred from mutant phenotype Ref.9. Source: UniProtKB

regulation of transcription factor import into nucleus

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from Biological aspect of Ancestor. Source: RefGenome

Golgi membrane

Traceable author statement. Source: Reactome

Golgi stack

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum lumen

Traceable author statement PubMed 9809072. Source: ProtInc

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionserine-type endopeptidase activity

Inferred from mutant phenotype Ref.9. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717
Propeptide18 – 186169
PRO_0000027051
Chain187 – 1052866Membrane-bound transcription factor site-1 protease
PRO_0000027052

Regions

Topological domain187 – 998812Lumenal Potential
Transmembrane999 – 102123Helical; Potential
Topological domain1022 – 105231Cytoplasmic Potential
Region218 – 414197Serine protease
Compositional bias1023 – 105028Arg/Lys/Pro-rich (basic)

Sites

Active site2181Charge relay system By similarity
Active site2491Charge relay system By similarity
Active site4141Charge relay system By similarity
Site186 – 1872Cleavage; by autolysis

Amino acid modifications

Glycosylation2361N-linked (GlcNAc...) Potential
Glycosylation3051N-linked (GlcNAc...) Potential
Glycosylation5151N-linked (GlcNAc...) Potential
Glycosylation7281N-linked (GlcNAc...) Potential
Glycosylation9391N-linked (GlcNAc...) Potential

Natural variations

Natural variant61I → T.
Corresponds to variant rs34701895 [ dbSNP | Ensembl ].
VAR_051822
Natural variant901R → G.
Corresponds to variant rs34076105 [ dbSNP | Ensembl ].
VAR_051823

Experimental info

Sequence conflict8431L → Q in BAF84462. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q14703 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: CA6F013588595B45

FASTA1,052117,749
        10         20         30         40         50         60 
MKLVNIWLLL LVVLLCGKKH LGDRLEKKSF EKAPCPGCSH LTLKVEFSST VVEYEYIVAF 

        70         80         90        100        110        120 
NGYFTAKARN SFISSALKSS EVDNWRIIPR NNPSSDYPSD FEVIQIKEKQ KAGLLTLEDH 

       130        140        150        160        170        180 
PNIKRVTPQR KVFRSLKYAE SDPTVPCNET RWSQKWQSSR PLRRASLSLG SGFWHATGRH 

       190        200        210        220        230        240 
SSRRLLRAIP RQVAQTLQAD VLWQMGYTGA NVRVAVFDTG LSEKHPHFKN VKERTNWTNE 

       250        260        270        280        290        300 
RTLDDGLGHG TFVAGVIASM RECQGFAPDA ELHIFRVFTN NQVSYTSWFL DAFNYAILKK 

       310        320        330        340        350        360 
IDVLNLSIGG PDFMDHPFVD KVWELTANNV IMVSAIGNDG PLYGTLNNPA DQMDVIGVGG 

       370        380        390        400        410        420 
IDFEDNIARF SSRGMTTWEL PGGYGRMKPD IVTYGAGVRG SGVKGGCRAL SGTSVASPVV 

       430        440        450        460        470        480 
AGAVTLLVST VQKRELVNPA SMKQALIASA RRLPGVNMFE QGHGKLDLLR AYQILNSYKP 

       490        500        510        520        530        540 
QASLSPSYID LTECPYMWPY CSQPIYYGGM PTVVNVTILN GMGVTGRIVD KPDWQPYLPQ 

       550        560        570        580        590        600 
NGDNIEVAFS YSSVLWPWSG YLAISISVTK KAASWEGIAQ GHVMITVASP AETESKNGAE 

       610        620        630        640        650        660 
QTSTVKLPIK VKIIPTPPRS KRVLWDQYHN LRYPPGYFPR DNLRMKNDPL DWNGDHIHTN 

       670        680        690        700        710        720 
FRDMYQHLRS MGYFVEVLGA PFTCFDASQY GTLLMVDSEE EYFPEEIAKL RRDVDNGLSL 

       730        740        750        760        770        780 
VIFSDWYNTS VMRKVKFYDE NTRQWWMPDT GGANIPALNE LLSVWNMGFS DGLYEGEFTL 

       790        800        810        820        830        840 
ANHDMYYASG CSIAKFPEDG VVITQTFKDQ GLEVLKQETA VVENVPILGL YQIPAEGGGR 

       850        860        870        880        890        900 
IVLYGDSNCL DDSHRQKDCF WLLDALLQYT SYGVTPPSLS HSGNRQRPPS GAGSVTPERM 

       910        920        930        940        950        960 
EGNHLHRYSK VLEAHLGDPK PRPLPACPRL SWAKPQPLNE TAPSNLWKHQ KLLSIDLDKV 

       970        980        990       1000       1010       1020 
VLPNFRSNRP QVRPLSPGES GAWDIPGGIM PGRYNQEVGQ TIPVFAFLGA MVVLAFFVVQ 

      1030       1040       1050 
INKAKSRPKR RKPRVKRPQL MQQVHPPKTP SV 

« Hide

References

« Hide 'large scale' references
[1]"Genomic structure and chromosomal mapping of the human site-1 protease (S1P) gene."
Nakajima T., Iwaki K., Kodama T., Inazawa J., Emi M.
J. Hum. Genet. 45:212-217(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Myeloid.
[2]"Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1."
Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.
DNA Res. 2:37-43(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Bone marrow.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[4]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 735-1052.
Tissue: Testis.
[7]"Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegment."
Toure B.B., Munzer J.S., Basak A., Benjannet S., Rochemont J., Lazure C., Chretien M., Seidah N.G.
J. Biol. Chem. 275:2349-2358(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"Mammalian subtilisin/kexin isozyme SKI-1: a widely expressed proprotein convertase with a unique cleavage specificity and cellular localization."
Seidah N.G., Mowla S.J., Hamelin J., Mamarbachi A.M., Benjannet S., Toure B.B., Basak A., Munzer J.S., Marcinkiewicz J., Zhong M., Barale J.-C., Lazure C., Murphy R.A., Chretien M., Marcinkiewicz M.
Proc. Natl. Acad. Sci. U.S.A. 96:1321-1326(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism."
Marschner K., Kollmann K., Schweizer M., Braulke T., Pohl S.
Science 333:87-90(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D42053 mRNA. Translation: BAA07653.2. Different initiation.
AK291773 mRNA. Translation: BAF84462.1.
AC040169 Genomic RNA. No translation available.
BC114555 mRNA. Translation: AAI14556.1.
BC114961 mRNA. Translation: AAI14962.1.
AL133583 mRNA. Translation: CAB63727.1.
CCDSCCDS10941.1.
PIRT43492.
RefSeqNP_003782.1. NM_003791.3.
UniGeneHs.75890.

3D structure databases

ProteinModelPortalQ14703.
SMRQ14703. Positions 53-473.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114259. 10 interactions.
IntActQ14703. 7 interactions.
MINTMINT-6774172.
STRING9606.ENSP00000344223.

Chemistry

BindingDBQ14703.
ChEMBLCHEMBL5916.

Protein family/group databases

MEROPSS08.063.

PTM databases

PhosphoSiteQ14703.

Polymorphism databases

DMDM17368466.

Proteomic databases

MaxQBQ14703.
PaxDbQ14703.
PRIDEQ14703.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000343411; ENSP00000344223; ENSG00000140943.
GeneID8720.
KEGGhsa:8720.
UCSCuc002fhh.3. human.

Organism-specific databases

CTD8720.
GeneCardsGC16M084087.
HGNCHGNC:15456. MBTPS1.
HPAHPA006239.
MIM603355. gene.
neXtProtNX_Q14703.
PharmGKBPA30671.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1404.
HOGENOMHOG000030053.
HOVERGENHBG052421.
InParanoidQ14703.
KOK08653.
OMALPERMEG.
OrthoDBEOG7TBC1F.
PhylomeDBQ14703.
TreeFamTF324501.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.
SignaLinkQ14703.

Gene expression databases

ArrayExpressQ14703.
BgeeQ14703.
CleanExHS_MBTPS1.
GenevestigatorQ14703.

Family and domain databases

Gene3D3.40.50.200. 2 hits.
InterProIPR000209. Peptidase_S8/S53_dom.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
[Graphical view]
PANTHERPTHR10795. PTHR10795. 1 hit.
PfamPF00082. Peptidase_S8. 1 hit.
[Graphical view]
PRINTSPR00723. SUBTILISIN.
SUPFAMSSF52743. SSF52743. 2 hits.
PROSITEPS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMBTPS1. human.
GenomeRNAi8720.
NextBio32705.
PMAP-CutDBQ14703.
PROQ14703.
SOURCESearch...

Entry information

Entry nameMBTP1_HUMAN
AccessionPrimary (citable) accession number: Q14703
Secondary accession number(s): A8K6V8, Q24JQ2, Q9UF67
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM