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Q8TCT6 (SPPL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Signal peptide peptidase-like 3

Short name=SPP-like 3
EC=3.4.23.-
Alternative name(s):
Intramembrane protease 2
Short name=IMP-2
Presenilin homologous protein 1
Short name=PSH1
Presenilin-like protein 4
Gene names
Name:SPPL3
Synonyms:IMP2, PSL4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length385 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Ref.10

Enzyme regulation

Its proteolytic activity is blocked by signal peptide peptidase (SPP) inhibitors. Ref.10

Subunit structure

Monomer. Homodimer. Ref.10

Subcellular location

Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein. Note: Restricted to the early secretory compartment. Ref.9 Ref.11

Tissue specificity

Ubiquitous. Ref.8

Domain

The PAL motif is required for normal active site conformation By similarity. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP.

The first transmembrane domain may act as a type I signal anchor.

Post-translational modification

Not glycosylated.

Sequence similarities

Belongs to the peptidase A22B family.

Sequence caution

The sequence BAC11290.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q8TCT6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8TCT6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     59-82: EQEPIIGFQPMDSTRARFLPMGAC → NSTNNSIQTIDSTQALFLPIGAS
Isoform 3 (identifier: Q8TCT6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-216: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 385385Signal peptide peptidase-like 3
PRO_0000073912

Regions

Topological domain1 – 88Lumenal Potential
Transmembrane9 – 2921Helical; Potential
Topological domain30 – 7546Cytoplasmic Potential
Transmembrane76 – 9621Helical; Potential
Topological domain97 – 982Lumenal Potential
Transmembrane99 – 11921Helical; Potential
Topological domain120 – 13718Cytoplasmic Potential
Transmembrane138 – 16023Helical; Potential
Topological domain161 – 1655Lumenal Potential
Transmembrane166 – 18621Helical; Potential
Topological domain187 – 1915Cytoplasmic Potential
Transmembrane192 – 21221Helical; Potential
Topological domain213 – 26351Lumenal Potential
Transmembrane264 – 28421Helical; Potential
Topological domain285 – 31228Cytoplasmic Potential
Transmembrane313 – 33321Helical; Potential
Topological domain334 – 3407Lumenal Potential
Transmembrane341 – 36121Helical; Potential
Topological domain362 – 38524Cytoplasmic Potential
Motif342 – 3443PAL
Compositional bias375 – 3806Poly-Ser

Sites

Active site2011 By similarity
Active site2721 By similarity

Natural variations

Alternative sequence1 – 216216Missing in isoform 3.
VSP_005205
Alternative sequence59 – 8224EQEPI…PMGAC → NSTNNSIQTIDSTQALFLPI GAS in isoform 2.
VSP_005206

Experimental info

Sequence conflict1401F → Y in BAC11290. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2002. Version 1.
Checksum: BF829565E14A2996

FASTA38542,563
        10         20         30         40         50         60 
MAEQTYSWAY SLVDSSQVST FLISILLIVY GSFRSLNMDF ENQDKEKDSN SSSGSFNGEQ 

        70         80         90        100        110        120 
EPIIGFQPMD STRARFLPMG ACVSLLVMFF FFDSVQVVFT ICTAVLATIA FAFLLLPMCQ 

       130        140        150        160        170        180 
YLTRPCSPQN KISFGCCGRF TAAELLSFSL SVMLVLIWVL TGHWLLMDAL AMGLCVAMIA 

       190        200        210        220        230        240 
FVRLPSLKVS CLLLSGLLIY DVFWVFFSAY IFNSNVMVKV ATQPADNPLD VLSRKLHLGP 

       250        260        270        280        290        300 
NVGRDVPRLS LPGKLVFPSS TGSHFSMLGI GDIVMPGLLL CFVLRYDNYK KQASGDSCGA 

       310        320        330        340        350        360 
PGPANISGRM QKVSYFHCTL IGYFVGLLTA TVASRIHRAA QPALLYLVPF TLLPLLTMAY 

       370        380 
LKGDLRRMWS EPFHSKSSSS RFLEV 

« Hide

Isoform 2 [UniParc].

Checksum: 04D8C036355B32A1
Show »

FASTA38442,261
Isoform 3 [UniParc].

Checksum: 7A97E2C1713CB938
Show »

FASTA16918,478

References

« Hide 'large scale' references
[1]"Characterization of a new protein family with homology to presenilins."
Irmler M., Tomiuk S., Korner M.R., Hofmann K., Conradt M.
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Identification of signal peptide peptidase, a presenilin-type aspartic protease."
Weihofen A., Binns K., Lemberg M.K., Ashman K., Martoglio B.
Science 296:2215-2218(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Cervix carcinoma.
[3]"Novel class of polytopic proteins with domains associated with putative protease activity."
Grigorenko A.P., Moliaka Y.K., Korovaitseva G.I., Rogaev E.I.
Biochemistry (Mosc.) 67:826-834(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Blood.
[4]"Proteolytic processing, N-glycosylation, and proteasomal degradation of human signal peptide peptidase-like protein 3: the YD and PAL motifs, but not the GXGD motif, are critical for protein stability."
Kondo K., Heike T., Yorifuji T., Nishikomori R., Kawai M., Ma F., Ma L., Adachi S., Nakahata T.
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORMS 1; 2 AND 3).
Tissue: Liver, Pancreas and Testis.
[7]"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] OF 12-385 (ISOFORM 2).
Tissue: Teratocarcinoma.
[8]"Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins."
Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U., Rovelli G., Martoglio B.
J. Biol. Chem. 279:50790-50798(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY, TISSUE SPECIFICITY.
[9]"Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3."
Krawitz P., Haffner C., Fluhrer R., Steiner H., Schmid B., Haass C.
J. Biol. Chem. 280:39515-39523(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase."
Nyborg A.C., Ladd T.B., Jansen K., Kukar T., Golde T.E.
FASEB J. 20:1671-1679(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, HOMODIMERIZATION.
[11]"SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production."
Friedmann E., Hauben E., Maylandt K., Schleeger S., Vreugde S., Lichtenthaler S.F., Kuhn P.H., Stauffer D., Rovelli G., Martoglio B.
Nat. Cell Biol. 8:843-848(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ345030 mRNA. Translation: CAC87791.1.
AJ420898 mRNA. Translation: CAD13135.1.
AY169313 mRNA. Translation: AAO12538.1.
AB252457 mRNA. Translation: BAF30928.1.
CH471054 Genomic DNA. Translation: EAW98220.1.
BC009551 mRNA. Translation: AAH09551.1.
BC025781 mRNA. Translation: AAH25781.1.
BC073910 mRNA. Translation: AAH73910.1.
BC101625 mRNA. Translation: AAI01626.1.
BC101627 mRNA. Translation: AAI01628.1.
AK074916 mRNA. Translation: BAC11290.1. Different initiation.
CCDSCCDS9208.1. [Q8TCT6-2]
RefSeqNP_620584.2. NM_139015.4. [Q8TCT6-2]
UniGeneHs.507087.
Hs.683964.

3D structure databases

ProteinModelPortalQ8TCT6.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125743. 3 interactions.

Protein family/group databases

MEROPSA22.005.

Polymorphism databases

DMDM25008979.

Proteomic databases

MaxQBQ8TCT6.
PaxDbQ8TCT6.
PRIDEQ8TCT6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000353487; ENSP00000288680; ENSG00000157837. [Q8TCT6-2]
GeneID121665.
KEGGhsa:121665.
UCSCuc001tzc.3. human. [Q8TCT6-1]
uc001tzd.3. human. [Q8TCT6-2]

Organism-specific databases

CTD121665.
GeneCardsGC12M121231.
HGNCHGNC:30424. SPPL3.
HPAHPA059958.
MIM608240. gene.
neXtProtNX_Q8TCT6.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG250196.
HOGENOMHOG000243413.
HOVERGENHBG023986.
InParanoidQ8TCT6.
KOK09598.
OMAYKKQANG.
OrthoDBEOG7NW69W.
PhylomeDBQ8TCT6.
TreeFamTF323842.

Gene expression databases

ArrayExpressQ8TCT6.
GenevestigatorQ8TCT6.

Family and domain databases

InterProIPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
[Graphical view]
PANTHERPTHR12174. PTHR12174. 1 hit.
PfamPF04258. Peptidase_A22B. 1 hit.
[Graphical view]
SMARTSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSPPL3. human.
GeneWikiUNQ1887.
GenomeRNAi121665.
NextBio80798.
PROQ8TCT6.
SOURCESearch...

Entry information

Entry nameSPPL3_HUMAN
AccessionPrimary (citable) accession number: Q8TCT6
Secondary accession number(s): Q3MJ04, Q8TAU4, Q96DD9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: June 1, 2002
Last modified: July 9, 2014
This is version 110 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 chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM