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P29508 (SPB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serpin B3
Alternative name(s):
Protein T4-A
Squamous cell carcinoma antigen 1
Short name=SCCA-1
Gene names
Name:SERPINB3
Synonyms:SCCA, SCCA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length390 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells. Also functions as an inhibitor of UV-induced apoptosis via suppression of the activity of c-Jun NH(2)-terminal kinase (JNK1). Ref.17

Subunit structure

Interacts with MAPK8/JNK1. Ref.17

Subcellular location

Cytoplasm. Note: Seems to also be secreted in plasma by cancerous cells but at a low level. Ref.14 Ref.15

Tissue specificity

Squamous cells. Expressed in some hepatocellular carcinoma (at protein level). Ref.14

Developmental stage

Its expression is closely related to cellular differentiation in both normal and malignant squamous cells.

Induction

Strongly up-regulated in the upper epidermis of sun-exposed skin. Ref.17

Sequence similarities

Belongs to the serpin family. Ov-serpin subfamily.

Sequence caution

The sequence AAO11731.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   Molecular functionProtease inhibitor
Serine protease inhibitor
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of catalytic activity

Inferred from direct assay Ref.15. Source: UniProtKB

negative regulation of endopeptidase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of peptidase activity

Inferred from direct assay PubMed 12949073. Source: UniProtKB

negative regulation of proteolysis

Inferred from direct assay Ref.4. Source: UniProtKB

regulation of proteolysis

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to virus

Inferred from direct assay Ref.4. Source: GOC

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Inferred from Biological aspect of Ancestor. Source: RefGenome

extracellular space

Inferred from electronic annotation. Source: InterPro

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

   Molecular_functionserine-type endopeptidase inhibitor activity

Non-traceable author statement Ref.2. Source: UniProtKB

virus receptor activity

Inferred from direct assay Ref.4. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P29508-1)

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: P29508-2)

Also known as: SCCA1b;

The sequence of this isoform differs from the canonical sequence as follows:
     205-256: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 390390Serpin B3
PRO_0000094103

Sites

Site354 – 3552Reactive bond

Amino acid modifications

Modified residue11N-acetylmethionine Ref.13

Natural variations

Alternative sequence205 – 25652Missing in isoform 2.
VSP_032657
Natural variant3511G → A Increased antiprotease activity and increased MAPK8 inhibition activity. Ref.4 Ref.6 Ref.14 Ref.18
Corresponds to variant rs3180227 [ dbSNP | Ensembl ].
VAR_024351
Natural variant3571T → A. Ref.1 Ref.3 Ref.9
Corresponds to variant rs1065205 [ dbSNP | Ensembl ].
VAR_024352

Experimental info

Mutagenesis3411A → R: Loss of inhibitory activity. Ref.4
Mutagenesis3521F → A: Loss of inhibitory activity. Ref.4 Ref.17
Mutagenesis3521F → G: Loss of inhibitory activity to papain but does not decrease the suppression activity to MAPK8. Ref.4 Ref.17
Mutagenesis354 – 3552SS → PP: Loss of inhibitory activity.
Sequence conflict161F → S in CAD56658. Ref.4
Sequence conflict471D → N in CAD56658. Ref.4
Sequence conflict1051N → T in CAD56658. Ref.4
Sequence conflict1851Q → R in AAO92272. Ref.5
Sequence conflict2021P → S in AAO92272. Ref.5
Sequence conflict2781T → A in AAO92269. Ref.5
Sequence conflict3491V → E in AAO92272. Ref.5

Secondary structure

.................................................................... 390
Helix Strand Turn

Details...

Sequences

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

Last modified January 23, 2002. Version 2.
Checksum: E5F27F986C752CFA

FASTA39044,565
        10         20         30         40         50         60 
MNSLSEANTK FMFDLFQQFR KSKENNIFYS PISITSALGM VLLGAKDNTA QQIKKVLHFD 

        70         80         90        100        110        120 
QVTENTTGKA ATYHVDRSGN VHHQFQKLLT EFNKSTDAYE LKIANKLFGE KTYLFLQEYL 

       130        140        150        160        170        180 
DAIKKFYQTS VESVDFANAP EESRKKINSW VESQTNEKIK NLIPEGNIGS NTTLVLVNAI 

       190        200        210        220        230        240 
YFKGQWEKKF NKEDTKEEKF WPNKNTYKSI QMMRQYTSFH FASLEDVQAK VLEIPYKGKD 

       250        260        270        280        290        300 
LSMIVLLPNE IDGLQKLEEK LTAEKLMEWT SLQNMRETRV DLHLPRFKVE ESYDLKDTLR 

       310        320        330        340        350        360 
TMGMVDIFNG DADLSGMTGS RGLVLSGVLH KAFVEVTEEG AEAAAATAVV GFGSSPTSTN 

       370        380        390 
EEFHCNHPFL FFIRQNKTNS ILFYGRFSSP 

« Hide

Isoform 2 (SCCA1b) [UniParc].

Checksum: 5AA4782FF0C1ABDF
Show »

FASTA33838,550

References

« Hide 'large scale' references
[1]"Squamous cell carcinoma antigen is a new member of the serine protease inhibitors."
Suminami Y., Kishi F., Sekiguchi K., Kato H.
Biochem. Biophys. Res. Commun. 181:51-58(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT ALA-357.
[2]"A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene."
Schneider S.S., Schick C., Fish K.E., Miller E., Pena J.C., Treter S.D., Hui S.M., Silverman G.A.
Proc. Natl. Acad. Sci. U.S.A. 92:3147-3151(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[3]"Novel forms of SCC antigen transcripts produced by alternative splicing."
Suminami Y., Kishi F., Murakami A., Sakaguchi Y., Kato H.
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ALA-357.
[4]"Squamous cell carcinoma antigen 1-mediated binding of hepatitis B virus to hepatocytes does not involve the hepatic serpin clearance system."
Moore P.L., Ong S., Harrison T.J.
J. Biol. Chem. 278:46709-46717(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-351, MUTAGENESIS OF ALA-341; PHE-352 AND 354-SER-SER-355.
Tissue: Hepatoma.
[5]"SCCA1 mRNA sequence from human hepatocellular carcinoma cell line HepG2, complete cds."
Tong C., Chenyu X., Jun Z., Ningshao X.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Hepatoma.
[6]"Characterization of the new isoform of squamous cell carcinoma antigen-1 (SCCA-PD) detected in hepatocellular carcinoma."
Turato C., Biasiolo A., Quarta S., Beneduce L., Zuin J., Fassina G., Gatta A., Pontisso P.
Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-351.
Tissue: Liver.
[7]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]"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] (ISOFORM 1).
Tissue: Trachea.
[9]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ALA-357.
Tissue: Dermoid cancer.
[10]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]Mural R.J., Istrail S., Sutton G.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].
[12]"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] (ISOFORM 1).
Tissue: Lung.
[13]Bienvenut W.V., Bensaad K., Vousden K.H.
Submitted (FEB-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-21; 88-94; 112-125; 147-160; 215-260; 266-300; 322-331 AND 378-386, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Osteosarcoma.
[14]"Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma."
Pontisso P., Calabrese F., Benvegnu L., Lise M., Belluco C., Ruvoletto M.G., De Falco S., Marino M., Valente M., Nitti D., Gatta A., Fassina G.
Br. J. Cancer 90:833-837(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 109-390 (ISOFORM 1), VARIANT ALA-351, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Liver cancer.
[15]"Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted but reside in the cytosol of squamous carcinoma cells."
Uemura Y., Pak S.C., Luke C., Cataltepe S., Tsu C., Schick C., Kamachi Y., Pomeroy S.L., Perlmutter D.H., Silverman G.A.
Int. J. Cancer 89:368-377(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Crystal structure of SCCA1 and insight about the interaction with JNK1."
Zheng B., Matoba Y., Kumagai T., Katagiri C., Hibino T., Sugiyama M.
Biochem. Biophys. Res. Commun. 380:143-147(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-390, FUNCTION, INDUCTION, MUTAGENESIS OF PHE-352, INTERACTION WITH MAPK8.
[18]"Increased antiprotease activity of the SERPINB3 polymorphic variant SCCA-PD."
Turato C., Biasiolo A., Pengo P., Frecer V., Quarta S., Fasolato S., Ruvoletto M., Beneduce L., Zuin J., Fassina G., Gatta A., Pontisso P.
Exp. Biol. Med. 236:281-290(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-351.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S66896 mRNA. Translation: AAB20405.1.
U19556 mRNA. Translation: AAA97552.1.
U19568 expand/collapse EMBL AC list , U19559, U19560, U19562, U19565, U19567 Genomic DNA. Translation: AAA86317.1.
U19562, U19559, U19560 Genomic DNA. Translation: AAA86316.1.
AB046399 mRNA. Translation: BAB40772.1.
AJ515706 mRNA. Translation: CAD56658.1.
AY245778 mRNA. Translation: AAO92269.1.
AY245781 mRNA. Translation: AAO92272.1.
EU852041 mRNA. Translation: ACF21012.1.
BT006748 mRNA. Translation: AAP35394.1.
AK222746 mRNA. Translation: BAD96466.1.
AK222753 mRNA. Translation: BAD96473.1.
AK314805 mRNA. Translation: BAG37332.1.
AC069356 Genomic DNA. No translation available.
CH471096 Genomic DNA. Translation: EAW63156.1.
CH471096 Genomic DNA. Translation: EAW63157.1.
BC005224 mRNA. Translation: AAH05224.1.
AY190327 mRNA. Translation: AAO11731.1. Different initiation.
CCDSCCDS11987.1. [P29508-1]
PIRI38201.
RefSeqNP_008850.1. NM_006919.2. [P29508-1]
UniGeneHs.227948.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZV6X-ray2.70A/B/C2-390[»]
ProteinModelPortalP29508.
SMRP29508. Positions 2-390.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112223. 11 interactions.
IntActP29508. 5 interactions.
MINTMINT-1139917.

PTM databases

PhosphoSiteP29508.

Polymorphism databases

DMDM20141712.

2D gel databases

SWISS-2DPAGEP29508.
UCD-2DPAGEP29508.

Proteomic databases

MaxQBP29508.
PaxDbP29508.
PRIDEP29508.

Protocols and materials databases

DNASU6317.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000283752; ENSP00000283752; ENSG00000057149. [P29508-1]
ENST00000332821; ENSP00000329498; ENSG00000057149. [P29508-2]
GeneID6317.
KEGGhsa:6317.
UCSCuc002lji.3. human. [P29508-1]
uc010dqa.3. human. [P29508-2]

Organism-specific databases

CTD6317.
GeneCardsGC18M061295.
HGNCHGNC:10569. SERPINB3.
HPACAB018772.
MIM600517. gene.
neXtProtNX_P29508.
PharmGKBPA35538.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4826.
HOVERGENHBG005957.
InParanoidP29508.
KOK13963.
OMAKSIQMMR.
OrthoDBEOG7327PB.
PhylomeDBP29508.
TreeFamTF352619.

Gene expression databases

ArrayExpressP29508.
BgeeP29508.
GenevestigatorP29508.

Family and domain databases

InterProIPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERPTHR11461. PTHR11461. 1 hit.
PfamPF00079. Serpin. 1 hit.
[Graphical view]
SMARTSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMSSF56574. SSF56574. 1 hit.
PROSITEPS00284. SERPIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP29508.
GeneWikiSERPINB3.
GenomeRNAi6317.
NextBio24512.
PROP29508.
SOURCESearch...

Entry information

Entry nameSPB3_HUMAN
AccessionPrimary (citable) accession number: P29508
Secondary accession number(s): A6NDM2 expand/collapse secondary AC list , B2RBT5, B3W5Y6, Q53H28, Q53YB5, Q86VF3, Q86W04, Q8IWL4, Q8IXI3, Q96J21, Q9BYF8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2002
Last modified: July 9, 2014
This is version 144 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 18

Human chromosome 18: entries, gene names and cross-references to MIM