P29508 (SPB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	390 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of proteolysis Inferred from direct assay Ref.4. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from Biological aspect of Ancestor. Source: RefGenome extracellular vesicular exosome Inferred from direct assay PubMed 21557262. Source: UniProtKB
Molecular_function	serine-type endopeptidase inhibitor activity Non-traceable author statement Ref.2. Source: UniProtKB viral 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 390

390

Serpin B3

PRO_0000094103

Sites

Site

354 – 355

2

Reactive bond

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.13

Natural variations

Alternative sequence

205 – 256

52

Missing in isoform 2.

VSP_032657

Natural variant

351

1

G → A Increased antiprotease activity and increased MAPK8 inhibition activity.
Corresponds to variant rs3180227 [ dbSNP | Ensembl ].

VAR_024351

Natural variant

357

1

T → A. Ref.1 Ref.3 Ref.9
Corresponds to variant rs1065205 [ dbSNP | Ensembl ].

VAR_024352

Experimental info

Mutagenesis

341

1

A → R: Loss of inhibitory activity. Ref.4

Mutagenesis

352

1

F → A: Loss of inhibitory activity. Ref.4 Ref.17

Mutagenesis

352

1

F → G: Loss of inhibitory activity to papain but does not decrease the suppression activity to MAPK8. Ref.4 Ref.17

Mutagenesis

354 – 355

2

SS → PP: Loss of inhibitory activity.

Sequence conflict

16

1

F → S in CAD56658. Ref.4

Sequence conflict

47

1

D → N in CAD56658. Ref.4

Sequence conflict

105

1

N → T in CAD56658. Ref.4

Sequence conflict

185

1

Q → R in AAO92272. Ref.5

Sequence conflict

202

1

P → S in AAO92272. Ref.5

Sequence conflict

278

1

T → A in AAO92269. Ref.5

Sequence conflict

349

1

V → E in AAO92272. Ref.5

Secondary structure

1

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390

Helix Strand Turn

Details...

Helix

3 – 22

20

Beta strand

27 – 29

3

Helix

31 – 43

13

Helix

48 – 56

9

Helix

82 – 93

12

Beta strand

101 – 104

4

Beta strand

107 – 110

4

Helix

117 – 127

11

Beta strand

131 – 134

4

Turn

136 – 138

3

Helix

140 – 154

15

Turn

155 – 157

3

Turn

165 – 167

3

Beta strand

174 – 182

9

Beta strand

186 – 188

3

Beta strand

194 – 200

7

Beta strand

202 – 205

4

Beta strand

208 – 221

14

Turn

225 – 228

4

Beta strand

229 – 236

8

Beta strand

239 – 250

12

Helix

254 – 260

7

Helix

263 – 269

7

Helix

272 – 274

3

Beta strand

276 – 285

10

Beta strand

288 – 294

7

Helix

296 – 301

6

Helix

306 – 308

3

Helix

315 – 318

4

Beta strand

319 – 321

3

Beta strand

325 – 335

11

Beta strand

361 – 364

4

Beta strand

369 – 373

5

Turn

376 – 379

4

Beta strand

384 – 387

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2002. Version 2. Checksum: E5F27F986C752CFA	FASTA	390	44,565
	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
	Isoform 2 (SCCA1b) [UniParc]. Checksum: 5AA4782FF0C1ABDF	FASTA	338	38,550
	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 WPNKLEEKLT AEKLMEWTSL QNMRETRVDL HLPRFKVEES 250 260 270 280 290 300 YDLKDTLRTM GMVDIFNGDA DLSGMTGSRG LVLSGVLHKA FVEVTEEGAE AAAATAVVGF 310 320 330 GSSPTSTNEE FHCNHPFLFF IRQNKTNSIL FYGRFSSP

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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 , 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.

IPI

IPI00022204.
IPI00307466.

PIR

I38201.

RefSeq

NP_008850.1. NM_006919.2.

UniGene

Hs.227948.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZV6	X-ray	2.70	A/B/C	2-390	[»]

ProteinModelPortal

P29508.

ModBase

Search...

Protein-protein interaction databases

IntAct

P29508. 2 interactions.

MINT

MINT-1139917.

PTM databases

PhosphoSite

P29508.

Polymorphism databases

DMDM

20141712.

2D gel databases

SWISS-2DPAGE

P29508.

UCD-2DPAGE

P29508.

Proteomic databases

PaxDb

P29508.

PRIDE

P29508.

Protocols and materials databases

DNASU

6317.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000283752; ENSP00000283752; ENSG00000057149.
ENST00000332821; ENSP00000329498; ENSG00000057149.

GeneID

6317.

KEGG

hsa:6317.

UCSC

uc002lji.3. human.
uc010dqa.3. human.

Organism-specific databases

CTD

6317.

GeneCards

GC18M061295.

HGNC

HGNC:10569. SERPINB3.

HPA

CAB018772.

MIM

600517. gene.

neXtProt

NX_P29508.

PharmGKB

PA35538.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4826.

HOVERGEN

HBG005957.

InParanoid

P29508.

KO

K13963.

OMA

FHFASLE.

OrthoDB

EOG4FBHTJ.

Gene expression databases

ArrayExpress

P29508.

Bgee

P29508.

Genevestigator

P29508.

GermOnline

ENSG00000206073. Homo sapiens.

Family and domain databases

InterPro

IPR023795. Protease_inhib_I4_serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]

PANTHER

PTHR11461. PTHR11461. 1 hit.

Pfam

PF00079. Serpin. 1 hit.
[Graphical view]

SMART

SM00093. SERPIN. 1 hit.
[Graphical view]

SUPFAM

SSF56574. Prot_inh_serpin. 1 hit.

PROSITE

PS00284. SERPIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P29508.

GenomeRNAi

6317.

NextBio

24512.

SOURCE

Search...

Entry information

Entry name

SPB3_HUMAN

Accession

Primary (citable) accession number: P29508
Secondary accession number(s): A6NDM2 , 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:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.