P35237 (SPB6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serpin B6

Alternative name(s):
Cytoplasmic antiproteinase
Short name=CAP
Peptidase inhibitor 6
Short name=PI-6
Placental thrombin inhibitor

Gene names

Name:	SERPINB6
Synonyms:	PI6, PTI

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	376 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in the regulation of serine proteinases present in the brain or extravasated from the blood By similarity. Inhibitor of cathepsin G, kallikrein-8 and thrombin. May play an important role in the inner ear in the protection against leakage of lysosomal content during stress and loss of this protection results in cell death and sensorineural hearing loss. Ref.1 Ref.2 Ref.10 Ref.12 Ref.14
Subunit structure	Forms a complex with the monomeric form of beta-tryptase.
Subcellular location	Cytoplasm Ref.9 Ref.11 Ref.12 Ref.14.
Tissue specificity	Expressed in keratinocytes (at protein level). Highest levels in skeletal muscle. Also found in placenta, cardiac muscle, lung, liver, kidney and pancreas. Expressed in the inner ear hair cells. Expressed abundantly by normal mast cells in different tissues and by mast cells in mastocytoma lesions. Ref.11 Ref.12 Ref.14
Involvement in disease	Deafness, autosomal recessive, 91 (DFNB91) [MIM:613453]: A form of non-syndromic deafness characterized by progressive and age-dependent sensorineural hearing loss. Vestibular function is normal. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14
Sequence similarities	Belongs to the serpin family. Ov-serpin subfamily.
Sequence caution	The sequence BAD92800.1 differs from that shown. Reason: Erroneous initiation. The sequence CAD98106.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Deafness Non-syndromic deafness
Molecular function	Protease inhibitor Serine protease inhibitor
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	regulation of proteolysis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	centrosome Inferred from direct assay. Source: HPA cytosol Traceable author statement Ref.1. Source: ProtInc protein complex Inferred from direct assay Ref.12. Source: BHF-UCL
Molecular_function	serine-type endopeptidase inhibitor activity Inferred from direct assay Ref.12. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 376	376	Serpin B6		PRO_0000094106
Sites
	Site	341 – 342	2	Reactive bond
Natural variations
	Natural variant	90	1	M → V. Ref.1 Ref.2 Ref.3 Ref.4 Corresponds to variant rs2295769 [ dbSNP | Ensembl ].		VAR_037295
	Natural variant	153	1	G → S. Corresponds to variant rs2295766 [ dbSNP | Ensembl ].		VAR_037296
Experimental info
	Sequence conflict	175	1	E → G in CAA80373. Ref.1
	Sequence conflict	200	1	M → V in BAG37155. Ref.3
	Sequence conflict	362	1	S → R in CAA80373. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P35237 [UniParc]. Last modified December 4, 2007. Version 3. Checksum: 3A06BC26A7510E1A	FASTA	376	42,622
	10 20 30 40 50 60 MDVLAEANGT FALNLLKTLG KDNSKNVFFS PMSMSCALAM VYMGAKGNTA AQMAQILSFN 70 80 90 100 110 120 KSGGGGDIHQ GFQSLLTEVN KTGTQYLLRM ANRLFGEKSC DFLSSFRDSC QKFYQAEMEE 130 140 150 160 170 180 LDFISAVEKS RKHINTWVAE KTEGKIAELL SPGSVDPLTR LVLVNAVYFR GNWDEQFDKE 190 200 210 220 230 240 NTEERLFKVS KNEEKPVQMM FKQSTFKKTY IGEIFTQILV LPYVGKELNM IIMLPDETTD 250 260 270 280 290 300 LRTVEKELTY EKFVEWTRLD MMDEEEVEVS LPRFKLEESY DMESVLRNLG MTDAFELGKA 310 320 330 340 350 360 DFSGMSQTDL SLSKVVHKSF VEVNEEGTEA AAATAAIMMM RCARFVPRFC ADHPFLFFIQ 370 HSKTNGILFC GRFSSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and molecular characterization of a human intracellular serine proteinase inhibitor." Coughlin P., Sun J., Cerruti L., Salem H.H., Bird P. Proc. Natl. Acad. Sci. U.S.A. 90:9417-9421(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-90, FUNCTION. Tissue: Placenta.
[2]	"Complementary DNA cloning and kinetic characterization of a novel intracellular serine proteinase inhibitor: mechanism of action with trypsin and factor Xa as model proteinases." Morgenstern K.A., Sprecher C.A., Holth L., Foster D., Grant F.J., Ching A., Kisiel W. Biochemistry 33:3432-3441(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 67-73 AND 144-149, VARIANT VAL-90, FUNCTION. Tissue: Placenta.
[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. , 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], VARIANT VAL-90. Tissue: Testis.
[4]	"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], VARIANT VAL-90. Tissue: Small intestine.
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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]. Tissue: Chondrosarcoma and Colon.
[8]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-372. Tissue: Brain.
[9]	"Identification and purification of a novel serine proteinase inhibitor." Coughlin P.B., Tetaz T., Salem H.H. J. Biol. Chem. 268:9541-9547(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 47-60; 63-81 AND 91-98, SUBCELLULAR LOCATION. Tissue: Leukemia.
[10]	"The intracellular serpin proteinase inhibitor 6 is expressed in monocytes and granulocytes and is a potent inhibitor of the azurophilic granule protease, cathepsin G." Scott F.L., Hirst C.E., Sun J., Bird C.H., Bottomley S.P., Bird P.I. Blood 93:2089-2097(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with beta-tryptase monomers." Strik M.C., Wolbink A., Wouters D., Bladergroen B.A., Verlaan A.R., van Houdt I.S., Hijlkema S., Hack C.E., Kummer J.A. Blood 103:2710-2717(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, COMPLEX FORMATION WITH BETA-TRYPTASE.
[12]	"SerpinB6 is an inhibitor of kallikrein-8 in keratinocytes." Scott F.L., Sun J., Whisstock J.C., Kato K., Bird P.I. J. Biochem. 142:435-442(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss." Sirmaci A., Erbek S., Price J., Huang M., Duman D., Cengiz F.B., Bademci G., Tokgoz-Yilmaz S., Hismi B., Ozdag H., Ozturk B., Kulaksizoglu S., Yildirim E., Kokotas H., Grigoriadou M., Petersen M.B., Shahin H., Kanaan M. , King M.C., Chen Z.Y., Blanton S.H., Liu X.Z., Zuchner S., Akar N., Tekin M. Am. J. Hum. Genet. 86:797-804(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN DFNB91, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[15]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z22658 mRNA. Translation: CAA80373.1. S69272 mRNA. Translation: AAB30320.1. AK314578 mRNA. Translation: BAG37155.1. BX538343 mRNA. Translation: CAD98106.1. Different initiation. AL133351 Genomic DNA. Translation: CAI23292.1. CH471087 Genomic DNA. Translation: EAW55097.1. BC001394 mRNA. Translation: AAH01394.1. BC098564 mRNA. Translation: AAH98564.1. AB209563 mRNA. Translation: BAD92800.1. Different initiation.
IPI	IPI00413451.
PIR	A48681.
RefSeq	NP_001182220.2. NM_001195291.2. NP_001258751.1. NM_001271822.1. NP_001258752.1. NM_001271823.1. NP_001258753.1. NM_001271824.1. NP_001258754.1. NM_001271825.1. NP_004559.4. NM_004568.5.
UniGene	Hs.519523. Hs.731506.
3D structure databases
ProteinModelPortal	P35237.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35237. 1 interaction.
MINT	MINT-5005332.
STRING	9606.ENSP00000338358.
Protein family/group databases
MEROPS	I04.011.
PTM databases
PhosphoSite	P35237.
Polymorphism databases
DMDM	161784343.
2D gel databases
OGP	P35237.
Proteomic databases
PaxDb	P35237.
PRIDE	P35237.
Protocols and materials databases
DNASU	5269.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000335686; ENSP00000338358; ENSG00000124570. ENST00000380520; ENSP00000369891; ENSG00000124570. ENST00000380524; ENSP00000369896; ENSG00000124570. ENST00000380529; ENSP00000369901; ENSG00000124570. ENST00000380539; ENSP00000369912; ENSG00000124570. ENST00000380546; ENSP00000369919; ENSG00000124570.
GeneID	5269.
KEGG	hsa:5269.
UCSC	uc003mui.3. human.
Organism-specific databases
CTD	5269.
GeneCards	GC06M002948.
H-InvDB	HIX0005534.
HGNC	HGNC:8950. SERPINB6.
HPA	HPA009668. HPA012736.
MIM	173321. gene. 613453. phenotype.
neXtProt	NX_P35237.
Orphanet	90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
PharmGKB	PA35516.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4826.
HOGENOM	HOG000238519.
HOVERGEN	HBG005957.
InParanoid	P35237.
KO	K13963.
OMA	FKITYIG.
OrthoDB	EOG412M5X.
PhylomeDB	P35237.
Gene expression databases
ArrayExpress	P35237.
Bgee	P35237.
CleanEx	HS_SERPINB6.
Genevestigator	P35237.
GermOnline	ENSG00000124570. 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
ChiTaRS	SERPINB6. human.
DrugBank	DB00055. Drotrecogin alfa.
GenomeRNAi	5269.
NextBio	20356.
SOURCE	Search...

Entry information

Entry name

SPB6_HUMAN

Accession

Primary (citable) accession number: P35237
Secondary accession number(s): B2RBA8 , Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	December 4, 2007
Last modified:	May 29, 2013
This is version 130 of the entry and version 3 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.