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Protein

Serpin A12

Gene

SERPINA12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues.4 Publications

Activity regulationi

Inhibition of KLK7 is enhanced by heparin.2 Publications

Temperature dependencei

Highly thermostable, with a Tm value of 70 degrees Celsius. Incubation at 60 degrees Celsius for two hours has no apparent effect on KLK7 inhibition activity. Polymerization is observed at 70 degrees Celsius and above.2 Publications

GO - Molecular functioni

  • serine-type endopeptidase inhibitor activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor

Protein family/group databases

MEROPSiI04.091

Names & Taxonomyi

Protein namesi
Recommended name:
Serpin A12
Alternative name(s):
OL-64
Visceral adipose tissue-derived serine protease inhibitor
Short name:
Vaspin
Visceral adipose-specific serpin
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000165953.9
HGNCiHGNC:18359 SERPINA12
MIMi617471 gene
neXtProtiNX_Q8IW75

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi221N → A: Reduced N-glycosylation. Loss of N-glycosylation; when associated with A-233 and A-267. 1 Publication1
Mutagenesisi233N → A: Reduced N-glycosylation. Loss of N-glycosylation; when associated with A-221 and A-267. 1 Publication1
Mutagenesisi267N → A: Reduced N-glycosylation. Loss of N-glycosylation; when associated with A-221 and A-233. 1 Publication1
Mutagenesisi302R → A or E: Significantly impairs KLK7 inhibition activity. Slightly enhances KLK7 inhibition activity; when associated with S-379. 1 Publication1
Mutagenesisi305D → C: Results in formation of an artificial disulfide bond which stabilizes the reactive center loop and enhances KLK7 inhibition activity; when associated with C-383. 1 Publication1
Mutagenesisi365T → R: Fails to inhibit KLK7 activity. Increased protein stability in cleaved form and conformational changes which may allow escape of the substrate. 2 Publications1
Mutagenesisi369A → P: Fails to inhibit KLK7 activity. Increased protein stability in cleaved form and conformational changes which may allow escape of the substrate. 2 Publications1
Mutagenesisi379E → S: Significantly enhances KLK7 inhibition activity. Slightly enhances KLK7 inhibition activity; when associated with E-302. 1 Publication1
Mutagenesisi383V → C: Results in formation of an artificial disulfide bond which stabilizes the reactive center loop and enhances KLK7 inhibition activity; when associated with C-305. 1 Publication1

Organism-specific databases

DisGeNETi145264
OpenTargetsiENSG00000165953
PharmGKBiPA134863157

Polymorphism and mutation databases

BioMutaiSERPINA12
DMDMi74728144

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20By similarityAdd BLAST20
ChainiPRO_000004197621 – 414Serpin A12Add BLAST394

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi221N-linked (GlcNAc...) (complex) asparagine1 Publication1
Glycosylationi233N-linked (GlcNAc...) (complex) asparagine1 Publication1
Glycosylationi267N-linked (GlcNAc...) (high mannose) asparagine1 Publication1

Post-translational modificationi

Glycosylation slightly decreases affinity for heparin, but otherwise has no significant effect on KLK7 inhibitory activity or thermal stability of the protein.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei378 – 379Cleavage1 Publication2

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8IW75
PeptideAtlasiQ8IW75
PRIDEiQ8IW75
ProteomicsDBi70821
TopDownProteomicsiQ8IW75

PTM databases

iPTMnetiQ8IW75
PhosphoSitePlusiQ8IW75

Expressioni

Tissue specificityi

Expressed in visceral adipose tissues.1 Publication

Gene expression databases

BgeeiENSG00000165953 Expressed in 65 organ(s), highest expression level in skin of leg
CleanExiHS_SERPINA12
GenevisibleiQ8IW75 HS

Interactioni

Subunit structurei

Forms a stable complex with KLK7.1 Publication

Protein-protein interaction databases

BioGridi126901, 48 interactors
IntActiQ8IW75, 1 interactor
STRINGi9606.ENSP00000342109

Structurei

Secondary structure

1414
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8IW75
SMRiQ8IW75
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni364 – 382Reactive center loop2 Publications1 PublicationAdd BLAST19

Domaini

The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.3 Publications

Sequence similaritiesi

Belongs to the serpin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2392 Eukaryota
COG4826 LUCA
GeneTreeiENSGT00760000118839
HOGENOMiHOG000238521
HOVERGENiHBG005957
InParanoidiQ8IW75
KOiK04525
OMAiRWQHEFD
OrthoDBiEOG091G0ION
PhylomeDBiQ8IW75
TreeFamiTF343201

Family and domain databases

InterProiView protein in InterPro
IPR023796 Serpin_dom
IPR000215 Serpin_fam
IPR036186 Serpin_sf
PANTHERiPTHR11461 PTHR11461, 1 hit
PfamiView protein in Pfam
PF00079 Serpin, 1 hit
SMARTiView protein in SMART
SM00093 SERPIN, 1 hit
SUPFAMiSSF56574 SSF56574, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8IW75-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNPTLGLAIF LAVLLTVKGL LKPSFSPRNY KALSEVQGWK QRMAAKELAR
60 70 80 90 100
QNMDLGFKLL KKLAFYNPGR NIFLSPLSIS TAFSMLCLGA QDSTLDEIKQ
110 120 130 140 150
GFNFRKMPEK DLHEGFHYII HELTQKTQDL KLSIGNTLFI DQRLQPQRKF
160 170 180 190 200
LEDAKNFYSA ETILTNFQNL EMAQKQINDF ISQKTHGKIN NLIENIDPGT
210 220 230 240 250
VMLLANYIFF RARWKHEFDP NVTKEEDFFL EKNSSVKVPM MFRSGIYQVG
260 270 280 290 300
YDDKLSCTIL EIPYQKNITA IFILPDEGKL KHLEKGLQVD TFSRWKTLLS
310 320 330 340 350
RRVVDVSVPR LHMTGTFDLK KTLSYIGVSK IFEEHGDLTK IAPHRSLKVG
360 370 380 390 400
EAVHKAELKM DERGTEGAAG TGAQTLPMET PLVVKIDKPY LLLIYSEKIP
410
SVLFLGKIVN PIGK
Length:414
Mass (Da):47,175
Last modified:March 1, 2003 - v1
Checksum:i5C70F1AB5935661C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051943142Q → K. Corresponds to variant dbSNP:rs17090972Ensembl.1
Natural variantiVAR_077875219D → G1 PublicationCorresponds to variant dbSNP:rs192558870Ensembl.1
Natural variantiVAR_051944394I → V. Corresponds to variant dbSNP:rs34519784Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY326420 mRNA Translation: AAP88384.1
AY177692 mRNA Translation: AAO18649.1
BC040857 mRNA Translation: AAH40857.1
CCDSiCCDS9926.1
RefSeqiNP_001291390.1, NM_001304461.1
NP_776249.1, NM_173850.3
XP_011534753.1, XM_011536451.2
XP_011534754.1, XM_011536452.2
XP_011534755.1, XM_011536453.2
XP_011534756.1, XM_011536454.2
XP_016876478.1, XM_017020989.1
XP_016876479.1, XM_017020990.1
UniGeneiHs.99476

Genome annotation databases

EnsembliENST00000341228; ENSP00000342109; ENSG00000165953
ENST00000556881; ENSP00000451738; ENSG00000165953
GeneIDi145264
KEGGihsa:145264
UCSCiuc001ydj.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY326420 mRNA Translation: AAP88384.1
AY177692 mRNA Translation: AAO18649.1
BC040857 mRNA Translation: AAH40857.1
CCDSiCCDS9926.1
RefSeqiNP_001291390.1, NM_001304461.1
NP_776249.1, NM_173850.3
XP_011534753.1, XM_011536451.2
XP_011534754.1, XM_011536452.2
XP_011534755.1, XM_011536453.2
XP_011534756.1, XM_011536454.2
XP_016876478.1, XM_017020989.1
XP_016876479.1, XM_017020990.1
UniGeneiHs.99476

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4IF8X-ray2.08A/B22-414[»]
4Y3KX-ray2.20A/B22-414[»]
4Y40X-ray2.20A/B22-414[»]
5EI0X-ray2.50A/E22-414[»]
ProteinModelPortaliQ8IW75
SMRiQ8IW75
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126901, 48 interactors
IntActiQ8IW75, 1 interactor
STRINGi9606.ENSP00000342109

Protein family/group databases

MEROPSiI04.091

PTM databases

iPTMnetiQ8IW75
PhosphoSitePlusiQ8IW75

Polymorphism and mutation databases

BioMutaiSERPINA12
DMDMi74728144

Proteomic databases

PaxDbiQ8IW75
PeptideAtlasiQ8IW75
PRIDEiQ8IW75
ProteomicsDBi70821
TopDownProteomicsiQ8IW75

Protocols and materials databases

DNASUi145264
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000341228; ENSP00000342109; ENSG00000165953
ENST00000556881; ENSP00000451738; ENSG00000165953
GeneIDi145264
KEGGihsa:145264
UCSCiuc001ydj.3 human

Organism-specific databases

CTDi145264
DisGeNETi145264
EuPathDBiHostDB:ENSG00000165953.9
GeneCardsiSERPINA12
HGNCiHGNC:18359 SERPINA12
MIMi617471 gene
neXtProtiNX_Q8IW75
OpenTargetsiENSG00000165953
PharmGKBiPA134863157
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2392 Eukaryota
COG4826 LUCA
GeneTreeiENSGT00760000118839
HOGENOMiHOG000238521
HOVERGENiHBG005957
InParanoidiQ8IW75
KOiK04525
OMAiRWQHEFD
OrthoDBiEOG091G0ION
PhylomeDBiQ8IW75
TreeFamiTF343201

Miscellaneous databases

GenomeRNAii145264
PROiPR:Q8IW75
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165953 Expressed in 65 organ(s), highest expression level in skin of leg
CleanExiHS_SERPINA12
GenevisibleiQ8IW75 HS

Family and domain databases

InterProiView protein in InterPro
IPR023796 Serpin_dom
IPR000215 Serpin_fam
IPR036186 Serpin_sf
PANTHERiPTHR11461 PTHR11461, 1 hit
PfamiView protein in Pfam
PF00079 Serpin, 1 hit
SMARTiView protein in SMART
SM00093 SERPIN, 1 hit
SUPFAMiSSF56574 SSF56574, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSPA12_HUMAN
AccessioniPrimary (citable) accession number: Q8IW75
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 125 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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