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Protein

Baculoviral IAP repeat-containing protein 3

Gene

BIRC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8.2 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.2 Publications

Enzyme regulationi

USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi292ZincPROSITE-ProRule annotation1
Metal bindingi295ZincPROSITE-ProRule annotation1
Metal bindingi312ZincPROSITE-ProRule annotation1
Metal bindingi319ZincPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri557 – 592RING-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

GO - Biological processi

  • cell surface receptor signaling pathway Source: ProtInc
  • I-kappaB kinase/NF-kappaB signaling Source: Reactome
  • inhibition of cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
  • negative regulation of apoptotic process Source: ProtInc
  • negative regulation of necroptotic process Source: GO_Central
  • NIK/NF-kappaB signaling Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
  • protein heterooligomerization Source: Ensembl
  • regulation of apoptotic process Source: UniProtKB
  • regulation of cysteine-type endopeptidase activity Source: UniProtKB
  • regulation of inflammatory response Source: UniProtKB
  • regulation of innate immune response Source: UniProtKB
  • regulation of necroptotic process Source: UniProtKB
  • regulation of necrotic cell death Source: Reactome
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway Source: UniProtKB
  • regulation of RIG-I signaling pathway Source: UniProtKB
  • regulation of toll-like receptor signaling pathway Source: UniProtKB
  • regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
  • spermatogenesis Source: Ensembl
  • TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  • tumor necrosis factor-mediated signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Apoptosis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-5213460. RIPK1-mediated regulated necrosis.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5675482. Regulation of necroptotic cell death.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
SignaLinkiQ13489.
SIGNORiQ13489.

Protein family/group databases

MEROPSiI32.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Baculoviral IAP repeat-containing protein 3 (EC:2.3.2.272 Publications)
Alternative name(s):
Apoptosis inhibitor 2
Short name:
API2
Cellular inhibitor of apoptosis 2
Short name:
C-IAP21 Publication
IAP homolog C
Inhibitor of apoptosis protein 1
Short name:
hIAP-1
Short name:
hIAP1
RING finger protein 49
RING-type E3 ubiquitin transferase BIRC3Curated
TNFR2-TRAF-signaling complex protein 1
Gene namesi
Name:BIRC3
Synonyms:API2, MIHC, RNF49
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:591. BIRC3.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • membrane raft Source: Ensembl
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving BIRC3 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with MALT1. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei442 – 443Breakpoint for translocation to form BIRC3-MALT12

Organism-specific databases

DisGeNETi330.
MalaCardsiBIRC3.
OpenTargetsiENSG00000023445.
Orphaneti52417. MALT lymphoma.
PharmGKBiPA25360.

Chemistry databases

ChEMBLiCHEMBL5335.
GuidetoPHARMACOLOGYi2792.

Polymorphism and mutation databases

BioMutaiBIRC3.
DMDMi2497236.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001223491 – 604Baculoviral IAP repeat-containing protein 3Add BLAST604

Post-translational modificationi

Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ13489.
MaxQBiQ13489.
PaxDbiQ13489.
PeptideAtlasiQ13489.
PRIDEiQ13489.

PTM databases

iPTMnetiQ13489.
PhosphoSitePlusiQ13489.

Miscellaneous databases

PMAP-CutDBQ13489.

Expressioni

Tissue specificityi

Highly expressed in fetal lung, and kidney. In the adult, expression is mainly seen in lymphoid tissues, including spleen, thymus and peripheral blood lymphocytes.

Gene expression databases

BgeeiENSG00000023445.
CleanExiHS_BIRC3.
ExpressionAtlasiQ13489. baseline and differential.
GenevisibleiQ13489. HS.

Organism-specific databases

HPAiHPA002317.

Interactioni

Subunit structurei

Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. The BIR motifs region interacts with TNF receptor associated factors 1 and 2 (TRAF1 and TRAF2) to form a heteromeric complex, which is then recruited to the tumor necrosis factor receptor 2 (TNFR2). Interaction with TRAF2 is required for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Interacts with RIP1, RIP2, RIP3, RIP4 and USP19.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CASP9P552112EBI-517709,EBI-516799
RIPK1Q135463EBI-517709,EBI-358507
RIPK2O433533EBI-517709,EBI-358522
RIPK3Q9Y5723EBI-517709,EBI-298250
RIPK4P570783EBI-517709,EBI-4422308
TRAF1Q130772EBI-517709,EBI-359224
TRAF2Q129337EBI-517709,EBI-355744
UBE2NP610882EBI-517709,EBI-1052908

Protein-protein interaction databases

BioGridi106827. 77 interactors.
DIPiDIP-33720N.
IntActiQ13489. 39 interactors.
MINTiMINT-216139.
STRINGi9606.ENSP00000263464.

Chemistry databases

BindingDBiQ13489.

Structurei

Secondary structure

1604
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi28 – 34Combined sources7
Helixi35 – 38Combined sources4
Helixi47 – 52Combined sources6
Beta strandi55 – 57Combined sources3
Beta strandi64 – 66Combined sources3
Turni67 – 69Combined sources3
Helixi82 – 89Combined sources8
Turni94 – 97Combined sources4
Helixi250 – 252Combined sources3
Helixi255 – 260Combined sources6
Helixi261 – 264Combined sources4
Helixi273 – 278Combined sources6
Beta strandi281 – 285Combined sources5
Turni286 – 288Combined sources3
Beta strandi289 – 292Combined sources4
Turni293 – 295Combined sources3
Beta strandi298 – 301Combined sources4
Helixi308 – 315Combined sources8
Helixi320 – 334Combined sources15
Helixi544 – 555Combined sources12
Turni558 – 560Combined sources3
Beta strandi561 – 564Combined sources4
Beta strandi567 – 570Combined sources4
Beta strandi575 – 577Combined sources3
Turni579 – 581Combined sources3
Helixi582 – 584Combined sources3
Beta strandi589 – 591Combined sources3
Beta strandi597 – 600Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2UVLX-ray1.91A/B244-337[»]
3EB5X-ray2.00A536-604[»]
3EB6X-ray3.40A536-604[»]
3M0AX-ray2.61D26-99[»]
3M0DX-ray2.80D26-99[»]
ProteinModelPortaliQ13489.
SMRiQ13489.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13489.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati29 – 96BIR 1Add BLAST68
Repeati169 – 235BIR 2Add BLAST67
Repeati255 – 322BIR 3Add BLAST68
Domaini439 – 529CARDPROSITE-ProRule annotationAdd BLAST91

Sequence similaritiesi

Belongs to the IAP family.Curated
Contains 3 BIR repeats.PROSITE-ProRule annotation
Contains 1 CARD domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri557 – 592RING-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1101. Eukaryota.
ENOG410YPNM. LUCA.
GeneTreeiENSGT00500000044782.
HOGENOMiHOG000232059.
HOVERGENiHBG004848.
InParanoidiQ13489.
KOiK16060.
OMAiCAMNTEK.
OrthoDBiEOG091G0CXH.
PhylomeDBiQ13489.
TreeFamiTF105356.

Family and domain databases

CDDicd00022. BIR. 3 hits.
Gene3Di1.10.1170.10. 4 hits.
1.10.533.10. 1 hit.
InterProiIPR001370. BIR_rpt.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001841. Znf_RING.
[Graphical view]
PfamiPF00653. BIR. 3 hits.
PF00619. CARD. 1 hit.
[Graphical view]
SMARTiSM00238. BIR. 3 hits.
SM00114. CARD. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50209. CARD. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q13489-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNIVENSIFL SNLMKSANTF ELKYDLSCEL YRMSTYSTFP AGVPVSERSL
60 70 80 90 100
ARAGFYYTGV NDKVKCFCCG LMLDNWKRGD SPTEKHKKLY PSCRFVQSLN
110 120 130 140 150
SVNNLEATSQ PTFPSSVTNS THSLLPGTEN SGYFRGSYSN SPSNPVNSRA
160 170 180 190 200
NQDFSALMRS SYHCAMNNEN ARLLTFQTWP LTFLSPTDLA KAGFYYIGPG
210 220 230 240 250
DRVACFACGG KLSNWEPKDN AMSEHLRHFP KCPFIENQLQ DTSRYTVSNL
260 270 280 290 300
SMQTHAARFK TFFNWPSSVL VNPEQLASAG FYYVGNSDDV KCFCCDGGLR
310 320 330 340 350
CWESGDDPWV QHAKWFPRCE YLIRIKGQEF IRQVQASYPH LLEQLLSTSD
360 370 380 390 400
SPGDENAESS IIHFEPGEDH SEDAIMMNTP VINAAVEMGF SRSLVKQTVQ
410 420 430 440 450
RKILATGENY RLVNDLVLDL LNAEDEIREE ERERATEEKE SNDLLLIRKN
460 470 480 490 500
RMALFQHLTC VIPILDSLLT AGIINEQEHD VIKQKTQTSL QARELIDTIL
510 520 530 540 550
VKGNIAATVF RNSLQEAEAV LYEHLFVQQD IKYIPTEDVS DLPVEEQLRR
560 570 580 590 600
LQEERTCKVC MDKEVSIVFI PCGHLVVCKD CAPSLRKCPI CRSTIKGTVR

TFLS
Length:604
Mass (Da):68,372
Last modified:November 1, 1997 - v2
Checksum:i8581A00BA9AAB4A7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18N → Y in AAC83232 (PubMed:10233894).Curated1
Sequence conflicti119N → H in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti153D → E in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti163H → P in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti165A → P in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti191K → R in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti364F → L in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti552Q → P in AAC50371 (PubMed:8552191).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021069260K → R.1 PublicationCorresponds to variant rs2276113dbSNPEnsembl.1
Natural variantiVAR_049536386V → M.Corresponds to variant rs12222256dbSNPEnsembl.1
Natural variantiVAR_021070401R → K.1 PublicationCorresponds to variant rs17881197dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L49432 mRNA. Translation: AAC41943.1.
U45878 mRNA. Translation: AAC50371.1.
U37546 mRNA. Translation: AAC50507.1.
AF070674 mRNA. Translation: AAC83232.1.
AY764389 Genomic DNA. Translation: AAU88144.1.
BC037420 mRNA. Translation: AAH37420.1.
AF178945 Genomic DNA. Translation: AAG09369.1.
CCDSiCCDS8315.1.
PIRiS68449.
RefSeqiNP_001156.1. NM_001165.4.
NP_892007.1. NM_182962.2.
XP_016873132.1. XM_017017643.1.
UniGeneiHs.127799.

Genome annotation databases

EnsembliENST00000263464; ENSP00000263464; ENSG00000023445.
ENST00000532808; ENSP00000432907; ENSG00000023445.
ENST00000615299; ENSP00000481903; ENSG00000023445.
GeneIDi330.
KEGGihsa:330.
UCSCiuc001pgx.5. human.

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L49432 mRNA. Translation: AAC41943.1.
U45878 mRNA. Translation: AAC50371.1.
U37546 mRNA. Translation: AAC50507.1.
AF070674 mRNA. Translation: AAC83232.1.
AY764389 Genomic DNA. Translation: AAU88144.1.
BC037420 mRNA. Translation: AAH37420.1.
AF178945 Genomic DNA. Translation: AAG09369.1.
CCDSiCCDS8315.1.
PIRiS68449.
RefSeqiNP_001156.1. NM_001165.4.
NP_892007.1. NM_182962.2.
XP_016873132.1. XM_017017643.1.
UniGeneiHs.127799.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2UVLX-ray1.91A/B244-337[»]
3EB5X-ray2.00A536-604[»]
3EB6X-ray3.40A536-604[»]
3M0AX-ray2.61D26-99[»]
3M0DX-ray2.80D26-99[»]
ProteinModelPortaliQ13489.
SMRiQ13489.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106827. 77 interactors.
DIPiDIP-33720N.
IntActiQ13489. 39 interactors.
MINTiMINT-216139.
STRINGi9606.ENSP00000263464.

Chemistry databases

BindingDBiQ13489.
ChEMBLiCHEMBL5335.
GuidetoPHARMACOLOGYi2792.

Protein family/group databases

MEROPSiI32.003.

PTM databases

iPTMnetiQ13489.
PhosphoSitePlusiQ13489.

Polymorphism and mutation databases

BioMutaiBIRC3.
DMDMi2497236.

Proteomic databases

EPDiQ13489.
MaxQBiQ13489.
PaxDbiQ13489.
PeptideAtlasiQ13489.
PRIDEiQ13489.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263464; ENSP00000263464; ENSG00000023445.
ENST00000532808; ENSP00000432907; ENSG00000023445.
ENST00000615299; ENSP00000481903; ENSG00000023445.
GeneIDi330.
KEGGihsa:330.
UCSCiuc001pgx.5. human.

Organism-specific databases

CTDi330.
DisGeNETi330.
GeneCardsiBIRC3.
HGNCiHGNC:591. BIRC3.
HPAiHPA002317.
MalaCardsiBIRC3.
MIMi601721. gene.
neXtProtiNX_Q13489.
OpenTargetsiENSG00000023445.
Orphaneti52417. MALT lymphoma.
PharmGKBiPA25360.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1101. Eukaryota.
ENOG410YPNM. LUCA.
GeneTreeiENSGT00500000044782.
HOGENOMiHOG000232059.
HOVERGENiHBG004848.
InParanoidiQ13489.
KOiK16060.
OMAiCAMNTEK.
OrthoDBiEOG091G0CXH.
PhylomeDBiQ13489.
TreeFamiTF105356.

Enzyme and pathway databases

ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-5213460. RIPK1-mediated regulated necrosis.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5675482. Regulation of necroptotic cell death.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
SignaLinkiQ13489.
SIGNORiQ13489.

Miscellaneous databases

ChiTaRSiBIRC3. human.
EvolutionaryTraceiQ13489.
GeneWikiiBaculoviral_IAP_repeat-containing_protein_3.
GenomeRNAii330.
PMAP-CutDBQ13489.
PROiQ13489.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000023445.
CleanExiHS_BIRC3.
ExpressionAtlasiQ13489. baseline and differential.
GenevisibleiQ13489. HS.

Family and domain databases

CDDicd00022. BIR. 3 hits.
Gene3Di1.10.1170.10. 4 hits.
1.10.533.10. 1 hit.
InterProiIPR001370. BIR_rpt.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001841. Znf_RING.
[Graphical view]
PfamiPF00653. BIR. 3 hits.
PF00619. CARD. 1 hit.
[Graphical view]
SMARTiSM00238. BIR. 3 hits.
SM00114. CARD. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50209. CARD. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBIRC3_HUMAN
AccessioniPrimary (citable) accession number: Q13489
Secondary accession number(s): Q16628, Q9HC27, Q9UP46
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 175 of the entry and version 2 of the sequence. [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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.