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Protein

Caspase recruitment domain-containing protein 14

Gene

CARD14

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

Functioni

Plays a role in signaling mediated by TRAF2, TRAF3 and TRAF6 and protects cells against apoptosis. Activates NF-kappa-B via BCL10 and IKK. Stimulates the phosphorylation of BCL10.1 Publication

GO - Molecular functioni

  • CARD domain binding Source: UniProtKB

GO - Biological processi

  • activation of NF-kappaB-inducing kinase activity Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141527-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase recruitment domain-containing protein 14
Alternative name(s):
CARD-containing MAGUK protein 2
Short name:
Carma 2
Gene namesi
Name:CARD14
Synonyms:CARMA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:16446. CARD14.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Psoriasis 2 (PSORS2)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.
See also OMIM:602723
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068224117G → S in PSORS2; may result in altered splicing of exon 3; results in increased NF-kappa-B activation. 2 PublicationsCorresponds to variant rs281875215dbSNPEnsembl.1
Natural variantiVAR_068225138E → A in PSORS2; results in increased NF-kappa-B activation. 2 PublicationsCorresponds to variant rs281875214dbSNPEnsembl.1
Natural variantiVAR_068226142E → G in PSORS2; results in increased NF-kappa-B activation. 1 PublicationCorresponds to variant rs281875213dbSNPEnsembl.1
Natural variantiVAR_068227142E → K in PSORS2; results in increased NF-kappa-B activation. 1 PublicationCorresponds to variant rs281875212dbSNPEnsembl.1
Pityriasis rubra pilaris (PRP)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare, papulosquamous skin disease characterized by the appearance of keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Most cases are sporadic. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression. Familial PRP usually presents at birth or appears during the first years of life and runs a chronic course. It is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema.
See also OMIM:173200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068819138Missing in PRP. 1 Publication1
Natural variantiVAR_068820156L → P in PRP. 1 PublicationCorresponds to variant rs387907240dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi79092.
MalaCardsiCARD14.
MIMi173200. phenotype.
602723. phenotype.
OpenTargetsiENSG00000141527.
Orphaneti2897. Pityriasis rubra pilaris.
PharmGKBiPA134959119.

Polymorphism and mutation databases

BioMutaiCARD14.
DMDMi296434421.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001440881 – 1004Caspase recruitment domain-containing protein 14Add BLAST1004

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei544PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9BXL6.
PaxDbiQ9BXL6.
PeptideAtlasiQ9BXL6.
PRIDEiQ9BXL6.

PTM databases

iPTMnetiQ9BXL6.
PhosphoSitePlusiQ9BXL6.

Expressioni

Tissue specificityi

Isoform 1 is detected in placenta and epidermal keratinocytes. Isoform 2 is detected in leukocytes and fetal brain.1 Publication

Gene expression databases

BgeeiENSG00000141527.
CleanExiHS_CARD14.
ExpressionAtlasiQ9BXL6. baseline and differential.
GenevisibleiQ9BXL6. HS.

Organism-specific databases

HPAiHPA022533.
HPA023388.

Interactioni

Subunit structurei

Interacts with BCL10 by CARD-CARD interaction. Interacts with TRAF2, TRAF3 and TRAF6.1 Publication

GO - Molecular functioni

  • CARD domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122540. 7 interactors.
IntActiQ9BXL6. 6 interactors.
MINTiMINT-193865.
STRINGi9606.ENSP00000344549.

Structurei

3D structure databases

ProteinModelPortaliQ9BXL6.
SMRiQ9BXL6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 107CARDPROSITE-ProRule annotationAdd BLAST93
Domaini568 – 658PDZPROSITE-ProRule annotationAdd BLAST91
Domaini807 – 990Guanylate kinase-likePROSITE-ProRule annotationAdd BLAST184

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili128 – 409Sequence analysisAdd BLAST282

Sequence similaritiesi

Contains 1 CARD domain.PROSITE-ProRule annotation
Contains 1 guanylate kinase-like domain.PROSITE-ProRule annotation
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0708. Eukaryota.
COG0194. LUCA.
GeneTreeiENSGT00530000063108.
HOGENOMiHOG000049174.
HOVERGENiHBG106927.
InParanoidiQ9BXL6.
OMAiMEKNTHA.
OrthoDBiEOG091G0T58.
PhylomeDBiQ9BXL6.
TreeFamiTF315606.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
2.30.42.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR008145. GK/Ca_channel_bsu.
IPR008144. Guanylate_kin-like_dom.
IPR027417. P-loop_NTPase.
IPR001478. PDZ.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
PF00625. Guanylate_kin. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS50052. GUANYLATE_KINASE_2. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BXL6-1) [UniParc]FASTAAdd to basket
Also known as: CARMA2fl

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.

« Hide

        10         20         30         40         50
MGELCRRDSA LTALDEETLW EMMESHRHRI VRCICPSRLT PYLRQAKVLC
60 70 80 90 100
QLDEEEVLHS PRLTNSAMRA GHLLDLLKTR GKNGAIAFLE SLKFHNPDVY
110 120 130 140 150
TLVTGLQPDV DFSNFSGLME TSKLTECLAG AIGSLQEELN QEKGQKEVLL
160 170 180 190 200
RRCQQLQEHL GLAETRAEGL HQLEADHSRM KREVSAHFHE VLRLKDEMLS
210 220 230 240 250
LSLHYSNALQ EKELAASRCR SLQEELYLLK QELQRANMVS SCELELQEQS
260 270 280 290 300
LRTASDQESG DEELNRLKEE NEKLRSLTFS LAEKDILEQS LDEARGSRQE
310 320 330 340 350
LVERIHSLRE RAVAAERQRE QYWEEKEQTL LQFQKSKMAC QLYREKVNAL
360 370 380 390 400
QAQVCELQKE RDQAYSARDS AQREISQSLV EKDSLRRQVF ELTDQVCELR
410 420 430 440 450
TQLRQLQAEP PGVLKQEART REPCPREKQR LVRMHAICPR DDSDCSLVSS
460 470 480 490 500
TESQLLSDLS ATSSRELVDS FRSSSPAPPS QQSLYKRVAE DFGEEPWSFS
510 520 530 540 550
SCLEIPEGDP GALPGAKAGD PHLDYELLDT ADLPQLESSL QPVSPGRLDV
560 570 580 590 600
SESGVLMRRR PARRILSQVT MLAFQGDALL EQISVIGGNL TGIFIHRVTP
610 620 630 640 650
GSAADQMALR PGTQIVMVDY EASEPLFKAV LEDTTLEEAV GLLRRVDGFC
660 670 680 690 700
CLSVKVNTDG YKRLLQDLEA KVATSGDSFY IRVNLAMEGR AKGELQVHCN
710 720 730 740 750
EVLHVTDTMF QGCGCWHAHR VNSYTMKDTA AHGTIPNYSR AQQQLIALIQ
760 770 780 790 800
DMTQQCTVTR KPSSGGPQKL VRIVSMDKAK ASPLRLSFDR GQLDPSRMEG
810 820 830 840 850
SSTCFWAESC LTLVPYTLVR PHRPARPRPV LLVPRAVGKI LSEKLCLLQG
860 870 880 890 900
FKKCLAEYLS QEEYEAWSQR GDIIQEGEVS GGRCWVTRHA VESLMEKNTH
910 920 930 940 950
ALLDVQLDSV CTLHRMDIFP IVIHVSVNEK MAKKLKKGLQ RLGTSEEQLL
960 970 980 990 1000
EAARQEEGDL DRAPCLYSSL APDGWSDLDG LLSCVRQAIA DEQKKVVWTE

QSPR
Length:1,004
Mass (Da):113,270
Last modified:May 18, 2010 - v2
Checksum:i761CBAC219956076
GO
Isoform 2 (identifier: Q9BXL6-2) [UniParc]FASTAAdd to basket
Also known as: Short, CARMA2sh

The sequence of this isoform differs from the canonical sequence as follows:
     741-1004: Missing.

Show »
Length:740
Mass (Da):83,679
Checksum:i90FCA1B1C2DB28D1
GO
Isoform 3 (identifier: Q9BXL6-3) [UniParc]FASTAAdd to basket
Also known as: Cardless, CARMA2cl

The sequence of this isoform differs from the canonical sequence as follows:
     1-237: Missing.
     619-671: DYEASEPLFK...KRLLQDLEAK → SRARPLLSPG...WADVKRSAHL
     672-1004: Missing.

Show »
Length:434
Mass (Da):48,505
Checksum:iD351699781B6D6EB
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06822238R → C.1 PublicationCorresponds to variant rs281875217dbSNPEnsembl.1
Natural variantiVAR_06822362R → Q.1 PublicationCorresponds to variant rs115582620dbSNPEnsembl.1
Natural variantiVAR_068224117G → S in PSORS2; may result in altered splicing of exon 3; results in increased NF-kappa-B activation. 2 PublicationsCorresponds to variant rs281875215dbSNPEnsembl.1
Natural variantiVAR_068225138E → A in PSORS2; results in increased NF-kappa-B activation. 2 PublicationsCorresponds to variant rs281875214dbSNPEnsembl.1
Natural variantiVAR_068819138Missing in PRP. 1 Publication1
Natural variantiVAR_068226142E → G in PSORS2; results in increased NF-kappa-B activation. 1 PublicationCorresponds to variant rs281875213dbSNPEnsembl.1
Natural variantiVAR_068227142E → K in PSORS2; results in increased NF-kappa-B activation. 1 PublicationCorresponds to variant rs281875212dbSNPEnsembl.1
Natural variantiVAR_068228150L → R.1 PublicationCorresponds to variant rs146214639dbSNPEnsembl.1
Natural variantiVAR_068820156L → P in PRP. 1 PublicationCorresponds to variant rs387907240dbSNPEnsembl.1
Natural variantiVAR_068229171H → N May be associated with susceptibility to psoriasis. 1 PublicationCorresponds to variant rs281875216dbSNPEnsembl.1
Natural variantiVAR_068230176D → H.1 PublicationCorresponds to variant rs144475004dbSNPEnsembl.1
Natural variantiVAR_068231179R → H.1 PublicationCorresponds to variant rs199517469dbSNPEnsembl.1
Natural variantiVAR_068232191V → L.1 PublicationCorresponds to variant rs281875218dbSNPEnsembl.1
Natural variantiVAR_068233200S → N.1 PublicationCorresponds to variant rs114688446dbSNPEnsembl.1
Natural variantiVAR_068234285D → G May be associated with susceptibility to psoriasis. 1 PublicationCorresponds to variant rs281875219dbSNPEnsembl.1
Natural variantiVAR_024401547R → S.Corresponds to variant rs2066964dbSNPEnsembl.1
Natural variantiVAR_048608585V → I.Corresponds to variant rs34367357dbSNPEnsembl.1
Natural variantiVAR_068235593I → N.1 PublicationCorresponds to variant rs281875220dbSNPEnsembl.1
Natural variantiVAR_068236682R → W.1 PublicationCorresponds to variant rs117918077dbSNPEnsembl.1
Natural variantiVAR_068237714G → S.1 PublicationCorresponds to variant rs151150961dbSNPEnsembl.1
Natural variantiVAR_059196820R → W.2 PublicationsCorresponds to variant rs11652075dbSNPEnsembl.1
Natural variantiVAR_022043883R → H.Corresponds to variant rs2289541dbSNPEnsembl.1
Natural variantiVAR_061080962R → Q.Corresponds to variant rs34850974dbSNPEnsembl.1
Natural variantiVAR_068238973D → E.1 PublicationCorresponds to variant rs144285237dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0474001 – 237Missing in isoform 3. 2 PublicationsAdd BLAST237
Alternative sequenceiVSP_047401619 – 671DYEAS…DLEAK → SRARPLLSPGLLMGTVAAGG VTQADFTSPRRCRSTLGWAS ALSWADVKRSAHL in isoform 3. 2 PublicationsAdd BLAST53
Alternative sequenceiVSP_047402672 – 1004Missing in isoform 3. 2 PublicationsAdd BLAST333
Alternative sequenceiVSP_047403741 – 1004Missing in isoform 2. 2 PublicationsAdd BLAST264

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF322642 mRNA. Translation: AAG53403.1.
AY032927 mRNA. Translation: AAK54453.1.
EU652409 mRNA. Translation: ACF49506.1.
AC087741 Genomic DNA. No translation available.
BC018142 mRNA. Translation: AAH18142.1.
BC001326 mRNA. Translation: AAH01326.1.
CCDSiCCDS11768.1. [Q9BXL6-1]
CCDS58605.1. [Q9BXL6-2]
RefSeqiNP_001244899.1. NM_001257970.1. [Q9BXL6-2]
NP_077015.2. NM_024110.4. [Q9BXL6-1]
NP_438170.1. NM_052819.2. [Q9BXL6-3]
XP_011523514.1. XM_011525212.1. [Q9BXL6-1]
XP_011523515.1. XM_011525213.1. [Q9BXL6-1]
XP_011523517.1. XM_011525215.1. [Q9BXL6-1]
XP_011523518.1. XM_011525216.1. [Q9BXL6-1]
XP_011523519.1. XM_011525217.1. [Q9BXL6-1]
XP_011523520.1. XM_011525218.2. [Q9BXL6-1]
UniGeneiHs.675480.
Hs.696253.
Hs.735899.

Genome annotation databases

EnsembliENST00000344227; ENSP00000344549; ENSG00000141527. [Q9BXL6-1]
ENST00000570421; ENSP00000461806; ENSG00000141527. [Q9BXL6-2]
ENST00000573882; ENSP00000458715; ENSG00000141527. [Q9BXL6-1]
GeneIDi79092.
KEGGihsa:79092.
UCSCiuc002jxw.3. human. [Q9BXL6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Caspase recruitment domain family, member 14 (CARD14)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF322642 mRNA. Translation: AAG53403.1.
AY032927 mRNA. Translation: AAK54453.1.
EU652409 mRNA. Translation: ACF49506.1.
AC087741 Genomic DNA. No translation available.
BC018142 mRNA. Translation: AAH18142.1.
BC001326 mRNA. Translation: AAH01326.1.
CCDSiCCDS11768.1. [Q9BXL6-1]
CCDS58605.1. [Q9BXL6-2]
RefSeqiNP_001244899.1. NM_001257970.1. [Q9BXL6-2]
NP_077015.2. NM_024110.4. [Q9BXL6-1]
NP_438170.1. NM_052819.2. [Q9BXL6-3]
XP_011523514.1. XM_011525212.1. [Q9BXL6-1]
XP_011523515.1. XM_011525213.1. [Q9BXL6-1]
XP_011523517.1. XM_011525215.1. [Q9BXL6-1]
XP_011523518.1. XM_011525216.1. [Q9BXL6-1]
XP_011523519.1. XM_011525217.1. [Q9BXL6-1]
XP_011523520.1. XM_011525218.2. [Q9BXL6-1]
UniGeneiHs.675480.
Hs.696253.
Hs.735899.

3D structure databases

ProteinModelPortaliQ9BXL6.
SMRiQ9BXL6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122540. 7 interactors.
IntActiQ9BXL6. 6 interactors.
MINTiMINT-193865.
STRINGi9606.ENSP00000344549.

PTM databases

iPTMnetiQ9BXL6.
PhosphoSitePlusiQ9BXL6.

Polymorphism and mutation databases

BioMutaiCARD14.
DMDMi296434421.

Proteomic databases

MaxQBiQ9BXL6.
PaxDbiQ9BXL6.
PeptideAtlasiQ9BXL6.
PRIDEiQ9BXL6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344227; ENSP00000344549; ENSG00000141527. [Q9BXL6-1]
ENST00000570421; ENSP00000461806; ENSG00000141527. [Q9BXL6-2]
ENST00000573882; ENSP00000458715; ENSG00000141527. [Q9BXL6-1]
GeneIDi79092.
KEGGihsa:79092.
UCSCiuc002jxw.3. human. [Q9BXL6-1]

Organism-specific databases

CTDi79092.
DisGeNETi79092.
GeneCardsiCARD14.
H-InvDBHIX0173685.
HGNCiHGNC:16446. CARD14.
HPAiHPA022533.
HPA023388.
MalaCardsiCARD14.
MIMi173200. phenotype.
602723. phenotype.
607211. gene.
neXtProtiNX_Q9BXL6.
OpenTargetsiENSG00000141527.
Orphaneti2897. Pityriasis rubra pilaris.
PharmGKBiPA134959119.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0708. Eukaryota.
COG0194. LUCA.
GeneTreeiENSGT00530000063108.
HOGENOMiHOG000049174.
HOVERGENiHBG106927.
InParanoidiQ9BXL6.
OMAiMEKNTHA.
OrthoDBiEOG091G0T58.
PhylomeDBiQ9BXL6.
TreeFamiTF315606.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141527-MONOMER.

Miscellaneous databases

ChiTaRSiCARD14. human.
GeneWikiiCARD14.
GenomeRNAii79092.
PROiQ9BXL6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141527.
CleanExiHS_CARD14.
ExpressionAtlasiQ9BXL6. baseline and differential.
GenevisibleiQ9BXL6. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
2.30.42.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR008145. GK/Ca_channel_bsu.
IPR008144. Guanylate_kin-like_dom.
IPR027417. P-loop_NTPase.
IPR001478. PDZ.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
PF00625. Guanylate_kin. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS50052. GUANYLATE_KINASE_2. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCAR14_HUMAN
AccessioniPrimary (citable) accession number: Q9BXL6
Secondary accession number(s): B8QQJ3, Q9BVB5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 138 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

Caution

Supposed to contain a SH3 domain which is not detected by PROSITE, Pfam or SMART.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. 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.