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Protein

Brefeldin A-inhibited guanine nucleotide-exchange protein 2

Gene

ARFGEF2

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

Functioni

Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways.7 Publications

Enzyme regulationi

Inhibited by brefeldin A.

GO - Molecular functioni

  • ARF guanyl-nucleotide exchange factor activity Source: UniProtKB
  • GABA receptor binding Source: UniProtKB
  • guanyl-nucleotide exchange factor activity Source: MGI
  • protein kinase A regulatory subunit binding Source: UniProtKB

GO - Biological processi

  • endomembrane system organization Source: UniProtKB
  • endosome organization Source: UniProtKB
  • exocytosis Source: ProtInc
  • Golgi to plasma membrane transport Source: UniProtKB
  • intracellular signal transduction Source: MGI
  • positive regulation of tumor necrosis factor production Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • receptor recycling Source: UniProtKB
  • regulation of ARF protein signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124198-MONOMER.
ReactomeiR-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Brefeldin A-inhibited guanine nucleotide-exchange protein 2
Short name:
Brefeldin A-inhibited GEP 2
Alternative name(s):
ADP-ribosylation factor guanine nucleotide-exchange factor 2
Gene namesi
Name:ARFGEF2
Synonyms:ARFGEP2, BIG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:15853. ARFGEF2.

Subcellular locationi

GO - Cellular componenti

  • asymmetric synapse Source: UniProtKB
  • axonemal microtubule Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: UniProtKB
  • cytosol Source: MGI
  • dendritic spine Source: UniProtKB
  • Golgi membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • microtubule organizing center Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • recycling endosome Source: UniProtKB
  • symmetric synapse Source: UniProtKB
  • trans-Golgi network Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endosome, Golgi apparatus, Membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Periventricular nodular heterotopia 2 (PVNH2)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH2 is an autosomal recessive form characterized by microcephaly (small brain), severe developmental delay and recurrent infections. No anomalies extrinsic to the central nervous system, such as dysmorphic features or grossly abnormal endocrine or other conditions, are associated with PVNH2.
See also OMIM:608097
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037438209E → K in PVNH2; unknown pathological significance. 1 PublicationCorresponds to variant rs28937880dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi289V → W: Abolishes interaction with PRKAR2B and impairs TNFRSF1A release. 1 Publication1
Mutagenesisi534V → W: Abolishes interaction with PRKAR2B and impairs TNFRSF1A release. 1 Publication1
Mutagenesisi738E → K: Disturbs membrane organization at the TGN, impairs association of the AP-1 complex and GGA1 with the TGN membranes. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10564.
MalaCardsiARFGEF2.
MIMi608097. phenotype.
OpenTargetsiENSG00000124198.
Orphaneti98892. Periventricular nodular heterotopia.
PharmGKBiPA24945.

Polymorphism and mutation databases

BioMutaiARFGEF2.
DMDMi146329988.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001202081 – 1785Brefeldin A-inhibited guanine nucleotide-exchange protein 2Add BLAST1785

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei214PhosphoserineCombined sources1
Modified residuei218PhosphoserineCombined sources1
Modified residuei227PhosphoserineCombined sources1
Modified residuei244PhosphothreonineCombined sources1
Modified residuei277PhosphoserineCombined sources1
Modified residuei348PhosphoserineBy similarity1
Modified residuei349PhosphoserineCombined sources1
Modified residuei614PhosphoserineCombined sources1
Modified residuei616PhosphothreonineBy similarity1
Modified residuei617PhosphoserineBy similarity1
Modified residuei626PhosphothreonineBy similarity1
Modified residuei700PhosphoserineCombined sources1
Modified residuei1511PhosphoserineCombined sources1
Modified residuei1513PhosphoserineBy similarity1
Modified residuei1514PhosphoserineBy similarity1
Modified residuei1525PhosphoserineCombined sources1
Modified residuei1528PhosphoserineCombined sources1
Modified residuei1534PhosphoserineBy similarity1
Modified residuei1782PhosphoserineCombined sources1

Post-translational modificationi

In vitro phosphorylated by PKA reducing its GEF activity and dephosphorylated by phosphatase PP1.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y6D5.
MaxQBiQ9Y6D5.
PaxDbiQ9Y6D5.
PeptideAtlasiQ9Y6D5.
PRIDEiQ9Y6D5.

PTM databases

iPTMnetiQ9Y6D5.
PhosphoSitePlusiQ9Y6D5.

Expressioni

Tissue specificityi

Expressed in placenta, lung, heart, brain, kidney and pancreas.

Gene expression databases

BgeeiENSG00000124198.
CleanExiHS_ARFGEF2.
GenevisibleiQ9Y6D5. HS.

Organism-specific databases

HPAiCAB026382.
HPA026078.

Interactioni

Subunit structurei

Homodimer (Probable). Interacts with ARFGEF1/BIG1; both proteins are probably part of the same or very similar macromolecular complexes. Interacts with PRKAR1A, PRKAR2A, PRKAR1B, PRKAR2B, PPP1CC, PDE3A, TNFRSF1A, MYCBP and EXOC7. Interacts with GABRB1, GABRB2 and GABRB3 (By similarity).By similarityCurated

Binary interactionsi

WithEntry#Exp.IntActNotes
ARFGEF1Q9Y6D63EBI-2837511,EBI-1044254
EXOC7Q9UPT5-14EBI-2837511,EBI-6251402
MYCBPQ994175EBI-2837511,EBI-716185

GO - Molecular functioni

  • GABA receptor binding Source: UniProtKB
  • protein kinase A regulatory subunit binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115815. 41 interactors.
DIPiDIP-48794N.
IntActiQ9Y6D5. 12 interactors.
MINTiMINT-1200143.
STRINGi9606.ENSP00000360985.

Structurei

Secondary structure

11785
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi641 – 643Combined sources3
Turni644 – 648Combined sources5
Helixi649 – 654Combined sources6
Helixi658 – 667Combined sources10
Turni674 – 678Combined sources5
Helixi679 – 682Combined sources4
Helixi690 – 694Combined sources5
Turni695 – 698Combined sources4
Turni702 – 705Combined sources4
Helixi706 – 712Combined sources7
Helixi723 – 729Combined sources7
Helixi739 – 753Combined sources15
Helixi766 – 777Combined sources12
Turni778 – 782Combined sources5
Turni796 – 798Combined sources3
Beta strandi799 – 801Combined sources3
Beta strandi804 – 808Combined sources5
Helixi812 – 822Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L8NX-ray2.86A635-836[»]
3SWVX-ray3.00A635-836[»]
ProteinModelPortaliQ9Y6D5.
SMRiQ9Y6D5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini654 – 785SEC7PROSITE-ProRule annotationAdd BLAST132

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 224DCB; DCB:DCB domain and DCB:HUS domain interactionAdd BLAST223
Regioni508 – 528HUS; DCB:HUS domain interactionAdd BLAST21

Sequence similaritiesi

Contains 1 SEC7 domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0929. Eukaryota.
COG5307. LUCA.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000181045.
HOVERGENiHBG004846.
InParanoidiQ9Y6D5.
KOiK18442.
OMAiHALYAVC.
OrthoDBiEOG091G00F0.
PhylomeDBiQ9Y6D5.
TreeFamiTF300714.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
1.25.10.10. 1 hit.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR032629. DCB_dom.
IPR023394. Sec7_alpha_orthog.
IPR015403. Sec7_C.
IPR000904. Sec7_dom.
IPR032691. Sec7_N.
[Graphical view]
PfamiPF16213. DCB. 1 hit.
PF09324. DUF1981. 1 hit.
PF01369. Sec7. 1 hit.
PF12783. Sec7_N. 1 hit.
[Graphical view]
SMARTiSM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 3 hits.
SSF48425. SSF48425. 1 hit.
PROSITEiPS50190. SEC7. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Y6D5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQESQTKSMF VSRALEKILA DKEVKRPQHS QLRRACQVAL DEIKAEIEKQ
60 70 80 90 100
RLGTAAPPKA NFIEADKYFL PFELACQSKS PRVVSTSLDC LQKLIAYGHI
110 120 130 140 150
TGNAPDSGAP GKRLIDRIVE TICSCFQGPQ TDEGVQLQII KALLTAVTSP
160 170 180 190 200
HIEIHEGTIL QTVRTCYNIY LASKNLINQT TAKATLTQML NVIFTRMENQ
210 220 230 240 250
VLQEARELEK PIQSKPQSPV IQAAAVSPKF VRLKHSQAQS KPTTPEKTDL
260 270 280 290 300
TNGEHARSDS GKVSTENGDA PRERGSSLSG TDDGAQEVVK DILEDVVTSA
310 320 330 340 350
IKEAAEKHGL TEPERVLGEL ECQECAIPPG VDENSQTNGI ADDRQSLSSA
360 370 380 390 400
DNLESDAQGH QVAARFSHVL QKDAFLVFRS LCKLSMKPLG EGPPDPKSHE
410 420 430 440 450
LRSKVVSLQL LLSVLQNAGP VFRTHEMFIN AIKQYLCVAL SKNGVSSVPD
460 470 480 490 500
VFELSLAIFL TLLSNFKMHL KMQIEVFFKE IFLNILETST SSFEHRWMVI
510 520 530 540 550
QTLTRICADA QCVVDIYVNY DCDLNAANIF ERLVNDLSKI AQGRSGHELG
560 570 580 590 600
MTPLQELSLR KKGLECLVSI LKCMVEWSKD LYVNPNHQTS LGQERLTDQE
610 620 630 640 650
IGDGKGLDMA RRCSVTSMES TVSSGTQTTV QDDPEQFEVI KQQKEIIEHG
660 670 680 690 700
IELFNKKPKR GIQFLQEQGM LGTSVEDIAQ FLHQEERLDS TQVGDFLGDS
710 720 730 740 750
ARFNKEVMYA YVDQLDFCEK EFVSALRTFL EGFRLPGEAQ KIDRLMEKFA
760 770 780 790 800
ARYIECNQGQ TLFASADTAY VLAYSIIMLT TDLHSPQVKN KMTKEQYIKM
810 820 830 840 850
NRGINDSKDL PEEYLSSIYE EIEGKKIAMK ETKELTIATK STKQNVASEK
860 870 880 890 900
QRRLLYNLEM EQMAKTAKAL MEAVSHAKAP FTSATHLDHV RPMFKLVWTP
910 920 930 940 950
LLAAYSIGLQ NCDDTEVASL CLEGIRCAIR IACIFGMQLE RDAYVQALAR
960 970 980 990 1000
FSLLTASSSI TEMKQKNIDT IKTLITVAHT DGNYLGNSWH EILKCISQLE
1010 1020 1030 1040 1050
LAQLIGTGVK TRYLSGSGRE REGSLKGHTL AGEEFMGLGL GNLVSGGVDK
1060 1070 1080 1090 1100
RQMASFQESV GETSSQSVVV AVDRIFTGST RLDGNAIVDF VRWLCAVSMD
1110 1120 1130 1140 1150
ELASPHHPRM FSLQKIVEIS YYNMNRIRLQ WSRIWHVIGD HFNKVGCNPN
1160 1170 1180 1190 1200
EDVAIFAVDS LRQLSMKFLE KGELANFRFQ KDFLRPFEHI MKKNRSPTIR
1210 1220 1230 1240 1250
DMAIRCIAQM VNSQAANIRS GWKNIFAVFH QAASDHDGNI VELAFQTTCH
1260 1270 1280 1290 1300
IVTTIFQHHF PAAIDSFQDA VKCLSEFACN AAFPDTSMEA IRLIRFCGKY
1310 1320 1330 1340 1350
VSERPRVLQE YTSDDMNVAP GDRVWVRGWF PILFELSCII NRCKLDVRTR
1360 1370 1380 1390 1400
GLTVMFEIMK SYGHTFEKHW WQDLFRIVFR IFDNMKLPEQ LSEKSEWMTT
1410 1420 1430 1440 1450
TCNHALYAIC DVFTQFYEAL NEVLLSDVFA QLQWCVKQDN EQLARSGTNC
1460 1470 1480 1490 1500
LENLVISNGE KFSPEVWDET CNCMLDIFKT TIPHVLLTWR PVGMEEDSSE
1510 1520 1530 1540 1550
KHLDVDLDRQ SLSSIDKNPS ERGQSQLSNP TDDSWKGRPY ANQKLFASLL
1560 1570 1580 1590 1600
IKCVVQLELI QTIDNIVFYP ATSKKEDAEH MVAAQQDTLD ADIHIETEDQ
1610 1620 1630 1640 1650
GMYKYMSSQH LFKLLDCLQE SHSFSKAFNS NYEQRTVLWR AGFKGKSKPN
1660 1670 1680 1690 1700
LLKQETSSLA CCLRILFRMY VDENRRDSWE EIQQRLLTVC SEALAYFITV
1710 1720 1730 1740 1750
NSESHREAWT SLLLLLLTKT LKINDEKFKA HASMYYPYLC EIMQFDLIPE
1760 1770 1780
LRAVLRKFFL RIGVVYKIWI PEEPSQVPAA LSPVW
Length:1,785
Mass (Da):202,038
Last modified:March 6, 2007 - v3
Checksum:iD419106E5BAF19C2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti207E → R in AAD38428 (PubMed:10212200).Curated1
Sequence conflicti962E → K in AAD38428 (PubMed:10212200).Curated1
Sequence conflicti1049D → N in AAD38428 (PubMed:10212200).Curated1
Sequence conflicti1763G → S in AAD38428 (PubMed:10212200).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037438209E → K in PVNH2; unknown pathological significance. 1 PublicationCorresponds to variant rs28937880dbSNPEnsembl.1
Natural variantiVAR_028750527A → V.Corresponds to variant rs6063343dbSNPEnsembl.1
Natural variantiVAR_036156794K → E in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_069404802R → Q.1 PublicationCorresponds to variant rs748482139dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084521 mRNA. Translation: AAD38428.1.
AL049537, AL121903 Genomic DNA. Translation: CAI19320.1.
AL121903, AL049537 Genomic DNA. Translation: CAI19614.1.
CCDSiCCDS13411.1.
RefSeqiNP_006411.2. NM_006420.2.
UniGeneiHs.62578.

Genome annotation databases

EnsembliENST00000371917; ENSP00000360985; ENSG00000124198.
GeneIDi10564.
KEGGihsa:10564.
UCSCiuc002xtx.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084521 mRNA. Translation: AAD38428.1.
AL049537, AL121903 Genomic DNA. Translation: CAI19320.1.
AL121903, AL049537 Genomic DNA. Translation: CAI19614.1.
CCDSiCCDS13411.1.
RefSeqiNP_006411.2. NM_006420.2.
UniGeneiHs.62578.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L8NX-ray2.86A635-836[»]
3SWVX-ray3.00A635-836[»]
ProteinModelPortaliQ9Y6D5.
SMRiQ9Y6D5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115815. 41 interactors.
DIPiDIP-48794N.
IntActiQ9Y6D5. 12 interactors.
MINTiMINT-1200143.
STRINGi9606.ENSP00000360985.

PTM databases

iPTMnetiQ9Y6D5.
PhosphoSitePlusiQ9Y6D5.

Polymorphism and mutation databases

BioMutaiARFGEF2.
DMDMi146329988.

Proteomic databases

EPDiQ9Y6D5.
MaxQBiQ9Y6D5.
PaxDbiQ9Y6D5.
PeptideAtlasiQ9Y6D5.
PRIDEiQ9Y6D5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371917; ENSP00000360985; ENSG00000124198.
GeneIDi10564.
KEGGihsa:10564.
UCSCiuc002xtx.5. human.

Organism-specific databases

CTDi10564.
DisGeNETi10564.
GeneCardsiARFGEF2.
H-InvDBHIX0015895.
HGNCiHGNC:15853. ARFGEF2.
HPAiCAB026382.
HPA026078.
MalaCardsiARFGEF2.
MIMi605371. gene.
608097. phenotype.
neXtProtiNX_Q9Y6D5.
OpenTargetsiENSG00000124198.
Orphaneti98892. Periventricular nodular heterotopia.
PharmGKBiPA24945.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0929. Eukaryota.
COG5307. LUCA.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000181045.
HOVERGENiHBG004846.
InParanoidiQ9Y6D5.
KOiK18442.
OMAiHALYAVC.
OrthoDBiEOG091G00F0.
PhylomeDBiQ9Y6D5.
TreeFamiTF300714.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124198-MONOMER.
ReactomeiR-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.

Miscellaneous databases

ChiTaRSiARFGEF2. human.
GeneWikiiARFGEF2.
GenomeRNAii10564.
PROiQ9Y6D5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124198.
CleanExiHS_ARFGEF2.
GenevisibleiQ9Y6D5. HS.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
1.25.10.10. 1 hit.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR032629. DCB_dom.
IPR023394. Sec7_alpha_orthog.
IPR015403. Sec7_C.
IPR000904. Sec7_dom.
IPR032691. Sec7_N.
[Graphical view]
PfamiPF16213. DCB. 1 hit.
PF09324. DUF1981. 1 hit.
PF01369. Sec7. 1 hit.
PF12783. Sec7_N. 1 hit.
[Graphical view]
SMARTiSM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 3 hits.
SSF48425. SSF48425. 1 hit.
PROSITEiPS50190. SEC7. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBIG2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6D5
Secondary accession number(s): Q5TFT9, Q9NTS1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: March 6, 2007
Last modified: November 30, 2016
This is version 151 of the entry and version 3 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 20
    Human chromosome 20: 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.