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Protein

DENN domain-containing protein 1B

Gene

DENND1B

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

Functioni

Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form (PubMed:20154091, PubMed:20937701). Plays a role in clathrin-mediated endocytosis (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity (PubMed:26774822). Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells (PubMed:26774822).4 Publications

GO - Molecular functioni

  • Rab guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

  • endocytic recycling Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of immune response Source: UniProtKB
  • T cell receptor signaling pathway Source: UniProtKB
  • T-helper 2 cell cytokine production Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Names & Taxonomyi

Protein namesi
Recommended name:
DENN domain-containing protein 1BImported
Alternative name(s):
Connecdenn 21 Publication
Protein FAM31BImported
Gene namesi
Name:DENND1BImported
Synonyms:C1orf218Imported, FAM31BImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:28404. DENND1B.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication
  • Cytoplasmic vesicleclathrin-coated vesicle 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle

Pathology & Biotechi

Involvement in diseasei

Asthma (ASTHMA)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. Asthma susceptibility is probably caused by decreased TCR down-modulation and recycling in TH2 cells, causing prolonged TCR signaling and increased cytokine production in TH2 lymphocytes (PubMed:26774822).1 Publication
Disease descriptionThe most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi.
See also OMIM:600807

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi489K → A: Causes only a slight reduction in AP2B1-binding. 1 Publication1
Mutagenesisi500K → A: Greatly reduce AP2B1-binding. 1 Publication1
Mutagenesisi501R → A: No effect. 1 Publication1
Mutagenesisi502K → A: Almost completely abolishes AP2B1-binding. 1 Publication1
Mutagenesisi507R → A: No effect. 1 Publication1
Mutagenesisi509K → A: Greatly reduce AP2B1-binding. 1 Publication1

Keywords - Diseasei

Asthma

Organism-specific databases

DisGeNETi163486.
MIMi600807. phenotype.
OpenTargetsiENSG00000213047.
PharmGKBiPA134951951.

Polymorphism and mutation databases

BioMutaiDENND1B.
DMDMi74749089.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003046741 – 775DENN domain-containing protein 1BAdd BLAST775

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei520PhosphotyrosineBy similarity1
Modified residuei535PhosphoserineBy similarity1
Modified residuei536PhosphoserineBy similarity1
Modified residuei549PhosphoserineBy similarity1
Modified residuei552PhosphoserineBy similarity1
Modified residuei652PhosphoserineCombined sources1
Modified residuei653PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on serine and/or threonine, possibly regulating the guanine nucleotide exchange factor (GEF) activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ6P3S1.
PaxDbiQ6P3S1.
PeptideAtlasiQ6P3S1.
PRIDEiQ6P3S1.

PTM databases

iPTMnetiQ6P3S1.
PhosphoSitePlusiQ6P3S1.

Expressioni

Tissue specificityi

Highly expressed in dendritic and natural killer cells and at lower levels in other myeloid lineage cells and in pituitary. Significantly up-regulated in effector memory T-cells as compared with naive T-cells.1 Publication

Gene expression databases

BgeeiENSG00000213047.
CleanExiHS_DENND1B.
ExpressionAtlasiQ6P3S1. baseline and differential.
GenevisibleiQ6P3S1. HS.

Organism-specific databases

HPAiHPA042586.
HPA045494.

Interactioni

Subunit structurei

Interacts with RAB35 (PubMed:24520163, PubMed:22065758). Interacts with clathrin heavy chain/CLTC (PubMed:20154091). Interacts with components of the adapter protein complex 2 (AP-2) AP2A2 and AP2B1 (PubMed:20154091). Interacts with CD3E (By similarity).By similarity3 Publications

Protein-protein interaction databases

BioGridi127867. 2 interactors.
IntActiQ6P3S1. 2 interactors.
STRINGi9606.ENSP00000356366.

Structurei

Secondary structure

1775
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi10 – 12Combined sources3
Beta strandi14 – 20Combined sources7
Beta strandi30 – 36Combined sources7
Helixi42 – 52Combined sources11
Helixi57 – 60Combined sources4
Helixi61 – 63Combined sources3
Beta strandi66 – 74Combined sources9
Beta strandi80 – 87Combined sources8
Beta strandi91 – 101Combined sources11
Helixi104 – 119Combined sources16
Helixi123 – 135Combined sources13
Helixi188 – 196Combined sources9
Helixi199 – 209Combined sources11
Turni210 – 212Combined sources3
Beta strandi214 – 220Combined sources7
Helixi222 – 234Combined sources13
Turni235 – 238Combined sources4
Beta strandi243 – 248Combined sources6
Helixi251 – 258Combined sources8
Beta strandi263 – 268Combined sources6
Turni269 – 271Combined sources3
Helixi272 – 276Combined sources5
Beta strandi284 – 287Combined sources4
Turni288 – 291Combined sources4
Beta strandi292 – 294Combined sources3
Helixi300 – 302Combined sources3
Helixi305 – 315Combined sources11
Helixi318 – 321Combined sources4
Helixi325 – 338Combined sources14
Helixi339 – 341Combined sources3
Helixi357 – 360Combined sources4
Helixi366 – 375Combined sources10
Helixi379 – 391Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TW8X-ray2.10A/C1-410[»]
ProteinModelPortaliQ6P3S1.
SMRiQ6P3S1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 89UDENNAdd BLAST68
Domaini90 – 291DENNPROSITE-ProRule annotationAdd BLAST202
Domaini322 – 388dDENNPROSITE-ProRule annotationAdd BLAST67

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi398 – 402FXDXF motif1 Publication5
Motifi566 – 575Clathrin box1 Publication10

Domaini

The FXDXF motif mediates interaction the AP-2 complex.By similarity
The clathrin box motif mediates interaction with clathrin.By similarity

Sequence similaritiesi

Contains 1 dDENN domain.PROSITE-ProRule annotation
Contains 1 DENN domain.PROSITE-ProRule annotation
Contains 1 uDENN domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3569. Eukaryota.
ENOG410XT3N. LUCA.
GeneTreeiENSGT00760000118819.
HOVERGENiHBG059209.
InParanoidiQ6P3S1.
KOiK20160.
OMAiFAKSHAR.
OrthoDBiEOG091G083L.
TreeFamiTF320336.

Family and domain databases

InterProiIPR005112. dDENN_dom.
IPR001194. DENN_dom.
IPR005113. uDENN_dom.
[Graphical view]
PfamiPF03455. dDENN. 1 hit.
PF02141. DENN. 1 hit.
PF03456. uDENN. 1 hit.
[Graphical view]
SMARTiSM00801. dDENN. 1 hit.
SM00799. DENN. 1 hit.
SM00800. uDENN. 1 hit.
[Graphical view]
PROSITEiPS50947. DDENN. 1 hit.
PS50211. DENN. 1 hit.
PS50946. UDENN. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 5 (identifier: Q6P3S1-1) [UniParc]FASTAAdd to basket

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
MDCRTKANPD RTFDLVLKVK CHASENEDPV VLWKFPEDFG DQEILQSVPK
60 70 80 90 100
FCFPFDVERV SQNQVGQHFT FVLTDIESKQ RFGFCRLTSG GTICLCILSY
110 120 130 140 150
LPWFEVYYKL LNTLADYLAK ELENDLNETL RSLYNHPVPK ANTPVNLSVN
160 170 180 190 200
QEIFIACEQV LKDQPALVPH SYFIAPDVTG LPTIPESRNL TEYFVAVDVN
210 220 230 240 250
NMLQLYASML HERRIVIISS KLSTLTACIH GSAALLYPMY WQHIYIPVLP
260 270 280 290 300
PHLLDYCCAP MPYLIGIHSS LIERVKNKSL EDVVMLNVDT NTLESPFSDL
310 320 330 340 350
NNLPSDVVSA LKNKLKKQST ATGDGVARAF LRAQAALFGS YRDALRYKPG
360 370 380 390 400
EPITFCEESF VKHRSSVMKQ FLETAINLQL FKQFIDGRLA KLNAGRGFSD
410 420 430 440 450
VFEEEITSGG FCGGNPRSYQ QWVHTVKKGG ALFNTAMTKA TPAVRTAYKF
460 470 480 490 500
AKNHAKLGLK EVKSKLKHKE NEEDYGTCSS SVQYTPVYKL HNEKGGNSEK
510 520 530 540 550
RKLAQARLKR PLKSLDGALY DDEDDDDIER ASKLSSEDGE EASAYLYESD
560 570 580 590 600
DSVETRVKTP YSGEMDLLGE ILDTLSTHSS DQGKLAAAKS LDFFRSMDDI
610 620 630 640 650
DYKPTNKSNA PSENNLAFLC GGSGDQAEWN LGQDDSALHG KHLPPSPRKR
660 670 680 690 700
VSSSGLTDSL FILKEENSNK HLGADNVSDP TSGLDFQLTS PEVSQTDKGK
710 720 730 740 750
TEKRETLSQI SDDLLIPGLG RHSSTFVPWE KEGKEAKETS EDIGLLHEVV
760 770
SLCHMTSDFQ QSLNISDKNT NGNQT
Length:775
Mass (Da):86,552
Last modified:March 16, 2016 - v2
Checksum:iED44D8F693DF3983
GO
Isoform 2 (identifier: Q6P3S1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-169: Missing.
     415-775: NPRSYQQWVH...SDKNTNGNQT → KDKLQYDYPFSQ

Show »
Length:406
Mass (Da):46,023
Checksum:iF447B1AC261D9D1C
GO
Isoform 3 (identifier: Q6P3S1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-169: Missing.
     310-315: ALKNKL → MKAIQW
     316-775: Missing.

Note: No experimental confirmation available.
Show »
Length:295
Mass (Da):33,701
Checksum:iAEE0F8F8B6791EF4
GO
Isoform 4 (identifier: Q6P3S1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MDCRTKANPDRTFDLVLKVKCHASENED → MAAAPREEKRWPQPVFSN
     150-169: Missing.
     415-775: NPRSYQQWVH...SDKNTNGNQT → KDKLQYDYPFSQ

Note: No experimental confirmation available.
Show »
Length:396
Mass (Da):44,901
Checksum:iEE50301A6487BABF
GO
Isoform 1 (identifier: Q6P3S1-5) [UniParc]FASTAAdd to basket
Also known as: DENND1B-S

The sequence of this isoform differs from the canonical sequence as follows:
     415-775: NPRSYQQWVH...SDKNTNGNQT → KDKLQYDYPFSQ

Show »
Length:426
Mass (Da):48,260
Checksum:i811670F3F2F6897F
GO

Sequence cautioni

The sequence AAH74735 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA90918 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB15024 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EAW91280 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti340S → Y in AAH22561 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035055216V → M.Corresponds to variant rs7546381dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0280821 – 28MDCRT…SENED → MAAAPREEKRWPQPVFSN in isoform 4. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_028083150 – 169Missing in isoform 2, isoform 3 and isoform 4. 2 PublicationsAdd BLAST20
Alternative sequenceiVSP_028084310 – 315ALKNKL → MKAIQW in isoform 3. 1 Publication6
Alternative sequenceiVSP_028085316 – 775Missing in isoform 3. 1 PublicationAdd BLAST460
Alternative sequenceiVSP_034515415 – 775NPRSY…NGNQT → KDKLQYDYPFSQ in isoform 4, isoform 2 and isoform 1. 2 PublicationsAdd BLAST361

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL139136 Genomic DNA. Translation: CAI15312.2.
AL139136, AL365258 Genomic DNA. Translation: CAI15313.2.
AL139136, AL365258 Genomic DNA. Translation: CAI15314.1.
AL139136, AL365258 Genomic DNA. Translation: CAI15315.1.
AL365258, AL139136 Genomic DNA. Translation: CAI14212.2.
AL365258, AL139136 Genomic DNA. Translation: CAI14213.1.
AL365258, AL139136 Genomic DNA. Translation: CAI14214.1.
CH471067 Genomic DNA. Translation: EAW91280.1. Sequence problems.
CH471067 Genomic DNA. Translation: EAW91281.1.
CH471067 Genomic DNA. Translation: EAW91285.1.
BC022561 mRNA. Translation: AAH22561.1.
BC063877 mRNA. Translation: AAH63877.1.
BC074735 mRNA. Translation: AAH74735.2. Different initiation.
AL831839 mRNA. Translation: CAD38548.1.
AK000061 mRNA. Translation: BAA90918.1. Different initiation.
AK024832 mRNA. Translation: BAB15024.1. Different initiation.
BK006960 mRNA. Translation: DAA12502.1.
CCDSiCCDS41452.2. [Q6P3S1-5]
CCDS72996.1. [Q6P3S1-4]
CCDS72997.1. [Q6P3S1-1]
RefSeqiNP_001182144.1. NM_001195215.1. [Q6P3S1-1]
NP_001182145.1. NM_001195216.1.
NP_001287787.1. NM_001300858.1. [Q6P3S1-4]
NP_659414.2. NM_144977.4. [Q6P3S1-5]
UniGeneiHs.125056.
Hs.745032.

Genome annotation databases

EnsembliENST00000235453; ENSP00000235453; ENSG00000213047. [Q6P3S1-4]
ENST00000367396; ENSP00000356366; ENSG00000213047. [Q6P3S1-5]
ENST00000620048; ENSP00000479816; ENSG00000213047. [Q6P3S1-1]
GeneIDi163486.
KEGGihsa:163486.
UCSCiuc001gue.4. human. [Q6P3S1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL139136 Genomic DNA. Translation: CAI15312.2.
AL139136, AL365258 Genomic DNA. Translation: CAI15313.2.
AL139136, AL365258 Genomic DNA. Translation: CAI15314.1.
AL139136, AL365258 Genomic DNA. Translation: CAI15315.1.
AL365258, AL139136 Genomic DNA. Translation: CAI14212.2.
AL365258, AL139136 Genomic DNA. Translation: CAI14213.1.
AL365258, AL139136 Genomic DNA. Translation: CAI14214.1.
CH471067 Genomic DNA. Translation: EAW91280.1. Sequence problems.
CH471067 Genomic DNA. Translation: EAW91281.1.
CH471067 Genomic DNA. Translation: EAW91285.1.
BC022561 mRNA. Translation: AAH22561.1.
BC063877 mRNA. Translation: AAH63877.1.
BC074735 mRNA. Translation: AAH74735.2. Different initiation.
AL831839 mRNA. Translation: CAD38548.1.
AK000061 mRNA. Translation: BAA90918.1. Different initiation.
AK024832 mRNA. Translation: BAB15024.1. Different initiation.
BK006960 mRNA. Translation: DAA12502.1.
CCDSiCCDS41452.2. [Q6P3S1-5]
CCDS72996.1. [Q6P3S1-4]
CCDS72997.1. [Q6P3S1-1]
RefSeqiNP_001182144.1. NM_001195215.1. [Q6P3S1-1]
NP_001182145.1. NM_001195216.1.
NP_001287787.1. NM_001300858.1. [Q6P3S1-4]
NP_659414.2. NM_144977.4. [Q6P3S1-5]
UniGeneiHs.125056.
Hs.745032.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TW8X-ray2.10A/C1-410[»]
ProteinModelPortaliQ6P3S1.
SMRiQ6P3S1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127867. 2 interactors.
IntActiQ6P3S1. 2 interactors.
STRINGi9606.ENSP00000356366.

PTM databases

iPTMnetiQ6P3S1.
PhosphoSitePlusiQ6P3S1.

Polymorphism and mutation databases

BioMutaiDENND1B.
DMDMi74749089.

Proteomic databases

MaxQBiQ6P3S1.
PaxDbiQ6P3S1.
PeptideAtlasiQ6P3S1.
PRIDEiQ6P3S1.

Protocols and materials databases

DNASUi163486.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000235453; ENSP00000235453; ENSG00000213047. [Q6P3S1-4]
ENST00000367396; ENSP00000356366; ENSG00000213047. [Q6P3S1-5]
ENST00000620048; ENSP00000479816; ENSG00000213047. [Q6P3S1-1]
GeneIDi163486.
KEGGihsa:163486.
UCSCiuc001gue.4. human. [Q6P3S1-1]

Organism-specific databases

CTDi163486.
DisGeNETi163486.
GeneCardsiDENND1B.
HGNCiHGNC:28404. DENND1B.
HPAiHPA042586.
HPA045494.
MIMi600807. phenotype.
613292. gene.
neXtProtiNX_Q6P3S1.
OpenTargetsiENSG00000213047.
PharmGKBiPA134951951.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3569. Eukaryota.
ENOG410XT3N. LUCA.
GeneTreeiENSGT00760000118819.
HOVERGENiHBG059209.
InParanoidiQ6P3S1.
KOiK20160.
OMAiFAKSHAR.
OrthoDBiEOG091G083L.
TreeFamiTF320336.

Enzyme and pathway databases

ReactomeiR-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Miscellaneous databases

GenomeRNAii163486.
PROiQ6P3S1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213047.
CleanExiHS_DENND1B.
ExpressionAtlasiQ6P3S1. baseline and differential.
GenevisibleiQ6P3S1. HS.

Family and domain databases

InterProiIPR005112. dDENN_dom.
IPR001194. DENN_dom.
IPR005113. uDENN_dom.
[Graphical view]
PfamiPF03455. dDENN. 1 hit.
PF02141. DENN. 1 hit.
PF03456. uDENN. 1 hit.
[Graphical view]
SMARTiSM00801. dDENN. 1 hit.
SM00799. DENN. 1 hit.
SM00800. uDENN. 1 hit.
[Graphical view]
PROSITEiPS50947. DDENN. 1 hit.
PS50211. DENN. 1 hit.
PS50946. UDENN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDEN1B_HUMAN
AccessioniPrimary (citable) accession number: Q6P3S1
Secondary accession number(s): B5MD89
, D3PFD5, Q5T3B8, Q5T3B9, Q5T3C1, Q5TAI8, Q6B0I8, Q8NDT1, Q8TBE6, Q9H774, Q9NXU2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: March 16, 2016
Last modified: November 30, 2016
This is version 112 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 1
    Human chromosome 1: 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.