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Protein

Tubulin polyglutamylase TTLL5

Gene

TTLL5

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

Functioni

Polyglutamylase which preferentially modifies alpha-tubulin. Involved in the side-chain initiation step of the polyglutamylation reaction rather than in the elongation step (By similarity). Required for CCSAP localization to both spindle and cilia microtubules. Increases the effects of NCOA2 in glucocorticoid receptor-mediated repression and induction and in androgen receptor-mediated induction (PubMed:17116691, PubMed:22493317).By similarity2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei221 – 2211ATPBy similarity
Binding sitei223 – 2231ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi208 – 2114ATP bindingBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Transcription

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Tubulin polyglutamylase TTLL5 (EC:6.-.-.-)
Alternative name(s):
SRC1 and TIF2-associated modulatory protein
Tubulin--tyrosine ligase-like protein 5
Gene namesi
Name:TTLL5
Synonyms:KIAA0998, STAMP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:19963. TTLL5.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cilium Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB-SubCell
  • microtubule Source: UniProtKB-KW
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Cytoskeleton, Microtubule, Nucleus

Pathology & Biotechi

Involvement in diseasei

Cone-rod dystrophy 19 (CORD19)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.
See also OMIM:615860
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti543 – 5431E → K in CORD19. 1 Publication
Corresponds to variant rs199882533 [ dbSNP | Ensembl ].
VAR_071327

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi467 – 4737KVLRRVK → DVLDDVD: Decreased binding to microtubules and polyglutamylase activity. 1 Publication

Keywords - Diseasei

Cone-rod dystrophy, Disease mutation

Organism-specific databases

MalaCardsiTTLL5.
MIMi615860. phenotype.
PharmGKBiPA164742694.

Polymorphism and mutation databases

BioMutaiTTLL5.
DMDMi239938834.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12811281Tubulin polyglutamylase TTLL5PRO_0000223341Add
BLAST

Proteomic databases

EPDiQ6EMB2.
MaxQBiQ6EMB2.
PaxDbiQ6EMB2.
PeptideAtlasiQ6EMB2.
PRIDEiQ6EMB2.

PTM databases

iPTMnetiQ6EMB2.
PhosphoSiteiQ6EMB2.

Expressioni

Tissue specificityi

Expressed in the retina, found in the rod and cone photoreceptors (at protein level). Widely expressed with highest levels in heart and skeletal muscle and low levels in other tissues.2 Publications

Gene expression databases

BgeeiENSG00000119685.
CleanExiHS_TTLL5.
ExpressionAtlasiQ6EMB2. baseline and differential.
GenevisibleiQ6EMB2. HS.

Organism-specific databases

HPAiHPA032128.

Interactioni

Subunit structurei

Interacts with the transcriptional coactivators NCOA1/SRC-1 and NCOA2/TIF2.1 Publication

Protein-protein interaction databases

BioGridi116721. 25 interactions.
IntActiQ6EMB2. 18 interactions.
MINTiMINT-6776340.
STRINGi9606.ENSP00000298832.

Structurei

3D structure databases

ProteinModelPortaliQ6EMB2.
SMRiQ6EMB2. Positions 74-385.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini62 – 407346TTLPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni378 – 488111c-MTBD region1 PublicationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi552 – 5576Poly-Arg
Compositional biasi582 – 5909Poly-Glu
Compositional biasi776 – 7805Poly-Glu
Compositional biasi827 – 8304Poly-Asn

Domaini

The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.By similarity1 Publication

Sequence similaritiesi

Belongs to the tubulin--tyrosine ligase family.Curated
Contains 1 TTL domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2156. Eukaryota.
KOG2157. Eukaryota.
ENOG410XQDM. LUCA.
GeneTreeiENSGT00760000118951.
HOVERGENiHBG055655.
InParanoidiQ6EMB2.
KOiK16602.
OrthoDBiEOG091G03QY.
PhylomeDBiQ6EMB2.
TreeFamiTF313087.

Family and domain databases

InterProiIPR004344. TTL/TTLL_fam.
[Graphical view]
PfamiPF03133. TTL. 1 hit.
[Graphical view]
PROSITEiPS51221. TTL. 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: Q6EMB2-1) [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
MPIVMARDLE ETASSSEDEE VISQEDHPCI MWTGGCRRIP VLVFHADAIL
60 70 80 90 100
TKDNNIRVIG ERYHLSYKIV RTDSRLVRSI LTAHGFHEVH PSSTDYNLMW
110 120 130 140 150
TGSHLKPFLL RTLSEAQKVN HFPRSYELTR KDRLYKNIIR MQHTHGFKAF
160 170 180 190 200
HILPQTFLLP AEYAEFCNSY SKDRGPWIVK PVASSRGRGV YLINNPNQIS
210 220 230 240 250
LEENILVSRY INNPLLIDDF KFDVRLYVLV TSYDPLVIYL YEEGLARFAT
260 270 280 290 300
VRYDQGAKNI RNQFMHLTNY SVNKKSGDYV SCDDPEVEDY GNKWSMSAML
310 320 330 340 350
RYLKQEGRDT TALMAHVEDL IIKTIISAEL AIATACKTFV PHRSSCFELY
360 370 380 390 400
GFDVLIDSTL KPWLLEVNLS PSLACDAPLD LKIKASMISD MFTVVGFVCQ
410 420 430 440 450
DPAQRASTRP IYPTFESSRR NPFQKPQRCR PLSASDAEMK NLVGSAREKG
460 470 480 490 500
PGKLGGSVLG LSMEEIKVLR RVKEENDRRG GFIRIFPTSE TWEIYGSYLE
510 520 530 540 550
HKTSMNYMLA TRLFQDRMTA DGAPELKIES LNSKAKLHAA LYERKLLSLE
560 570 580 590 600
VRKRRRRSSR LRAMRPKYPV ITQPAEMNVK TETESEEEEE VALDNEDEEQ
610 620 630 640 650
EASQEESAGF LRENQAKYTP SLTALVENTP KENSMKVREW NNKGGHCCKL
660 670 680 690 700
ETQELEPKFN LMQILQDNGN LSKMQARIAF SAYLQHVQIR LMKDSGGQTF
710 720 730 740 750
SASWAAKEDE QMELVVRFLK RASNNLQHSL RMVLPSRRLA LLERRRILAH
760 770 780 790 800
QLGDFIIVYN KETEQMAEKK SKKKVEEEEE DGVNMENFQE FIRQASEAEL
810 820 830 840 850
EEVLTFYTQK NKSASVFLGT HSKISKNNNN YSDSGAKGDH PETIMEEVKI
860 870 880 890 900
KPPKQQQTTE IHSDKLSRFT TSAEKEAKLV YSNSSSGPTA TLQKIPNTHL
910 920 930 940 950
SSVTTSDLSP GPCHHSSLSQ IPSAIPSMPH QPTILLNTVS ASASPCLHPG
960 970 980 990 1000
AQNIPSPTGL PRCRSGSHTI GPFSSFQSAA HIYSQKLSRP SSAKAGSCYL
1010 1020 1030 1040 1050
NKHHSGIAKT QKEGEDASLY SKRYNQSMVT AELQRLAEKQ AARQYSPSSH
1060 1070 1080 1090 1100
INLLTQQVTN LNLATGIINR SSASAPPTLR PIISPSGPTW STQSDPQAPE
1110 1120 1130 1140 1150
NHSSSPGSRS LQTGGFAWEG EVENNVYSQA TGVVPQHKYH PTAGSYQLQF
1160 1170 1180 1190 1200
ALQQLEQQKL QSRQLLDQSR ARHQAIFGSQ TLPNSNLWTM NNGAGCRISS
1210 1220 1230 1240 1250
ATASGQKPTT LPQKVVPPPS SCASLVPKPP PNHEQVLRRA TSQKASKGSS
1260 1270 1280
AEGQLNGLQS SLNPAAFVPI TSSTDPAHTK I
Length:1,281
Mass (Da):143,577
Last modified:June 16, 2009 - v3
Checksum:i01441AFE6925AEDF
GO
Isoform 2 (identifier: Q6EMB2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-462: Missing.
     516-516: D → DRGNPRRSLLTGRT
     1247-1281: KGSSAEGQLNGLQSSLNPAAFVPITSSTDPAHTKI → NTRFRSSFQNYLWYFFQAVS

Show »
Length:817
Mass (Da):91,522
Checksum:iA1E1B97B1FA46DC4
GO
Isoform 3 (identifier: Q6EMB2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     248-269: FATVRYDQGAKNIRNQFMHLTN → KCNWKMGNTMDKRRLPIYVQVL
     270-1281: Missing.

Show »
Length:269
Mass (Da):31,401
Checksum:iFAD96940A3CF5ABB
GO

Sequence cautioni

The sequence AAF23275 differs from that shown. Reason: Erroneous gene model prediction. Curated
The sequence AAP75557 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti149 – 1491A → V.4 Publications
Corresponds to variant rs2303345 [ dbSNP | Ensembl ].
VAR_057895
Natural varianti203 – 2031E → D.
Corresponds to variant rs17856074 [ dbSNP | Ensembl ].
VAR_057896
Natural varianti543 – 5431E → K in CORD19. 1 Publication
Corresponds to variant rs199882533 [ dbSNP | Ensembl ].
VAR_071327
Natural varianti592 – 5921A → T.
Corresponds to variant rs11848004 [ dbSNP | Ensembl ].
VAR_057897
Natural varianti1223 – 12231A → S.
Corresponds to variant rs10130991 [ dbSNP | Ensembl ].
VAR_057898
Natural varianti1231 – 12311P → T.
Corresponds to variant rs11844617 [ dbSNP | Ensembl ].
VAR_057899
Natural varianti1267 – 12671F → S.2 Publications
Corresponds to variant rs1133834 [ dbSNP | Ensembl ].
VAR_057900

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 462462Missing in isoform 2. 2 PublicationsVSP_037453Add
BLAST
Alternative sequencei248 – 26922FATVR…MHLTN → KCNWKMGNTMDKRRLPIYVQ VL in isoform 3. 2 PublicationsVSP_037454Add
BLAST
Alternative sequencei270 – 12811012Missing in isoform 3. 2 PublicationsVSP_037455Add
BLAST
Alternative sequencei516 – 5161D → DRGNPRRSLLTGRT in isoform 2. 2 PublicationsVSP_037456
Alternative sequencei1247 – 128135KGSSA…AHTKI → NTRFRSSFQNYLWYFFQAVS in isoform 2. 2 PublicationsVSP_037457Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY237126 mRNA. Translation: AAP75557.1. Different initiation.
AC007182 Genomic DNA. No translation available.
AC009399 Genomic DNA. Translation: AAF23275.2. Sequence problems.
AF107885 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81247.1.
CR533554 mRNA. Translation: CAG38585.1.
AL136808 mRNA. Translation: CAB66742.1.
BC002766 mRNA. Translation: AAH02766.2.
BC136472 mRNA. Translation: AAI36473.1.
BC136473 mRNA. Translation: AAI36474.1.
AK024259 mRNA. Translation: BAB14862.1.
AB023215 mRNA. Translation: BAA76842.1.
CCDSiCCDS32124.1. [Q6EMB2-1]
RefSeqiNP_055887.3. NM_015072.4. [Q6EMB2-1]
UniGeneiHs.709609.

Genome annotation databases

EnsembliENST00000286650; ENSP00000286650; ENSG00000119685. [Q6EMB2-3]
ENST00000298832; ENSP00000298832; ENSG00000119685. [Q6EMB2-1]
ENST00000556893; ENSP00000452524; ENSG00000119685. [Q6EMB2-2]
GeneIDi23093.
KEGGihsa:23093.
UCSCiuc001xrw.3. human. [Q6EMB2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY237126 mRNA. Translation: AAP75557.1. Different initiation.
AC007182 Genomic DNA. No translation available.
AC009399 Genomic DNA. Translation: AAF23275.2. Sequence problems.
AF107885 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81247.1.
CR533554 mRNA. Translation: CAG38585.1.
AL136808 mRNA. Translation: CAB66742.1.
BC002766 mRNA. Translation: AAH02766.2.
BC136472 mRNA. Translation: AAI36473.1.
BC136473 mRNA. Translation: AAI36474.1.
AK024259 mRNA. Translation: BAB14862.1.
AB023215 mRNA. Translation: BAA76842.1.
CCDSiCCDS32124.1. [Q6EMB2-1]
RefSeqiNP_055887.3. NM_015072.4. [Q6EMB2-1]
UniGeneiHs.709609.

3D structure databases

ProteinModelPortaliQ6EMB2.
SMRiQ6EMB2. Positions 74-385.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116721. 25 interactions.
IntActiQ6EMB2. 18 interactions.
MINTiMINT-6776340.
STRINGi9606.ENSP00000298832.

PTM databases

iPTMnetiQ6EMB2.
PhosphoSiteiQ6EMB2.

Polymorphism and mutation databases

BioMutaiTTLL5.
DMDMi239938834.

Proteomic databases

EPDiQ6EMB2.
MaxQBiQ6EMB2.
PaxDbiQ6EMB2.
PeptideAtlasiQ6EMB2.
PRIDEiQ6EMB2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286650; ENSP00000286650; ENSG00000119685. [Q6EMB2-3]
ENST00000298832; ENSP00000298832; ENSG00000119685. [Q6EMB2-1]
ENST00000556893; ENSP00000452524; ENSG00000119685. [Q6EMB2-2]
GeneIDi23093.
KEGGihsa:23093.
UCSCiuc001xrw.3. human. [Q6EMB2-1]

Organism-specific databases

CTDi23093.
GeneCardsiTTLL5.
H-InvDBHIX0011830.
HGNCiHGNC:19963. TTLL5.
HPAiHPA032128.
MalaCardsiTTLL5.
MIMi612268. gene.
615860. phenotype.
neXtProtiNX_Q6EMB2.
PharmGKBiPA164742694.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2156. Eukaryota.
KOG2157. Eukaryota.
ENOG410XQDM. LUCA.
GeneTreeiENSGT00760000118951.
HOVERGENiHBG055655.
InParanoidiQ6EMB2.
KOiK16602.
OrthoDBiEOG091G03QY.
PhylomeDBiQ6EMB2.
TreeFamiTF313087.

Miscellaneous databases

ChiTaRSiTTLL5. human.
GenomeRNAii23093.
PROiQ6EMB2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119685.
CleanExiHS_TTLL5.
ExpressionAtlasiQ6EMB2. baseline and differential.
GenevisibleiQ6EMB2. HS.

Family and domain databases

InterProiIPR004344. TTL/TTLL_fam.
[Graphical view]
PfamiPF03133. TTL. 1 hit.
[Graphical view]
PROSITEiPS51221. TTL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTTLL5_HUMAN
AccessioniPrimary (citable) accession number: Q6EMB2
Secondary accession number(s): B9EGH8
, B9EGH9, Q9BUB0, Q9H0G4, Q9H7W2, Q9P1V5, Q9UPZ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: June 16, 2009
Last modified: September 7, 2016
This is version 105 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: 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.