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Protein

Tubulin polyglutamylase TTLL4

Gene

TTLL4

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

Functioni

Glutamylase which preferentially modifies beta-tubulin and non-tubulin proteins, such as NAP1L1, NAP1L4 and CGAS. Involved in the side-chain initiation step of the polyglutamylation reaction rather than in the elongation step. Involved in formation of short side-chains. Mediates initiation of polyglutamylation of nucleosome assembly proteins NAP1L1 and NAP1L4. Also acts as a monoglutamylase: generates monoglutamylation of CGAS, leading to impair the nucleotidyltransferase activity of CGAS.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei762ATPBy similarity1
Binding sitei764ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi749 – 752ATP bindingBy similarity4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein-glutamic acid ligase activity Source: UniProtKB
  • tubulin binding Source: UniProtKB
  • tubulin-glutamic acid ligase activity Source: Reactome

GO - Biological processi

  • peptidyl-glutamic acid modification Source: UniProtKB
  • protein polyglutamylation Source: UniProtKB

Keywordsi

Molecular functionLigase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-8955332 Carboxyterminal post-translational modifications of tubulin

Names & Taxonomyi

Protein namesi
Recommended name:
Tubulin polyglutamylase TTLL4 (EC:6.-.-.-)
Alternative name(s):
Tubulin--tyrosine ligase-like protein 4
Gene namesi
Name:TTLL4
Synonyms:KIAA0173
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000135912.10
HGNCiHGNC:28976 TTLL4
neXtProtiNX_Q14679

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Cytoskeleton, Microtubule

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi978 – 981KMKK → EMEE: Decreased binding to microtubules and polyglutamylase activity. 1 Publication4

Organism-specific databases

DisGeNETi9654
OpenTargetsiENSG00000135912
PharmGKBiPA134935712

Polymorphism and mutation databases

BioMutaiTTLL4
DMDMi143811470

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002124421 – 1199Tubulin polyglutamylase TTLL4Add BLAST1199

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei691PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ14679
MaxQBiQ14679
PaxDbiQ14679
PeptideAtlasiQ14679
PRIDEiQ14679
ProteomicsDBi60114

PTM databases

iPTMnetiQ14679
PhosphoSitePlusiQ14679

Expressioni

Gene expression databases

BgeeiENSG00000135912
CleanExiHS_TTLL4
ExpressionAtlasiQ14679 baseline and differential
GenevisibleiQ14679 HS

Organism-specific databases

HPAiHPA027091
HPA050252

Interactioni

GO - Molecular functioni

  • tubulin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115012, 8 interactors
IntActiQ14679, 2 interactors
STRINGi9606.ENSP00000258398

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5T6XX-ray1.69C295-304[»]
ProteinModelPortaliQ14679
SMRiQ14679
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini604 – 947TTLPROSITE-ProRule annotationAdd BLAST344

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni918 – 1029c-MTBD region1 PublicationAdd BLAST112

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

Phylogenomic databases

eggNOGiKOG2156 Eukaryota
ENOG410XTI2 LUCA
GeneTreeiENSGT00760000118951
HOGENOMiHOG000154712
HOVERGENiHBG058942
InParanoidiQ14679
KOiK16601
OMAiYKPMLNN
OrthoDBiEOG091G03UM
PhylomeDBiQ14679
TreeFamiTF313087

Family and domain databases

Gene3Di3.30.1490.20, 1 hit
InterProiView protein in InterPro
IPR013815 ATP_grasp_subdomain_1
IPR004344 TTL/TTLL_fam
IPR027748 TTLL-4
PANTHERiPTHR12241:SF145 PTHR12241:SF145, 1 hit
PfamiView protein in Pfam
PF03133 TTL, 1 hit
PROSITEiView protein in PROSITE
PS51221 TTL, 1 hit

Sequencei

Sequence statusi: Complete.

Q14679-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASAGTQHYS IGLRQKNSFK QSGPSGTVPA TPPEKPSEGR VWPQAHQQVK
60 70 80 90 100
PIWKLEKKQV ETLSAGLGPG LLGVPPQPAY FFCPSTLCSS GTTAVIAGHS
110 120 130 140 150
SSCYLHSLPD LFNSTLLYRR SSYRQKPYQQ LESFCLRSSP SEKSPFSLPQ
160 170 180 190 200
KSLPVSLTAN KATSSMVFSM AQPMASSSTE PYLCLAAAGE NPSGKSLASA
210 220 230 240 250
ISGKIPSPLS SSYKPMLNNN SFMWPNSTPV PLLQTTQGLK PVSPPKIQPV
260 270 280 290 300
SWHHSGGTGD CAPQPVDHKV PKSIGTVPAD ASAHIALSTA SSHDTSTTSV
310 320 330 340 350
ASSWYNRNNL AMRAEPLSCA LDDSSDSQDP TKEIRFTEAV RKLTARGFEK
360 370 380 390 400
MPRQGCQLEQ SSFLNPSFQW NVLNRSRRWK PPAVNQQFPQ EDAGSVRRVL
410 420 430 440 450
PGASDTLGLD NTVFCTKRIS IHLLASHASG LNHNPACESV IDSSAFGEGK
460 470 480 490 500
APGPPFPQTL GIANVATRLS SIQLGQSEKE RPEEARELDS SDRDISSATD
510 520 530 540 550
LQPDQAETED TEEELVDGLE DCCSRDENEE EEGDSECSSL SAVSPSESVA
560 570 580 590 600
MISRSCMEIL TKPLSNHEKV VRPALIYSLF PNVPPTIYFG TRDERVEKLP
610 620 630 640 650
WEQRKLLRWK MSTVTPNIVK QTIGRSHFKI SKRNDDWLGC WGHHMKSPSF
660 670 680 690 700
RSIREHQKLN HFPGSFQIGR KDRLWRNLSR MQSRFGKKEF SFFPQSFILP
710 720 730 740 750
QDAKLLRKAW ESSSRQKWIV KPPASARGIG IQVIHKWSQL PKRRPLLVQR
760 770 780 790 800
YLHKPYLISG SKFDLRIYVY VTSYDPLRIY LFSDGLVRFA SCKYSPSMKS
810 820 830 840 850
LGNKFMHLTN YSVNKKNAEY QANADEMACQ GHKWALKALW NYLSQKGVNS
860 870 880 890 900
DAIWEKIKDV VVKTIISSEP YVTSLLKMYV RRPYSCHELF GFDIMLDENL
910 920 930 940 950
KPWVLEVNIS PSLHSSSPLD ISIKGQMIRD LLNLAGFVLP NAEDIISSPS
960 970 980 990 1000
SCSSSTTSLP TSPGDKCRMA PEHVTAQKMK KAYYLTQKIP DQDFYASVLD
1010 1020 1030 1040 1050
VLTPDDVRIL VEMEDEFSRR GQFERIFPSH ISSRYLRFFE QPRYFNILTT
1060 1070 1080 1090 1100
QWEQKYHGNK LKGVDLLRSW CYKGFHMGVV SDSAPVWSLP TSLLTISKDD
1110 1120 1130 1140 1150
VILNAFSKSE TSKLGKQSSC EVSLLLSEDG TTPKSKKTQA GLSPYPQKPS
1160 1170 1180 1190
SSKDSEDTSK EPSLSTQTLP VIKCSGQTSR LSASSTFQSI SDSLLAVSP
Length:1,199
Mass (Da):133,378
Last modified:April 3, 2007 - v2
Checksum:i9B95597237588956
GO

Sequence cautioni

The sequence BAA11490 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03146417N → S1 PublicationCorresponds to variant dbSNP:rs11542786Ensembl.1
Natural variantiVAR_03146534E → Q1 PublicationCorresponds to variant dbSNP:rs3731877Ensembl.1
Natural variantiVAR_031466364L → P. Corresponds to variant dbSNP:rs3731875Ensembl.1
Natural variantiVAR_013140418R → H. Corresponds to variant dbSNP:rs2114664Ensembl.1
Natural variantiVAR_031467518G → S1 PublicationCorresponds to variant dbSNP:rs17851914Ensembl.1
Natural variantiVAR_031468524S → G1 PublicationCorresponds to variant dbSNP:rs17851915Ensembl.1
Natural variantiVAR_031469852A → S1 PublicationCorresponds to variant dbSNP:rs17856640Ensembl.1
Natural variantiVAR_0573151138T → I. Corresponds to variant dbSNP:rs9989776Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D79995 mRNA Translation: BAA11490.2 Different initiation.
AK291770 mRNA Translation: BAF84459.1
CH471063 Genomic DNA Translation: EAW70651.1
BC021707 mRNA Translation: AAH21707.1
CCDSiCCDS2422.1
RefSeqiNP_055455.3, NM_014640.4
UniGeneiHs.471405

Genome annotation databases

EnsembliENST00000258398; ENSP00000258398; ENSG00000135912
ENST00000392102; ENSP00000375951; ENSG00000135912
GeneIDi9654
KEGGihsa:9654
UCSCiuc002viy.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTTLL4_HUMAN
AccessioniPrimary (citable) accession number: Q14679
Secondary accession number(s): A8K6V5, Q8WW29
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: April 3, 2007
Last modified: June 20, 2018
This is version 142 of the entry and version 2 of the sequence. See 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

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