TTLL13

Summary

TTLL13 (tubulin tyrosine ligase like 13, HGNC:32484) is a protein-coding gene on chromosome 15q26.1, encoding Tubulin polyglutamylase TTLL13 (A6NNM8). Polyglutamylase which modifies tubulin, generating polyglutamate side chains of variable lengths on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin.

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule bundle formation. Predicted to be located in cytosol. Predicted to be active in ciliary basal body.

Source: NCBI Gene 440307 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001396017

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32484
Approved symbol	TTLL13
Name	tubulin tyrosine ligase like 13
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46079, MGC33417
Ensembl gene	ENSG00000213471
Ensembl biotype	protein_coding
OMIM	620485
Entrez	440307

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000339615, ENST00000438251, ENST00000612615, ENST00000617037, ENST00000621485, ENST00000641754

RefSeq mRNA: 1 — MANE Select: NM_001396017 NM_001396017

CCDS: CCDS92063

Canonical transcript exons

ENST00000641754 — 15 exons

Exon	Start	End
ENSE00001754056	90262492	90262669
ENSE00001758040	90262966	90263145
ENSE00003537752	90262006	90262191
ENSE00003628539	90258743	90258927
ENSE00003717891	90250620	90250887
ENSE00003801789	90257138	90257281
ENSE00003802812	90257637	90257722
ENSE00003805226	90258038	90258269
ENSE00003806453	90256141	90256297
ENSE00003807016	90251554	90251594
ENSE00003807136	90255755	90255885
ENSE00003810118	90253249	90253367
ENSE00003813265	90263947	90264058
ENSE00003972314	90249556	90249808
ENSE00003972315	90264720	90265477

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 81.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1192 / max 50.0704, expressed in 19 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148428	0.0987	16
148427	0.0205	4

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.51	gold quality
testis	UBERON:0000473	80.83	gold quality
left testis	UBERON:0004533	80.82	gold quality
right testis	UBERON:0004534	80.64	gold quality
right uterine tube	UBERON:0001302	62.03	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	60.61	gold quality
mucosa of transverse colon	UBERON:0004991	58.77	gold quality
granulocyte	CL:0000094	58.60	gold quality
apex of heart	UBERON:0002098	57.04	gold quality
cerebellum	UBERON:0002037	53.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.86	silver quality
cerebellar cortex	UBERON:0002129	53.80	gold quality
cerebellar hemisphere	UBERON:0002245	53.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	53.57	gold quality
cortical plate	UBERON:0005343	53.21	gold quality
nucleus accumbens	UBERON:0001882	51.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.37	gold quality
prefrontal cortex	UBERON:0000451	51.05	gold quality
putamen	UBERON:0001874	50.84	gold quality
frontal cortex	UBERON:0001870	50.75	gold quality
right frontal lobe	UBERON:0002810	50.54	gold quality
brain	UBERON:0000955	50.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	50.07	gold quality
cerebral cortex	UBERON:0000956	49.92	gold quality
bone marrow	UBERON:0002371	49.92	silver quality
caudate nucleus	UBERON:0001873	49.90	gold quality
substantia nigra	UBERON:0002038	49.83	gold quality
pituitary gland	UBERON:0000007	49.81	gold quality
duodenum	UBERON:0002114	49.81	gold quality
right lobe of liver	UBERON:0001114	49.71	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.59

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ttll13	ENSMUSG00000045467
rattus_norvegicus	Ttll13	ENSRNOG00000056362
drosophila_melanogaster	TTLL6A	FBGN0034459

Paralogs (12): TTLL1 (ENSG00000100271), TTLL12 (ENSG00000100304), TTLL2 (ENSG00000120440), TTLL9 (ENSG00000131044), TTLL4 (ENSG00000135912), TTLL7 (ENSG00000137941), TTLL8 (ENSG00000138892), TTLL10 (ENSG00000162571), TTLL6 (ENSG00000170703), TTLL11 (ENSG00000175764), KPRP (ENSG00000203786), TTLL3 (ENSG00000214021)

Protein

Protein identifiers

Tubulin polyglutamylase TTLL13 — A6NNM8 (reviewed: A6NNM8)

Alternative names: Tubulin tyrosine ligase like 13, Tubulin tyrosine ligase-like family member 13 pseudogene, Tubulin–tyrosine ligase-like protein 13

All UniProt accessions (4): A0A1W2PP44, A0A1W2PRM3, A0A286YFC2, A6NNM8

UniProt curated annotations — full annotation on UniProt →

Function. Polyglutamylase which modifies tubulin, generating polyglutamate side chains of variable lengths on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin. Mediates ATP-dependent polyglutamate side-chain elongation of the polyglutamylation reaction but not the initiation step. Preferentially modifies the alpha-tubulin tail over a beta-tail.

Domain organisation. 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. Gln-208 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin–tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.

Miscellaneous. May be due to an intron retention.

Similarity. Belongs to the tubulin–tyrosine ligase family.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NNM8-1	1	yes
A6NNM8-2	2

RefSeq proteins (1): NP_001382946* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004344	TTL/TTLL_fam	Family

Pfam: PF03133

Catalyzed reactions (Rhea), 1 shown:

• (L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + L-glutamate + ATP = (L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein] + ADP + phosphate + H(+) (RHEA:60148)

UniProt features (28 total): binding site 14, region of interest 2, splice variant 2, sequence variant 2, mutagenesis site 2, chain 1, domain 1, site 1, sequence conflict 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NNM8-F1	65.71	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 208 (essential for specifying alpha-elongation versus initiation step of the polyglutamylase activity)

Ligand- & substrate-binding residues (14): 243–245; 269; 291–292; 293; 311; 376; 389; 389; 391; 407; 202; 208–209 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
425–427	decreased binding to microtubules and polyglutamylase activity; when associated with 451-e-e-452.
451–452	decreased binding to microtubules and polyglutamylase activity; when associated with 425-e–e-427.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin

MSigDB gene sets: 67 (showing top): GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_PEPTIDYL_GLUTAMIC_ACID_MODIFICATION, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_NITROGEN_BONDS, GOMF_ACID_AMINO_ACID_LIGASE_ACTIVITY, GOCC_CILIUM, GOCC_CILIARY_BASAL_BODY, GOMF_CYTOSKELETAL_PROTEIN_BINDING, chr15q26, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_ADENYL_NUCLEOTIDE_BINDING, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, GOBP_PROTEIN_POLYGLUTAMYLATION, GOCC_SUPRAMOLECULAR_COMPLEX

GO Biological Process (2): microtubule bundle formation (GO:0001578), protein modification process (GO:0036211)

GO Molecular Function (7): ATP binding (GO:0005524), tubulin binding (GO:0015631), metal ion binding (GO:0046872), tubulin-glutamic acid ligase activity (GO:0070740), protein-glutamic acid ligase activity, elongating (GO:0106438), nucleotide binding (GO:0000166), ligase activity (GO:0016874)

GO Cellular Component (3): cytosol (GO:0005829), microtubule (GO:0005874), ciliary basal body (GO:0036064)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-glutamic acid ligase activity	2
microtubule cytoskeleton organization	1
protein metabolic process	1
macromolecule modification	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cytoskeletal protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
microtubule organizing center	1
cilium	1

Protein interactions and networks

STRING

184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTLL13	AGBL4	Q5VU57	532
TTLL13	BTBD8	Q5XKL5	510
TTLL13	CATSPER2	Q96P56	445
TTLL13	RNF17	Q9BXT8	395
TTLL13	TTLL5	Q6EMB2	394
TTLL13	PPP1R3C	Q9UQK1	387
TTLL13	CWC15	Q9P013	378
TTLL13	TTLL10	Q6ZVT0	372
TTLL13	OSTN	P61366	362
TTLL13	ROPN1L	Q96C74	360
TTLL13	SALL3	Q9BXA9	358
TTLL13	CCDC40	Q4G0X9	353
TTLL13	TTLL4	Q14679	352
TTLL13	TTLL8	A6PVC2	343
TTLL13	TTLL3	Q9Y4R7	328

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TTLL13	S100A10	psi-mi:“MI:0915”(physical association)	0.400
TTLL13	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0JM98, A1L1H3, A4Q9E8, A4Q9F0, A4Q9F6, A6NNM8, A7MBJ2, A8CVX7, D3ZF42, O54928, O75159, O88866, P51957, P57058, P59110, Q08D35, Q0P4M4, Q14679, Q29RN6, Q5NC05, Q5QJC4, Q5R978, Q5RHD1, Q5SUS0, Q5T7B8, Q63679, Q68UT7, Q6EEF3, Q6EMB2, Q6GQJ2, Q6IE81, Q6IE82, Q6IRU7, Q6NWW5, Q6P1H6, Q6P7W0, Q6PCM1, Q6PJP8, Q6ZPI0, Q7TP65

Diamond homologs: A2APC3, A4Q9E4, A4Q9E5, A4Q9E8, A4Q9F6, A6NNM8, A6PVC2, A8CVX7, B2GUB3, O95922, P0CAZ0, Q0VC71, Q1ECV4, Q23K29, Q23SI8, Q3SXZ7, Q3SZH6, Q4R7H0, Q564U4, Q5PPI9, Q5R978, Q641W7, Q6EEF3, Q6EMB2, Q8CHB8, Q8N841, Q91V51, Q9BWV7, Q9Y4R7, A4Q9F0, A4Q9F1, A4Q9F4, A8X9V4, E9P886, F7E540, H2KZM9, P38160, P38584, Q09647, Q14679

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2551 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90249672:G:GT	donor_gain	1.0000
15:90249703:G:GT	donor_gain	1.0000
15:90249744:C:G	donor_gain	1.0000
15:90253247:A:AG	acceptor_gain	1.0000
15:90253248:G:GA	acceptor_gain	1.0000
15:90253248:GTGC:G	acceptor_gain	1.0000
15:90255884:GA:G	donor_gain	1.0000
15:90255886:G:GG	donor_gain	1.0000
15:90256140:GCTAT:G	acceptor_gain	1.0000
15:90256264:A:T	donor_gain	1.0000
15:90257119:T:TA	acceptor_gain	1.0000
15:90257128:A:AG	acceptor_gain	1.0000
15:90258866:GAGGA:G	donor_gain	1.0000
15:90258887:G:GT	donor_gain	1.0000
15:90258888:A:T	donor_gain	1.0000
15:90258920:GAATC:G	donor_gain	1.0000
15:90258924:C:G	donor_gain	1.0000
15:90262004:A:AG	acceptor_gain	1.0000
15:90262004:AG:A	acceptor_gain	1.0000
15:90262004:AGG:A	acceptor_loss	1.0000
15:90262005:G:GA	acceptor_gain	1.0000
15:90262005:GG:G	acceptor_gain	1.0000
15:90262005:GGA:G	acceptor_gain	1.0000
15:90262005:GGAA:G	acceptor_gain	1.0000
15:90262005:GGAAA:G	acceptor_gain	1.0000
15:90262111:G:GT	donor_gain	1.0000
15:90262189:CAG:C	donor_loss	1.0000
15:90262190:AG:A	donor_loss	1.0000
15:90262191:GGT:G	donor_loss	1.0000
15:90262193:T:C	donor_loss	1.0000

AlphaMissense

4923 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90255795:A:T	K153I	1.000
15:90255792:G:C	R152P	0.999
15:90255794:A:C	K153Q	0.999
15:90255796:A:C	K153N	0.999
15:90255796:A:T	K153N	0.999
15:90256198:G:C	K202N	0.999
15:90256198:G:T	K202N	0.999
15:90258229:A:T	D376V	0.999
15:90253314:T:A	W122R	0.998
15:90253314:T:C	W122R	0.998
15:90255794:A:G	K153E	0.998
15:90255816:T:C	L160P	0.998
15:90255869:T:A	W178R	0.998
15:90255869:T:C	W178R	0.998
15:90256196:A:G	K202E	0.998
15:90258229:A:C	D376A	0.998
15:90255763:C:A	N142K	0.997
15:90255763:C:G	N142K	0.997
15:90255795:A:C	K153T	0.997
15:90256196:A:C	K202Q	0.997
15:90256277:T:C	C229R	0.997
15:90256281:A:C	Q230P	0.997
15:90257663:C:A	N292K	0.997
15:90257663:C:G	N292K	0.997
15:90253302:T:A	W118R	0.996
15:90253302:T:C	W118R	0.996
15:90255764:C:G	H143D	0.996
15:90255822:G:C	R162P	0.996
15:90255871:G:C	W178C	0.996
15:90255871:G:T	W178C	0.996

dbSNP variants (sampled 300 via entrez): RS1000076592 (15:90257050 A>G,T), RS1000127743 (15:90261675 G>A,T), RS1000258463 (15:90250306 G>A), RS1000515748 (15:90249955 A>T), RS1000551771 (15:90250252 C>T), RS1000723477 (15:90261924 C>A,T), RS1000982471 (15:90251669 G>A), RS1001280062 (15:90256572 T>C), RS1001515918 (15:90248619 G>T), RS1001999333 (15:90258371 G>A), RS1002492242 (15:90252041 T>A), RS1002554820 (15:90247650 G>C,T), RS1002681141 (15:90253030 G>A), RS1002768103 (15:90259534 G>A), RS1003604254 (15:90247866 C>CT)

Disease associations

OMIM: gene MIM:620485 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	increases expression	1
Benzo(a)pyrene	increases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.