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Protein

N-acetylated-alpha-linked acidic dipeptidase-like protein

Gene

NAALADL1

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

Functioni

NAALADase-like activity unknown. Has no NAAG hydrolyzing activity. Exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC (By similarity).By similarity

Catalytic activityi

Release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma-glutamates.

Cofactori

Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi368Zinc 1By similarity1
Metal bindingi378Zinc 1By similarity1
Metal bindingi378Zinc 2By similarity1
Active sitei416Nucleophile; for NAALADase activityBy similarity1
Metal bindingi417Zinc 2By similarity1
Metal bindingi445Zinc 1By similarity1
Metal bindingi545Zinc 2By similarity1
Active sitei617Charge relay systemSequence analysis1
Active sitei657Charge relay systemSequence analysis1
Active sitei680Charge relay systemSequence analysis1

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS09686-MONOMER.

Protein family/group databases

MEROPSiM28.011.

Names & Taxonomyi

Protein namesi
Recommended name:
N-acetylated-alpha-linked acidic dipeptidase-like protein (EC:3.4.17.21)
Short name:
NAALADase L
Alternative name(s):
100 kDa ileum brush border membrane protein
Short name:
I100
Ileal dipeptidylpeptidase
Gene namesi
Name:NAALADL1
Synonyms:NAALADASEL, NAALADL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:23536. NAALADL1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6CytoplasmicSequence analysis6
Transmembranei7 – 28Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST22
Topological domaini29 – 740ExtracellularSequence analysisAdd BLAST712

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi10004.
OpenTargetsiENSG00000168060.
PharmGKBiPA134867982.

Polymorphism and mutation databases

BioMutaiNAALADL1.
DMDMi313104139.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001741231 – 740N-acetylated-alpha-linked acidic dipeptidase-like proteinAdd BLAST740

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi136N-linked (GlcNAc...)Sequence analysis1
Glycosylationi274N-linked (GlcNAc...)Sequence analysis1
Glycosylationi299N-linked (GlcNAc...)Sequence analysis1
Glycosylationi334N-linked (GlcNAc...)Sequence analysis1
Glycosylationi345N-linked (GlcNAc...)Sequence analysis1
Glycosylationi451N-linked (GlcNAc...)Sequence analysis1
Glycosylationi492N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9UQQ1.
PeptideAtlasiQ9UQQ1.
PRIDEiQ9UQQ1.

PTM databases

iPTMnetiQ9UQQ1.
PhosphoSitePlusiQ9UQQ1.

Expressioni

Tissue specificityi

Mainly expressed in the distal small intestine. Also expressed in the spleen and testis. Weak expression in the brain, locating mainly to the brain stem, amygdala, thalamus and ventral striatum. Isoform 2 and 3 isoform 3 are found in the small intestine and colon.

Gene expression databases

BgeeiENSG00000168060.
CleanExiHS_NAALADL1.
ExpressionAtlasiQ9UQQ1. baseline and differential.
GenevisibleiQ9UQQ1. HS.

Organism-specific databases

HPAiHPA047123.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000351484.

Structurei

Secondary structure

1740
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi42 – 51Combined sources10
Helixi54 – 64Combined sources11
Helixi74 – 88Combined sources15
Turni90 – 92Combined sources3
Beta strandi95 – 108Combined sources14
Beta strandi111 – 113Combined sources3
Beta strandi116 – 120Combined sources5
Beta strandi126 – 129Combined sources4
Beta strandi137 – 143Combined sources7
Beta strandi163 – 165Combined sources3
Helixi171 – 179Combined sources9
Beta strandi188 – 196Combined sources9
Helixi198 – 206Combined sources9
Turni207 – 209Combined sources3
Beta strandi212 – 216Combined sources5
Helixi219 – 222Combined sources4
Helixi229 – 231Combined sources3
Beta strandi235 – 238Combined sources4
Beta strandi251 – 254Combined sources4
Helixi272 – 274Combined sources3
Beta strandi283 – 285Combined sources3
Helixi288 – 295Combined sources8
Beta strandi300 – 302Combined sources3
Helixi305 – 307Combined sources3
Beta strandi310 – 313Combined sources4
Beta strandi319 – 321Combined sources3
Beta strandi325 – 327Combined sources3
Beta strandi332 – 337Combined sources6
Beta strandi340 – 353Combined sources14
Beta strandi356 – 368Combined sources13
Beta strandi372 – 374Combined sources3
Turni376 – 379Combined sources4
Helixi380 – 398Combined sources19
Beta strandi405 – 414Combined sources10
Turni417 – 419Combined sources3
Helixi421 – 429Combined sources9
Helixi431 – 437Combined sources7
Beta strandi438 – 443Combined sources6
Beta strandi447 – 449Combined sources3
Beta strandi451 – 458Combined sources8
Helixi460 – 462Combined sources3
Helixi463 – 471Combined sources9
Beta strandi476 – 480Combined sources5
Helixi483 – 487Combined sources5
Turni488 – 490Combined sources3
Beta strandi491 – 495Combined sources5
Turni496 – 498Combined sources3
Beta strandi499 – 502Combined sources4
Beta strandi509 – 511Combined sources3
Helixi513 – 518Combined sources6
Beta strandi524 – 530Combined sources7
Turni533 – 535Combined sources3
Turni542 – 545Combined sources4
Helixi551 – 556Combined sources6
Helixi563 – 581Combined sources19
Helixi589 – 591Combined sources3
Helixi592 – 613Combined sources22
Helixi619 – 643Combined sources25
Helixi649 – 661Combined sources13
Helixi662 – 666Combined sources5
Beta strandi675 – 677Combined sources3
Turni681 – 683Combined sources3
Beta strandi688 – 690Combined sources3
Helixi694 – 703Combined sources10
Helixi711 – 734Combined sources24

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4TWEX-ray1.75A/B28-740[»]
ProteinModelPortaliQ9UQQ1.
SMRiQ9UQQ1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni263 – 579NAALADaseAdd BLAST317

Sequence similaritiesi

Belongs to the peptidase M28 family. M28B subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2195. Eukaryota.
COG2234. LUCA.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000211921.
HOVERGENiHBG051639.
InParanoidiQ9UQQ1.
KOiK01301.
OMAiTSMDLAY.
OrthoDBiEOG091G02ZM.
PhylomeDBiQ9UQQ1.
TreeFamiTF312981.

Family and domain databases

Gene3Di1.20.930.40. 1 hit.
InterProiIPR003137. PA_domain.
IPR007484. Peptidase_M28.
IPR007365. TFR-like_dimer_dom.
[Graphical view]
PfamiPF02225. PA. 1 hit.
PF04389. Peptidase_M28. 1 hit.
PF04253. TFR_dimer. 1 hit.
[Graphical view]
SUPFAMiSSF47672. SSF47672. 1 hit.

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UQQ1-1) [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
MQWTKVLGLG LGAAALLGLG IILGHFAIPK KANSLAPQDL DLEILETVMG
60 70 80 90 100
QLDAHRIREN LRELSREPHL ASSPRDEDLV QLLLQRWKDP ESGLDSAEAS
110 120 130 140 150
TYEVLLSFPS QEQPNVVDIV GPTGGIIHSC HRTEENVTGE QGGPDVVQPY
160 170 180 190 200
AAYAPSGTPQ GLLVYANRGA EEDFKELQTQ GIKLEGTIAL TRYGGVGRGA
210 220 230 240 250
KAVNAAKHGV AGVLVYTDPA DINDGLSSPD ETFPNSWYLP PSGVERGSYY
260 270 280 290 300
EYFGDPLTPY LPAVPSSFRV DLANVSGFPP IPTQPIGFQD ARDLLCNLNG
310 320 330 340 350
TLAPATWQGA LGCHYRLGPG FRPDGDFPAD SQVNVSVYNR LELRNSSNVL
360 370 380 390 400
GIIRGAVEPD RYVLYGNHRD SWVHGAVDPS SGTAVLLELS RVLGTLLKKG
410 420 430 440 450
TWRPRRSIVF ASWGAEEFGL IGSTEFTEEF FNKLQERTVA YINVDISVFA
460 470 480 490 500
NATLRVQGTP PVQSVVFSAT KEIRSPGPGD LSIYDNWIRY FNRSSPVYGL
510 520 530 540 550
VPSLGSLGAG SDYAPFVHFL GISSMDIAYT YDRSKTSARI YPTYHTAFDT
560 570 580 590 600
FDYVDKFLDP GFSSHQAVAR TAGSVILRLS DSFFLPLKVS DYSETLRSFL
610 620 630 640 650
QAAQQDLGAL LEQHSISLGP LVTAVEKFEA EAAALGQRIS TLQKGSPDPL
660 670 680 690 700
QVRMLNDQLM LLERTFLNPR AFPEERYYSH VLWAPRTGSV VTFPGLSNAC
710 720 730 740
SRARDTASGS EAWAEVQRQL SIVVTALEGA AATLRPVADL
Length:740
Mass (Da):80,558
Last modified:November 30, 2010 - v2
Checksum:i018D59835F2C48AC
GO
Isoform 2 (identifier: Q9UQQ1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     161-201: Missing.

Show »
Length:699
Mass (Da):76,195
Checksum:iBDF2C67F921ED4CA
GO
Isoform 3 (identifier: Q9UQQ1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     296-330: Missing.

Show »
Length:705
Mass (Da):76,887
Checksum:iB043A0DBBDEBFB8D
GO
Isoform 4 (identifier: Q9UQQ1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     359-359: P → PGEPSSCCLHPRPLLCSGCRCPHPALPLPPPSPAPPAHLSLSSGSLPLFLWP

Show »
Length:791
Mass (Da):85,832
Checksum:i8872DB91F3669FD7
GO
Isoform 5 (identifier: Q9UQQ1-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     502-522: PSLGSLGAGSDYAPFVHFLGI → PRLQQPSGCGPDSGECDSPAQ
     523-740: Missing.

Show »
Length:522
Mass (Da):56,573
Checksum:iD9C30160F01AC93B
GO
Isoform 6 (identifier: Q9UQQ1-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     502-543: PSLGSLGAGS...SKTSARIYPT → PRARLQPGSP...IRLWPGQRGV
     544-740: Missing.

Show »
Length:543
Mass (Da):59,132
Checksum:i3DEF010A089357C9
GO
Isoform 7 (identifier: Q9UQQ1-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     562-579: FSSHQAVARTAGSVILRL → FEEGDKGHPETRTGEAED
     580-740: Missing.

Show »
Length:579
Mass (Da):63,077
Checksum:i62FAEF2C2C593E0F
GO
Isoform 8 (identifier: Q9UQQ1-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     619-635: GPLVTAVEKFEAEAAAL → GMHSPDPEVWGALHPHD
     636-740: Missing.

Show »
Length:635
Mass (Da):69,188
Checksum:i1388AE658E962A2C
GO

Sequence cautioni

The sequence AAB87645 differs from that shown. Reason: Frameshift at positions 686 and 693.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti420 – 424LIGST → SPGLQ in AAB87645 (PubMed:9388249).Curated5

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0571552Q → H.Corresponds to variant rs35422506dbSNPEnsembl.1
Natural variantiVAR_057156398K → T.Corresponds to variant rs12223986dbSNPEnsembl.1
Natural variantiVAR_057157611L → V.Corresponds to variant rs36053340dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005343161 – 201Missing in isoform 2. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_005344296 – 330Missing in isoform 3. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_005345359P → PGEPSSCCLHPRPLLCSGCR CPHPALPLPPPSPAPPAHLS LSSGSLPLFLWP in isoform 4. 1 Publication1
Alternative sequenceiVSP_005348502 – 543PSLGS…RIYPT → PRARLQPGSPPTTQPLTPLT MWTSFWTRASAAIRLWPGQR GV in isoform 6. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_005346502 – 522PSLGS…HFLGI → PRLQQPSGCGPDSGECDSPA Q in isoform 5. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_005347523 – 740Missing in isoform 5. 1 PublicationAdd BLAST218
Alternative sequenceiVSP_005349544 – 740Missing in isoform 6. 1 PublicationAdd BLAST197
Alternative sequenceiVSP_005350562 – 579FSSHQ…VILRL → FEEGDKGHPETRTGEAED in isoform 7. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_005351580 – 740Missing in isoform 7. 1 PublicationAdd BLAST161
Alternative sequenceiVSP_005352619 – 635GPLVT…EAAAL → GMHSPDPEVWGALHPHD in isoform 8. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_005353636 – 740Missing in isoform 8. 1 PublicationAdd BLAST105

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ012371 mRNA. Translation: CAB39968.1.
AP003068 Genomic DNA. No translation available.
AF010141 mRNA. Translation: AAB87645.1. Frameshift.
CCDSiCCDS31604.1. [Q9UQQ1-1]
RefSeqiNP_005459.2. NM_005468.2. [Q9UQQ1-1]
XP_011543012.1. XM_011544710.2. [Q9UQQ1-5]
UniGeneiHs.13967.

Genome annotation databases

EnsembliENST00000340252; ENSP00000344244; ENSG00000168060. [Q9UQQ1-4]
ENST00000355721; ENSP00000347955; ENSG00000168060. [Q9UQQ1-2]
ENST00000358658; ENSP00000351484; ENSG00000168060. [Q9UQQ1-1]
GeneIDi10004.
KEGGihsa:10004.
UCSCiuc001ocn.4. human. [Q9UQQ1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ012371 mRNA. Translation: CAB39968.1.
AP003068 Genomic DNA. No translation available.
AF010141 mRNA. Translation: AAB87645.1. Frameshift.
CCDSiCCDS31604.1. [Q9UQQ1-1]
RefSeqiNP_005459.2. NM_005468.2. [Q9UQQ1-1]
XP_011543012.1. XM_011544710.2. [Q9UQQ1-5]
UniGeneiHs.13967.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4TWEX-ray1.75A/B28-740[»]
ProteinModelPortaliQ9UQQ1.
SMRiQ9UQQ1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000351484.

Protein family/group databases

MEROPSiM28.011.

PTM databases

iPTMnetiQ9UQQ1.
PhosphoSitePlusiQ9UQQ1.

Polymorphism and mutation databases

BioMutaiNAALADL1.
DMDMi313104139.

Proteomic databases

PaxDbiQ9UQQ1.
PeptideAtlasiQ9UQQ1.
PRIDEiQ9UQQ1.

Protocols and materials databases

DNASUi10004.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340252; ENSP00000344244; ENSG00000168060. [Q9UQQ1-4]
ENST00000355721; ENSP00000347955; ENSG00000168060. [Q9UQQ1-2]
ENST00000358658; ENSP00000351484; ENSG00000168060. [Q9UQQ1-1]
GeneIDi10004.
KEGGihsa:10004.
UCSCiuc001ocn.4. human. [Q9UQQ1-1]

Organism-specific databases

CTDi10004.
DisGeNETi10004.
GeneCardsiNAALADL1.
H-InvDBHIX0035851.
HGNCiHGNC:23536. NAALADL1.
HPAiHPA047123.
MIMi602640. gene.
neXtProtiNX_Q9UQQ1.
OpenTargetsiENSG00000168060.
PharmGKBiPA134867982.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2195. Eukaryota.
COG2234. LUCA.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000211921.
HOVERGENiHBG051639.
InParanoidiQ9UQQ1.
KOiK01301.
OMAiTSMDLAY.
OrthoDBiEOG091G02ZM.
PhylomeDBiQ9UQQ1.
TreeFamiTF312981.

Enzyme and pathway databases

BioCyciZFISH:HS09686-MONOMER.

Miscellaneous databases

GenomeRNAii10004.
PROiQ9UQQ1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168060.
CleanExiHS_NAALADL1.
ExpressionAtlasiQ9UQQ1. baseline and differential.
GenevisibleiQ9UQQ1. HS.

Family and domain databases

Gene3Di1.20.930.40. 1 hit.
InterProiIPR003137. PA_domain.
IPR007484. Peptidase_M28.
IPR007365. TFR-like_dimer_dom.
[Graphical view]
PfamiPF02225. PA. 1 hit.
PF04389. Peptidase_M28. 1 hit.
PF04253. TFR_dimer. 1 hit.
[Graphical view]
SUPFAMiSSF47672. SSF47672. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNALDL_HUMAN
AccessioniPrimary (citable) accession number: Q9UQQ1
Secondary accession number(s): C9J8A1
, C9J964, C9JL35, C9JSN0, O43176
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: November 30, 2010
Last modified: November 2, 2016
This is version 140 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, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.