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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi368 – 3681Zinc 1By similarity
Metal bindingi378 – 3781Zinc 1By similarity
Metal bindingi378 – 3781Zinc 2By similarity
Active sitei416 – 4161Nucleophile; for NAALADase activityBy similarity
Metal bindingi417 – 4171Zinc 2By similarity
Metal bindingi445 – 4451Zinc 1By similarity
Metal bindingi545 – 5451Zinc 2By similarity
Active sitei617 – 6171Charge relay systemSequence Analysis
Active sitei657 – 6571Charge relay systemSequence Analysis
Active sitei680 – 6801Charge relay systemSequence Analysis

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

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
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:23536. NAALADL1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66CytoplasmicSequence Analysis
Transmembranei7 – 2822Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini29 – 740712ExtracellularSequence AnalysisAdd
BLAST

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

PharmGKBiPA134867982.

Polymorphism and mutation databases

BioMutaiNAALADL1.
DMDMi313104139.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 740740N-acetylated-alpha-linked acidic dipeptidase-like proteinPRO_0000174123Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi136 – 1361N-linked (GlcNAc...)Sequence Analysis
Glycosylationi274 – 2741N-linked (GlcNAc...)Sequence Analysis
Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence Analysis
Glycosylationi334 – 3341N-linked (GlcNAc...)Sequence Analysis
Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence Analysis
Glycosylationi451 – 4511N-linked (GlcNAc...)Sequence Analysis
Glycosylationi492 – 4921N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9UQQ1.
PRIDEiQ9UQQ1.

PTM databases

PhosphoSiteiQ9UQQ1.

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

BgeeiQ9UQQ1.
CleanExiHS_NAALADL1.
ExpressionAtlasiQ9UQQ1. baseline and differential.
GenevisibleiQ9UQQ1. HS.

Organism-specific databases

HPAiHPA047123.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000351484.

Structurei

Secondary structure

1
740
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi42 – 5110Combined sources
Helixi54 – 6411Combined sources
Helixi74 – 8815Combined sources
Turni90 – 923Combined sources
Beta strandi95 – 10814Combined sources
Beta strandi111 – 1133Combined sources
Beta strandi116 – 1205Combined sources
Beta strandi126 – 1294Combined sources
Beta strandi137 – 1437Combined sources
Beta strandi163 – 1653Combined sources
Helixi171 – 1799Combined sources
Beta strandi188 – 1969Combined sources
Helixi198 – 2069Combined sources
Turni207 – 2093Combined sources
Beta strandi212 – 2165Combined sources
Helixi219 – 2224Combined sources
Helixi229 – 2313Combined sources
Beta strandi235 – 2384Combined sources
Beta strandi251 – 2544Combined sources
Helixi272 – 2743Combined sources
Beta strandi283 – 2853Combined sources
Helixi288 – 2958Combined sources
Beta strandi300 – 3023Combined sources
Helixi305 – 3073Combined sources
Beta strandi310 – 3134Combined sources
Beta strandi319 – 3213Combined sources
Beta strandi325 – 3273Combined sources
Beta strandi332 – 3376Combined sources
Beta strandi340 – 35314Combined sources
Beta strandi356 – 36813Combined sources
Beta strandi372 – 3743Combined sources
Turni376 – 3794Combined sources
Helixi380 – 39819Combined sources
Beta strandi405 – 41410Combined sources
Turni417 – 4193Combined sources
Helixi421 – 4299Combined sources
Helixi431 – 4377Combined sources
Beta strandi438 – 4436Combined sources
Beta strandi447 – 4493Combined sources
Beta strandi451 – 4588Combined sources
Helixi460 – 4623Combined sources
Helixi463 – 4719Combined sources
Beta strandi476 – 4805Combined sources
Helixi483 – 4875Combined sources
Turni488 – 4903Combined sources
Beta strandi491 – 4955Combined sources
Turni496 – 4983Combined sources
Beta strandi499 – 5024Combined sources
Beta strandi509 – 5113Combined sources
Helixi513 – 5186Combined sources
Beta strandi524 – 5307Combined sources
Turni533 – 5353Combined sources
Turni542 – 5454Combined sources
Helixi551 – 5566Combined sources
Helixi563 – 58119Combined sources
Helixi589 – 5913Combined sources
Helixi592 – 61322Combined sources
Helixi619 – 64325Combined sources
Helixi649 – 66113Combined sources
Helixi662 – 6665Combined sources
Beta strandi675 – 6773Combined sources
Turni681 – 6833Combined sources
Beta strandi688 – 6903Combined sources
Helixi694 – 70310Combined sources
Helixi711 – 73424Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4TWEX-ray1.75A/B28-740[»]
ProteinModelPortaliQ9UQQ1.
SMRiQ9UQQ1. Positions 48-737.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni263 – 579317NAALADaseAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase M28 family. M28B subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2234.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000211921.
HOVERGENiHBG051639.
InParanoidiQ9UQQ1.
KOiK01301.
OMAiRGAEEDF.
OrthoDBiEOG7QK0BC.
PhylomeDBiQ9UQQ1.
TreeFamiTF312981.

Family and domain databases

Gene3Di1.20.930.40. 1 hit.
InterProiIPR007484. Peptidase_M28.
IPR003137. Protease-assoc_domain.
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 AAB87645.1 differs from that shown. Reason: Frameshift at positions 686 and 693. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti420 – 4245LIGST → SPGLQ in AAB87645 (PubMed:9388249).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti2 – 21Q → H.
Corresponds to variant rs35422506 [ dbSNP | Ensembl ].
VAR_057155
Natural varianti398 – 3981K → T.
Corresponds to variant rs12223986 [ dbSNP | Ensembl ].
VAR_057156
Natural varianti611 – 6111L → V.
Corresponds to variant rs36053340 [ dbSNP | Ensembl ].
VAR_057157

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei161 – 20141Missing in isoform 2. 1 PublicationVSP_005343Add
BLAST
Alternative sequencei296 – 33035Missing in isoform 3. 1 PublicationVSP_005344Add
BLAST
Alternative sequencei359 – 3591P → PGEPSSCCLHPRPLLCSGCR CPHPALPLPPPSPAPPAHLS LSSGSLPLFLWP in isoform 4. 1 PublicationVSP_005345
Alternative sequencei502 – 54342PSLGS…RIYPT → PRARLQPGSPPTTQPLTPLT MWTSFWTRASAAIRLWPGQR GV in isoform 6. 1 PublicationVSP_005348Add
BLAST
Alternative sequencei502 – 52221PSLGS…HFLGI → PRLQQPSGCGPDSGECDSPA Q in isoform 5. 1 PublicationVSP_005346Add
BLAST
Alternative sequencei523 – 740218Missing in isoform 5. 1 PublicationVSP_005347Add
BLAST
Alternative sequencei544 – 740197Missing in isoform 6. 1 PublicationVSP_005349Add
BLAST
Alternative sequencei562 – 57918FSSHQ…VILRL → FEEGDKGHPETRTGEAED in isoform 7. 1 PublicationVSP_005350Add
BLAST
Alternative sequencei580 – 740161Missing in isoform 7. 1 PublicationVSP_005351Add
BLAST
Alternative sequencei619 – 63517GPLVT…EAAAL → GMHSPDPEVWGALHPHD in isoform 8. 1 PublicationVSP_005352Add
BLAST
Alternative sequencei636 – 740105Missing in isoform 8. 1 PublicationVSP_005353Add
BLAST

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_011544710.1. [Q9UQQ1-5]
UniGeneiHs.13967.

Genome annotation databases

EnsembliENST00000340252; ENSP00000344244; ENSG00000168060. [Q9UQQ1-4]
ENST00000355721; ENSP00000347955; ENSG00000168060. [Q9UQQ1-2]
ENST00000358658; ENSP00000351484; ENSG00000168060.
GeneIDi10004.
KEGGihsa:10004.
UCSCiuc001ocn.3. 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_011544710.1. [Q9UQQ1-5]
UniGeneiHs.13967.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4TWEX-ray1.75A/B28-740[»]
ProteinModelPortaliQ9UQQ1.
SMRiQ9UQQ1. Positions 48-737.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000351484.

Protein family/group databases

MEROPSiM28.011.

PTM databases

PhosphoSiteiQ9UQQ1.

Polymorphism and mutation databases

BioMutaiNAALADL1.
DMDMi313104139.

Proteomic databases

PaxDbiQ9UQQ1.
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.
GeneIDi10004.
KEGGihsa:10004.
UCSCiuc001ocn.3. human. [Q9UQQ1-1]

Organism-specific databases

CTDi10004.
GeneCardsiGC11M064812.
H-InvDBHIX0035851.
HGNCiHGNC:23536. NAALADL1.
HPAiHPA047123.
MIMi602640. gene.
neXtProtiNX_Q9UQQ1.
PharmGKBiPA134867982.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2234.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000211921.
HOVERGENiHBG051639.
InParanoidiQ9UQQ1.
KOiK01301.
OMAiRGAEEDF.
OrthoDBiEOG7QK0BC.
PhylomeDBiQ9UQQ1.
TreeFamiTF312981.

Miscellaneous databases

GenomeRNAii10004.
NextBioi37785.
PROiQ9UQQ1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UQQ1.
CleanExiHS_NAALADL1.
ExpressionAtlasiQ9UQQ1. baseline and differential.
GenevisibleiQ9UQQ1. HS.

Family and domain databases

Gene3Di1.20.930.40. 1 hit.
InterProiIPR007484. Peptidase_M28.
IPR003137. Protease-assoc_domain.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity."
    Pangalos M.N., Neefs J.-M., Somers M., Verhasselt P., Bekkers M., van der Helm L., Fraiponts E., Ashton D., Gordon R.D.
    J. Biol. Chem. 274:8470-8483(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7 AND 8).
    Tissue: Small intestine.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 419-740.
    Tissue: Ileum.

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: July 22, 2015
This is version 131 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

External Data

Dasty 3

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 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.