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88  structures 4454  species 0  interactions 36712  sequences 316  architectures

Family: AA_permease (PF00324)

Summary: Amino acid permease

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "APC Family". More...

APC Family Edit Wikipedia article

The Amino Acid-Polyamine-Organocation (APC) Family (TC# 2.A.3) of transport proteins includes members that function as solute:cation symporters and solute:solute antiporters. [1][2][3] They occur in bacteria, archaea, fungi, unicellular eukaryotic protists, slime molds, plants and animals [1]. They vary in length, being as small as 350 residues and as large as 850 residues. The smaller proteins are generally of prokaryotic origin while the larger ones are of eukaryotic origin. Most of them possess twelve transmembrane α-helical spanners but have a re-entrant loop involving TMSs 2 and 3 [4][5]. The APC family (TC# 2.A.3) used serve as a sort of superfamily for solute:cation and solute:solute porters and includes several subfamilies, hence the reoccuring use of "superfamily" on the APC family page. The [[APC Superfamily] was later established to encompass a wider range of homologues after extensive bioinformatic and phylogenetic analysis. TCDB embodies a static system for numbering and classification, therefore the APC family classification could not be altered to accommodate newly discovered relatives.

Members of APC Family

Members of one subfamily within the APC family (SGP; TC# 2.A.3.9) are amino acid receptors rather than transporters [6] and are truncated at their C-termini, relative to the transporters, having 10 TMSs.[7]


The eukaryotic members of another subfamily (CAT; TC# 2.A.3.3) and the members of a prokaryotic subfamily (AGT; TC #2.A.3.11) have 14 TMSs [8].


The larger eukaryotic and archaeal proteins possess N- and C-terminal hydrophilic extensions. Some animal proteins, for example, those in the LAT subfamily (TC# 2.A.3.8) including ASUR4 (gbY12716) and SPRM1 (gbL25068) associate with a type 1 transmembrane glycoprotein that is essential for insertion or activity of the permease and forms a disulfide bridge with it. These glycoproteins include the CD98 heavy chain protein of Mus musculus (gbU25708) and the orthologous 4F2 cell surface antigen heavy chain of Homo sapiens (spP08195). The latter protein is required for the activity of the cystine/glutamate antiporter (2.A.3.8.5), which maintains cellular redox balance and cysteine/glutathione levels.[9] They are members of the rBAT family of mammalian proteins (TC #8.A.9).


Two APC family members, LAT1 and LAT2 (TC #2.A.3.8.7), transport a neurotoxicant, the methylmercury-L-cysteine complex, by molecular mimicry [10].


Hip1 of S. cerevisiae (TC #2.A.3.1.5) has been implicated in heavy metal transport.


Subfamilies

Subfamilies of the APC family, and the proteins in these families, can be found in the Transporter Classification Database: [5]

  • 2.A.3.1: The Amino Acid Transporter (AAT) Family
  • 2.A.3.2: The Basic Amino Acid/Polyamine Antiporter (APA) Family
  • 2.A.3.3: The Cationic Amino Acid Transporter (CAT) Family
  • 2.A.3.4: The Amino Acid/Choline Transporter (ACT) Family
  • 2.A.3.5: The Ethanolamine Transporter (EAT) Family
  • 2.A.3.6: The Archaeal/Bacterial Transporter (ABT) Family
  • 2.A.3.7: The Glutamate:GABA Antiporter (GGA) Family
  • 2.A.3.8: The L-type Amino Acid Transporter (LAT) Family (Many LAT family members function as heterooligomers with rBAT and/or 4F2hc (TC #8.A.9))
  • 2.A.3.9: The Spore Germination Protein (SGP) Family
  • 2.A.3.10: The Yeast Amino Acid Transporter (YAT) Family
  • 2.A.3.11: The Aspartate/Glutamate Transporter (AGT) Family
  • 2.A.3.12: The Polyamine:H+ Symporter (PHS) Family
  • 2.A.3.13: The Amino Acid Efflux (AAE) Family
  • 2.A.3.14: The Unknown APC-1 (U-APC1) Family
  • 2.A.3.15: The Unknown APC-2 (U-APC2) Family

Structure and Function

In CadB of E. coli (2.A.3.2.2), amino acid residues involved in both uptake and excretion, or solely in excretion are located in the cytoplasmic loops and the cytoplasmic side of transmembrane segments, whereas residues involved in uptake are located in the periplasmic loops and the transmembrane segments [11]. A hydrophilic cavity is proposed to be formed by the transmembrane segments II, III, IV, VI, VII, X, XI, and XII [11]. Based on 3-d structures of APC superfamily members, Rudnick (2011) [12][13] has proposed the pathway for transport and suggested a rocking bundle mechanism. [5]

The structure and function of the cadaverine-lysine antiporter, CadB (2.A.3.2.2), and the putrescine-ornithine antiporter, PotE (2.A.3.2.1), in E. coli have been evaluated using model structures based on the crystal structure of AdiC (2.A.3.2.5), an agmatine-arginine antiporter. The central cavity of CadB, containing the substrate-binding site is wider than that of PotE, mirroring the different sizes of cadaverine and putrescine. The size of the central cavity of CadB and PotE is dependent on the angle of transmembrane helix 6 (TM6) against the periplasm. Tyr(73), Tyr(89), Tyr(90), Glu(204), Tyr(235), Asp(303), and Tyr(423) of CadB, and Cys(62), Trp(201), Glu(207), Trp(292), and Tyr(425) of PotE are strongly involved in the antiport activities. In addition, Trp(43), Tyr(57), Tyr(107), Tyr(366), and Tyr(368) of CadB are involved preferentially in cadaverine uptake at neutral pH, while only Tyr(90) of PotE is involved preferentially in putrescine uptake. The results indicated that the central cavity of CadB consists of TMs 2, 3, 6, 7, 8, and 10, and that of PotE consists of TMs 2, 3, 6, and 8. Several residues are necessary for recognition of cadaverine in the periplasm because the level of cadaverine is much lower than that of putrescine at neutral pH. [5]

Transport Reactions

Transport reactions generally catalyzed by APC Superfamily members include: [5]

Solute:proton symport
Solute (out) + nH+ (out) → Solute (in) + nH+  (in).
Solute:solute antiport
Solute-1 (out) + Solute-2 (in) ⇌ Solute-1 (in) + Solute-2 (out).

See Also


References

  1. ^ a b Saier, MH Jr. (August 2000). "Families of transmembrane transporters selective for amino acids and their derivatives". Microbiology. 146 (8): 1775–95. PMID 10931885.
  2. ^ Wong, FH; Chen, JS; Reddy, V; Day, JL; Shlykov, MA; Wakabayashi, ST; Saier, MH Jr. (2012). "The amino acid-polyamine-organocation superfamily". J Mol Microbiol Biotechnol. 22 (2): 105–13. doi:10.1159/000338542. PMID 22627175.
  3. ^ Schweikhard, ES; Ziegler, CM (2012). "Amino acid secondary transporters: toward a common transport mechanism". Current Topics in Membranes. 70: 1–28. doi:10.1016/B978-0-12-394316-3.00001-6. PMID 23177982.
  4. ^ Gasol, E; Jiménez-Vidal, M; Chillarón, J; Zorzano, A; Palacín, M (July 23, 2014). "Membrane topology of system xc- light subunit reveals a re-entrant loop with substrate-restricted accessibility". Journal of Biological Chemistry. 279 (30): 31228–36. PMID 15151999.
  5. ^ a b c d e Saier, MH Jr. "2.A.3 The Amino Acid-Polyamine-Organocation (APC) Superfamily". Transporter Classification Database. Saier Lab Bioinformatics Group / SDSC.
  6. ^ Cabrera-Martinez, RM; Tovar-Rojo, F; Vepachedu, VR; Setlow, P (April 2003). "Effects of overexpression of nutrient receptors on germination of spores of Bacillus subtilis". Journal of Bacteriology. 185 (8): 2457–64. PMID 12670969.
  7. ^ Jack, DL; Paulsen, IT; Saier, MH (August 2000). "The amino acid/polyamine/organocation (APC) superfamily of transporters specific for amino acids, polyamines and organocations". Microbiology. 146 (8): 1797–814. PMID 10931886.
  8. ^ Lorca, G; Winnen, B; Saier, MH Jr. (May 2003). "Identification of the L-aspartate transporter in Bacillus subtilis". Journal of Bacteriology. 185 (10): 3218–22. PMID 12730183.
  9. ^ Sato, H; Shiiya, A; Kimata, M; Maebara, K; Tamba, M; Sakakura, Y; Makino, N; Sugiyama, F; Yagami, K; Moriguchi, T; Takahashi, S; Bannai, S (Nov 11, 2005). "Redox imbalance in cystine/glutamate transporter-deficient mice". Journal of Biological Chemistry. 280 (45): 37423–9. PMID 16144837.
  10. ^ Simmons-Willis, TA; Koh, AS; Clarkson, TW; Ballatori, N (October 1, 2002). "Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2". Biochemical Journal. 367 (1): 239–46. PMID 12117417.
  11. ^ a b Soksawatmaekhin, W; Uemura, T; Fukiwake, N; Kashiwagi, K; Igarashi, K (Sep 29, 2006). "Identification of the cadaverine recognition site on the cadaverine-lysine antiporter CadB". Journal of Biological Chemistry. 281 (39): 29213–20. PMID 16877381.
  12. ^ Forrest, L; Rudnick, G (December 8, 2009). "The rocking bundle: a mechanism for ion-coupled solute flux by symmetrical transporters". American Physiological Society. 24 (6): 377–386. doi:10.1152/physiol.00030.2009.
  13. ^ Rudnick, G (2011). "Cytoplasmic permeation pathway of neurotransmitter transporters". Biochemistry. 50 (35): 7462–7475. doi:10.1021/bi200926b.


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Amino acid permease". More...

Amino acid permease Edit Wikipedia article

Amino acid permease
Identifiers
SymbolAA_permease
PfamPF00324
InterProIPR004841
PROSITEPDOC00191
TCDB2.A.3
OPM superfamily67
OPM protein3gia

Amino acid permeases are integral membrane proteins involved in the transport of amino acids into the cell. A number of such proteins have been found to be evolutionary related[1][2][3]. These proteins seem to contain up to 12 transmembrane segments. The best conserved region in this family is located in the second transmembrane segment.

Human proteins containing this domain

CIP1; SLC12A1; SLC12A2; SLC12A3; SLC12A4; SLC12A5; SLC12A6; SLC12A7; SLC12A8; SLC12A9; SLC7A1; SLC7A10; SLC7A11; SLC7A13; SLC7A14; SLC7A2; SLC7A3; SLC7A4; SLC7A5; SLC7A6; SLC7A7; SLC7A8; SLC7A9;

References

  1. ^ Weber E, Jund R, Chevallier MR (1988). "Evolutionary relationship and secondary structure predictions in four transport proteins of Saccharomyces cerevisiae". J. Mol. Evol. 27 (4): 341–350. PMID 3146645.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Vandenbol M, Grenson M, Jauniaux JC (1989). "Nucleotide sequence of the Saccharomyces cerevisiae PUT4 proline-permease-encoding gene: similarities between CAN1, HIP1 and PUT4 permeases". Gene. 83 (1): 153–159. PMID 2687114.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Reizer J, Reizer A, Finley K, Kakuda D, Saier Jr MH, MacLeod CL (1993). "Mammalian integral membrane receptors are homologous to facilitators and antiporters of yeast, fungi, and eubacteria". Protein Sci. 2 (1): 20–30. PMID 8382989.{{cite journal}}: CS1 maint: multiple names: authors list (link)
This article incorporates text from the public domain Pfam and InterPro: IPR004841

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004841

Amino acid permeases are integral membrane proteins involved in the transport of amino acids into the cell. A number of such proteins have been found to be evolutionary related [ PUBMED:3146645 ], [ PUBMED:2687114 ], [ PUBMED:8382989 ]. These proteins seem to contain up to 12 transmembrane segments. The best conserved region in this family is located in the second transmembrane segment.

This domain is found in amino acid permeases, as well as in solute carrier family 12A (SLC12A) members.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan APC (CL0062), which has the following description:

This large superfamily contains a variety of transporters including amino acid permeases that according to TCDB belong to the APC (Amino acid-Polyamine-organoCation) superfamily.

The clan contains the following 21 members:

AA_permease AA_permease_2 AA_permease_C Aa_trans BCCT BenE Branch_AA_trans CstA DUF3360 HCO3_cotransp K_trans MFS_MOT1 Na_Ala_symp Nramp SNF Spore_permease SSF Sulfate_transp Transp_cyt_pur Trp_Tyr_perm Xan_ur_permease

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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  Seed
(25)
Full
(36712)
Representative proteomes UniProt
(124600)
RP15
(3885)
RP35
(12558)
RP55
(29103)
RP75
(51102)
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  Seed
(25)
Full
(36712)
Representative proteomes UniProt
(124600)
RP15
(3885)
RP35
(12558)
RP55
(29103)
RP75
(51102)
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  Seed
(25)
Full
(36712)
Representative proteomes UniProt
(124600)
RP15
(3885)
RP35
(12558)
RP55
(29103)
RP75
(51102)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: aa_permeases;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Bateman A
Number in seed: 25
Number in full: 36712
Average length of the domain: 381.8 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 67.87 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.6 24.6
Trusted cut-off 24.6 24.6
Noise cut-off 24.5 24.5
Model length: 479
Family (HMM) version: 24
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the AA_permease domain has been found. There are 88 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044QUE0 View 3D Structure Click here
A0A044S9G6 View 3D Structure Click here
A0A044T5P7 View 3D Structure Click here
A0A044TC79 View 3D Structure Click here
A0A044U4I5 View 3D Structure Click here
A0A077YXW4 View 3D Structure Click here
A0A077Z4B0 View 3D Structure Click here
A0A077Z4Q7 View 3D Structure Click here
A0A077Z5N4 View 3D Structure Click here
A0A077Z7L1 View 3D Structure Click here
A0A077Z8J7 View 3D Structure Click here
A0A077ZAG4 View 3D Structure Click here
A0A077ZAT1 View 3D Structure Click here
A0A077ZC29 View 3D Structure Click here
A0A077ZC59 View 3D Structure Click here
A0A077ZCE5 View 3D Structure Click here
A0A077ZFZ5 View 3D Structure Click here
A0A077ZGV7 View 3D Structure Click here
A0A077ZMV7 View 3D Structure Click here
A0A077ZND0 View 3D Structure Click here
A0A077ZQA7 View 3D Structure Click here
A0A0A2V297 View 3D Structure Click here
A0A0A2V3F6 View 3D Structure Click here
A0A0A2V5H2 View 3D Structure Click here
A0A0A2V734 View 3D Structure Click here
A0A0B4LGD3 View 3D Structure Click here
A0A0D2DN69 View 3D Structure Click here
A0A0D2DX05 View 3D Structure Click here
A0A0D2E369 View 3D Structure Click here
A0A0D2EKB7 View 3D Structure Click here
A0A0D2F0C3 View 3D Structure Click here
A0A0D2F5Z7 View 3D Structure Click here
A0A0D2F952 View 3D Structure Click here
A0A0D2FCU5 View 3D Structure Click here
A0A0D2FFM4 View 3D Structure Click here
A0A0D2G905 View 3D Structure Click here
A0A0D2GFN3 View 3D Structure Click here
A0A0D2GG93 View 3D Structure Click here
A0A0D2GJN8 View 3D Structure Click here
A0A0D2GPM4 View 3D Structure Click here