UniProtKB - Q75N73 (S39AE_MOUSE)
Protein
Metal cation symporter ZIP14
Gene
Slc39a14
Organism
Mus musculus (Mouse)
Status
Functioni
Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:15863613, PubMed:16950869, PubMed:18270315, PubMed:19179618, PubMed:21653899, PubMed:28673968). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (PubMed:18270315). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (PubMed:18270315). Controls the cellular uptake by the intestinal epithelium of systemic zinc, which is in turn required to maintain tight junctions and the intestinal permeability (PubMed:25428902). Modifies the activity of zinc-dependent phosphodiesterases, thereby indirectly regulating G protein-coupled receptor signaling pathways important for gluconeogenesis and chondrocyte differentiation (PubMed:21445361). Regulates insulin receptor signaling, glucose uptake, glycogen synthesis and gluconeogenesis in hepatocytes through the zinc-dependent intracellular catabolism of insulin (PubMed:27703010). Through zinc cellular uptake also plays a role in the adaptation of cells to endoplasmic reticulum stress (PubMed:28673968). Major manganese transporter of the basolateral membrane of intestinal epithelial cells, it plays a central role in manganese systemic homeostasis through intestinal manganese uptake (PubMed:31028174). Also involved in manganese extracellular uptake by cells of the blood-brain barrier (By similarity). May also play a role in manganese and zinc homeostasis participating in their elimination from the blood through the hepatobiliary excretion (PubMed:28536273). Also functions in the extracellular uptake of free iron (PubMed:16950869, PubMed:19179618, PubMed:21653899, PubMed:23110240, PubMed:26028554). May also function intracellularly and mediate the transport from endosomes to cytosol of iron endocytosed by transferrin (PubMed:20682781). Plays a role in innate immunity by regulating the expression of cytokines by activated macrophages (By similarity).By similarity14 Publications
Catalytic activityi
- This reaction proceeds in the forward4 Publications direction.
- This reaction proceeds in the forward2 Publications direction.
- This reaction proceeds in the forward2 Publications direction.
- This reaction proceeds in the forward1 Publication direction.
Activity regulationi
Inhibited by cyanide and therefore dependent of an energy source (PubMed:18270315). Inhibited by DIDS/4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, an inhibitor hydrogencarbonate-dependent transporters (PubMed:18270315).1 Publication
Kineticsi
- KM=0.14 mM for Cd2+1 Publication
- KM=4.4 mM for Mn2+1 Publication
- KM=2.3 µM for Fe2+1 Publication
- KM=1.9 µM for Zn2+1 Publication
- Vmax=25 pmol/min/mg enzyme for the transport of Cd2+1 Publication
- Vmax=330 pmol/min/mg enzyme for the transport of Mn2+1 Publication
- KM=1.1 mM for Cd2+1 Publication
- KM=18.2 mM for Mn2+1 Publication
- Vmax=113 pmol/min/mg enzyme for the transport of Cd2+1 Publication
- Vmax=1140 pmol/min/mg enzyme for the transport of Mn2+1 Publication
pH dependencei
Optimum pH is 7.5.1 Publication
Optimum pH is 7.5.2 Publications
Optimum pH is 7.5 (PubMed:18270315). Optimum temperature is 37 degrees Celsius (PubMed:18270315).1 Publication
Temperature dependencei
Optimum temperature is 37 degrees Celsius.1 Publication
Optimum temperature is 37 degrees Celsius.1 Publication
GO - Molecular functioni
- anion:cation symporter activity Source: UniProtKB
- cadmium ion transmembrane transporter activity Source: UniProtKB
- ferrous iron transmembrane transporter activity Source: MGI
- iron ion transmembrane transporter activity Source: UniProtKB
- manganese ion transmembrane transporter activity Source: UniProtKB
- zinc ion transmembrane transporter activity Source: UniProtKB
GO - Biological processi
- cadmium ion transmembrane transport Source: UniProtKB
- cellular response to glucose stimulus Source: UniProtKB
- cellular response to insulin stimulus Source: UniProtKB
- cellular zinc ion homeostasis Source: UniProtKB
- chondrocyte differentiation Source: UniProtKB
- gluconeogenesis Source: UniProtKB
- import across plasma membrane Source: MGI
- insulin receptor signaling pathway Source: UniProtKB
- iron import into cell Source: UniProtKB
- iron ion transmembrane transport Source: UniProtKB
- iron ion transport Source: MGI
- manganese ion homeostasis Source: UniProtKB
- manganese ion transmembrane transport Source: UniProtKB
- negative regulation of cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
- positive regulation of G protein-coupled receptor signaling pathway Source: UniProtKB
- regulation of hormone levels Source: UniProtKB
- zinc ion import across plasma membrane Source: UniProtKB
- zinc ion transmembrane transport Source: UniProtKB
- zinc ion transport Source: MGI
Keywordsi
Biological process | Ion transport, Transport, Zinc transport |
Ligand | Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-442380, Zinc influx into cells by the SLC39 gene family |
Names & Taxonomyi
Protein namesi | Recommended name: Metal cation symporter ZIP141 PublicationAlternative name(s): Factor for adipocyte differentiation 123Imported Short name: FAD-123Imported Solute carrier family 39 member 14Imported Zrt- and Irt-like protein 141 Publication Short name: ZIP-141 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2384851, Slc39a14 |
Subcellular locationi
Endosome
- Early endosome membrane By similarity; Multi-pass membrane protein Sequence analysis
- Late endosome membrane By similarity; Multi-pass membrane protein Sequence analysis
Lysosome
- Lysosome membrane By similarity; Multi-pass membrane protein Sequence analysis
Plasma membrane
- Cell membrane 4 Publications; Multi-pass membrane protein Sequence analysis
- Apical cell membrane 1 Publication; Multi-pass membrane protein Sequence analysis
- Basolateral cell membrane 2 Publications; Multi-pass membrane protein Sequence analysis
Note: Localized at the basolateral membrane of enterocytes (PubMed:25428902, PubMed:28536273). Enriched at the plasma membrane upon glucose uptake (By similarity). Localized and functional at both apical and basolateral membranes of microvascular capillary endothelial cells that constitute the blood-brain barrier (By similarity).By similarity2 Publications
Endosome
- early endosome membrane Source: UniProtKB
- late endosome membrane Source: UniProtKB
Lysosome
- lysosomal membrane Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- basolateral plasma membrane Source: UniProtKB
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 29 – 155 | ExtracellularSequence analysisAdd BLAST | 127 | |
Transmembranei | 156 – 176 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 177 – 184 | CytoplasmicSequence analysis | 8 | |
Transmembranei | 185 – 205 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 206 – 221 | ExtracellularSequence analysisAdd BLAST | 16 | |
Transmembranei | 222 – 242 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 243 – 349 | CytoplasmicSequence analysisAdd BLAST | 107 | |
Transmembranei | 350 – 370 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 371 – 394 | ExtracellularSequence analysisAdd BLAST | 24 | |
Transmembranei | 395 – 415 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 416 – 421 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 422 – 442 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 443 – 457 | ExtracellularSequence analysisAdd BLAST | 15 | |
Transmembranei | 458 – 478 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 479 – 489 | CytoplasmicSequence analysisAdd BLAST | 11 |
Keywords - Cellular componenti
Cell membrane, Endosome, Lysosome, MembranePathology & Biotechi
Disruption phenotypei
Homozygous knockout mice exhibit growth retardation and dwarfism, visible even in neonates (PubMed:21445361). They exhibit moderate osteoporotic phenotypes associated with decreased bone volume and trabecular number, and increased trabecular separation (PubMed:21445361). The length of the long bones is also significantly reduced (PubMed:21445361). The decrease in bone mass is associated with increased bone resorption (PubMed:29632817). The metabolism of these mice is also affected and they constitute a model of metabolic endotoxemia with high body fat, hypoglycemia and hyperinsulinemia (PubMed:23110240, PubMed:27703010). The knockout of the gene also results in less effective blood manganese elimination and accumulation in the brain where it alters motor functions (PubMed:28536273). Knockout mice also display increased iron absorption and decreased lipopolysaccharide/LPS-induced IL-6 production (PubMed:23110240, PubMed:26028554). The permeability of the intestinal barrier is also compromised (PubMed:25428902). Conditional intestinal-specific knockout of the gene results in increased manganese levels in brain and liver while the liver-specific knockout reduces manganese levels only in liver (PubMed:31028174).8 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 438 | L → R: When overexpressed ubiquitously in conditional knockin mice, perinatally lethal; when overexpressed in osteoblasts in conditional knockin mice, produces a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation; when overexpressed in osteoclasts in conditional knockin mice, no effect on bone hemostasis. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 28 | Sequence analysisAdd BLAST | 28 | |
ChainiPRO_0000312195 | 29 – 489 | Metal cation symporter ZIP14Add BLAST | 461 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 52 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 75 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 85 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 100 | N-linked (GlcNAc...) asparagine2 Publications | 1 |
Post-translational modificationi
Ubiquitinated. Ubiquitination occurs upon iron depletion. The ubiquitinated form undergoes proteasomal degradation.By similarity
N-glycosylated (PubMed:18270315, PubMed:21445361). N-glycosylation at Asn-100 is required for iron-regulated extraction of the transporter from membranes and subsequent proteasomal degradation (By similarity).By similarity2 Publications
Keywords - PTMi
Glycoprotein, Ubl conjugationProteomic databases
EPDi | Q75N73 |
jPOSTi | Q75N73 |
PaxDbi | Q75N73 |
PeptideAtlasi | Q75N73 |
PRIDEi | Q75N73 |
PTM databases
GlyConnecti | 2832, 1 N-Linked glycan (1 site) |
GlyGeni | Q75N73, 4 sites |
iPTMneti | Q75N73 |
PhosphoSitePlusi | Q75N73 |
SwissPalmi | Q75N73 |
Expressioni
Tissue specificityi
Widely expressed (PubMed:18270315). Highly and transiently expressed during the early stage of adipocyte differentiation. Strongly expressed in liver, preadipocyte, duodenum and jejunum, moderately in brain, heart, skeletal muscle, spleen, pancreas, kidney and white adipose cells. Expression is almost undetectable in lung, testis and brown adipose cells (PubMed:15794747, PubMed:15863613, PubMed:16950869, PubMed:17065364, PubMed:25428902). Expressed by chondrocytes and pituitary cells (PubMed:21445361).7 Publications
More strongly expressed in brain.1 Publication
More strongly expressed in liver, kidney and duodenum.1 Publication
Developmental stagei
In the KS483 cell model for osteoblast differentiation, expression levels peaks during the mineralization phase (days 18-21 of differentiation).1 Publication
Inductioni
Up-regulated during the lipopolysaccharide/LPS-induced inflammatory response (at protein level) (PubMed:16950869). Up-regulated by IL6 (PubMed:15863613, PubMed:16950869, PubMed:17065364). Up-regulated by interleukin-1/IL1 via nitric oxide (PubMed:19179618). Up-regulated upon endoplasmic reticulum stress induced by tunicamycin or high-fat diet (at protein level) (PubMed:28673968). Up-regulated into hepatocytes upon glucose uptake (at protein level) (PubMed:27703010). Up-regulated by iron in retina (at protein level) (PubMed:28057442).7 Publications
Gene expression databases
Bgeei | ENSMUSG00000022094, Expressed in ectoplacental cone and 285 other tissues |
ExpressionAtlasi | Q75N73, baseline and differential |
Genevisiblei | Q75N73, MM |
Interactioni
Subunit structurei
Homotrimer.
By similarityProtein-protein interaction databases
BioGRIDi | 229393, 1 interactor |
IntActi | Q75N73, 2 interactors |
MINTi | Q75N73 |
STRINGi | 10090.ENSMUSP00000066108 |
Miscellaneous databases
RNActi | Q75N73, protein |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 248 – 255 | HHHGHXHX-motifBy similarity | 8 | |
Motifi | 373 – 378 | XEXPHE-motifBy similarity | 6 |
Sequence similaritiesi
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2693, Eukaryota |
GeneTreei | ENSGT00940000157986 |
HOGENOMi | CLU_015114_13_0_1 |
InParanoidi | Q75N73 |
OMAi | PCTERAF |
OrthoDBi | 657777at2759 |
PhylomeDBi | Q75N73 |
TreeFami | TF318470 |
Family and domain databases
InterProi | View protein in InterPro IPR003689, ZIP |
Pfami | View protein in Pfam PF02535, Zip, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q75N73-1) [UniParc]FASTAAdd to basket
Also known as: ZIP14B1 Publication
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKRLHPALPS CLLLVLFGIW RTAPQTHASS AGLPPLSATS FLEDLMDRYG
60 70 80 90 100
KNDSLTLTQL KSLLDHLHVG VGRDNVSQPK EGPRNLSTCF SSGDLFAAHN
110 120 130 140 150
LSERSQIGAS EFQEFCPTIL QQLDSQACTS ENQKSEENEQ TEEGKPSAIE
160 170 180 190 200
VWGYGFLCVT VISLCSLMGA SVVPFMKKTF YKRLLLYFIA LAIGTLYSNA
210 220 230 240 250
LFQLIPEAFG FNPQDNYVSK SAVVFGGFYL FFFTEKILKM LLKQKNEHHH
260 270 280 290 300
GHNHFTSETL PSKKDQEEGV TEKLQNGDLD HMIPQHCNSE LDGKAPGTDE
310 320 330 340 350
KVIVNSMSVQ DLQASQSACY WLKGVRYSDI GTLAWMITLS DGLHNFIDGL
360 370 380 390 400
AIGASFTVSV FQGISTSVAI LCEEFPHELG DFVILLNAGM SIQQALFFNF
410 420 430 440 450
LSACCCYLGL AFGILAGSHF SANWIFALAG GMFLYIALAD MFPEMNEVCQ
460 470 480
EDEKNDSFLV PFVIQNLGLL TGFSIMLVLT MYSGQIQIG
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3Z3C5 | D3Z3C5_MOUSE | Metal cation symporter ZIP14 | Slc39a14 | 48 | Annotation score: | ||
D3Z6P5 | D3Z6P5_MOUSE | Metal cation symporter ZIP14 | Slc39a14 | 164 | Annotation score: | ||
D3YXD7 | D3YXD7_MOUSE | Metal cation symporter ZIP14 | Slc39a14 | 129 | Annotation score: | ||
D3Z354 | D3Z354_MOUSE | Metal cation symporter ZIP14 | Slc39a14 | 109 | Annotation score: | ||
D3Z4Q7 | D3Z4Q7_MOUSE | Metal cation symporter ZIP14 | Slc39a14 | 64 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 154 | Y → F in AAH21530 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 158 – 186 | CVTVI…KRLLL → SVSLINLASLLGVLVLPCTE KAFFSRVLT in AAH21530 (PubMed:15489334).CuratedAdd BLAST | 29 | |
Sequence conflicti | 192 | A → S in AAH21530 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 197 | Y → L in AAH21530 (PubMed:15489334).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_060552 | 151 – 207 | VWGYG…QLIPE → VWGFGFLSVSLINLASLLGV LVLPCTEKAFFSRVLTYFIA LSIGTLLSNALFQLIPE in isoform 2. Add BLAST | 57 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB177995 mRNA Translation: BAD16742.1 AC025669 Genomic DNA No translation available. BC021530 mRNA Translation: AAH21530.1 AK122197 Transcribed RNA Translation: BAC65479.2 Sequence problems. |
CCDSi | CCDS36969.1 [Q75N73-1] CCDS49536.1 [Q75N73-3] |
RefSeqi | NP_001128623.1, NM_001135151.1 [Q75N73-3] NP_001128624.1, NM_001135152.1 [Q75N73-3] NP_659057.2, NM_144808.4 [Q75N73-1] XP_006518851.1, XM_006518788.3 [Q75N73-3] XP_006518852.1, XM_006518789.3 [Q75N73-3] |
Genome annotation databases
Ensembli | ENSMUST00000022688; ENSMUSP00000022688; ENSMUSG00000022094 [Q75N73-3] ENSMUST00000068044; ENSMUSP00000066108; ENSMUSG00000022094 [Q75N73-1] ENSMUST00000152067; ENSMUSP00000119040; ENSMUSG00000022094 [Q75N73-3] |
GeneIDi | 213053 |
KEGGi | mmu:213053 |
UCSCi | uc007uns.1, mouse [Q75N73-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB177995 mRNA Translation: BAD16742.1 AC025669 Genomic DNA No translation available. BC021530 mRNA Translation: AAH21530.1 AK122197 Transcribed RNA Translation: BAC65479.2 Sequence problems. |
CCDSi | CCDS36969.1 [Q75N73-1] CCDS49536.1 [Q75N73-3] |
RefSeqi | NP_001128623.1, NM_001135151.1 [Q75N73-3] NP_001128624.1, NM_001135152.1 [Q75N73-3] NP_659057.2, NM_144808.4 [Q75N73-1] XP_006518851.1, XM_006518788.3 [Q75N73-3] XP_006518852.1, XM_006518789.3 [Q75N73-3] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 229393, 1 interactor |
IntActi | Q75N73, 2 interactors |
MINTi | Q75N73 |
STRINGi | 10090.ENSMUSP00000066108 |
PTM databases
GlyConnecti | 2832, 1 N-Linked glycan (1 site) |
GlyGeni | Q75N73, 4 sites |
iPTMneti | Q75N73 |
PhosphoSitePlusi | Q75N73 |
SwissPalmi | Q75N73 |
Proteomic databases
EPDi | Q75N73 |
jPOSTi | Q75N73 |
PaxDbi | Q75N73 |
PeptideAtlasi | Q75N73 |
PRIDEi | Q75N73 |
Protocols and materials databases
Antibodypediai | 9517, 181 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000022688; ENSMUSP00000022688; ENSMUSG00000022094 [Q75N73-3] ENSMUST00000068044; ENSMUSP00000066108; ENSMUSG00000022094 [Q75N73-1] ENSMUST00000152067; ENSMUSP00000119040; ENSMUSG00000022094 [Q75N73-3] |
GeneIDi | 213053 |
KEGGi | mmu:213053 |
UCSCi | uc007uns.1, mouse [Q75N73-1] |
Organism-specific databases
CTDi | 23516 |
MGIi | MGI:2384851, Slc39a14 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | KOG2693, Eukaryota |
GeneTreei | ENSGT00940000157986 |
HOGENOMi | CLU_015114_13_0_1 |
InParanoidi | Q75N73 |
OMAi | PCTERAF |
OrthoDBi | 657777at2759 |
PhylomeDBi | Q75N73 |
TreeFami | TF318470 |
Enzyme and pathway databases
Reactomei | R-MMU-442380, Zinc influx into cells by the SLC39 gene family |
Miscellaneous databases
BioGRID-ORCSi | 213053, 1 hit in 19 CRISPR screens |
ChiTaRSi | Slc39a14, mouse |
PROi | PR:Q75N73 |
RNActi | Q75N73, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000022094, Expressed in ectoplacental cone and 285 other tissues |
ExpressionAtlasi | Q75N73, baseline and differential |
Genevisiblei | Q75N73, MM |
Family and domain databases
InterProi | View protein in InterPro IPR003689, ZIP |
Pfami | View protein in Pfam PF02535, Zip, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | S39AE_MOUSE | |
Accessioni | Q75N73Primary (citable) accession number: Q75N73 Secondary accession number(s): A0A0R4J1V1, Q80U85, Q8VDL0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 4, 2007 |
Last sequence update: | July 5, 2004 | |
Last modified: | December 2, 2020 | |
This is version 116 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families