UniProtKB - Q8WYL5 (SSH1_HUMAN)
Protein phosphatase Slingshot homolog 1
SSH1
Functioni
Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein.
10 PublicationsMiscellaneous
Catalytic activityi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 393 | Phosphocysteine intermediatePROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- actin binding Source: UniProtKB
- phosphoprotein phosphatase activity Source: UniProtKB
- protein serine phosphatase activity Source: UniProtKB-EC
- protein threonine phosphatase activity Source: UniProtKB-EC
- protein tyrosine/serine/threonine phosphatase activity Source: InterPro
- protein tyrosine phosphatase activity Source: UniProtKB-EC
GO - Biological processi
- actin cytoskeleton organization Source: UniProtKB
- cell morphogenesis Source: UniProtKB
- cellular response to ATP Source: MGI
- negative regulation of actin filament polymerization Source: GO_Central
- protein dephosphorylation Source: UniProtKB
- regulation of cellular protein metabolic process Source: MGI
Keywordsi
Molecular function | Actin-binding, Hydrolase, Protein phosphatase |
Enzyme and pathway databases
PathwayCommonsi | Q8WYL5 |
SignaLinki | Q8WYL5 |
SIGNORi | Q8WYL5 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:SSH1 Synonyms:KIAA1298, SSH1L |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:30579, SSH1 |
MIMi | 606778, gene |
neXtProti | NX_Q8WYL5 |
VEuPathDBi | HostDB:ENSG00000084112 |
Subcellular locationi
Cytoskeleton
Other locations
Note: Also recruited to actin rich membrane protrusions such as lamellipodia, which may allow local control of actin dynamics at sites of cell locomotion. Also localized to the cleavage furrow and the midbody during cytokinesis.
Cytoskeleton
- cytoskeleton Source: UniProtKB-SubCell
Plasma Membrane
- cleavage furrow Source: UniProtKB-SubCell
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- lamellipodium Source: UniProtKB-SubCell
- midbody Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell projection, Cytoplasm, CytoskeletonPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 393 | C → S: Abrogates phosphatase activity. 8 Publications | 1 | |
Mutagenesisi | 458 | W → A: Impairs stimulation of phosphatase activity by actin but does not affect basal activity. 1 Publication | 1 | |
Mutagenesisi | 937 | S → A: Reduces binding to YWHAB, YWHAG, YWHAQ and YWHAZ. Abolishes binding to YWHAB, YWHAG, YWHAQ and YWHAZ and increases association with F-actin; when associated with A-978. 1 Publication | 1 | |
Mutagenesisi | 978 | S → A: Reduces binding to YWHAB, YWHAG, YWHAQ and YWHAZ. Abolishes binding to YWHAB, YWHAG, YWHAQ and YWHAZ and increases association with F-actin; when associated with A-937. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 54434 |
OpenTargetsi | ENSG00000084112 |
PharmGKBi | PA134941788 |
Miscellaneous databases
Pharosi | Q8WYL5, Tbio |
Genetic variation databases
BioMutai | SSH1 |
DMDMi | 82582267 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000094841 | 2 – 1049 | Protein phosphatase Slingshot homolog 1Add BLAST | 1048 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 37 | PhosphoserineCombined sources | 1 | |
Modified residuei | 57 | PhosphoserineCombined sources | 1 | |
Modified residuei | 515 | PhosphoserineBy similarity | 1 | |
Modified residuei | 576 | PhosphoserineCombined sources | 1 | |
Modified residuei | 897 | PhosphoserineCombined sources | 1 | |
Modified residuei | 978 | Phosphoserine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q8WYL5 |
jPOSTi | Q8WYL5 |
MassIVEi | Q8WYL5 |
MaxQBi | Q8WYL5 |
PaxDbi | Q8WYL5 |
PeptideAtlasi | Q8WYL5 |
PRIDEi | Q8WYL5 |
ProteomicsDBi | 75168 [Q8WYL5-1] 75169 [Q8WYL5-2] 75170 [Q8WYL5-3] 75171 [Q8WYL5-4] 75172 [Q8WYL5-5] |
PTM databases
DEPODi | SSH1 |
iPTMneti | Q8WYL5 |
PhosphoSitePlusi | Q8WYL5 |
Expressioni
Gene expression databases
Bgeei | ENSG00000084112, Expressed in colon and 243 other tissues |
ExpressionAtlasi | Q8WYL5, baseline and differential |
Genevisiblei | Q8WYL5, HS |
Organism-specific databases
HPAi | ENSG00000084112, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with actin and this stimulates phosphatase activity.
Also interacts with LIMK1 and with the 14-3-3 proteins YWHAB, YWHAG, YWHAQ, and YWHAZ. Interaction with 14-3-3 proteins inhibits phosphatase activity and also blocks recruitment to lamellipodia and stimulation by actin.
4 PublicationsBinary interactionsi
Q8WYL5
GO - Molecular functioni
- actin binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 119950, 66 interactors |
IntActi | Q8WYL5, 21 interactors |
MINTi | Q8WYL5 |
STRINGi | 9606.ENSP00000315713 |
Miscellaneous databases
RNActi | Q8WYL5, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 251 – 303 | DEK C-terminalSequence analysisAdd BLAST | 53 | |
Domaini | 308 – 449 | Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST | 142 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 28 | DisorderedSequence analysisAdd BLAST | 28 | |
Regioni | 456 – 499 | DisorderedSequence analysisAdd BLAST | 44 | |
Regioni | 544 – 603 | DisorderedSequence analysisAdd BLAST | 60 | |
Regioni | 693 – 787 | DisorderedSequence analysisAdd BLAST | 95 | |
Regioni | 825 – 899 | DisorderedSequence analysisAdd BLAST | 75 | |
Regioni | 897 – 1049 | Interaction with YWHAG1 PublicationAdd BLAST | 153 | |
Regioni | 923 – 955 | DisorderedSequence analysisAdd BLAST | 33 | |
Regioni | 989 – 1049 | DisorderedSequence analysisAdd BLAST | 61 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1 – 24 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 768 – 787 | Basic and acidic residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 923 – 943 | Polar residuesSequence analysisAdd BLAST | 21 | |
Compositional biasi | 989 – 1017 | Polar residuesSequence analysisAdd BLAST | 29 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1716, Eukaryota |
GeneTreei | ENSGT00940000156133 |
HOGENOMi | CLU_006650_1_0_1 |
InParanoidi | Q8WYL5 |
OMAi | DKNPPSM |
OrthoDBi | 1576308at2759 |
PhylomeDBi | Q8WYL5 |
TreeFami | TF319444 |
Family and domain databases
CDDi | cd11652, SSH-N, 1 hit |
Gene3Di | 3.90.190.10, 1 hit |
InterProi | View protein in InterPro IPR014876, DEK_C IPR000340, Dual-sp_phosphatase_cat-dom IPR043587, Phosphatase_SSH-like IPR029021, Prot-tyrosine_phosphatase-like IPR043588, SSH-N IPR027233, SSH1 IPR016130, Tyr_Pase_AS IPR000387, Tyr_Pase_dom IPR020422, TYR_PHOSPHATASE_DUAL_dom |
PANTHERi | PTHR45864, PTHR45864, 1 hit PTHR45864:SF5, PTHR45864:SF5, 1 hit |
Pfami | View protein in Pfam PF08766, DEK_C, 1 hit PF00782, DSPc, 1 hit |
SMARTi | View protein in SMART SM00195, DSPc, 1 hit |
SUPFAMi | SSF52799, SSF52799, 1 hit |
PROSITEi | View protein in PROSITE PS00383, TYR_PHOSPHATASE_1, 1 hit PS50056, TYR_PHOSPHATASE_2, 1 hit PS50054, TYR_PHOSPHATASE_DUAL, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
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
MALVTLQRSP TPSAASSSAS NSELEAGSEE DRKLNLSLSE SFFMVKGAAL
60 70 80 90 100
FLQQGSSPQG QRSLQHPHKH AGDLPQHLQV MINLLRCEDR IKLAVRLESA
110 120 130 140 150
WADRVRYMVV VYSSGRQDTE ENILLGVDFS SKESKSCTIG MVLRLWSDTK
160 170 180 190 200
IHLDGDGGFS VSTAGRMHIF KPVSVQAMWS ALQVLHKACE VARRHNYFPG
210 220 230 240 250
GVALIWATYY ESCISSEQSC INEWNAMQDL ESTRPDSPAL FVDKPTEGER
260 270 280 290 300
TERLIKAKLR SIMMSQDLEN VTSKEIRNEL EKQMNCNLKE LKEFIDNEML
310 320 330 340 350
LILGQMDKPS LIFDHLYLGS EWNASNLEEL QGSGVDYILN VTREIDNFFP
360 370 380 390 400
GLFAYHNIRV YDEETTDLLA HWNEAYHFIN KAKRNHSKCL VHCKMGVSRS
410 420 430 440 450
ASTVIAYAMK EFGWPLEKAY NYVKQKRSIT RPNAGFMRQL SEYEGILDAS
460 470 480 490 500
KQRHNKLWRQ QTDSSLQQPV DDPAGPGDFL PETPDGTPES QLPFLDDAAQ
510 520 530 540 550
PGLGPPLPCC FRRLSDPLLP SPEDETGSLV HLEDPEREAL LEEAAPPAEV
560 570 580 590 600
HRPARQPQQG SGLCEKDVKK KLEFGSPKGR SGSLLQVEET EREEGLGAGR
610 620 630 640 650
WGQLPTQLDQ NLLNSENLNN NSKRSCPNGM EDDAIFGILN KVKPSYKSCA
660 670 680 690 700
DCMYPTASGA PEASRERCED PNAPAICTQP AFLPHITSSP VAHLASRSRV
710 720 730 740 750
PEKPASGPTE PPPFLPPAGS RRADTSGPGA GAALEPPASL LEPSRETPKV
760 770 780 790 800
LPKSLLLKNS HCDKNPPSTE VVIKEESSPK KDMKPAKDLR LLFSNESEKP
810 820 830 840 850
TTNSYLMQHQ ESIIQLQKAG LVRKHTKELE RLKSVPADPA PPSRDGPASR
860 870 880 890 900
LEASIPEESQ DPAALHELGP LVMPSQAGSD EKSEAAPASL EGGSLKSPPP
910 920 930 940 950
FFYRLDHTSS FSKDFLKTIC YTPTSSSMSS NLTRSSSSDS IHSVRGKPGL
960 970 980 990 1000
VKQRTQEIET RLRLAGLTVS SPLKRSHSLA KLGSLTFSTE DLSSEADPST
1010 1020 1030 1040
VADSQDTTLS ESSFLHEPQG TPRDPAATSK PSGKPAPENL KSPSWMSKS
The sequence of this isoform differs from the canonical sequence as follows:
632-692: DDAIFGILNK...LPHITSSPVA → VGRARPAGWH...LQGPEGSFTG
693-1049: Missing.
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YHR3 | H0YHR3_HUMAN | Protein phosphatase Slingshot homol... | SSH1 | 95 | Annotation score: | ||
F8W1D9 | F8W1D9_HUMAN | Protein phosphatase Slingshot homol... | SSH1 | 154 | Annotation score: | ||
F8VS18 | F8VS18_HUMAN | Protein phosphatase Slingshot homol... | SSH1 | 37 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 2 | A → V in AAH62341 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 230 | L → P in BAB84116 (PubMed:11832213).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016311 | 1 – 312 | Missing in isoform 4. 1 PublicationAdd BLAST | 312 | |
Alternative sequenceiVSP_016312 | 1 – 73 | Missing in isoform 3. 1 PublicationAdd BLAST | 73 | |
Alternative sequenceiVSP_016313 | 1 – 37 | MALVT…KLNLS → MARARRAVVGSVRDVSTAAT NLFYFTDFCIFLQPTHCFCC PEVSSSNY in isoform 5. 1 PublicationAdd BLAST | 37 | |
Alternative sequenceiVSP_016314 | 74 – 93 | LPQHL…DRIKL → MGGRHHLQRQVSESMSALFQ in isoform 3. 1 PublicationAdd BLAST | 20 | |
Alternative sequenceiVSP_016315 | 135 – 157 | Missing in isoform 3. 1 PublicationAdd BLAST | 23 | |
Alternative sequenceiVSP_016316 | 245 – 1049 | Missing in isoform 3. 1 PublicationAdd BLAST | 805 | |
Alternative sequenceiVSP_016317 | 313 – 334 | FDHLY…LQGSG → MRCYLSWDRWTSPPLSSIIF IS in isoform 4. 1 PublicationAdd BLAST | 22 | |
Alternative sequenceiVSP_016318 | 632 – 692 | DDAIF…SSPVA → VGRARPAGWHTPSLPSHSNW PTSASVVGTTGTRHHTQLIF FYCLLWAPSSHLQGPEGSFT G in isoform 2 and isoform 5. 2 PublicationsAdd BLAST | 61 | |
Alternative sequenceiVSP_016319 | 693 – 1049 | Missing in isoform 2 and isoform 5. 2 PublicationsAdd BLAST | 357 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB072355 mRNA Translation: BAB84114.1 AB072356 mRNA Translation: BAB84115.1 AB072357 mRNA Translation: BAB84116.1 AB037719 mRNA Translation: BAA92536.1 Different initiation. AK095421 mRNA Translation: BAC04546.1 BC062341 mRNA Translation: AAH62341.1 |
CCDSi | CCDS53825.1 [Q8WYL5-5] CCDS55882.1 [Q8WYL5-2] CCDS9121.1 [Q8WYL5-1] |
RefSeqi | NP_001154802.1, NM_001161330.1 [Q8WYL5-2] NP_001154803.1, NM_001161331.1 [Q8WYL5-5] NP_061857.3, NM_018984.3 [Q8WYL5-1] XP_016874982.1, XM_017019493.1 [Q8WYL5-4] XP_016874983.1, XM_017019494.1 [Q8WYL5-4] |
Genome annotation databases
Ensembli | ENST00000326470; ENSP00000326107; ENSG00000084112 [Q8WYL5-5] ENST00000326495; ENSP00000315713; ENSG00000084112 ENST00000551165; ENSP00000448824; ENSG00000084112 [Q8WYL5-2] |
GeneIDi | 54434 |
KEGGi | hsa:54434 |
MANE-Selecti | ENST00000326495.10; ENSP00000315713.5; NM_018984.4; NP_061857.3 |
UCSCi | uc001tnm.4, human [Q8WYL5-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB072355 mRNA Translation: BAB84114.1 AB072356 mRNA Translation: BAB84115.1 AB072357 mRNA Translation: BAB84116.1 AB037719 mRNA Translation: BAA92536.1 Different initiation. AK095421 mRNA Translation: BAC04546.1 BC062341 mRNA Translation: AAH62341.1 |
CCDSi | CCDS53825.1 [Q8WYL5-5] CCDS55882.1 [Q8WYL5-2] CCDS9121.1 [Q8WYL5-1] |
RefSeqi | NP_001154802.1, NM_001161330.1 [Q8WYL5-2] NP_001154803.1, NM_001161331.1 [Q8WYL5-5] NP_061857.3, NM_018984.3 [Q8WYL5-1] XP_016874982.1, XM_017019493.1 [Q8WYL5-4] XP_016874983.1, XM_017019494.1 [Q8WYL5-4] |
3D structure databases
SMRi | Q8WYL5 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 119950, 66 interactors |
IntActi | Q8WYL5, 21 interactors |
MINTi | Q8WYL5 |
STRINGi | 9606.ENSP00000315713 |
PTM databases
DEPODi | SSH1 |
iPTMneti | Q8WYL5 |
PhosphoSitePlusi | Q8WYL5 |
Genetic variation databases
BioMutai | SSH1 |
DMDMi | 82582267 |
Proteomic databases
EPDi | Q8WYL5 |
jPOSTi | Q8WYL5 |
MassIVEi | Q8WYL5 |
MaxQBi | Q8WYL5 |
PaxDbi | Q8WYL5 |
PeptideAtlasi | Q8WYL5 |
PRIDEi | Q8WYL5 |
ProteomicsDBi | 75168 [Q8WYL5-1] 75169 [Q8WYL5-2] 75170 [Q8WYL5-3] 75171 [Q8WYL5-4] 75172 [Q8WYL5-5] |
Protocols and materials databases
Antibodypediai | 18311, 194 antibodies from 23 providers |
DNASUi | 54434 |
Genome annotation databases
Ensembli | ENST00000326470; ENSP00000326107; ENSG00000084112 [Q8WYL5-5] ENST00000326495; ENSP00000315713; ENSG00000084112 ENST00000551165; ENSP00000448824; ENSG00000084112 [Q8WYL5-2] |
GeneIDi | 54434 |
KEGGi | hsa:54434 |
MANE-Selecti | ENST00000326495.10; ENSP00000315713.5; NM_018984.4; NP_061857.3 |
UCSCi | uc001tnm.4, human [Q8WYL5-1] |
Organism-specific databases
CTDi | 54434 |
DisGeNETi | 54434 |
GeneCardsi | SSH1 |
HGNCi | HGNC:30579, SSH1 |
HPAi | ENSG00000084112, Low tissue specificity |
MIMi | 606778, gene |
neXtProti | NX_Q8WYL5 |
OpenTargetsi | ENSG00000084112 |
PharmGKBi | PA134941788 |
VEuPathDBi | HostDB:ENSG00000084112 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1716, Eukaryota |
GeneTreei | ENSGT00940000156133 |
HOGENOMi | CLU_006650_1_0_1 |
InParanoidi | Q8WYL5 |
OMAi | DKNPPSM |
OrthoDBi | 1576308at2759 |
PhylomeDBi | Q8WYL5 |
TreeFami | TF319444 |
Enzyme and pathway databases
PathwayCommonsi | Q8WYL5 |
SignaLinki | Q8WYL5 |
SIGNORi | Q8WYL5 |
Miscellaneous databases
BioGRID-ORCSi | 54434, 10 hits in 1047 CRISPR screens |
ChiTaRSi | SSH1, human |
GeneWikii | SSH1 |
GenomeRNAii | 54434 |
Pharosi | Q8WYL5, Tbio |
PROi | PR:Q8WYL5 |
RNActi | Q8WYL5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000084112, Expressed in colon and 243 other tissues |
ExpressionAtlasi | Q8WYL5, baseline and differential |
Genevisiblei | Q8WYL5, HS |
Family and domain databases
CDDi | cd11652, SSH-N, 1 hit |
Gene3Di | 3.90.190.10, 1 hit |
InterProi | View protein in InterPro IPR014876, DEK_C IPR000340, Dual-sp_phosphatase_cat-dom IPR043587, Phosphatase_SSH-like IPR029021, Prot-tyrosine_phosphatase-like IPR043588, SSH-N IPR027233, SSH1 IPR016130, Tyr_Pase_AS IPR000387, Tyr_Pase_dom IPR020422, TYR_PHOSPHATASE_DUAL_dom |
PANTHERi | PTHR45864, PTHR45864, 1 hit PTHR45864:SF5, PTHR45864:SF5, 1 hit |
Pfami | View protein in Pfam PF08766, DEK_C, 1 hit PF00782, DSPc, 1 hit |
SMARTi | View protein in SMART SM00195, DSPc, 1 hit |
SUPFAMi | SSF52799, SSF52799, 1 hit |
PROSITEi | View protein in PROSITE PS00383, TYR_PHOSPHATASE_1, 1 hit PS50056, TYR_PHOSPHATASE_2, 1 hit PS50054, TYR_PHOSPHATASE_DUAL, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SSH1_HUMAN | |
Accessioni | Q8WYL5Primary (citable) accession number: Q8WYL5 Secondary accession number(s): Q6P6C0 Q9P2P8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 22, 2005 |
Last sequence update: | November 22, 2005 | |
Last modified: | February 23, 2022 | |
This is version 172 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families