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Conserved domains on  [gi|1958799802|ref|XP_038938590|]
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ALS2 C-terminal-like protein isoform X4 [Rattus norvegicus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
COG4642 COG4642
Uncharacterized conserved protein [Function unknown];
358-557 1.34e-32

Uncharacterized conserved protein [Function unknown];


:

Pssm-ID: 443680 [Multi-domain]  Cd Length: 271  Bit Score: 126.61  E-value: 1.34e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 358 YDGEWSRAKPHGKGTLKWPDGRNHVGDFYQGLEHGFGICLVPQASE-------DKFDCYKCHWREGRMCEYGICEYGTDE 430
Cdd:COG4642    69 EGGVTAAGGGGGGGGGKGDGGDGGGGEGGFGGGGGGGGGKKGGGGGgggvlegDDGGGYGGGTADGGRGGGGIYTFPNGD 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 431 VYKGYFQAGVRHGFGVLDSAPQApqpfRYTGHWERGQRSGYGIEEDRDrGERYIGMWQADQRHGPGIVVTQAGVCYQGTF 510
Cdd:COG4642   149 VYEGEFKNGKPHGQGTLTYADGD----RYEGEFKNGKRHGQGTLTYAN-GDVYEGEFKNGQRHGQGTYTYADGDRYEGEF 223

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1958799802 511 QGDKMAGPGILLCEDDSLYEGTFTRELtLLGKGKVTFPNGFTLEGSF 557
Cdd:COG4642   224 KNGKRHGQGTLTYADGDRYEGEFKNGK-RHGQGTMTYADGSVYEGEW 269
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 223-321 1.02e-13

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13269:

Pssm-ID: 473070  Cd Length: 106  Bit Score: 67.42  E-value: 1.02e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 223 DVLCTPTHRLLQDSQDIPV-VVTPLR--AERVLLFDDTLVLLQGHNVHTFDLKLVWVDPSQD----KCVLHILTPEDEFS 295
Cdd:cd13269     1 DSLRSPDRRLIRESSTRPLtLQNAGRfsSHWFILFNDALVHAQFSTHHIFPLATLWVEPIPDedsgQNALKITTPEESFT 80

                          90       100
                  ....*....|....*....|....*.
gi 1958799802 296 FCTRDPQGQVVWQWKVTQAVCQALCG 321
Cdd:cd13269    81 LVASTPQEKAEWLRAINQAIDQALNG 106
 
Name Accession Description Interval E-value
COG4642 COG4642
Uncharacterized conserved protein [Function unknown];
358-557 1.34e-32

Uncharacterized conserved protein [Function unknown];


Pssm-ID: 443680 [Multi-domain]  Cd Length: 271  Bit Score: 126.61  E-value: 1.34e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 358 YDGEWSRAKPHGKGTLKWPDGRNHVGDFYQGLEHGFGICLVPQASE-------DKFDCYKCHWREGRMCEYGICEYGTDE 430
Cdd:COG4642    69 EGGVTAAGGGGGGGGGKGDGGDGGGGEGGFGGGGGGGGGKKGGGGGgggvlegDDGGGYGGGTADGGRGGGGIYTFPNGD 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 431 VYKGYFQAGVRHGFGVLDSAPQApqpfRYTGHWERGQRSGYGIEEDRDrGERYIGMWQADQRHGPGIVVTQAGVCYQGTF 510
Cdd:COG4642   149 VYEGEFKNGKPHGQGTLTYADGD----RYEGEFKNGKRHGQGTLTYAN-GDVYEGEFKNGQRHGQGTYTYADGDRYEGEF 223

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1958799802 511 QGDKMAGPGILLCEDDSLYEGTFTRELtLLGKGKVTFPNGFTLEGSF 557
Cdd:COG4642   224 KNGKRHGQGTLTYADGDRYEGEFKNGK-RHGQGTMTYADGSVYEGEW 269
PLN03185 PLN03185
phosphatidylinositol phosphate kinase; Provisional
 357-550 2.95e-15

phosphatidylinositol phosphate kinase; Provisional


Pssm-ID: 215619 [Multi-domain]  Cd Length: 765  Bit Score: 79.11  E-value: 2.95e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 357 TYDGEWSRAKPHGKGTLKWPDGRNHVGDFYQGLEHGFGICLVPQASedkfdCYKCHWREGRMCEYGICEYGTDEVYKGYF 436
Cdd:PLN03185   33 MYEGEWRRGMRHGNGKISWPSGATYEGEFSGGYMHGSGTYTGTDGT-----TYKGRWRLNLKHGLGYQRYPNGDVFEGSW 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 437 QAGVRHGFGvldsapqapqpfRYTghWERGQrsgygieedrdrgeRYIGMWQADQRHGPGIVVTQAGVCYQGTFQGDKMA 516
Cdd:PLN03185  108 IQGLQEGPG------------KYT--WANGN--------------VYLGDMKGGKMSGKGTLTWVSGDSYEGQWLDGMMH 159

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1958799802 517 GPGILLCEDDSLYEGTFTRELTlLGKGkVTFPNG 550
Cdd:PLN03185  160 GFGVYTWSDGGCYVGTWTRGLK-DGKG-VFYPAG 191
PH_alsin cd13269
Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual ...
 223-321 1.02e-13

Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241423  Cd Length: 106  Bit Score: 67.42  E-value: 1.02e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 223 DVLCTPTHRLLQDSQDIPV-VVTPLR--AERVLLFDDTLVLLQGHNVHTFDLKLVWVDPSQD----KCVLHILTPEDEFS 295
Cdd:cd13269     1 DSLRSPDRRLIRESSTRPLtLQNAGRfsSHWFILFNDALVHAQFSTHHIFPLATLWVEPIPDedsgQNALKITTPEESFT 80

                          90       100
                  ....*....|....*....|....*.
gi 1958799802 296 FCTRDPQGQVVWQWKVTQAVCQALCG 321
Cdd:cd13269    81 LVASTPQEKAEWLRAINQAIDQALNG 106
MORN pfam02493
MORN repeat; The MORN (Membrane Occupation and Recognition Nexus) repeat is found in multiple ...
 358-378 2.78e-05

MORN repeat; The MORN (Membrane Occupation and Recognition Nexus) repeat is found in multiple copies in several proteins including junctophilins (See Takeshima et al. Mol. Cell 2000;6:11-22). A MORN-repeat protein has been identified in the parasite Toxoplasma gondiis a dynamic component of cell division apparatus in Toxoplasma gondii. It has been hypothesized to functions as a linker protein between certain membrane regions and the parasite's cytoskeleton.


Pssm-ID: 308220 [Multi-domain]  Cd Length: 23  Bit Score: 40.85  E-value: 2.78e-05
                          10        20
                  ....*....|....*....|.
gi 1958799802 358 YDGEWSRAKPHGKGTLKWPDG 378
Cdd:pfam02493   1 YEGEWKNGKRHGKGVYTWPDG 21
MORN smart00698
Possible plasma membrane-binding motif in junctophilins, PIP-5-kinases and protein kinases;
356-377 3.10e-04

Possible plasma membrane-binding motif in junctophilins, PIP-5-kinases and protein kinases;


Pssm-ID: 197832 [Multi-domain]  Cd Length: 22  Bit Score: 38.09  E-value: 3.10e-04
                           10        20
                   ....*....|....*....|..
gi 1958799802  356 ATYDGEWSRAKPHGKGTLKWPD 377
Cdd:smart00698   1 DRYEGEWRNGKRHGRGVYTYAN 22
 
Name Accession Description Interval E-value
COG4642 COG4642
Uncharacterized conserved protein [Function unknown];
358-557 1.34e-32

Uncharacterized conserved protein [Function unknown];


Pssm-ID: 443680 [Multi-domain]  Cd Length: 271  Bit Score: 126.61  E-value: 1.34e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 358 YDGEWSRAKPHGKGTLKWPDGRNHVGDFYQGLEHGFGICLVPQASE-------DKFDCYKCHWREGRMCEYGICEYGTDE 430
Cdd:COG4642    69 EGGVTAAGGGGGGGGGKGDGGDGGGGEGGFGGGGGGGGGKKGGGGGgggvlegDDGGGYGGGTADGGRGGGGIYTFPNGD 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 431 VYKGYFQAGVRHGFGVLDSAPQApqpfRYTGHWERGQRSGYGIEEDRDrGERYIGMWQADQRHGPGIVVTQAGVCYQGTF 510
Cdd:COG4642   149 VYEGEFKNGKPHGQGTLTYADGD----RYEGEFKNGKRHGQGTLTYAN-GDVYEGEFKNGQRHGQGTYTYADGDRYEGEF 223

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1958799802 511 QGDKMAGPGILLCEDDSLYEGTFTRELtLLGKGKVTFPNGFTLEGSF 557
Cdd:COG4642   224 KNGKRHGQGTLTYADGDRYEGEFKNGK-RHGQGTMTYADGSVYEGEW 269
COG4642 COG4642
Uncharacterized conserved protein [Function unknown];
356-510 5.00e-28

Uncharacterized conserved protein [Function unknown];


Pssm-ID: 443680 [Multi-domain]  Cd Length: 271  Bit Score: 113.51  E-value: 5.00e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 356 ATYDGEWSRAKPHGKGTLKWPDGRNHVGDFYQGLEHGfgiclvpqasedkfdcykchwregrmceYGICEYGTDEVYKGY 435
Cdd:COG4642   148 DVYEGEFKNGKPHGQGTLTYADGDRYEGEFKNGKRHG----------------------------QGTLTYANGDVYEGE 199

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958799802 436 FQAGVRHGFGVLdsapQAPQPFRYTGHWERGQRSGYGIEEDRDrGERYIGMWQADQRHGPGIVVTQAGVCYQGTF 510
Cdd:COG4642   200 FKNGQRHGQGTY----TYADGDRYEGEFKNGKRHGQGTLTYAD-GDRYEGEFKNGKRHGQGTMTYADGSVYEGEW 269
PLN03185 PLN03185
phosphatidylinositol phosphate kinase; Provisional
 357-550 2.95e-15

phosphatidylinositol phosphate kinase; Provisional


Pssm-ID: 215619 [Multi-domain]  Cd Length: 765  Bit Score: 79.11  E-value: 2.95e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 357 TYDGEWSRAKPHGKGTLKWPDGRNHVGDFYQGLEHGFGICLVPQASedkfdCYKCHWREGRMCEYGICEYGTDEVYKGYF 436
Cdd:PLN03185   33 MYEGEWRRGMRHGNGKISWPSGATYEGEFSGGYMHGSGTYTGTDGT-----TYKGRWRLNLKHGLGYQRYPNGDVFEGSW 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 437 QAGVRHGFGvldsapqapqpfRYTghWERGQrsgygieedrdrgeRYIGMWQADQRHGPGIVVTQAGVCYQGTFQGDKMA 516
Cdd:PLN03185  108 IQGLQEGPG------------KYT--WANGN--------------VYLGDMKGGKMSGKGTLTWVSGDSYEGQWLDGMMH 159

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1958799802 517 GPGILLCEDDSLYEGTFTRELTlLGKGkVTFPNG 550
Cdd:PLN03185  160 GFGVYTWSDGGCYVGTWTRGLK-DGKG-VFYPAG 191
COG4642 COG4642
Uncharacterized conserved protein [Function unknown];
347-436 7.87e-14

Uncharacterized conserved protein [Function unknown];


Pssm-ID: 443680 [Multi-domain]  Cd Length: 271  Bit Score: 71.91  E-value: 7.87e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 347 FHREGRLYQA---TYDGEWSRAKPHGKGTLKWPDGRNHVGDFYQGLEHGFGICLVPqaseDKfDCYKCHWREGRMCEYGI 423
Cdd:COG4642   182 RHGQGTLTYAngdVYEGEFKNGQRHGQGTYTYADGDRYEGEFKNGKRHGQGTLTYA----DG-DRYEGEFKNGKRHGQGT 256

                          90
                  ....*....|...
gi 1958799802 424 CEYGTDEVYKGYF 436
Cdd:COG4642   257 MTYADGSVYEGEW 269
PH_alsin cd13269
Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual ...
 223-321 1.02e-13

Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241423  Cd Length: 106  Bit Score: 67.42  E-value: 1.02e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 223 DVLCTPTHRLLQDSQDIPV-VVTPLR--AERVLLFDDTLVLLQGHNVHTFDLKLVWVDPSQD----KCVLHILTPEDEFS 295
Cdd:cd13269     1 DSLRSPDRRLIRESSTRPLtLQNAGRfsSHWFILFNDALVHAQFSTHHIFPLATLWVEPIPDedsgQNALKITTPEESFT 80

                          90       100
                  ....*....|....*....|....*.
gi 1958799802 296 FCTRDPQGQVVWQWKVTQAVCQALCG 321
Cdd:cd13269    81 LVASTPQEKAEWLRAINQAIDQALNG 106
PLN03185 PLN03185
phosphatidylinositol phosphate kinase; Provisional
 356-473 3.03e-07

phosphatidylinositol phosphate kinase; Provisional


Pssm-ID: 215619 [Multi-domain]  Cd Length: 765  Bit Score: 53.68  E-value: 3.03e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958799802 356 ATYDGEWSRAKPHGKGTLKWPDGRNHVGDFYQGLEHGFGICLVPQAseDKFD--------------------CYKCHWRE 415
Cdd:PLN03185   55 ATYEGEFSGGYMHGSGTYTGTDGTTYKGRWRLNLKHGLGYQRYPNG--DVFEgswiqglqegpgkytwangnVYLGDMKG 132

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958799802 416 GRMCEYGICEYGTDEVYKGYFQAGVRHGFGVLDSAPQApqpfRYTGHWERGQRSGYGI 473
Cdd:PLN03185  133 GKMSGKGTLTWVSGDSYEGQWLDGMMHGFGVYTWSDGG----CYVGTWTRGLKDGKGV 186
MORN pfam02493
MORN repeat; The MORN (Membrane Occupation and Recognition Nexus) repeat is found in multiple ...
 358-378 2.78e-05

MORN repeat; The MORN (Membrane Occupation and Recognition Nexus) repeat is found in multiple copies in several proteins including junctophilins (See Takeshima et al. Mol. Cell 2000;6:11-22). A MORN-repeat protein has been identified in the parasite Toxoplasma gondiis a dynamic component of cell division apparatus in Toxoplasma gondii. It has been hypothesized to functions as a linker protein between certain membrane regions and the parasite's cytoskeleton.


Pssm-ID: 308220 [Multi-domain]  Cd Length: 23  Bit Score: 40.85  E-value: 2.78e-05
                          10        20
                  ....*....|....*....|.
gi 1958799802 358 YDGEWSRAKPHGKGTLKWPDG 378
Cdd:pfam02493   1 YEGEWKNGKRHGKGVYTWPDG 21
MORN smart00698
Possible plasma membrane-binding motif in junctophilins, PIP-5-kinases and protein kinases;
356-377 3.10e-04

Possible plasma membrane-binding motif in junctophilins, PIP-5-kinases and protein kinases;


Pssm-ID: 197832 [Multi-domain]  Cd Length: 22  Bit Score: 38.09  E-value: 3.10e-04
                           10        20
                   ....*....|....*....|..
gi 1958799802  356 ATYDGEWSRAKPHGKGTLKWPD 377
Cdd:smart00698   1 DRYEGEWRNGKRHGRGVYTYAN 22
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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